Mycophenolate mofetil capsules (MMF) are indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney [see Clinical Studies (14.1)], heart [see Clinical Studies (14.2)] or liver transplants [see Clinical Studies (14.3)], in combination with other immunosuppressants.

{ "type": "p", "children": [], "text": "Mycophenolate mofetil capsules (MMF) are indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney [see Clinical Studies (14.1)], heart [see Clinical Studies (14.2)] or liver transplants [see Clinical Studies (14.3)], in combination with other immunosuppressants." }

Mycophenolate mofetil capsules should not be used without the supervision of a physician with experience in immunosuppressive therapy.

Mycophenolate Mofetil Capsules

Mycophenolate mofetil capsules should not be used interchangeably with mycophenolic acid delayed-release tablets without supervision of a physician with experience in immunosuppressive therapy because the rates of absorption following the administration of mycophenolate mofetil capsules and mycophenolic acid delayed-release tablets are not equivalent.

Mycophenolate mofetil capsules should not be opened or crushed. Patients should avoid inhalation or contact of the skin or mucous membranes with the powder contained in mycophenolate mofetil capsules. If such contact occurs, they must wash the area of contact thoroughly with soap and water. In case of ocular contact, rinse eyes with plain water.

The initial oral dose of mycophenolate mofetil capsules should be given as soon as possible following kidney, heart or liver transplant. It is recommended that mycophenolate mofetil capsules be administered on an empty stomach. In stable transplant patients, however, mycophenolate mofetil capsules may be administered with food if necessary [see Clinical Pharmacology (12.3)].

Patients should be instructed to take a missed dose as soon as they remember, except if it is closer than 2 hours to the next scheduled dose; in this case, they should continue to take mycophenolate mofetil capsules at the usual times.

Adults

The recommended dosage for adult kidney transplant patients is 1 g orally, twice daily (total daily dose of 2 g).

Pediatrics (3 months and older)

Pediatric dosing is based on body surface area (BSA). Pediatric patients with BSA ≥1.25 m2 may be dosed with capsules as follows:

<div class="scrollingtable"><table border="1" cellpadding="5" cellspacing="0" width="1000px"> <caption> <span>Table 1: Pediatric Kidney Transplant: Dosage Using Capsules </span> </caption> <col width="136.35pt"/> <col width="390.3pt"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Body Surface Area</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Dosage</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">1.25 m<span class="Sup">2</span> to &lt;1.5 m<span class="Sup">2</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Mycophenolate mofetil capsule 750 mg twice daily (1.5 g total daily dose)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">≥1.5 m<span class="Sup">2</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Mycophenolate mofetil capsules 1 g twice daily (2 g total daily dose)</p> </td> </tr> </tbody> </table></div>

Adults

The recommended dosage of mycophenolate mofetil for adult heart transplant patients is 1.5 g orally administered twice daily (total daily dose of 3 g).

Pediatric patients with BSA ≥1.25 m2 may be started on therapy with capsules as follows:

<div class="scrollingtable"><table cellpadding="5" width="800px"> <caption> <span>Table 2: Pediatric Heart Transplant: Pediatric Starting Dosage Using Capsules</span> </caption> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Body Surface Area</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Starting Dosage*</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> 1.25 m<span class="Sup">2</span> to &lt;1.5 m<span class="Sup">2</span></td><td class="Botrule Lrule Rrule Toprule"> Mycophenolate mofetil capsule 750 mg twice daily (1.5 g total daily dose)</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> ≥ 1.5 m<span class="Sup">2</span></td><td class="Botrule Lrule Rrule Toprule">Mycophenolate mofetil capsules 1 g twice daily (2 g total daily dose) </td> </tr> </tbody> </table></div>

*Maximum maintenance dose: 3 g total daily.

Adults

The recommended dosage of mycophenolate mofetil for adult liver transplant patients is 1.5 g administered orally twice daily (total daily dose of 3 g).

Pediatric patients with BSA ≥1.25 m2 may be started on therapy with capsules as follows:

<div class="scrollingtable"><table cellpadding="5" width="800px"> <caption> <span>Table 3: Pediatric Liver Transplant: Pediatric Starting Dosage Using Capsules</span> </caption> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Body Surface Area</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Starting Dosage*</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> 1.25 m<span class="Sup">2</span> to &lt;1.5 m<span class="Sup">2</span></td><td class="Botrule Lrule Rrule Toprule"> Mycophenolate mofetil capsule 750 mg twice daily (1.5 g total daily dose)</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> ≥ 1.5 m<span class="Sup">2</span></td><td class="Botrule Lrule Rrule Toprule">Mycophenolate mofetil capsules 1 g twice daily (2 g total daily dose) </td> </tr> </tbody> </table></div>

*Maximum maintenance dose: 3 g total daily.

Renal Impairment No dosage modifications are needed in kidney transplant patients with delayed graft function postoperatively [see Clinical Pharmacology (12.3)]. In kidney transplant patients with severe chronic impairment of the graft (GFR <25 mL/min/1.73 m2), do not administer doses of mycophenolate mofetil greater than 1 g twice a day. These patients should be carefully monitored [see Clinical Pharmacology (12.3)].

Neutropenia If neutropenia develops (ANC <1.3 x 103/µL), dosing with mycophenolate mofetil should be interrupted or reduced, appropriate diagnostic tests performed, and the patient managed appropriately [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)].

Mycophenolate Mofetil Capsules, USP are available in the following strength:

{ "type": "p", "children": [], "text": "Mycophenolate Mofetil Capsules, USP are available in the following strength:" }

<div class="scrollingtable"><table border="1" cellpadding="5" cellspacing="0" width="800px"> <col width="1px1pt1pt1px"/> <col width="414.75pt"/> <tbody class="Headless"> <tr class="First Last"> <td class="Lrule Toprule"> <p class="First">250 mg</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">hard gelatin capsules with a light blue opaque cap and a bright orange opaque body, filled with a white to off-white powder with small agglomerates; imprinted with "TEVA" on the cap and "7334" on the body</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"5\" cellspacing=\"0\" width=\"800px\">\n<col width=\"1px1pt1pt1px\"/>\n<col width=\"414.75pt\"/>\n<tbody class=\"Headless\">\n<tr class=\"First Last\">\n<td class=\"Lrule Toprule\">\n<p class=\"First\">250 mg</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">hard gelatin capsules with a light blue opaque cap and a bright orange opaque body, filled with a white to off-white powder with small agglomerates; imprinted with \"TEVA\" on the cap and \"7334\" on the body</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Allergic reactions to mycophenolate mofetil capsules have been observed; therefore, mycophenolate mofetil capsules are contraindicated in patients with a hypersensitivity to mycophenolate mofetil (MMF), mycophenolic acid (MPA) or any component of the drug product.

{ "type": "p", "children": [], "text": "Allergic reactions to mycophenolate mofetil capsules have been observed; therefore, mycophenolate mofetil capsules are contraindicated in patients with a hypersensitivity to mycophenolate mofetil (MMF), mycophenolic acid (MPA) or any component of the drug product." }

Use of MMF during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney and nervous system. Females of reproductive potential must be made aware of these risks and must be counseled regarding pregnancy prevention and planning. Avoid use of MMF during pregnancy if safer treatment options are available [see Use in Specific Populations (8.1, 8.3)].

Patients receiving immunosuppressants, including mycophenolate mofetil capsules, are at increased risk of developing lymphomas and other malignancies, particularly of the skin [see Adverse Reactions (6.1)]. The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. For patients with increased risk for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen with a high protection factor.

Post-transplant lymphoproliferative disorder (PTLD) developed in 0.4% to 1% of patients receiving mycophenolate mofetil capsules (2 g or 3 g) with other immunosuppressive agents in controlled clinical trials of kidney, heart and liver transplant patients [see Adverse Reactions (6.1)]. The majority of PTLD cases appear to be related to Epstein Barr Virus (EBV) infection. The risk of PTLD appears greatest in those individuals who are EBV seronegative, a population which includes many young children. In pediatric patients, no other malignancies besides PTLD were observed in clinical trials [see Adverse Reactions (6.1)].

Patients receiving immunosuppressants, including mycophenolate mofetil capsules, are at increased risk of developing bacterial, fungal, protozoal and new or reactivated viral infections, including opportunistic infections. The risk increases with the total immunosuppressive load. These infections may lead to serious outcomes, including hospitalizations and death [see Adverse Reactions (6.1, 6.2)].

Serious viral infections reported include:

Consider dose reduction or discontinuation of mycophenolate mofetil in patients who develop new infections or reactivate viral infections, weighing the risk that reduced immunosuppression represents to the functioning allograft.

PVAN, especially due to BK virus infection, is associated with serious outcomes, including deteriorating renal function and renal graft loss [see Adverse Reactions (6.2)]. Patient monitoring may help detect patients at risk for PVAN.

PML, which is sometimes fatal, commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia [see Adverse Reactions (6.2)]. In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms.

The risk of CMV viremia and CMV disease is highest among transplant recipients seronegative for CMV at time of transplant who receive a graft from a CMV seropositive donor. Therapeutic approaches to limiting CMV disease exist and should be routinely provided. Patient monitoring may help detect patients at risk for CMV disease.

Viral reactivation has been reported in patients infected with HBV or HCV. Monitoring infected patients for clinical and laboratory signs of active HBV or HCV infection is recommended.

Severe neutropenia [absolute neutrophil count (ANC) <0.5 x 103/μL] developed in transplant patients receiving mycophenolate mofetil capsules 3 g daily [see Adverse Reactions (6.1)]. Patients receiving mycophenolate mofetil capsules should be monitored for neutropenia. Neutropenia has been observed most frequently in the period from 31 to 180 days post-transplant in patients treated for prevention of kidney, heart and liver rejection. The development of neutropenia may be related to mycophenolate mofetil itself, concomitant medications, viral infections, or a combination of these causes. If neutropenia develops (ANC <1.3 x 103/μL), dosing with mycophenolate mofetil capsules should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately [see Dosage and Administration (2.5)]. 

Patients receiving mycophenolate mofetil capsules should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression.

Consider monitoring with complete blood counts weekly for the first month, twice monthly for the second and third months, and monthly for the remainder of the first year.

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate mofetil capsules in combination with other immunosuppressive agents. In some cases, PRCA was found to be reversible with dose reduction or cessation of mycophenolate mofetil capsule therapy. In transplant patients, however, reduced immunosuppression may place the graft at risk.

Gastrointestinal bleeding requiring hospitalization, ulceration and perforations were observed in clinical trials. Physicians should be aware of these serious adverse effects particularly when administering mycophenolate mofetil capsules to patients with a gastrointestinal disease.

Mycophenolate mofetil capsules are an inosine monophosphate dehydrogenase (IMPDH) inhibitor; therefore it should be avoided in patients with hereditary deficiencies of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndromes because it may cause an exacerbation of disease symptoms characterized by the overproduction and accumulation of uric acid leading to symptoms associated with gout such as acute arthritis, tophi, nephrolithiasis or urolithiasis and renal disease including renal failure.

Acute inflammatory syndrome (AIS) has been reported with the use of MMF and mycophenolate products, and some cases have resulted in hospitalization. AIS is a paradoxical pro-inflammatory reaction characterized by fever, arthralgias, arthritis, muscle pain and elevated inflammatory markers including, C-reactive protein and erythrocyte sedimentation rate, without evidence of infection or underlying disease recurrence. Symptoms occur within weeks to months of initiation of treatment or a dose increase. After discontinuation, improvement of symptoms and inflammatory markers are usually observed within 24 to 48 hours.

Monitor patients for symptoms and laboratory parameters of AIS when starting treatment with mycophenolate products or when increasing the dosage. Discontinue treatment and consider other treatment alternatives based on the risk and benefit for the patient.

During treatment with mycophenolate mofetil capsules, the use of live attenuated vaccines should be avoided (e.g., intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) and patients should be advised that vaccinations may be less effective. Advise patients to discuss with the physician before seeking any immunizations.

Patients should not donate blood during therapy and for at least 6 weeks following discontinuation of mycophenolate mofetil capsules because their blood or blood products might be administered to a female of reproductive potential or a pregnant woman.

Based on animal data, men should not donate semen during therapy and for 90 days following discontinuation of mycophenolate mofetil capsules [see Use in Specific Populations (8.3)].

A variety of drugs have potential to alter systemic MPA exposure when coadministered with mycophenolate mofetil capsules. Therefore, determination of MPA concentrations in plasma before and after making any changes to immunosuppressive therapy, or when adding or discontinuing concomitant medications, may be appropriate to ensure MPA concentrations remain stable.

Mycophenolate mofetil capsules may impact the ability to drive and use machines. Patients should avoid driving or using machines if they experience somnolence, confusion, dizziness, tremor, or hypotension during treatment with mycophenolate mofetil capsules [see Adverse Reactions (6.1)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

An estimated total of 1557 adult patients received mycophenolate mofetil capsules during pivotal clinical trials in the prevention of acute organ rejection. Of these, 991 were included in the three renal studies, 277 were included in one hepatic study, and 289 were included in one cardiac study. Patients in all study arms also received cyclosporine and corticosteroids.

The data described below primarily derive from five randomized, active-controlled double-blind 12-month trials of mycophenolate mofetil capsules in de novo kidney (3) heart (1) and liver (1) transplant patients [see Clinical Studies (14.1, 14.2, and 14.3)].

Mycophenolate Mofetil Oral

The incidence of adverse reactions for mycophenolate mofetil was determined in five randomized, comparative, double-blind trials in the prevention of rejection in kidney, heart and liver transplant patients (two active- and one placebo-controlled trials, one active-controlled trial, and one active-controlled trial, respectively) [see Clinical Studies (14.1, 14.2 and 14.3)].

The three de novo kidney studies with 12-month duration compared two dose levels of oral mycophenolate mofetil (1 g twice daily and 1.5 g twice daily) with azathioprine (2 studies) or placebo (1 study) when administered in combination with cyclosporine (Sandimmune®) and corticosteroids to prevent acute rejection episodes. One study also included anti-thymocyte globulin (ATGAM®) induction therapy.

In the de novo heart transplantation study with 12-month duration, patients received mycophenolate mofetil 1.5 g twice daily (n=289) or azathioprine 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune® or Neoral®) and corticosteroids as maintenance immunosuppressive therapy.

In the de novo liver transplantation study with 12-month duration, patients received mycophenolate mofetil 1 g twice daily intravenously for up to 14 days followed by mycophenolate mofetil 1.5 g twice daily orally or azathioprine 1 to 2 mg/kg/day intravenously followed by azathioprine 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral®) and corticosteroids as maintenance immunosuppressive therapy. The total number of patients enrolled was 565.

Approximately 53% of the kidney transplant patients, 65% of the heart transplant patients, and 48% of the liver transplant patients were treated for more than 1 year. Adverse reactions reported in ≥20% of patients in the mycophenolate mofetil treatment groups are presented below. The safety data of three kidney transplantation studies are pooled together.

<div class="scrollingtable"><table cellpadding="5" cellspacing="0" width="1000px"> <caption> <span>Table 5: Adverse Reactions in Controlled Studies of De Novo Kidney, Heart or Liver Transplantation Reported in ≥20% of Patients in the Mycophenolate Mofetil Group</span> </caption> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First"> <span class="Bold">Adverse drug reaction</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="3"> <p class="First"> <span class="Bold">Kidney Studies</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Heart Study</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Liver Study</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Rrule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First"> <span class="Bold">AZA</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First"> <span class="Bold">Placebo</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> </td><td align="center" class="Botrule"> <p class="First"> <span class="Bold">AZA</span> </p> </td><td align="center" class="Botrule Lrule Rrule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First"> <span class="Bold">AZA</span> </p> </td> </tr> <tr> <td class="Lrule" rowspan="3"> <p class="First"> <span class="Bold">System Organ Class</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">2g/day</span> </p> <p> <span class="Bold">(n=501)</span> </p> <p> <span class="Bold">or 3g/day (n=490)</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First"> <span class="Bold">1 to 2</span> </p> <p> <span class="Bold">mg/kg/day or 100 to</span> </p> <p> <span class="Bold">150</span> </p> <p> <span class="Bold">mg/day</span> </p> </td><td class="Rrule"></td><td align="center" class="Rrule"> <p class="First"> <span class="Bold">3g/day</span> </p> </td><td align="center" class="Rrule"> <p class="First"> <span class="Bold">1.5 to 3</span> </p> <p> <span class="Bold">mg/kg/day</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First"> <span class="Bold">3g/day</span> </p> </td><td align="center" class="Rrule"> <p class="First"> <span class="Bold">1 to 2</span> </p> <p> <span class="Bold">mg/kg/day</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"> <p class="First"> <span class="Bold">(n=991)</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First"> <span class="Bold">(n=326)</span> </p> </td><td align="center" class="Rrule Toprule"> <p class="First"> <span class="Bold">(n=166)</span> </p> </td><td align="center" class="Rrule Toprule"> <p class="First"> <span class="Bold">(n=289)</span> </p> </td><td align="center" class="Rrule Toprule"> <p class="First"> <span class="Bold">(n=289)</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First"> <span class="Bold">(n=277)</span> </p> </td><td align="center" class="Rrule Toprule"> <p class="First"> <span class="Bold">(n=287)</span> </p> </td> </tr> <tr> <td align="center" class="Lrule Rrule"> <p class="First"> <span class="Bold">%</span> </p> </td><td align="center" class="Rrule"> <p class="First"> <span class="Bold">%</span> </p> </td><td align="center" class="Rrule Toprule"> <p class="First"> <span class="Bold">%</span> </p> </td><td align="center" class="Rrule Toprule"> <p class="First"> <span class="Bold">%</span> </p> </td><td align="center" class="Rrule Toprule"> <p class="First"> <span class="Bold">%</span> </p> </td><td align="center" class="Rrule"> <p class="First"> <span class="Bold">%</span> </p> </td><td align="center" class="Rrule Toprule"> <p class="First"> <span class="Bold">%</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Infections and infestations</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule"> <p class="First">Bacterial infections</p> </td><td align="center" class="Rrule"> <p class="First">39.9</p> </td><td align="center" class="Rrule"> <p class="First">33.7</p> </td><td align="center" class="Botrule Rrule"> <p class="First">37.3</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">27.4</p> </td><td align="center" class="Rrule"> <p class="First">26.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule"> <p class="First">Viral infections</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">- <span class="Sup">a</span> </p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">31.1</p> </td><td align="center" class="Botrule Rrule"> <p class="First">24.9</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="8"> <p class="First"> <span class="Bold">Blood and lymphatic system disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule"> <p class="First">Anemia</p> </td><td align="center" class="Botrule Rrule"> <p class="First">20.0</p> </td><td align="center" class="Botrule Rrule"> <p class="First">23.6</p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.4</p> </td><td align="center" class="Botrule Rrule"> <p class="First">45.0</p> </td><td align="center" class="Botrule Rrule"> <p class="First">47.1</p> </td><td align="center" class="Botrule Rrule"> <p class="First">43.0</p> </td><td align="center" class="Botrule Rrule"> <p class="First">53.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule"> <p class="First">Ecchymosis</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule"> <p class="First">20.1</p> </td><td align="center" class="Botrule Rrule"> <p class="First">9.7</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule"> <p class="First">Leukocytosis</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule"> <p class="First">42.6</p> </td><td align="center" class="Botrule Rrule"> <p class="First">37.4</p> </td><td align="center" class="Botrule Rrule"> <p class="First">22.4</p> </td><td align="center" class="Botrule Rrule"> <p class="First">21.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule"> <p class="First">Leukopenia</p> </td><td align="center" class="Botrule Rrule"> <p class="First">28.6</p> </td><td align="center" class="Botrule Rrule"> <p class="First">24.8</p> </td><td align="center" class="Botrule Rrule"> <p class="First">4.2</p> </td><td align="center" class="Botrule Rrule"> <p class="First">34.3</p> </td><td align="center" class="Botrule Rrule"> <p class="First">43.3</p> </td><td align="center" class="Botrule Rrule"> <p class="First">45.8</p> </td><td align="center" class="Botrule Rrule"> <p class="First">39.0</p> </td> </tr> <tr> <td class="Lrule Rrule"> <p class="First">Thrombocytopenia</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">24.2</p> </td><td align="center" class="Rrule"> <p class="First">28.0</p> </td><td align="center" class="Rrule"> <p class="First">38.3</p> </td><td align="center" class="Rrule"> <p class="First">42.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Metabolism and nutrition disorders</span> </p> </td> </tr> <tr> <td class="Lrule Rrule"> <p class="First">Hypercholesterolemia</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">46.0</p> </td><td align="center" class="Rrule"> <p class="First">43.9</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Hyperglycemia</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">48.4</p> </td><td align="center" class="Rrule"> <p class="First">53.3</p> </td><td align="center" class="Rrule"> <p class="First">43.7</p> </td><td align="center" class="Rrule"> <p class="First">48.8</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Hyperkalemia</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">22.0</p> </td><td align="center" class="Rrule Toprule"> <p class="First">23.7</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Hypocalcemia</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">30.0</p> </td><td align="center" class="Rrule Toprule"> <p class="First">30.0</p> </td> </tr> <tr> <td class="Lrule Toprule"> <p class="First">Hypokalemia</p> </td><td align="center" class="Lrule Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Toprule"> <p class="First">32.5</p> </td><td align="center" class="Lrule Rrule Toprule"> <p class="First">26.3</p> </td><td align="center" class="Rrule Toprule"> <p class="First">37.2</p> </td><td align="center" class="Rrule Toprule"> <p class="First">41.1</p> </td> </tr> <tr> <td class="Lrule Toprule"> <p class="First">Hypomagnesemia</p> </td><td align="center" class="Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">20.1</p> </td><td align="center" class="Rrule Toprule"> <p class="First">14.2</p> </td><td align="center" class="Rrule Toprule"> <p class="First">39.0</p> </td><td align="center" class="Rrule Toprule"> <p class="First">37.6</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Psychiatric disorders</span> </p> </td> </tr> <tr> <td class="Lrule Toprule"> <p class="First">Depression</p> </td><td align="center" class="Lrule Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Toprule"> <p class="First">20.1</p> </td><td align="center" class="Lrule Toprule"> <p class="First">15.2</p> </td><td align="center" class="Lrule Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Insomnia</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">43.3</p> </td><td align="center" class="Rrule Toprule"> <p class="First">39.8</p> </td><td align="center" class="Rrule Toprule"> <p class="First">52.3</p> </td><td align="center" class="Rrule Toprule"> <p class="First">47.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Nervous system disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule"> <p class="First">Dizziness</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule"> <p class="First">34.3</p> </td><td align="center" class="Botrule"> <p class="First">33.9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule"> <p class="First">Headache</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule"> <p class="First">58.5</p> </td><td align="center" class="Botrule"> <p class="First">55.4</p> </td><td align="center" class="Botrule Lrule Rrule"> <p class="First">53.8</p> </td><td align="center" class="Botrule Rrule"> <p class="First">49.1</p> </td> </tr> <tr> <td class="Lrule Rrule"> <p class="First">Tremor</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">26.3</p> </td><td align="center"> <p class="First">25.6</p> </td><td align="center" class="Lrule Rrule"> <p class="First">33.9</p> </td><td align="center" class="Rrule"> <p class="First">35.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Cardiac disorders</span> </p> </td> </tr> <tr> <td class="Lrule"> <p class="First">Tachycardia</p> </td><td align="center" class="Lrule Rrule"> <p class="First">-</p> </td><td align="center"> <p class="First">-</p> </td><td align="center" class="Lrule Rrule"> <p class="First">-</p> </td><td align="center"> <p class="First">22.8</p> </td><td align="center" class="Lrule Rrule"> <p class="First">21.8</p> </td><td align="center"> <p class="First">22.0</p> </td><td align="center" class="Lrule Rrule"> <p class="First">15.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Vascular disorders</span> </p> </td> </tr> <tr> <td class="Lrule"> <p class="First">Hypertension</p> </td><td align="center" class="Lrule"> <p class="First">27.5</p> </td><td align="center" class="Lrule Rrule"> <p class="First">32.2</p> </td><td align="center"> <p class="First">19.3</p> </td><td align="center" class="Lrule"> <p class="First">78.9</p> </td><td align="center" class="Lrule Rrule"> <p class="First">74.0</p> </td><td align="center"> <p class="First">62.1</p> </td><td align="center" class="Lrule Rrule"> <p class="First">59.6</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Hypotension</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">34.3</p> </td><td align="center" class="Rrule Toprule"> <p class="First">40.1</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Respiratory, thoracic and mediastinal disorders</span> </p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Cough</p> </td><td align="center" class="Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">40.5</p> </td><td align="center" class="Rrule Toprule"> <p class="First">32.2</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Dyspnea</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">44.3</p> </td><td align="center" class="Rrule Toprule"> <p class="First">44.3</p> </td><td align="center" class="Rrule Toprule"> <p class="First">31.0</p> </td><td align="center" class="Rrule Toprule"> <p class="First">30.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Pleural effusion</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">34.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">35.9</p> </td> </tr> <tr> <td class="Lrule Rrule" colspan="8"> <p class="First"> <span class="Bold">Gastrointestinal disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Abdominal pain</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">22.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">23.0</p> </td><td align="center" class="Rrule Toprule"> <p class="First">11.4</p> </td><td align="center" class="Rrule Toprule"> <p class="First">41.9</p> </td><td align="center" class="Toprule"> <p class="First">39.4</p> </td><td align="center" class="Lrule Rrule Toprule"> <p class="First">62.5</p> </td><td align="center" class="Rrule Toprule"> <p class="First">51.2</p> </td> </tr> <tr> <td class="Lrule Rrule"> <p class="First">Constipation</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center"> <p class="First">-</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">43.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">38.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">37.9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">38.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Decreased appetite</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">-</p> </td><td align="center" class="Rrule"> <p class="First">25.3</p> </td><td align="center" class="Rrule"> <p class="First">17.1</p> </td> </tr> <tr> <td class="Lrule Rrule"> <p class="First">Diarrhea</p> </td><td align="center" class="Rrule Toprule"> <p class="First">30.4</p> </td><td align="center" class="Rrule Toprule"> <p class="First">20.9</p> </td><td align="center" class="Rrule Toprule"> <p class="First">13.9</p> </td><td align="center" class="Rrule Toprule"> <p class="First">52.6</p> </td><td align="center" class="Rrule Toprule"> <p class="First">39.4</p> </td><td align="center" class="Rrule Toprule"> <p class="First">51.3</p> </td><td align="center" class="Rrule Toprule"> <p class="First">49.8</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Dyspepsia</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">22.1</p> </td><td align="center" class="Rrule Toprule"> <p class="First">22.1</p> </td><td align="center" class="Rrule Toprule"> <p class="First">22.4</p> </td><td align="center" class="Rrule Toprule"> <p class="First">20.9</p> </td> </tr> <tr> <td class="Lrule Toprule"> <p class="First">Nausea</p> </td><td align="center" class="Lrule Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Toprule"> <p class="First">56.1</p> </td><td align="center" class="Lrule Toprule"> <p class="First">60.2</p> </td><td align="center" class="Lrule Toprule"> <p class="First">54.5</p> </td><td align="center" class="Lrule Rrule Toprule"> <p class="First">51.2</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Vomiting</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">39.1</p> </td><td align="center" class="Rrule Toprule"> <p class="First">34.6</p> </td><td align="center" class="Rrule Toprule"> <p class="First">32.9</p> </td><td align="center" class="Rrule Toprule"> <p class="First">33.4</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Hepatobiliary disorders</span> </p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Blood lactate dehydrogenase increased</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">23.5</p> </td><td align="center" class="Rrule Toprule"> <p class="First">18.3</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td class="Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Hepatic enzyme increased</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">24.9</p> </td><td align="center" class="Rrule Toprule"> <p class="First">19.2</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Skin and subcutaneous tissues disorders</span> </p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Rash</p> </td><td align="center" class="Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">26.0</p> </td><td align="center" class="Rrule Toprule"> <p class="First">20.8</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Renal and urinary disorders</span> </p> </td> </tr> <tr> <td class="Lrule Toprule"> <p class="First">Blood creatinine</p> <p>increased</p> </td><td align="center" class="Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Lrule Rrule Toprule"> <p class="First">42.2</p> </td><td align="center" class="Rrule Toprule"> <p class="First">39.8</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Blood urea increased</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">36.7</p> </td><td align="center" class="Rrule Toprule"> <p class="First">34.3</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">General disorders and administration site conditions</span> </p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Asthenia</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Rrule Toprule"> <p class="First">49.1</p> </td><td align="center" class="Rrule Toprule"> <p class="First">41.2</p> </td><td align="center" class="Rrule Toprule"> <p class="First">35.4</p> </td><td align="center" class="Rrule Toprule"> <p class="First">33.8</p> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <p class="First">Edema <span class="Sup">b</span> </p> </td><td align="center" class="Rrule Toprule"> <p class="First">21.0</p> </td><td align="center" class="Rrule Toprule"> <p class="First">28.2</p> </td><td align="center" class="Rrule Toprule"> <p class="First">8.4</p> </td><td align="center" class="Rrule Toprule"> <p class="First">67.5</p> </td><td align="center" class="Rrule Toprule"> <p class="First">55.7</p> </td><td align="center" class="Rrule Toprule"> <p class="First">48.4</p> </td><td align="center" class="Rrule Toprule"> <p class="First">47.7</p> </td> </tr> <tr> <td class="Botrule Lrule Toprule"> <p class="First">Pain <span class="Sup">c</span> </p> </td><td align="center" class="Botrule Lrule Toprule"> <p class="First">24.8</p> </td><td align="center" class="Botrule Lrule Toprule"> <p class="First">32.2</p> </td><td align="center" class="Lrule Toprule"> <p class="First">9.6</p> </td><td align="center" class="Lrule Toprule"> <p class="First">79.2</p> </td><td align="center" class="Lrule Rrule Toprule"> <p class="First">77.5</p> </td><td align="center" class="Rrule Toprule"> <p class="First">74.0</p> </td><td align="center" class="Rrule Toprule"> <p class="First">77.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Pyrexia</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">-</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">56.4</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">53.6</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">52.3</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">56.1</p> </td> </tr> <tr> <td class="Toprule" colspan="8"> <p class="First"> <span class="Sup">a</span>: “-” Indicates that the incidence was below the cutoff value of 20% for inclusion in the table.</p> </td> </tr> <tr> <td colspan="8"> <p class="First"> <span class="Sup">b</span>: “Edema” includes peripheral edema, facial edema, scrotal edema.</p> </td> </tr> <tr class="Last"> <td colspan="8"> <p class="First"> <span class="Sup">c</span>: “Pain” includes musculoskeletal pain (myalgia, neck pain, back pain).</p> </td> </tr> </tbody> </table></div>

In the three de novo kidney studies, patients receiving 2 g/day of mycophenolate mofetil had an overall better safety profile than did patients receiving 3 g/day of mycophenolate mofetil.

Post-transplant lymphoproliferative disease (PTLD, pseudolymphoma) developed in 0.4% to 1% of patients receiving mycophenolate mofetil (2 g or 3 g daily) with other immunosuppressive agents in controlled clinical trials of kidney, heart and liver transplant patients followed for at least 1 year [see Warnings and Precautions (5.2)]. Non-melanoma skin carcinomas occurred in 1.6% to 4.2% of patients, other types of malignancy in 0.7% to 2.1% of patients. Three-year safety data in kidney and heart transplant patients did not reveal any unexpected changes in incidence of malignancy compared to the 1-year data. In pediatric patients, PTLD was observed in 1.35% (2/148) by 12 months post-transplant.

Cytopenias, including leukopenia, anemia, thrombocytopenia and pancytopenia are a known risk associated with mycophenolate and may lead or contribute to the occurrence of infections and hemorrhages [see Warnings and Precautions (5.3)]. Severe neutropenia (ANC <0.5 x 103/µL) developed in up to 2% of kidney transplant patients, up to 2.8% of heart transplant patients and up to 3.6% of liver transplant patients receiving mycophenolate mofetil capsules 3 g daily [see Warnings and Precautions (5.4) and Dosage and Administration (2.5)].

The most common opportunistic infections in patients receiving mycophenolate mofetil capsules with other immunosuppressants were mucocutaneous candida, CMV viremia/syndrome, and herpes simplex. The proportion of patients with CMV viremia/syndrome was 13.5%. In patients receiving mycophenolate mofetil capsules (2 g or 3 g) in controlled studies for prevention of kidney, heart or liver rejection, fatal infection/sepsis occurred in approximately 2% of kidney and heart patients and in 5% of liver patients [see Warnings and Precautions (5.3)].

The most serious gastrointestinal disorders reported were ulceration and hemorrhage, which are known risks associated with mycophenolate mofetil capsules. Mouth, esophageal, gastric, duodenal, and intestinal ulcers often complicated by hemorrhage, as well as hematemesis, melena, and hemorrhagic forms of gastritis and colitis were commonly reported during the pivotal clinical trials, while the most common gastrointestinal disorders were diarrhea, nausea and vomiting. Endoscopic investigation of patients with mycophenolate mofetil capsules-related diarrhea revealed isolated cases of intestinal villous atrophy [see Warnings and Precautions (5.5)].

The following adverse reactions were reported with 3% to <20% incidence in kidney, heart, and liver transplant patients treated with mycophenolate mofetil, in combination with cyclosporine and corticosteroids.

<div class="scrollingtable"><table border="1" cellpadding="5" cellspacing="0" width="800px"> <caption> <span>Table 6: Adverse Reactions in Controlled Studies of De Novo Kidney, Heart or Liver Transplantation Reported in 3% to &lt;20% of Patients Treated with Mycophenolate Mofetil in Combination with Cyclosporine and Corticosteroids</span> </caption> <col width="140.4pt"/> <col width="392.8pt"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">System Organ Class</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Adverse Reactions</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Body as a Whole</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">cellulitis, chills, hernia, malaise </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Infections and Infestations</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">fungal infections</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Hematologic and Lymphatic</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">coagulation disorder, ecchymosis, pancytopenia</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Urogenital</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">hematuria</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Cardiovascular</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">hypotension </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Metabolic and Nutritional</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">acidosis, alkaline phosphatase increased, hyperlipemia, hypophosphatemia, weight loss </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Digestive</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">esophagitis, flatulence, gastritis, gastrointestinal hemorrhage, hepatitis, ileus, nausea and vomiting, stomach ulcer, stomatitis</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Neoplasm benign, malignant and unspecified</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">neoplasm</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Skin and Appendages</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">skin benign neoplasm, skin carcinoma</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Psychiatric</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">confusional state</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Nervous</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">hypertonia, paresthesia, somnolence</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Musculoskeletal</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">arthralgia, myasthenia</p> </td> </tr> </tbody> </table></div>

Pediatrics

The type and frequency of adverse events in a clinical study for prevention of kidney allograft rejection in 100 pediatric patients 3 months to 18 years of age dosed with mycophenolate mofetil oral suspension 600 mg/m2 twice daily (up to 1 g twice daily) were generally similar to those observed in adult patients dosed with mycophenolate mofetil capsules at a dose of 1 g twice daily with the exception of abdominal pain, fever, infection, pain, sepsis, diarrhea, vomiting, pharyngitis, respiratory tract infection, hypertension, leukopenia, and anemia, which were observed in a higher proportion in pediatric patients.

Safety information in pediatric heart transplant or pediatric liver transplant patients treated with mycophenolate mofetil is supported by an open-label study in pediatric liver transplant patients and publications; the type and frequency of the reported adverse reactions are consistent with those observed in pediatric patients following renal transplant and in adults.

Geriatrics

Geriatric patients (≥65 years), particularly those who are receiving mycophenolate mofetil as part of a combination immunosuppressive regimen, may be at increased risk of certain infections (including cytomegalovirus [CMV] tissue invasive disease) and possibly gastrointestinal hemorrhage and pulmonary edema, compared to younger individuals [see Warnings and Precautions (5.3) and Adverse Reactions (6.1)].

Mycophenolate Mofetil Intravenous

The safety profile of mycophenolate mofetil intravenous was determined from a single, double-blind, controlled comparative study of the safety of 2 g/day of intravenous and oral mycophenolate mofetil in kidney transplant patients in the immediate post-transplant period (administered for the first 5 days).

The potential venous irritation of mycophenolate mofetil intravenous was evaluated by comparing the adverse reactions attributable to peripheral venous infusion of mycophenolate mofetil intravenous with those observed in the intravenous placebo group; patients in the placebo group received active medication by the oral route.

Adverse reactions attributable to peripheral venous infusion were phlebitis and thrombosis, both observed at 4% in patients treated with mycophenolate mofetil intravenous.

The following adverse reactions have been identified during post-approval use of mycophenolate mofetil. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

                      -Facial malformations: cleft lip, cleft palate, micrognathia, hypertelorism of the orbits

                      -Abnormalities of the ear and eye: abnormally formed or absent external/middle ear, coloboma, microphthalmos

                      -Malformations of the fingers: polydactyly, syndactyly, brachydactyly

                      -Cardiac abnormalities: atrial and ventricular septal defects

                      -Esophageal malformations: esophageal atresia

                      -Nervous system malformations: such as spina bifida.

<div class="scrollingtable"><table border="1" cellpadding="8" cellspacing="0" width="1000px"> <caption> <span>Table 7: Drug Interactions with Mycophenolate Mofetil Capsules that Affect Mycophenolic Acid (MPA) Exposure</span> </caption> <col width="526.5pt"/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Antacids with Magnesium or Aluminum Hydroxide</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use with an antacid containing magnesium or aluminum hydroxide decreases MPA systemic exposure <span class="Italics">[see Clinical Pharmacology (12.3)]</span>, which may reduce mycophenolate mofetil efficacy.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Prevention or Management</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Administer magnesium or aluminum hydroxide containing antacids at least 2h after mycophenolate mofetil capsules administration.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Proton Pump Inhibitors (PPIs)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use with PPIs decreases MPA systemic exposure <span class="Italics">[see Clinical Pharmacology (12.3)]</span>, which may reduce mycophenolate mofetil efficacy.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Prevention or Management</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Monitor patients for alterations in efficacy when PPIs are coadministered with mycophenolate mofetil capsules.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Lansoprazole, pantoprazole</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Drugs that Interfere with Enterohepatic Recirculation</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use with drugs that directly interfere with enterohepatic recirculation, or indirectly interfere with enterohepatic recirculation by altering the gastrointestinal flora, can decrease MPA systemic exposure <span class="Italics">[see Clinical Pharmacology (12.3)]</span>, which may reduce mycophenolate mofetil efficacy.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Prevention or Management</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Monitor patients for alterations in efficacy or mycophenolate mofetil related adverse reactions when these drugs are coadministered with mycophenolate mofetil capsules.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Cyclosporine A, trimethoprim/sulfamethoxazole, bile acid sequestrants (cholestyramine), rifampin as well as aminoglycoside, cephalosporin, fluoroquinolone and penicillin classes of antimicrobials</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Drugs Modulating Glucuronidation</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use with drugs inducing glucuronidation decreases MPA systemic exposure, potentially reducing mycophenolate mofetil efficacy, while use with drugs inhibiting glucuronidation increases MPA systemic exposure <span class="Italics">[see Clinical Pharmacology (12.3)]</span>, which may increase the risk of mycophenolate mofetil related adverse reactions.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Prevention or Management</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Monitor patients for alterations in efficacy or mycophenolate mofetil related adverse reactions when these drugs are coadministered with mycophenolate mofetil capsules. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Telmisartan (induces glucuronidation); isavuconazole (inhibits glucuronidation).</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Calcium Free Phosphate Binders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use with calcium free phosphate binders decrease MPA systemic exposure <span class="Italics">[see Clinical Pharmacology (12.3)]</span>, which may reduce mycophenolate mofetil efficacy.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Prevention or Management</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Administer calcium free phosphate binders at least 2 hours after mycophenolate mofetil capsules.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Sevelamer</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table border="1" cellpadding="5" cellspacing="0" width="999px"> <caption> <span>Table 8: Drug Interactions with Mycophenolate Mofetil Capsules that Affect Other Drugs</span> </caption> <col width="526.5pt"/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2">  </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Drugs that Undergo Renal Tubular Secretion</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">When concomitantly used with mycophenolate mofetil capsules, its metabolite MPAG, may compete with drugs eliminated by renal tubular secretion which may increase plasma concentrations and/or adverse reactions associated with these drugs.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Prevention or Management</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Monitor for drug-related adverse reactions in patients with renal impairment.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Acyclovir, ganciclovir, probenecid, valacyclovir, valganciclovir</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Combination Oral Contraceptives</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use with mycophenolate mofetil capsules decreased the systemic exposure to levonorgestrel, but did not affect the systemic exposure to ethinyl estradiol <span class="Italics">[see Clinical Pharmacology (12.3)]</span>, which may result in reduced combination oral contraceptive effectiveness.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Prevention or Management</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Use additional barrier contraceptive methods.</p> </td> </tr> </tbody> </table></div>

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to mycophenolate during pregnancy and those becoming pregnant within 6 weeks of discontinuing mycophenolate mofetil capsule treatment. To report a pregnancy or obtain information about the registry, visit www.mycophenolateREMS.com or call 1-800-617-8191.

Risk Summary

Use of mycophenolate mofetil (MMF) during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of multiple congenital malformations in multiple organ systems [see Human Data].  Oral administration of mycophenolate to rats and rabbits during the period of organogenesis produced congenital malformations and pregnancy loss at doses less than the recommended clinical dose (0.01 to 0.05 times the recommended clinical doses in kidney and heart transplant patients) [see Animal Data].

Consider alternative immunosuppressants with less potential for embryofetal toxicity. Risks and benefits of mycophenolate mofetil capsules should be discussed with the pregnant woman.

The estimated background risk of pregnancy loss and congenital malformations in organ transplant populations is not clear. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Human Data

A spectrum of congenital malformations (including multiple malformations in individual newborns) has been reported in 23% to 27% of live births in MMF exposed pregnancies, based on published data from pregnancy registries. Malformations that have been documented include external ear, eye, and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system.

Based on published data from pregnancy registries, the risk of first trimester pregnancy loss has been reported at 45% to 49% following MMF exposure.

Animal Data

In animal reproductive toxicology studies, there were increased rates of fetal resorptions and malformations in the absence of maternal toxicity. Oral administration of MMF to pregnant rats from Gestational Day 7 to Day 16 produced increased embryofetal lethality and fetal malformations including anophthalmia, agnathia, and hydrocephaly at doses equivalent to 0.015 and 0.01 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA. Oral administration of MMF to pregnant rabbits from Gestational Day 7 to Day 19 produced increased embryofetal lethality and fetal malformations included ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia at dose equivalents as low as 0.05 and 0.03 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA.

Risk Summary

There are no data on the presence of mycophenolate in human milk, or the effects on milk production. There are limited data in the National Transplantation Pregnancy Registry on the effects of mycophenolate on a breastfed child [see Data]. Studies in rats treated with MMF have shown mycophenolic acid (MPA) to be present in milk. Because available data are limited, it is not possible to exclude potential risks to a breastfeeding infant.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for mycophenolate mofetil capsules and any potential adverse effects on the breastfed infant from mycophenolate mofetil capsules or from the underlying maternal condition.

Data

Limited information is available from the National Transplantation Pregnancy Registry. Of seven infants reported by the National Transplantation Pregnancy Registry to have been breastfed while the mother was taking mycophenolate, all were born at 34 to 40 weeks gestation, and breastfed for up to 14 months. No adverse events were reported.

Females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning.

Pregnancy Planning

For patients who are considering pregnancy, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible. Risks and benefits of mycophenolate mofetil capsules should be discussed with the patient.

Pregnancy Testing

To prevent unplanned exposure during pregnancy, all females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL immediately before starting mycophenolate mofetil capsules. Another pregnancy test with the same sensitivity should be done 8 to 10 days later. Repeat pregnancy tests should be performed during routine follow-up visits. Results of all pregnancy tests should be discussed with the patient. In the event of a positive pregnancy test, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible.

Contraception

Female Patients

Females of reproductive potential taking mycophenolate mofetil capsules must receive contraceptive counseling and use acceptable contraception (see Table 9 for acceptable contraception methods). Patients must use acceptable birth control during the entire mycophenolate mofetil capsule therapy, and for 6 weeks after stopping mycophenolate mofetil capsules, unless the patient chooses abstinence.

Patients should be aware that mycophenolate mofetil capsules reduce blood levels of the hormones from the oral contraceptive pill and could theoretically reduce its effectiveness [see Drug Interactions (7.2)].

<div class="scrollingtable"><table border="1" cellpadding="5" cellspacing="0" width="1000px"> <caption> <span>Table 9: Acceptable Contraception Methods for Females of Reproductive Potential Pick from the following birth control options:</span> </caption> <col width="515.55pt"/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">Option 1</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Methods to</span> </p> <p> <span class="Bold">Use Alone</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="3"> <ul class="Disc"> <li>Intrauterine devices (IUDs)</li> <li>Tubal sterilization</li> <li>Patient’s partner vasectomy</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">OR</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Option 2</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Hormone Methods</span> </p> <p>choose 1</p> </td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Barrier Methods</span> </p> <p>choose 1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Choose One Hormone Method </span><span class="Italics">AND</span> </p> <p> <span class="Bold">One Barrier</span> </p> <p> <span class="Bold">Method</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Estrogen and Progesterone</span> </p> <ul class="Disc"> <li>Oral Contraceptive Pill</li> <li>Transdermal patch</li> <li>Vaginal ring <p class="First"> <span class="Bold">Progesterone-only</span> </p> </li> <li>Injection</li> <li>Implant</li> </ul> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">AND</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li>Diaphragm with spermicide</li> <li>Cervical cap with spermicide</li> <li>Contraceptive sponge</li> <li>Male condom</li> <li>Female condom</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">OR</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Option 3</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Barrier Methods</span> </p> <p>choose 1</p> </td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Barrier Methods</span> </p> <p>choose 1</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Choose One Barrier Method from each column</span><span class="Italics">(must choose two methods)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li>Diaphragm with spermicide</li> <li>Cervical cap with spermicide</li> <li>Contraceptive sponge</li> </ul> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">AND</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li>Male condom</li> <li>Female condom</li> </ul> </td> </tr> </tbody> </table></div>

Male Patients

Genotoxic effects have been observed in animal studies at exposures exceeding the human therapeutic exposures by approximately 1.25 times. Thus, the risk of genotoxic effects on sperm cells cannot be excluded. Based on this potential risk, sexually active male patients and/or their female partners are recommended to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment. Also, based on the potential risk of genotoxic effects, male patients should not donate sperm during treatment with mycophenolate mofetil capsules and for at least 90 days after cessation of treatment [see Use in Specific Populations (8.1), Nonclinical Toxicology (13.1), Patient Counseling Information (17.9)].

Safety and effectiveness have been established in pediatric patients 3 months and older for the prophylaxis of organ rejection of allogenic kidney, heart or liver transplants.

Kidney Transplant

Use of mycophenolate mofetil capsules in this population is supported by evidence from adequate and well-controlled studies of mycophenolate mofetil capsules in adults with additional data from one open-label, pharmacokinetic and safety study of mycophenolate mofetil capsules in pediatric patients after receiving allogeneic kidney transplant (100 patients, 3 months to 18 years of age) [see Dosage and Administration (2.2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.1)].

Heart Transplant and Liver Transplant

Use of mycophenolate mofetil capsules in pediatric heart transplant and liver transplant patients is supported by adequate and wellcontrolled studies and pharmacokinetic data in adult heart transplant and liver transplant patients. Additional supportive data include pharmacokinetic data in pediatric kidney transplant and pediatric liver transplant patients (8 liver transplant patients, 9 months to 5 years of age, in an open-label, pharmacokinetic and safety study) and published evidence of clinical efficacy and safety in pediatric heart transplant and pediatric liver transplant patients [see Dosage and Administration (2.3, 2.4), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.1)].

Clinical studies of mycophenolate mofetil capsules did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between geriatric and younger patients. In general, dose selection for a geriatric patient should take into consideration the presence of decreased hepatic, renal or cardiac function and of concomitant drug therapies [see Adverse Reactions (6.1), Drug Interactions (7)].

Patients with Kidney Transplant

No dosage adjustments are needed in kidney transplant patients experiencing delayed graft function postoperatively but patients should be carefully monitored [see Clinical Pharmacology (12.3)]. In kidney transplant patients with severe chronic impairment of the graft (GFR <25 mL/min/1.73 m2), no dose adjustments are necessary; however, doses greater than 1 g administered twice a day should be avoided.

Patients with Heart and Liver Transplant

No data are available for heart or liver transplant patients with severe chronic renal impairment. Mycophenolate mofetil capsules may be used for heart or liver transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks.

Patients with Kidney Transplant

No dosage adjustments are recommended for kidney transplant patients with severe hepatic parenchymal disease. However, it is not known whether dosage adjustments are needed for hepatic disease with other etiologies [see Clinical Pharmacology (12.3)].

 Patients with Heart Transplant

No data are available for heart transplant patients with severe hepatic parenchymal disease.

Possible signs and symptoms of acute overdose include hematological abnormalities such as leukopenia and neutropenia, and gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, and dyspepsia.

{ "type": "p", "children": [], "text": "Possible signs and symptoms of acute overdose include hematological abnormalities such as leukopenia and neutropenia, and gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, and dyspepsia." }

The experience with overdose of mycophenolate mofetil capsules in humans is limited. The reported effects associated with overdose fall within the known safety profile of the drug. The highest dose administered to kidney transplant patients in clinical trials has been 4 g/day. In limited experience with heart and liver transplant patients in clinical trials, the highest doses used were 4 g/day or 5 g/day. At doses of 4 g/day or 5 g/day, there appears to be a higher rate, compared to the use of 3 g/day or less, of gastrointestinal intolerance (nausea, vomiting, and/or diarrhea), and occasional hematologic abnormalities, particularly neutropenia [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "The experience with overdose of mycophenolate mofetil capsules in humans is limited. The reported effects associated with overdose fall within the known safety profile of the drug. The highest dose administered to kidney transplant patients in clinical trials has been 4 g/day. In limited experience with heart and liver transplant patients in clinical trials, the highest doses used were 4 g/day or 5 g/day. At doses of 4 g/day or 5 g/day, there appears to be a higher rate, compared to the use of 3 g/day or less, of gastrointestinal intolerance (nausea, vomiting, and/or diarrhea), and occasional hematologic abnormalities, particularly neutropenia [see Warnings and Precautions (5.4)]." }

Treatment and Management

{ "type": "p", "children": [], "text": "\nTreatment and Management\n" }

MPA and the phenolic glucuronide metabolite of MPA (MPAG) are usually not removed by hemodialysis. However, at high MPAG plasma concentrations (>100 mcg/mL), small amounts of MPAG are removed. By increasing excretion of the drug, MPA can be removed by bile acid sequestrants, such as cholestyramine [see Clinical Pharmacology (12.3)].

{ "type": "p", "children": [], "text": "MPA and the phenolic glucuronide metabolite of MPA (MPAG) are usually not removed by hemodialysis. However, at high MPAG plasma concentrations (>100 mcg/mL), small amounts of MPAG are removed. By increasing excretion of the drug, MPA can be removed by bile acid sequestrants, such as cholestyramine [see Clinical Pharmacology (12.3)].\n" }

Mycophenolate mofetil, USP is an antimetabolite immunosuppressant. It is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine monophosphate dehydrogenase (IMPDH) inhibitor.

{ "type": "p", "children": [], "text": "Mycophenolate mofetil, USP is an antimetabolite immunosuppressant. It is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine monophosphate dehydrogenase (IMPDH) inhibitor." }

The chemical name for mycophenolate mofetil, USP (MMF) is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate. It has the following structural formula:

{ "type": "p", "children": [], "text": " The chemical name for mycophenolate mofetil, USP (MMF) is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate. It has the following structural formula:" }

C23H31NO7      M.W. 433.50

{ "type": "p", "children": [], "text": "C23H31NO7      M.W. 433.50" }

Mycophenolate mofetil, USP is a white to almost white crystalline powder. It is slightly soluble in water (43 mcg/mL at pH 7.4), freely soluble in acetone, soluble in methanol, sparingly soluble in anhydrous ethanol, and practically insoluble in water. No polymorphic form was found. The apparent partition coefficient in 1-octanol/water (pH 7.4) buffer solution is 238. The pKa values for mycophenolate mofetil, USP are 5.6 for the morpholino group and 8.5 for the phenolic group.

{ "type": "p", "children": [], "text": "Mycophenolate mofetil, USP is a white to almost white crystalline powder. It is slightly soluble in water (43 mcg/mL at pH 7.4), freely soluble in acetone, soluble in methanol, sparingly soluble in anhydrous ethanol, and practically insoluble in water. No polymorphic form was found. The apparent partition coefficient in 1-octanol/water (pH 7.4) buffer solution is 238. The pKa values for mycophenolate mofetil, USP are 5.6 for the morpholino group and 8.5 for the phenolic group." }

Mycophenolate mofetil, USP is available for oral administration as capsules containing 250 mg of mycophenolate mofetil, USP.

{ "type": "p", "children": [], "text": "Mycophenolate mofetil, USP is available for oral administration as capsules containing 250 mg of mycophenolate mofetil, USP." }

Inactive ingredients in Mycophenolate Mofetil Capsules, USP, 250 mg include: black iron oxide, croscarmellose sodium, D&C red #28, D&C yellow #10, FD&C blue #1, FD&C red #40, gelatin, magnesium stearate, povidone, pregelatinized corn starch, propylene glycol, shellac glaze, and titanium dioxide.

{ "type": "p", "children": [], "text": " Inactive ingredients in Mycophenolate Mofetil Capsules, USP, 250 mg include: black iron oxide, croscarmellose sodium, D&C red #28, D&C yellow #10, FD&C blue #1, FD&C red #40, gelatin, magnesium stearate, povidone, pregelatinized corn starch, propylene glycol, shellac glaze, and titanium dioxide." }

Mycophenolate mofetil (MMF) is absorbed following oral administration and hydrolyzed to mycophenolic acid (MPA), the active metabolite. MPA is a selective, uncompetitive inhibitor of the two isoforms (type I and type II) of inosine monophosphate dehydrogenase (IMPDH) leading to inhibition of the de novo pathway of guanosine nucleotide synthesis and blocks DNA synthesis. The mechanism of action of MPA is multifaceted and includes effects on cellular checkpoints responsible for metabolic programming of lymphocytes. MPA shifts transcriptional activities in lymphocytes from a proliferative state to catabolic processes. In vitro studies suggest that MPA modulates transcriptional activities in human CD4+ T-lymphocytes by suppressing the Akt/mTOR and STAT5 pathways that are relevant to metabolism and survival, leading to an anergic state of T-cells whereby the cells become less responsive to antigenic stimulation. Additionally, MPA enhanced the expression of negative co-stimulators such as CD70, PD-1, CTLA-4, and transcription factor FoxP3 as well as decreased the expression of positive co-stimulators CD27 and CD28.

MPA decreases proliferative responses of T- and B-lymphocytes to both mitogenic and allo-antigenic stimulation, antibody responses, as well as the production of cytokines from lymphocytes and monocytes such as GM-CSF, IFN-Ɣ, IL-17, and TNF-α. Additionally, MPA prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection.

Overall, the effect of MPA is cytostatic and reversible.

There is a lack of information regarding the pharmacodynamic effects of MMF.

Absorption

Following oral and intravenous administration, MMF undergoes complete conversion to MPA, the active metabolite. In 12 healthy volunteers, the mean absolute bioavailability of oral MMF relative to intravenous MMF was 94%. Two 500 mg mycophenolate mofetil tablets have been shown to be bioequivalent to four 250 mg mycophenolate mofetil capsules. Five mL of the 200 mg/mL constituted mycophenolate mofetil oral suspension have been shown to be bioequivalent to four 250 mg capsules.

The mean (±SD) pharmacokinetic parameters estimates for MPA following the administration of MMF given as single doses to healthy volunteers, and multiple doses to kidney, heart, and liver transplant patients, are shown in Table 10. The area under the plasma-concentration time curve (AUC) for MPA appears to increase in a dose-proportional fashion in kidney transplant patients receiving multiple oral doses of MMF up to a daily dose of 3 g (1.5g twice daily) (see Table 10).

<div class="scrollingtable"><table border="1" cellpadding="5" cellspacing="0" width="1000px"> <caption> <span>Table 10: Pharmacokinetic Parameters for MPA [mean (±SD)] Following Administration of MMF to Healthy Volunteers (Single Dose), and Kidney, Heart, and Liver Transplant Patients (Multiple Doses)</span> </caption> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="5">  </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Healthy Volunteers</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Dose/Route</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">T<span class="Sub">max</span> <br/> (h)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">C<span class="Sub">max</span> <br/> (mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Total AUC <br/> (mcg•h/mL)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">Single dose</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">1 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.80</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">24.5</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">63.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(±0.36)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±9.5)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±16.2)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=129)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=129)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=117)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Kidney Transplant Patients (twice daily dosing) Time After Transplantation</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Dose/Route</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">T<span class="Sub">max</span> <br/> (h)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">C<span class="Sub">max</span> <br/> (mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Interdosing Interval<br/> AUC<span class="Sub">(0-12h)</span></span> </p> <p> <span class="Bold">(mcg•h/mL)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">5 days</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">1 g/iv</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.58</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">12.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">40.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(±0.46)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±3.82)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±11.4)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=31)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=31)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=31)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">6 days</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">1 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.33</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">10.7</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">32.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(±1.05)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±4.83)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±15.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=31)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=31)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=31)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">Early (Less than 40 days)</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">1 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.31</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">8.16</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">27.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(±0.76)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±4.50)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±10.9)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=25)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=25)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=25)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">Early (Less than 40 days)</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">1.5 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.21</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">13.5</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">38.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(±0.81)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±8.18)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±15.4)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=27)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=27)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=27)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">Late (Greater than 3 months)</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">1.5 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.90</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">24.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">65.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(±0.24)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±12.1)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±35.4)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=23)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=23)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=23)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Heart transplant Patients (twice daily dosing) Time After Transplantation</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Dose/Route</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">T<span class="Sub">max</span> <br/> (h)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">C<span class="Sub">max</span> <br/> (mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Interdosing Interval<br/> AUC<span class="Sub">(0-12h)</span></span> </p> <p> <span class="Bold">(mcg•h/mL)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">Early (Day before discharge)</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">1.5 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">11.5</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">43.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(±1.3)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±6.8)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±20.8)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=11)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=11)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=9)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">Late (Greater than 6 months)</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">1.5 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">20.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">54.1<span class="Sup">a</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(±0.7)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±9.4)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±20.4)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=52)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=52)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=49)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Liver transplant Patients (twice daily dosing) Time After Transplantation</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Dose/Route</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">T<span class="Sub">max</span> <br/> (h)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">C<span class="Sub">max</span> <br/> (mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Interdosing Interval<br/> AUC<span class="Sub">(0-12h)</span></span> </p> <p> <span class="Bold">(mcg•h/mL)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">4 to 9 days</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">1 g/iv</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.50</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">17.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">34.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(±0.517)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±12.7)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±17.4)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=22)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=22)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=22)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">Early (5 to 8 days)</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">1.5 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.15</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">13.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">29.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(±0.432)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±6.76)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±11.9)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=20)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=20)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=20)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">Late (Greater than 6 months)</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">1.5 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.54</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">19.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">49.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(±0.51)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±11.7)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±14.8)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=6)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=6)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=6)</p> </td> </tr> <tr class="Last"> <td colspan="5"> <p class="First"> <span class="Sup">a</span>AUC<span class="Sub">(0-12h)</span> values quoted are extrapolated from data from samples collected over 4 hours.</p> </td> </tr> </tbody> </table></div>

In the early post-transplant period (less than 40 days post-transplant), kidney, heart, and liver transplant patients had mean MPA AUCs approximately 20% to 41% lower and mean Cmax approximately 32% to 44% lower compared to the late transplant period (i.e., 3 to 6 months post-transplant) (non-stationarity in MPA pharmacokinetics).

Mean MPA AUC values following administration of 1 g twice daily intravenous mycophenolate mofetil over 2 hours to kidney transplant patients for 5 days were about 24% higher than those observed after oral administration of a similar dose in the immediate post-transplant phase.

In liver transplant patients, administration of 1 g twice daily intravenous mycophenolate mofetil followed by 1.5 g twice daily oral mycophenolate mofetil resulted in mean MPA AUC estimates similar to those found in kidney transplant patients administered 1 g mycophenolate mofetil twice daily.

Effect of Food

Food (27 g fat, 650 calories) had no effect on the extent of absorption (MPA AUC) of MMF when administered at doses of 1.5 g twice daily to kidney transplant patients. However, MPA Cmax was decreased by 40% in the presence of food [see Dosage and Administration (2.1)].

Distribution

The mean (±SD) apparent volume of distribution of MPA in 12 healthy volunteers was approximately 3.6 (±1.5) L/kg. At clinically relevant concentrations, MPA is 97% bound to plasma albumin. The phenolic glucuronide metabolite of MPA (MPAG) is 82% bound to plasma albumin at MPAG concentration ranges that are normally seen in stable kidney transplant patients; however, at higher MPAG concentrations (observed in patients with kidney impairment or delayed kidney graft function), the binding of MPA may be reduced as a result of competition between MPAG and MPA for protein binding. Mean blood to plasma ratio of radioactivity concentrations was approximately 0.6 indicating that MPA and MPAG do not extensively distribute into the cellular fractions of blood.

In vitro studies to evaluate the effect of other agents on the binding of MPA to human serum albumin (HSA) or plasma proteins showed that salicylate (at 25 mg/dL with human serum albumin) and MPAG (at ≥460 mcg/mL with plasma proteins) increased the free fraction of MPA. MPA at concentrations as high as 100 mcg/mL had little effect on the binding of warfarin, digoxin or propranolol, but decreased the binding of theophylline from 53% to 45% and phenytoin from 90% to 87%.

Elimination

Mean (±SD) apparent half-life and plasma clearance of MPA are 17.9 (±6.5) hours and 193 (±48) mL/min following oral administration and 16.6 (±5.8) hours and 177 (±31) mL/min following intravenous administration, respectively.

Metabolism

The parent drug, MMF, can be measured systemically during the intravenous infusion; however, approximately 5 minutes after the infusion is stopped or after oral administration, MMF concentrations are below the limit of quantitation (0.4 mcg/mL).

Metabolism to MPA occurs pre-systemically after oral dosing. MPA is metabolized principally by glucuronyl transferase to form MPAG, which is not pharmacologically active. In vivo, MPAG is converted to MPA during enterohepatic recirculation. The following metabolites of the 2-hydroxyethyl-morpholino moiety are also recovered in the urine following oral administration of MMF to healthy subjects: N-(2-carboxymethyl)-morpholine, N-(2-hydroxyethyl)-morpholine, and the N-oxide of N-(2-hydroxyethyl)-morpholine.

Due to the enterohepatic recirculation of MPAG/MPA, secondary peaks in the plasma MPA concentration-time profile are usually observed 6 to 12 hours post-dose. Bile sequestrants, such as cholestyramine, reduce MPA AUC by interfering with this enterohepatic recirculation of the drug [see Overdosage (10) and Drug Interaction Studies below].

Excretion

Negligible amount of drug is excreted as MPA (less than 1% of dose) in the urine. Orally administered radiolabeled MMF resulted in complete recovery of the administered dose, with 93% of the administered dose recovered in the urine and 6% recovered in feces. Most (about 87%) of the administered dose is excreted in the urine as MPAG. At clinically encountered concentrations, MPA and MPAG are usually not removed by hemodialysis. However, at high MPAG plasma concentrations (> 100 mcg/mL), small amounts of MPAG are removed.

Increased plasma concentrations of MMF metabolites (MPA 50% increase and MPAG about a 3-fold to 6-fold increase) are observed in patients with renal insufficiency [see Specific Populations].

Specific Populations

Patients with Renal Impairment

The mean (±SD) pharmacokinetic parameters for MPA following the administration of oral MMF given as single doses to non-transplant subjects with renal impairment are presented in Table 11.

In a single-dose study, MMF was administered as a capsule or as an intravenous infusion over 40 minutes. Plasma MPA AUC observed after oral dosing to volunteers with severe chronic renal impairment (GFR <25 mL/min/1.73 m2) was about 75% higher relative to that observed in healthy volunteers (GFR >80 mL/min/1.73 m2). In addition, the single-dose plasma MPAG AUC was 3-fold to 6-fold higher in volunteers with severe renal impairment than in volunteers with mild renal impairment or healthy volunteers, consistent with the known renal elimination of MPAG. No data are available on the safety of long-term exposure to this level of MPAG.

Plasma MPA AUC observed after single-dose (1 g) intravenous dosing to volunteers (n=4) with severe chronic renal impairment (GFR <25 mL/min/1.73 m2) was 62.4 mcg•h/mL (±19.3). Multiple dosing of MMF in patients with severe chronic renal impairment has not been studied.

Patients with Delayed Graft Function or Nonfunction

In patients with delayed renal graft function post-transplant, mean MPA AUC(0-12h) was comparable to that seen in post-transplant patients without delayed renal graft function. There is a potential for a transient increase in the free fraction and concentration of plasma MPA in patients with delayed renal graft function. However, dose adjustment does not appear to be necessary in patients with delayed renal graft function. Mean plasma MPAG AUC(0-12h) was 2-fold to 3-fold higher than in post-transplant patients without delayed renal graft function [see Dosage and Administration (2.5)].

In eight patients with primary graft non-function following kidney transplantation, plasma concentrations of MPAG accumulated about 6-fold to 8-fold after multiple dosing for 28 days. Accumulation of MPA was about 1-fold to 2-fold.

The pharmacokinetics of MMF are not altered by hemodialysis. Hemodialysis usually does not remove MPA or MPAG. At high concentrations of MPAG (>100 mcg/mL), hemodialysis removes only small amounts of MPAG.

Patients with Hepatic Impairment

The mean (± SD) pharmacokinetic parameters for MPA following the administration of oral MMF given as single doses to non-transplant subjects with hepatic impairment is presented in Table 11.

In a single-dose (1 g oral) study of 18 volunteers with alcoholic cirrhosis and 6 healthy volunteers, hepatic MPA glucuronidation processes appeared to be relatively unaffected by hepatic parenchymal disease when pharmacokinetic parameters of healthy volunteers and alcoholic cirrhosis patients within this study were compared. However, it should be noted that for unexplained reasons, the healthy volunteers in this study had about a 50% lower AUC as compared to healthy volunteers in other studies, thus making comparisons between volunteers with alcoholic cirrhosis and healthy volunteers difficult. In a single-dose (1 g intravenous) study of 6 volunteers with severe hepatic impairment (aminopyrine breath test less than 0.2% of dose) due to alcoholic cirrhosis, MMF was rapidly converted to MPA. MPA AUC was 44.1 mcg•h/mL (±15.5).

<div class="scrollingtable"><table border="1" cellpadding="5" cellspacing="0" width="1000px"> <caption> <span>Table 11: Pharmacokinetic Parameters for MPA [mean (±SD)] Following Single Doses of MMF Capsules in Chronic Renal and Hepatic Impairment</span> </caption> <col width="528.85pt"/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">Pharmacokinetic Parameters for Renal Impairment</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold"> <br/> Dose</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">T<span class="Sub">max</span> <br/> (h)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">C<span class="Sub">max</span> <br/> (mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AUC<span class="Sub">(0-96h)</span> <br/> (mcg•h/mL)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Healthy Volunteers</p> <p>GFR greater than 80 mL/min/1.73 m<span class="Sup">2</span> <br/> (n=6)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.75</p> <p>(±0.27)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">25.3</p> <p>(±7.99)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">45.0</p> <p>(±22.6)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Mild Renal Impairment</p> <p>GFR 50 to 80 mL/min/1.73 m<span class="Sup">2</span> </p> <p>(n=6)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.75</p> <p>(±0.27)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">26.0</p> <p>(±3.82)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">59.9</p> <p>(±12.9)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Moderate Renal Impairment</p> <p>GFR 25 to 49 mL/min/1.73 m<span class="Sup">2</span> </p> <p>(n=6)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.75</p> <p>(±0.27)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">19.0</p> <p>(±13.2)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">52.9</p> <p>(±25.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Severe Renal Impairment</p> <p>GFR less than 25 mL/min/1.73 m<span class="Sup">2</span> </p> <p>(n=7)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.00</p> <p>(±0.41)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">16.3</p> <p>(±10.8)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">78.6</p> <p>(±46.4)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">Pharmacokinetic Parameters for Hepatic Impairment</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Dose</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">T<span class="Sub">max</span> <br/> (h)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">C<span class="Sub">max</span> <br/> (mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AUC<span class="Sub">(0-48h)</span> <br/> (mcg•h/mL)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Healthy Volunteers</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">1 g</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.63</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">24.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">29.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=6)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±0.14)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±5.73)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±5.78)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Alcoholic Cirrhosis</p> </td><td class="Botrule Rrule" rowspan="2"> <p class="First">1 g</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.85</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">22.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">29.8</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(n=18)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±0.58)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±10.1)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(±10.7)</p> </td> </tr> </tbody> </table></div>

Pediatric Patients

The pharmacokinetic parameters of MPA and MPAG have been evaluated in 55 pediatric patients (ranging from 1 year to 18 years of age) receiving mycophenolate mofetil oral suspension at a dose of 600 mg/m2 twice daily (up to a maximum of 1 g twice daily) after allogeneic kidney transplantation. The pharmacokinetic data for MPA is provided in Table 12.

<div class="scrollingtable"><table cellpadding="5" cellspacing="0" width="800px"> <caption> <span>Table 12: Mean (±SD) Computed Pharmacokinetic Parameters for MPA by Age and Time after Allogeneic Kidney Transplantation</span> </caption> <col width="99pt"/> <col width="40.5pt"/> <col width="72pt"/> <col width="100.6pt"/> <col width="99.15pt"/> <col width="104.8pt"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Toprule"> <p class="First"> <span class="Bold">Age Group</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">(n)</span> </p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Time</span> </p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">T<span class="Sub">max </span>(h)</span> </p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Dose Adjusted<span class="Sup">a</span></span> </p> <p> <span class="Bold">C<span class="Sub">max </span> <br/> (mcg/mL)</span> </p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Dose Adjusted<span class="Sup">a</span></span> </p> <p> <span class="Bold">AUC<span class="Sub">0-12</span></span> </p> <p> <span class="Bold">(mcg•h/mL)</span> </p> </td> </tr> <tr> <td class="Lrule"></td><td></td><td> <p class="First">Early (Day 7)</p> </td><td class="Rrule" colspan="3"></td> </tr> <tr> <td class="Lrule"> <p class="First">1 to less than 2 yr</p> </td><td class="Rrule"> <p class="First">(6)<span class="Sup">d</span> </p> </td><td class="Rrule"></td><td align="center" class="Rrule"> <p class="First">3.03 (4.70)</p> </td><td align="center" class="Rrule"> <p class="First">10.3 (5.80)</p> </td><td align="center" class="Rrule"> <p class="First">22.5 (6.66)</p> </td> </tr> <tr> <td class="Lrule"> <p class="First">1 to less than 6 yr</p> </td><td class="Rrule"> <p class="First">(17)</p> </td><td class="Rrule"></td><td align="center" class="Rrule"> <p class="First">1.63 (2.85)</p> </td><td align="center" class="Rrule"> <p class="First">13.2 (7.16)</p> </td><td align="center" class="Rrule"> <p class="First">27.4 (9.54)</p> </td> </tr> <tr> <td class="Lrule"> <p class="First">6 to less than 12 yr</p> </td><td class="Rrule"> <p class="First">(16)</p> </td><td class="Rrule"></td><td align="center" class="Rrule"> <p class="First">0.940 (0.546)</p> </td><td align="center" class="Rrule"> <p class="First">13.1 (6.30)</p> </td><td align="center" class="Rrule"> <p class="First">33.2 (12.1)</p> </td> </tr> <tr> <td class="Botrule Lrule"> <p class="First">12 to 18 yr</p> </td><td class="Botrule Rrule"> <p class="First">(21)</p> </td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule"> <p class="First">1.16 (0.830)</p> </td><td align="center" class="Botrule Rrule"> <p class="First">11.7 (10.7)</p> </td><td align="center" class="Botrule Rrule"> <p class="First">26.3 (9.14)<span class="Sup">b</span> </p> </td> </tr> <tr> <td class="Lrule"></td><td></td><td> <p class="First">Late (Month 3)</p> </td><td class="Rrule" colspan="3"></td> </tr> <tr> <td class="Lrule"> <p class="First">1 to less than 2 yr</p> </td><td class="Rrule"> <p class="First">(4)<span class="Sup"> d</span> </p> </td><td></td><td class="Lrule"> <p class="First">0.725 (0.276)</p> </td><td class="Lrule Rrule"> <p class="First">23.8 (13.4)</p> </td><td align="center" class="Rrule"> <p class="First">47.4 (14.7)</p> </td> </tr> <tr> <td class="Lrule"> <p class="First">1 to less than 6 yr</p> </td><td class="Rrule"> <p class="First">(15)</p> </td><td></td><td class="Lrule"> <p class="First">0.989 (0.511)</p> </td><td class="Lrule Rrule"> <p class="First">22.7 (10.1)</p> </td><td align="center" class="Rrule"> <p class="First">49.7 (18.2)</p> </td> </tr> <tr> <td class="Lrule"> <p class="First">6 to less than 12 yr</p> </td><td class="Rrule"> <p class="First">(14)</p> </td><td></td><td class="Lrule"> <p class="First">1.21 (0.532)</p> </td><td class="Lrule Rrule"> <p class="First">27.8 (14.3)</p> </td><td align="center" class="Rrule"> <p class="First">61.9 (19.6)</p> </td> </tr> <tr> <td class="Botrule Lrule"> <p class="First">12 to 18 yr</p> </td><td class="Botrule Rrule"> <p class="First">(17)</p> </td><td class="Botrule"></td><td class="Botrule Lrule"> <p class="First">0.978 (0.484)</p> </td><td class="Botrule Lrule Rrule"> <p class="First">17.9 (9.57)</p> </td><td align="center" class="Botrule Rrule"> <p class="First">53.6 (20.3)<span class="Sup">c</span> </p> </td> </tr> <tr> <td class="Lrule"></td><td></td><td> <p class="First">Late (Month 9)</p> </td><td class="Rrule" colspan="3"></td> </tr> <tr> <td class="Lrule"> <p class="First">1 to less than 2 yr</p> </td><td> <p class="First">(4)<span class="Sup"> d</span> </p> </td><td class="Lrule Rrule"></td><td> <p class="First">0.604 (0.208)</p> </td><td class="Lrule Rrule"> <p class="First">25.6 (4.25)</p> </td><td align="center" class="Rrule"> <p class="First">55.8 (11.6)</p> </td> </tr> <tr> <td class="Lrule"> <p class="First">1 to less than 6 yr</p> </td><td> <p class="First">(12)</p> </td><td class="Lrule Rrule"></td><td> <p class="First">0.869 (0.479)</p> </td><td class="Lrule Rrule"> <p class="First">30.4 (9.16)</p> </td><td align="center" class="Rrule"> <p class="First">61.0 (10.7)</p> </td> </tr> <tr> <td class="Lrule"> <p class="First">6 to less than 12 yr</p> </td><td> <p class="First">(11)</p> </td><td class="Lrule Rrule"></td><td> <p class="First">1.12 (0.462)</p> </td><td class="Lrule Rrule"> <p class="First">29.2 (12.6)</p> </td><td align="center" class="Rrule"> <p class="First">66.8 (21.2)</p> </td> </tr> <tr> <td class="Botrule Lrule"> <p class="First">12 to 18 yr</p> </td><td class="Botrule"> <p class="First">(14)</p> </td><td class="Botrule Lrule Rrule"></td><td class="Botrule"> <p class="First">1.09 (0.518)</p> </td><td class="Botrule Lrule Rrule"> <p class="First">18.1 (7.29)</p> </td><td align="center" class="Botrule Rrule"> <p class="First">56.7 (14.0)</p> </td> </tr> <tr> <td colspan="6"> <p class="First"> <span class="Sup">a</span> adjusted to a dose of 600 mg/m<span class="Sup">2</span> </p> </td> </tr> <tr> <td colspan="6"> <p class="First"> <span class="Sup">b</span> n=20</p> </td> </tr> <tr> <td colspan="6"> <p class="First"> <span class="Sup">c</span> n=16 </p> </td> </tr> <tr class="Last"> <td colspan="6"> <p class="First"> <span class="Sup">d</span> a subset of 1 to &lt;6 yr</p> </td> </tr> </tbody> </table></div>

The mycophenolate mofetil oral suspension dose of 600 mg/m2 twice daily (up to a maximum of 1 g twice daily) achieved mean MPA AUC values in pediatric patients similar to those seen in adult kidney transplant patients receiving mycophenolate mofetil capsules at a dose of 1 g twice daily in the early post-transplant period. There was wide variability in the data. As observed in adults, early post-transplant MPA AUC values were approximately 45% to 53% lower than those observed in the later post-transplant period (>3 months). MPA AUC values were similar in the early and late post-transplant period across the 1 to 18-year age range.

A comparison of dose-normalized (to 600 mg/m2) MPA AUC values in 12 pediatric kidney transplant patients less than 6 years of age at 9 months post-transplant with those values in 7 pediatric liver transplant patients [median age 17 months (range: 10 to 60 months)] and at 6 months and beyond post-transplant revealed that, at the same dose, there were on average 23% lower AUC values in the pediatric liver compared to pediatric kidney patients. This is consistent with the need for higher dosing in adult liver transplant patients compared to kidney transplant patients to achieve the same exposure.

In adult transplant patients administered the same dosage of mycophenolate mofetil, there is similar MPA exposure among kidney transplant and heart transplant patients. Based on the established similarity in MPA exposure between pediatric kidney transplant and adult kidney transplant patients at their respective approved doses, it is expected that MPA exposure at the recommended dosage will be similar in pediatric heart transplant and adult heart transplant patients.

Male and Female Patients

Data obtained from several studies were pooled to look at any gender-related differences in the pharmacokinetics of MPA (data were adjusted to 1 g oral dose). Mean (±SD) MPA AUC(0-12h) for males (n=79) was 32.0 (±14.5) and for females (n=41) was 36.5 (±18.8) mcg•h/mL while mean (±SD) MPA Cmax was 9.96 (±6.19) in the males and 10.6 (±5.64) mcg/mL in the females. These differences are not of clinical significance.

Geriatric Patients

The pharmacokinetics of mycophenolate mofetil and its metabolites have not been found to be altered in geriatric transplant patients when compared to younger transplant patients.

Drug Interaction Studies

Acyclovir

Coadministration of MMF (1 g) and acyclovir (800 mg) to 12 healthy volunteers resulted in no significant change in MPA AUC and Cmax. However, MPAG and acyclovir plasma AUCs were increased 10.6% and 21.9%, respectively.

Antacids with Magnesium and Aluminum Hydroxides

Absorption of a single dose of MMF (2 g) was decreased when administered to 10 rheumatoid arthritis patients also taking Maalox® TC (10 mL qid). The Cmax and AUC(0-24h) for MPA were 33% and 17% lower, respectively, than when MMF was administered alone under fasting conditions.

Proton Pump Inhibitors (PPIs)

Coadministration of PPIs (e.g., lansoprazole, pantoprazole) in single doses to healthy volunteers and multiple doses to transplant patients receiving mycophenolate mofetil capsules has been reported to reduce the exposure to MPA. An approximate reduction of 30 to 70% in the Cmax and 25% to 35% in the AUC of MPA has been observed, possibly due to a decrease in MPA solubility at an increased gastric pH.

Cholestyramine

Following single-dose administration of 1.5 g MMF to 12 healthy volunteers pretreated with 4 g three times a day of cholestyramine for 4 days, MPA AUC decreased approximately 40%. This decrease is consistent with interruption of enterohepatic recirculation which may be due to binding of recirculating MPAG with cholestyramine in the intestine.

Cyclosporine

Cyclosporine (Sandimmune®) pharmacokinetics (at doses of 275 to 415 mg/day) were unaffected by single and multiple doses of 1.5 g twice daily of MMF in 10 stable kidney transplant patients. The mean (±SD) AUC (0-12h) and Cmax of cyclosporine after 14 days of multiple doses of MMF were 3290 (±822) ng•h/mL and 753 (±161) ng/mL, respectively, compared to 3245 (±1088) ng•h/mL and 700 (±246) ng/mL, respectively, 1 week before administration of MMF.

Cyclosporine A interferes with MPA enterohepatic recirculation.  In kidney transplant patients, mean MPA exposure (AUC(0-12h)) was approximately 30 to 50% greater when MMF was administered without cyclosporine compared with when MMF was coadministered with cyclosporine.  This interaction is due to cyclosporine inhibition of multidrug-resistance­-associated protein 2 (MRP-2) transporter in the biliary tract, thereby preventing the excretion of  MPAG  into  the  bile  that  would  lead  to  enterohepatic recirculation  of  MPA.  This information should be taken into consideration when MMF is used without cyclosporine.

Drugs Affecting Glucuronidation

Concomitant administration of drugs inhibiting glucuronidation of MPA may increase MPA exposure (e.g., increase of MPA AUC(0-∞) by 35% was observed with concomitant administration of isavuconazole).

Concomitant administration of telmisartan and mycophenolate mofetil capsules resulted in an approximately 30% decrease in MPA concentrations. Telmisartan changes MPA’s elimination by enhancing PPAR gamma (peroxisome proliferator-activated receptor gamma) expression, which in turn results in an enhanced UGT1A9 expression and glucuronidation activity.

Ganciclovir

Following single-dose administration to 12 stable kidney transplant patients, no pharmacokinetic interaction was observed between MMF (1.5 g) and intravenous ganciclovir (5 mg/kg). Mean (±SD) ganciclovir AUC and Cmax (n=10) were 54.3 (±19.0) mcg•h/mL and 11.5 (±1.8) mcg/mL, respectively, after coadministration of the two drugs, compared to 51.0 (±17.0) mcg•h/mL and 10.6 (±2.0) mcg/mL, respectively, after administration of intravenous ganciclovir alone. The mean (±SD) AUC and Cmax of MPA (n=12) after coadministration were 80.9 (±21.6) mcg•h/mL and 27.8 (±13.9) mcg/mL, respectively, compared to values of 80.3 (±16.4) mcg•h/mL and 30.9 (±11.2) mcg/mL, respectively, after administration of MMF alone.

Oral Contraceptives

A study of coadministration of mycophenolate mofetil capsules (1 g twice daily) and combined oral contraceptives containing ethinyl estradiol (0.02 mg to 0.04 mg) and levonorgestrel (0.05 mg to 0.20 mg), desogestrel (0.15 mg) or gestodene (0.05 mg to 0.10 mg) was conducted in 18 women with psoriasis over 3 consecutive menstrual cycles. Mean serum levels of LH, FSH and progesterone were not significantly affected. Mean AUC(0-24h) was similar for ethinyl estradiol and 3-keto desogestrel; however, mean levonorgestrel AUC(0-24h) significantly decreased by about 15%. There was large inter-patient variability (%CV in the range of 60% to 70%) in the data, especially for ethinyl estradiol.

Sevelamer

Concomitant administration of sevelamer and MMF in adult and pediatric patients decreased the mean MPA Cmax and AUC (0-12h) by 36% and 26% respectively.

Antimicrobials

Antimicrobials eliminating beta-glucuronidase-producing bacteria in the intestine (e.g. aminoglycoside, cephalosporin, fluoroquinolone, and penicillin classes of antimicrobials) may interfere with the MPAG/MPA enterohepatic recirculation thus leading to reduced systemic MPA exposure. Information concerning antibiotics is as follows:

In a 104-week oral carcinogenicity study in mice, MMF in daily doses up to 180 mg/kg was not tumorigenic. The highest dose tested was 0.2 times the recommended clinical dose (2 g/day) in renal transplant patients and 0.15 times the recommended clinical dose (3 g/day) in cardiac transplant patients when corrected for differences in body surface area (BSA). In a 104-week oral carcinogenicity study in rats, MMF in daily doses up to 15 mg/kg was not tumorigenic. The highest dose was 0.035 times the recommended clinical dose in kidney transplant patients and 0.025 times the recommended clinical dose in heart transplant patients when corrected for BSA. While these animal doses were lower than those given to patients, they were maximal in those species and were considered adequate to evaluate the potential for human risk [see Warnings and Precautions (5.2)].

The genotoxic potential of MMF was determined in five assays. MMF was genotoxic in the mouse lymphoma/thymidine kinase assay and the in vivo mouse micronucleus assay. MMF was not genotoxic in the bacterial mutation assay, the yeast mitotic gene conversion assay or the Chinese hamster ovary cell chromosomal aberration assay.

MMF had no effect on fertility of male rats at oral doses up to 20 mg/kg/day. This dose represents 0.05 times the recommended clinical dose in renal transplant patients and 0.03 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. In a female fertility and reproduction study conducted in rats, oral doses of 4.5 mg/kg/day caused malformations (principally of the head and eyes) in the first generation offspring in the absence of maternal toxicity. This dose was 0.01 times the recommended clinical dose in renal transplant patients and 0.005 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. No effects on fertility or reproductive parameters were evident in the dams or in the subsequent generation.

Adults

The three de novo kidney transplantation studies compared two dose levels of oral mycophenolate mofetil (1 g twice daily and 1.5 g twice daily) with azathioprine (2 studies) or placebo (1 study) to prevent acute rejection episodes. One of the two studies with azathioprine (AZA) control arm also included anti-thymocyte globulin (ATGAM®) induction therapy. The geographic location of the investigational sites of these studies are included in Table 13.

In all three de novo kidney transplantation studies, the primary efficacy endpoint was the proportion of patients in each treatment group who experienced treatment failure within the first 6 months after transplantation. Treatment failure was defined as biopsy-proven acute rejection on treatment or the occurrence of death, graft loss or early termination from the study for any reason without prior biopsy-proven rejection.

Mycophenolate mofetil, in combination with corticosteroids and cyclosporine, reduced (statistically significant at 0.05 level) the incidence of treatment failure within the first 6 months following transplantation (Table 13). Patients who prematurely discontinued treatment were followed for the occurrence of death or graft loss, and the cumulative incidence of graft loss and patient death combined are summarized in Table 14. Patients who prematurely discontinued treatment were not followed for the occurrence of acute rejection after termination.

<div class="scrollingtable"><table border="1" cellpadding="5" cellspacing="0" width="1000px"> <caption> <span>Table 13: Treatment Failure in De Novo Kidney Transplantation Studies</span> </caption> <col width="163.05pt"/> <col width="115.75pt"/> <col width="115.7pt"/> <col width="126.25pt"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First"> <span class="Bold">USA Study</span> </p> <p> <span class="Bold">(N=499 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil 2 g/day <br/> (n=167 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil 3 g/day <br/> (n=166 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AZA</span> </p> <p> <span class="Bold">1 to 2 mg/kg/day <br/> (n=166 patients)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="3"> <p class="First">All 3 groups received anti-thymocyte globulin induction, cyclosporine and corticosteroids</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">All treatment failures</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">31.1%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">31.3%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">47.6%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Early termination without prior acute rejection</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">9.6%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">12.7%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">6.0%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Biopsy-proven rejection episode on treatment</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">19.8%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">17.5%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">38.0%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First"> <span class="Bold">Europe/Canada/Australia Study <br/> (N=503 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil 2 g/day <br/> (n=173 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil 3 g/day <br/> (n=164 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AZA</span> </p> <p> <span class="Bold">100 to 150 mg/day <br/> (n=166 patients)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="3"> <p class="First">No induction treatment administered; all 3 groups received cyclosporine and corticosteroids.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">All treatment failures</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">38.2%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">34.8%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">50.0%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Early termination without prior acute rejection</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">13.9%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">15.2%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">10.2%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Biopsy-proven rejection</p> <p>episode on treatment</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">19.7%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">15.9%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">35.5%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First"> <span class="Bold">Europe Study <br/> (N=491 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil 2 g/day <br/> (n=165 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil 3 g/day <br/> (n=160 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">(n=166 patients)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="3"> <p class="First">No induction treatment administered; all 3 groups received cyclosporine and corticosteroids.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">All treatment failures</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">30.3%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">38.8%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">56.0%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Early termination without prior acute rejection</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">11.5%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">22.5%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">7.2%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Biopsy-proven rejection</p> <p>episode on treatment</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">17.0%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">13.8%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">46.4%</p> </td> </tr> <tr class="Last"> <td colspan="4"> <p class="First">*Does not include death and graft loss as reason for early termination.</p> </td> </tr> </tbody> </table></div>

No advantage of mycophenolate mofetil at 12 months with respect to graft loss or patient death (combined) was established (Table 14). Numerically, patients receiving mycophenolate mofetil 2 g/day and 3 g/day experienced a better outcome than controls in all three studies; patients receiving mycophenolate mofetil 2 g/day experienced a better outcome than mycophenolate mofetil 3 g/day in two of the three studies. Patients in all treatment groups who terminated treatment early were found to have a poor outcome with respect to graft loss or patient death at 1 year.

<div class="scrollingtable"><table border="1" cellpadding="5" cellspacing="0" width="800px"> <caption> <span>Table 14: De Novo Kidney Transplantation Studies Cumulative Incidence of Combined Graft Loss or Patient Death at 12 Months</span> </caption> <col width="158.4pt"/> <col width="132.5pt"/> <col width="128.5pt"/> <col width="109pt"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Study</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">2 g/day</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">3 g/day</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Control <br/> (AZA or Placebo)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">USA</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">8.5%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">11.5%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">12.2%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Europe/Canada/Australia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">11.7%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">11.0%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">13.6%</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Europe</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">8.5%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">10.0%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">11.5%</p> </td> </tr> </tbody> </table></div>

Pediatrics- De Novo Kidney transplantation PK Study with Long Term Follow-Up

One open-label, safety and pharmacokinetic study of mycophenolate mofetil oral suspension 600 mg/m2 twice daily (up to 1 g twice daily) in combination with cyclosporine and corticosteroids was performed at centers in the United States (9), Europe (5) and Australia (1) in 100 pediatric patients (3 months to 18 years of age) for the prevention of renal allograft rejection. Mycophenolate mofetil was well tolerated in pediatric patients [see Adverse Reactions (6.1)], and the pharmacokinetics profile was similar to that seen in adult patients dosed with 1 g twice daily mycophenolate mofetil capsules [see Clinical Pharmacology (12.3)]. The rate of biopsy-proven rejection was similar across the age groups (3 months to <6 years, 6 years to <12 years, 12 years to 18 years). The overall biopsy-proven rejection rate at 6 months was comparable to adults. The combined incidence of graft loss (5%) and patient death (2%) at 12 months post-transplant was similar to that observed in adult kidney transplant patients.

A double-blind, randomized, comparative, parallel-group, multicenter study in primary de novo heart transplant recipients was performed at centers in the United States (20), in Canada (1), in Europe (5) and in Australia (2). The total number of patients enrolled (ITT population) was 650; 72 never received study drug and 578 received study drug (Safety Population). Patients received mycophenolate mofetil 1.5 g twice daily (n=289) or AZA 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune® or Neoral®) and corticosteroids as maintenance immunosuppressive therapy. The two primary efficacy endpoints were: (1) the proportion of patients who, after transplantation, had at least one endomyocardial biopsy-proven rejection with hemodynamic compromise, or were re-transplanted or died, within the first 6 months, and (2) the proportion of patients who died or were re-transplanted during the first 12 months following transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection for up to 6 months and for the occurrence of death for 1 year.

The analyses of the endpoints showed:

<div class="scrollingtable"><table cellpadding="5" width="800px"> <caption> <span>Table 15: De Novo Heart Transplantation Study Rejection at 6 Months/Death or Re-transplantation at 1 Year</span> </caption> <col width="149.95pt"/> <col width="197.55pt"/> <col width="186.95pt"/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" rowspan="2"></td><td class="Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">All Patients (ITT)</span> </p> </td><td class="Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Treated Patients</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AZA <br/> N = 323</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate <br/> Mofetil <br/> N = 327</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AZA <br/> N = 289</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate <br/> Mofetil <br/> N = 289</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Biopsy-proven rejection with hemodynamic compromise at 6 months<span class="Sup">a</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">121 (38%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">120 (37%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">100 (35%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">92 (32%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Death or re-transplantation at 1 year</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">49 (15.2%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">42 (12.8%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">33 (11.4%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">18 (6.2%)</p> </td> </tr> <tr class="Last"> <td colspan="5"> <p class="First"> <span class="Sup">a</span> Hemodynamic compromise occurred if any of the following criteria were met: pulmonary capillary wedge pressure ≥20 mm or a 25% increase; cardiac index &lt;2.0 L/min/m<span class="Sup">2</span> or a 25% decrease; ejection fraction ≤30%; pulmonary artery oxygen saturation ≤60% or a 25% decrease; presence of new S<span class="Sub">3</span> gallop; fractional shortening was ≤20% or a 25% decrease; inotropic support required to manage the clinical condition.</p> </td> </tr> </tbody> </table></div>

A double-blind, randomized, comparative, parallel-group, multicenter study in primary hepatic transplant recipients was performed at centers in the United States (16), in Canada (2), in Europe (4) and in Australia (1). The total number of patients enrolled was 565. Per protocol, patients received mycophenolate mofetil 1 g twice daily intravenously for up to 14 days followed by mycophenolate mofetil 1.5 g twice daily orally or AZA 1 to 2 mg/kg/day intravenously followed by AZA 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral®) and corticosteroids as maintenance immunosuppressive therapy. The actual median oral dose of AZA on study was 1.5 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) initially and 1.26 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) at 12 months. The two primary endpoints were: (1) the proportion of patients who experienced, in the first 6 months post-transplantation, one or more episodes of biopsy-proven and treated rejection or death or re-transplantation, and (2) the proportion of patients who experienced graft loss (death or re-transplantation) during the first 12 months post-transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection and for the occurrence of graft loss (death or re-transplantation) for 1 year.

In combination with corticosteroids and cyclosporine, mycophenolate mofetil demonstrated a lower rate of acute rejection at 6 months and a similar rate of death or re-transplantation at 1 year compared to AZA (Table 16).

<div class="scrollingtable"><table cellpadding="5" width="800px"> <caption> <span>Table 16: De Novo Liver Transplantation Study Rejection at 6 Months/Death or Retransplantation at 1 Year</span> </caption> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">AZA <br/> N = 287</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">Mycophenolate Mofetil <br/> N = 278</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Biopsy-proven, treated rejection at 6 months (includes death or re-transplantation)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 137 (47.7%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 107 (38.5%)</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> Death or re-transplantation at 1 year</td><td align="center" class="Botrule Lrule Rrule Toprule"> 42 (14.6%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 41 (14.7%)</td> </tr> </tbody> </table></div>

1. “OSHA Hazardous Drugs.” OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

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Mycophenolate mofetil (MMF) has demonstrated teratogenic effects in humans [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. Mycophenolate Mofetil Capsules, USP should not be opened or crushed. Avoid inhalation or direct contact with skin or mucous membranes of the powder contained in Mycophenolate Mofetil Capsules, USP. Follow applicable special handling and disposal procedures1.

Mycophenolate Mofetil Capsules, USP are available as follows:

250 mg – hard gelatin capsules with a light blue opaque cap and a bright orange opaque body, filled with a white to off-white powder with small agglomerates; imprinted with "TEVA" on the cap and "7334" on the body. They are available in bottles of 100 and 500 capsules. (NDC 0093-7334-01 and NDC 0093-7334-05)

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

Keep this and all medications out of the reach of children.

Pregnancy loss and malformations

Contraception

Inform patients that they are at increased risk of developing a variety of infections due to immunosuppression. Instruct them to contact their physician if they develop any of the signs and symptoms of infection explained in the Medication Guide [see Warnings and Precautions (5.3)].

Inform patients that they are at increased risk for developing blood adverse effects such as anemia or low white blood cells. Advise patients to immediately contact their healthcare provider if they experience any evidence of infection, unexpected bruising, or bleeding, or any other manifestation of bone marrow suppression [see Warnings and Precautions (5.4)].

Inform patients that mycophenolate mofetil capsules can cause gastrointestinal tract complications including bleeding, intestinal perforations, and gastric or duodenal ulcers. Advise the patient to contact their healthcare provider if they have symptoms of gastrointestinal bleeding, or sudden onset or persistent abdominal pain [see Warnings and Precautions (5.5)].

Inform patients that acute inflammatory reactions have been reported in some patients who received mycophenolate mofetil capsules. Some reactions were severe, requiring hospitalization. Advise patients to contact their physician if they develop fever, joint stiffness, joint pain or muscle pains [see Warnings and Precautions (5.7)].

Inform patients that mycophenolate mofetil capsules can interfere with the usual response to immunizations. Before seeking vaccines on their own, advise patients to discuss first with their physician [see Warnings and Precautions (5.8)].

Advise patients not to donate blood during therapy and for at least 6 weeks following discontinuation of mycophenolate mofetil capsules [see Warnings and Precautions (5.11)].

Advise males of childbearing potential not to donate semen during therapy and for 90 days following discontinuation of mycophenolate mofetil capsules [see Warnings and Precautions (5.12)].

Advise patients that mycophenolate mofetil capsules can affect the ability to drive or operate machines. Patients should avoid driving or operating machines if they experience somnolence, confusion, dizziness, tremor or hypotension during treatment with mycophenolate mofetil capsules [see Warnings and Precautions (5.14)].

Brands listed are the trademarks of their respective owners.

Dispense with Medication Guide available at: www.tevausa.com/medguides

Manufactured In Czech Republic By: Teva Czech Industries, s.r.o. Opava-Komarov, Czech Republic

Manufactured For: Teva Pharmaceuticals Parsippany, NJ 07054

Rev. S 7/2023

Dispense with Medication Guide available at: www.tevausa.com/medguides

{ "type": "p", "children": [], "text": "Dispense with Medication Guide available at: www.tevausa.com/medguides" }

<div class="scrollingtable"><table cellspacing="5" width="1000px"> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">MEDICATION GUIDE</span> </p> <p> <span class="Bold">Mycophenolate Mofetil (mye" koe fen' oh late moe' fe til) Capsules, 250 mg</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> Read the Medication Guide that comes with mycophenolate mofetil capsules before you start taking it and each time you refill your prescription. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment.</td> </tr> <tr> <td class="Lrule Rrule" colspan="2"> <p class="First"> <span class="Bold">What is the most important information I should know about mycophenolate mofetil capsules?</span> </p> <p> <span class="Bold">Mycophenolate mofetil capsules can cause serious side effects, including:</span> </p> <p> <span class="Bold">Increased risk of loss of a pregnancy (miscarriage) and higher risk of birth defects. </span>Females who take mycophenolate mofetil capsules during pregnancy have a higher risk of miscarriage during the first 3 months (first trimester), and a higher risk that their baby will be born with birth defects.</p> <ul class="Disc"> <li> <span class="Bold">If you are a female who can become pregnant</span>, your doctor must talk with you about acceptable birth control methods (contraceptive counseling) to use while taking mycophenolate mofetil capsules. You should have 1 pregnancy test immediately before starting mycophenolate mofetil capsules and another pregnancy test 8 to 10 days later. Pregnancy tests should be repeated during routine follow-up visits with your doctor. Talk to your doctor about the results of all of your pregnancy tests. <p class="First">You must use acceptable birth control during your entire mycophenolate mofetil capsule treatment and for 6 weeks after stopping mycophenolate mofetil capsules, unless at any time you choose to avoid sexual intercourse (abstinence) with a man completely. Mycophenolate mofetil capsules decrease blood levels of the hormones in birth control pills that you take by mouth. Birth control pills may not work as well while you take mycophenolate mofetil capsules, and you could become pregnant. If you take birth control pills while using mycophenolate mofetil capsules you must also use another form of birth control. Talk to your doctor about other birth control methods that you can use while taking mycophenolate mofetil capsules.</p> </li> <li> <span class="Bold">If you are a sexually active male whose female partner can become pregnant while you are taking mycophenolate mofetil capsules</span>, use effective contraception during treatment and for at least 90 days after stopping mycophenolate mofetil capsules.</li> <li> <span class="Bold">If you plan to become pregnant</span>, talk with your doctor. Your doctor will decide if other medicines to prevent rejection may be right for you.</li> <li> <span class="Bold">If you become pregnant while taking mycophenolate mofetil capsules</span>, <span class="Bold">do not stop taking mycophenolate mofetil capsules. Call your doctor right away.</span> <p class="First">You and your doctor may decide that other medicines to prevent rejection may be right for you. You and your doctor should report your pregnancy to the Mycophenolate Pregnancy Registry either:</p> <ul class="Circle"> <li>By phone at 1-800-617-8191 <span class="Bold">or</span> </li> <li>By visiting the REMS website at: <span class="Bold"><a href="http://www.mycophenolaterems.com/">www.mycophenolateREMS.com</a></span> </li> </ul> </li> </ul> <p>The purpose of this registry is to gather information about the health of you and your baby.</p> <span class="Bold">Increased risk of getting certain cancers. </span>People who take mycophenolate mofetil capsules have a higher risk of getting lymphoma, and other cancers, especially skin cancer. Tell your doctor if you have: </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li>unexplained fever, prolonged tiredness, weight loss or lymph node swelling</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li>a change in the size and color of a mole </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li>a brown or black skin lesion with uneven borders, or one part of the lesion does not look like the other  </li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li>a new skin lesion or bump </li> </ul> </td> </tr> <tr> <td class="Lrule"></td><td class="Rrule"> <ul class="Disk"> <li>any other changes to your health </li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2"> <p class="First"> <span class="Bold">Increased risk of getting serious infections. </span>Mycophenolate mofetil capsules weaken the body’s immune system and affects your ability to fight infections. Serious infections can happen with mycophenolate mofetil capsules and can lead to hospitalizations and death. These serious infections can include:</p> <ul class="Disc"> <li> <span class="Bold">Viral infections. </span>Certain viruses can live in your body and cause active infections when your immune system is weak. <p class="First">Viral infections that can happen with mycophenolate mofetil capsules include:</p> <ul class="Circle"> <li>Shingles, other herpes infections, and cytomegalovirus (CMV). CMV can cause serious tissue and blood infections.</li> <li>BK virus. BK virus can affect how your kidney works and cause your transplanted kidney to fail.</li> <li>Hepatitis B and C viruses. Hepatitis viruses can affect how your liver works. Talk to your doctor about how hepatitis viruses may affect you.</li> <li>COVID-19</li> </ul> </li> <li> <span class="Bold">A brain infection called Progressive Multifocal Leukoencephalopathy (PML). </span>In some patients, mycophenolate mofetil capsules may cause an infection of the brain that may cause death. You are at risk for this brain infection because you have a weakened immune system. Call your doctor right away if you have any of the following symptoms:</li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Circle"> <li>weakness on one side of the body</li> </ul> </td><td class="Rrule"> <ul class="Circle"> <li> you are confused or have problems thinking</li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Circle"> <li>you do not care about things you usually care about (apathy)</li> </ul> </td><td class="Rrule"> <ul class="Circle"> <li>you cannot control your muscles </li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2"> <ul class="Disk"> <li> <span class="Bold">Fungal infections. </span>Yeasts and other types of fungal infections can happen with mycophenolate mofetil capsules and can cause serious tissue and blood infections (See <span class="Bold">“What are the possible side effects of mycophenolate mofetil capsules?”</span>). </li> </ul> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Call your doctor right away if you have any of the following signs and symptoms of infection:</span> </p> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li> temperature of 100.5°F or greater</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li>pain during urination </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li> cold symptoms, such as a runny nose or sore throat</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li>white patches in the mouth or throat </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li>flu symptoms, such as an upset stomach, stomach pain, vomiting or diarrhea </li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li>unexpected bruising or bleeding </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li>earache or headache </li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li> cuts, scrapes or incisions that are red, warm and oozing pus</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2">  See <span class="Bold">“What are the possible side effects of mycophenolate mofetil capsules?” </span>for information about other serious side effects.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">What are mycophenolate mofetil capsules?</span> </p> <ul class="Disk"> <li>Mycophenolate mofetil capsules are a prescription medicine to prevent rejection (antirejection medicine) in people who have received a kidney, heart or liver transplant. Rejection is when the body’s immune system perceives the new organ as a “foreign” threat and attacks it.</li> <li> Mycophenolate mofetil capsules are used with other medicines containing cyclosporine and corticosteroids.</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Who should not take mycophenolate mofetil capsules?</span> </p> <span class="Bold">Do not take mycophenolate mofetil capsules if you are allergic to mycophenolate mofetil or any of the ingredients in mycophenolate mofetil capsules. </span>See the end of this Medication Guide for a complete list of ingredients in mycophenolate mofetil capsules. </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">What should I tell my doctor before taking mycophenolate mofetil capsules?</span> </p> <p> <span class="Bold">Tell your doctor about all of your medical conditions, including if you</span>:</p> <ul class="Disc"> <li>have any digestive problems, such as ulcers.</li> <li>have Lesch-Nyhan syndrome, Kelley-Seegmiller syndrome, or another rare inherited deficiency hypoxanthine-guanine phosphoribosyl-transferase (HGPRT). You should not take mycophenolate mofetil capsules if you have one of these disorders.</li> <li>plan to receive any vaccines. People taking mycophenolate mofetil capsules should not receive live vaccines. Some vaccines may not work as well during treatment with mycophenolate mofetil capsules.</li> <li>are pregnant or plan to become pregnant. See <span class="Bold">“What is the most important information I should know about mycophenolate mofetil capsules?”</span> </li> <li>are breastfeeding or plan to breastfeed. It is not known if mycophenolate mofetil passes into breast milk. You and your doctor will decide if you will take mycophenolate mofetil capsules or breastfeed.</li> </ul> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take, </span>including prescription and over-the-counter medicines, vitamins and herbal supplements. Some medicines may affect the way mycophenolate mofetil capsules work, and mycophenolate mofetil capsules may affect how some medicines work.</p> <p>Especially tell your doctor if you take:</p> <ul class="Disc"> <li>birth control pills (oral contraceptives). See <span class="Bold">“What is the most important information I should know about mycophenolate mofetil capsules?”</span> </li> <li>sevelamer (Renagel<span class="Sup">®</span>, Renvela<span class="Sup">™</span>). These products should be taken at least 2 hours after taking mycophenolate mofetil capsules.</li> <li>acyclovir (Zovirax<span class="Sup">®</span>), valacyclovir (Valtrex<span class="Sup">®</span>), ganciclovir (CYTOVENE<span class="Sup">®</span>-IV, Vitrasert<span class="Sup">®</span>), valganciclovir (VALCYTE<span class="Sup">®</span>).</li> <li>rifampin (Rifater<span class="Sup">®</span>, Rifamate<span class="Sup">®</span>, Rimactane<span class="Sup">®</span>, Rifadin<span class="Sup">®</span>).</li> <li>antacids that contain magnesium and aluminum (mycophenolate mofetil capsules and the antacid should not be taken at the same time).</li> <li>proton pump inhibitors (PPIs) (Prevacid<span class="Sup">®</span>, Protonix<span class="Sup">®</span>).</li> <li>sulfamethoxazole/trimethoprim (BACTRIM<span class="Sup">™</span>, BACTRIM DS<span class="Sup">™</span>).</li> <li>norfloxacin (Noroxin<span class="Sup">®</span>) and metronidazole (Flagyl<span class="Sup">®</span>, Flagyl<span class="Sup">®</span> ER, Flagyl<span class="Sup">®</span> IV, Metro IV, Helidac<span class="Sup">®</span>, Pylera<span class="Sup">™</span>).</li> <li>ciprofloxacin (Cipro<span class="Sup">®</span>, Cipro<span class="Sup">®</span> XR, Ciloxan<span class="Sup">®</span>, Proquin<span class="Sup">®</span> XR) and amoxicillin plus clavulanic acid (Augmentin<span class="Sup">®</span>, Augmentin XR<span class="Sup">™</span>).</li> <li>azathioprine (Azasan<span class="Sup">®</span>, Imuran<span class="Sup">®</span>).</li> <li>cholestyramine (Questran Light<span class="Sup">®</span>, Questran<span class="Sup">®</span>, Locholest Light, Locholest, Prevalite<span class="Sup">®</span>).</li> </ul> <p> Know the medicines you take. Keep a list of them to show to your doctor or nurse and pharmacist when you get a new medicine. <span class="Bold">Do not </span>take any new medicine without talking with your doctor.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <span class="Bold">How should I take mycophenolate mofetil capsules?</span> <ul class="Disc"> <li>Take mycophenolate mofetil capsules exactly as prescribed.</li> <li> <span class="Bold">Do not</span> stop taking mycophenolate mofetil capsules or change the dose unless your doctor tells you to.</li> <li>If you miss a dose of mycophenolate mofetil capsules, or you are not sure when you took your last dose, take your prescribed dose of mycophenolate mofetil capsules as soon as you remember. If your next dose is less than 2 hours away, skip the missed dose and take your next dose at your normal scheduled time. Do not take 2 doses at the same time. Call your doctor if you are not sure what to do.</li> <li>Take mycophenolate mofetil capsules on an empty stomach, unless your doctor tells you otherwise.</li> <li> <span class="Bold">Do no</span><span class="Bold">t</span> open or crush mycophenolate mofetil capsules.</li> <li>If you take too many mycophenolate mofetil capsules, call your doctor or the poison control center right away.</li> <li>If you are not able to swallow mycophenolate mofetil capsules, your doctor may prescribe mycophenolate mofetil oral suspension. This is a liquid form of mycophenolate mofetil capsules. Your pharmacist will mix the medicine before you pick it up from a pharmacy.</li> <li> <span class="Bold">Do not </span>breathe in (inhale) or let mycophenolate mofetil capsules powder come in contact with your skin or mucous membranes. <ul class="Circle"> <li>If you accidentally get the powder on the skin, wash the area well with soap and water.</li> <li>If you accidentally get the powder in your eyes or other mucous membranes, flush with plain water.</li> </ul> </li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <span class="Bold">What should I avoid while taking </span><span class="Bold">mycophenolate mofetil capsules?</span> <ul class="Disk"> <li> <span class="Bold"> </span>Avoid becoming pregnant. (See <span class="Bold">“What is the most important information I should know about </span><span class="Bold">mycophenolate mofetil capsules?”).</span> </li> <li>Limit the amount of time you spend in sunlight. Avoid using tanning beds or sunlamps. People who take mycophenolate mofetil capsules have a higher risk of getting skin cancer (See <span class="Bold">“What is the most important information I should know about </span><span class="Bold">mycophenolate mofetil capsules?”</span>). Wear protective clothing when you are in the sun and use a broad-spectrum sunscreen with a high protection factor. This is especially important if your skin is very fair or if you have a family history of skin cancer. </li> <li>You should not donate blood while taking mycophenolate mofetil capsules and for at least 6 weeks after stopping mycophenolate mofetil capsules. </li> <li>You should not donate sperm while taking mycophenolate mofetil capsules and for 90 days after stopping mycophenolate mofetil capsules. </li> <li>Mycophenolate mofetil capsules may influence your ability to drive and use machines (See<span class="Bold"> “<span class="Bold">What are the possible side effects of </span><span class="Bold">mycophenolate mofetil capsules?</span>”.</span> If you experience drowsiness, confusion, dizziness, tremor, or low blood pressure during treatment with mycophenolate mofetil capsules, you should be cautious about driving or using heavy machines.</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2"><span class="Bold">What are the possible side effects of </span><span class="Bold">mycophenolate mofetil capsules?</span> <p class="First"> <span class="Bold">Mycophenolate mofetil capsules may cause serious side effects, including: </span> </p> <ul class="Disc"> <li>See <span class="Bold">“What is the most important information I should know about </span><span class="Bold">mycophenolate mofetil capsules?” </span> </li> <li> <span class="Bold">Low blood cell counts. </span>People taking high doses of mycophenolate mofetil capsules each day may have a decrease in blood counts, including: <ul class="Circle"> <li> <span class="Bold">white blood cells, especially neutrophils. </span>Neutrophils fight against bacterial infections. You have a higher chance of getting an infection when your white blood cell count is low. This is most common from 1 month to 6 months after your transplant. </li> <li> <span class="Bold">red blood cells. </span>Red blood cells carry oxygen to your body tissues. You have a higher chance of getting severe anemia when your red blood cell count is low. </li> <li> <span class="Bold">platelets</span>. Platelets help with blood clotting. Your doctor will do blood tests before you start taking mycophenolate mofetil capsules and during treatment with mycophenolate mofetil capsules to check your blood cell counts. Tell your doctor right away if you have any signs of infection (See <span class="Bold">“What is the most important information I should know about </span><span class="Bold">mycophenolate mofetil capsules?”</span>), including any unexpected bruising or bleeding. Also, tell your doctor if you have unusual tiredness, lack of energy, dizziness or fainting. </li> </ul> </li> <li> <span class="Bold">Stomach problems. </span>Stomach problems including intestinal bleeding, a tear in your intestinal wall (perforation) or stomach ulcers can happen in people who take mycophenolate mofetil capsules. Bleeding can be severe and you may have to be hospitalized for treatment. Call your doctor right away if you have sudden or severe stomach-area pain or stomach-area pain that does not go away, or if you have diarrhea.</li> <li> <span class="Bold">Inflammatory reactions.</span> Some people taking mycophenolate mofetil capsules may have an inflammatory reaction with fever, joint stiffness, joint pain, and muscle pain. Some of these reactions may require hospitalization. This reaction could happen within weeks to months after your treatment with mycophenolate mofetil capsules starts or if your dose is increased. Call your doctor right away if you experience these symptoms.</li> </ul> <p> <span class="Bold">The most common side effects of </span><span class="Bold">mycophenolate mofetil capsules include:</span> </p> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li> diarrhea</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li> changes in laboratory blood levels, including high levels of blood sugar (hyperglycemia)</li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li> blood problems including low white and red blood cell counts </li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li> stomach problems including diarrhea, constipation, nausea and vomiting </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li> infections</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li> rash</li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li> blood pressure problems </li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li> nervous system problems such as headache, dizziness and tremor </li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li> fast heartbeat</li> </ul> </td><td class="Rrule"> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li> swelling of the lower legs, ankles and feet </li> </ul> </td><td class="Rrule"> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2"> <span class="Bold">Side effects that can happen more often in children than in adults taking </span><span class="Bold">mycophenolate mofetil capsules include</span>:</td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li> stomach area pain</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li> vomiting</li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li> fever</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li> sore throat</li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li> infection</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li> colds (respiratory tract infections)</li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li> pain</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li> high blood pressure</li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li> blood infection (sepsis)</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li> low white blood cell count</li> </ul> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li> diarrhea</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li> low red blood cell count</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2"> <p class="First"> These are not all of the possible side effects of mycophenolate mofetil capsules. Tell your doctor about any side effect that bothers you or that does not go away.</p> <p> <span class="Bold">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088</span>.</p> <p>You may also report side effects to Teva at 1-888-838-2872.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <span class="Bold">How should I store mycophenolate mofetil capsules?</span> <ul class="Disc"> <li>Store mycophenolate mofetil capsules at room temperature between 68°F to 77°F (20°C to 25°C). Keep the container closed tightly.</li> </ul> <ul class="Disk"> <li> <span class="Bold">Keep mycophenolate mofetil capsules and all medicines out of the reach of children.</span> </li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">General information about the safe and effective use of mycophenolate mofetil capsules.</span> <p class="First">Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use mycophenolate mofetil capsules for a condition for which they were not prescribed. Do not give mycophenolate mofetil capsules to other people, even if they have the same symptoms that you have. They may harm them.</p> This Medication Guide summarizes the most important information about mycophenolate mofetil capsules. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist about mycophenolate mofetil capsules that is written for health professionals.</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">What are the ingredients in mycophenolate mofetil capsules?</span> <p class="First"> <span class="Bold">Active ingredient: </span>mycophenolate mofetil</p> <p> <span class="Bold">Inactive ingredients:</span><span class="Bold"> </span>black iron oxide, croscarmellose sodium, D&amp;C red #28, D&amp;C yellow #10, FD&amp;C blue #1, FD&amp;C red #40, gelatin, magnesium stearate, povidone, pregelatinized corn starch, propylene glycol, shellac glaze, and titanium dioxide.</p> <p>Brands listed are the trademarks of their respective owners. </p> <p>Manufactured In Czech Republic By: <span class="Bold">Teva Czech Industries, s.r.o.</span> Opava-Komarov, Czech Republic</p> <p>Manufactured For:<span class="Bold"> Teva Pharmaceuticals,</span> Parsippany, NJ 07054</p> <p> For more information, call 1-888-838-2872 </p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellspacing=\"5\" width=\"1000px\">\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\"> <span class=\"Bold\">MEDICATION GUIDE</span>\n</p>\n<p>\n<span class=\"Bold\">Mycophenolate Mofetil (mye\" koe fen' oh late moe' fe til) Capsules, 250 mg</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"> Read the Medication Guide that comes with mycophenolate mofetil capsules before you start taking it and each time you refill your prescription. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment.</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about mycophenolate mofetil capsules?</span>\n</p>\n<p>\n<span class=\"Bold\">Mycophenolate mofetil capsules can cause serious side effects, including:</span>\n</p>\n<p>\n<span class=\"Bold\">Increased risk of loss of a pregnancy (miscarriage) and higher risk of birth defects. </span>Females who take mycophenolate mofetil capsules during pregnancy have a higher risk of miscarriage during the first 3 months (first trimester), and a higher risk that their baby will be born with birth defects.</p>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">If you are a female who can become pregnant</span>, your doctor must talk with you about acceptable birth control methods (contraceptive counseling) to use while taking mycophenolate mofetil capsules. You should have 1 pregnancy test immediately before starting mycophenolate mofetil capsules and another pregnancy test 8 to 10 days later. Pregnancy tests should be repeated during routine follow-up visits with your doctor. Talk to your doctor about the results of all of your pregnancy tests.\n <p class=\"First\">You must use acceptable birth control during your entire mycophenolate mofetil capsule treatment and for 6 weeks after stopping mycophenolate mofetil capsules, unless at any time you choose to avoid sexual intercourse (abstinence) with a man completely. Mycophenolate mofetil capsules decrease blood levels of the hormones in birth control pills that you take by mouth. Birth control pills may not work as well while you take mycophenolate mofetil capsules, and you could become pregnant. If you take birth control pills while using mycophenolate mofetil capsules you must also use another form of birth control. Talk to your doctor about other birth control methods that you can use while taking mycophenolate mofetil capsules.</p>\n</li>\n<li>\n<span class=\"Bold\">If you are a sexually active male whose female partner can become pregnant while you are taking mycophenolate mofetil capsules</span>, use effective contraception during treatment and for at least 90 days after stopping mycophenolate mofetil capsules.</li>\n<li>\n<span class=\"Bold\">If you plan to become pregnant</span>, talk with your doctor. Your doctor will decide if other medicines to prevent rejection may be right for you.</li>\n<li>\n<span class=\"Bold\">If you become pregnant while taking mycophenolate mofetil capsules</span>, <span class=\"Bold\">do not stop taking mycophenolate mofetil capsules. Call your doctor right away.</span>\n<p class=\"First\">You and your doctor may decide that other medicines to prevent rejection may be right for you. You and your doctor should report your pregnancy to the Mycophenolate Pregnancy Registry either:</p>\n<ul class=\"Circle\">\n<li>By phone at 1-800-617-8191 <span class=\"Bold\">or</span>\n</li>\n<li>By visiting the REMS website at: <span class=\"Bold\"><a href=\"http://www.mycophenolaterems.com/\">www.mycophenolateREMS.com</a></span>\n</li>\n</ul>\n</li>\n</ul>\n<p>The purpose of this registry is to gather information about the health of you and your baby.</p>\n<span class=\"Bold\">Increased risk of getting certain cancers. </span>People who take mycophenolate mofetil capsules have a higher risk of getting lymphoma, and other cancers, especially skin cancer. Tell your doctor if you have: </td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li>unexplained fever, prolonged tiredness, weight loss or lymph node swelling</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li>a change in the size and color of a mole </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li>a brown or black skin lesion with uneven borders, or one part of the lesion does not look like the other  </li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li>a new skin lesion or bump </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\"></td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li>any other changes to your health </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Increased risk of getting serious infections. </span>Mycophenolate mofetil capsules weaken the body’s immune system and affects your ability to fight infections. Serious infections can happen with mycophenolate mofetil capsules and can lead to hospitalizations and death. These serious infections can include:</p>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Viral infections. </span>Certain viruses can live in your body and cause active infections when your immune system is weak.\n <p class=\"First\">Viral infections that can happen with mycophenolate mofetil capsules include:</p>\n<ul class=\"Circle\">\n<li>Shingles, other herpes infections, and cytomegalovirus (CMV). CMV can cause serious tissue and blood infections.</li>\n<li>BK virus. BK virus can affect how your kidney works and cause your transplanted kidney to fail.</li>\n<li>Hepatitis B and C viruses. Hepatitis viruses can affect how your liver works. Talk to your doctor about how hepatitis viruses may affect you.</li>\n<li>COVID-19</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">A brain infection called Progressive Multifocal Leukoencephalopathy (PML). </span>In some patients, mycophenolate mofetil capsules may cause an infection of the brain that may cause death. You are at risk for this brain infection because you have a weakened immune system. Call your doctor right away if you have any of the following symptoms:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Circle\">\n<li>weakness on one side of the body</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Circle\">\n<li> you are confused or have problems thinking</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Circle\">\n<li>you do not care about things you usually care about (apathy)</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Circle\">\n<li>you cannot control your muscles </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\">\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">Fungal infections. </span>Yeasts and other types of fungal infections can happen with mycophenolate mofetil capsules and can cause serious tissue and blood infections (See <span class=\"Bold\">“What are the possible side effects of mycophenolate mofetil capsules?”</span>). </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Call your doctor right away if you have any of the following signs and symptoms of infection:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li> temperature of 100.5°F or greater</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li>pain during urination </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li> cold symptoms, such as a runny nose or sore throat</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li>white patches in the mouth or throat </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li>flu symptoms, such as an upset stomach, stomach pain, vomiting or diarrhea </li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li>unexpected bruising or bleeding </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li>earache or headache </li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li> cuts, scrapes or incisions that are red, warm and oozing pus</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\">  See <span class=\"Bold\">“What are the possible side effects of mycophenolate mofetil capsules?” </span>for information about other serious side effects.</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">What are mycophenolate mofetil capsules?</span>\n</p>\n<ul class=\"Disk\">\n<li>Mycophenolate mofetil capsules are a prescription medicine to prevent rejection (antirejection medicine) in people who have received a kidney, heart or liver transplant. Rejection is when the body’s immune system perceives the new organ as a “foreign” threat and attacks it.</li>\n<li> Mycophenolate mofetil capsules are used with other medicines containing cyclosporine and corticosteroids.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Who should not take mycophenolate mofetil capsules?</span>\n</p>\n<span class=\"Bold\">Do not take mycophenolate mofetil capsules if you are allergic to mycophenolate mofetil or any of the ingredients in mycophenolate mofetil capsules. </span>See the end of this Medication Guide for a complete list of ingredients in mycophenolate mofetil capsules. </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">What should I tell my doctor before taking mycophenolate mofetil capsules?</span>\n</p>\n<p>\n<span class=\"Bold\">Tell your doctor about all of your medical conditions, including if you</span>:</p>\n<ul class=\"Disc\">\n<li>have any digestive problems, such as ulcers.</li>\n<li>have Lesch-Nyhan syndrome, Kelley-Seegmiller syndrome, or another rare inherited deficiency hypoxanthine-guanine phosphoribosyl-transferase (HGPRT). You should not take mycophenolate mofetil capsules if you have one of these disorders.</li>\n<li>plan to receive any vaccines. People taking mycophenolate mofetil capsules should not receive live vaccines. Some vaccines may not work as well during treatment with mycophenolate mofetil capsules.</li>\n<li>are pregnant or plan to become pregnant. See <span class=\"Bold\">“What is the most important information I should know about mycophenolate mofetil capsules?”</span>\n</li>\n<li>are breastfeeding or plan to breastfeed. It is not known if mycophenolate mofetil passes into breast milk. You and your doctor will decide if you will take mycophenolate mofetil capsules or breastfeed.</li>\n</ul>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take, </span>including prescription and over-the-counter medicines, vitamins and herbal supplements. Some medicines may affect the way mycophenolate mofetil capsules work, and mycophenolate mofetil capsules may affect how some medicines work.</p>\n<p>Especially tell your doctor if you take:</p>\n<ul class=\"Disc\">\n<li>birth control pills (oral contraceptives). See <span class=\"Bold\">“What is the most important information I should know about mycophenolate mofetil capsules?”</span>\n</li>\n<li>sevelamer (Renagel<span class=\"Sup\">®</span>, Renvela<span class=\"Sup\">™</span>). These products should be taken at least 2 hours after taking mycophenolate mofetil capsules.</li>\n<li>acyclovir (Zovirax<span class=\"Sup\">®</span>), valacyclovir (Valtrex<span class=\"Sup\">®</span>), ganciclovir (CYTOVENE<span class=\"Sup\">®</span>-IV, Vitrasert<span class=\"Sup\">®</span>), valganciclovir (VALCYTE<span class=\"Sup\">®</span>).</li>\n<li>rifampin (Rifater<span class=\"Sup\">®</span>, Rifamate<span class=\"Sup\">®</span>, Rimactane<span class=\"Sup\">®</span>, Rifadin<span class=\"Sup\">®</span>).</li>\n<li>antacids that contain magnesium and aluminum (mycophenolate mofetil capsules and the antacid should not be taken at the same time).</li>\n<li>proton pump inhibitors (PPIs) (Prevacid<span class=\"Sup\">®</span>, Protonix<span class=\"Sup\">®</span>).</li>\n<li>sulfamethoxazole/trimethoprim (BACTRIM<span class=\"Sup\">™</span>, BACTRIM DS<span class=\"Sup\">™</span>).</li>\n<li>norfloxacin (Noroxin<span class=\"Sup\">®</span>) and metronidazole (Flagyl<span class=\"Sup\">®</span>, Flagyl<span class=\"Sup\">®</span> ER, Flagyl<span class=\"Sup\">®</span> IV, Metro IV, Helidac<span class=\"Sup\">®</span>, Pylera<span class=\"Sup\">™</span>).</li>\n<li>ciprofloxacin (Cipro<span class=\"Sup\">®</span>, Cipro<span class=\"Sup\">®</span> XR, Ciloxan<span class=\"Sup\">®</span>, Proquin<span class=\"Sup\">®</span> XR) and amoxicillin plus clavulanic acid (Augmentin<span class=\"Sup\">®</span>, Augmentin XR<span class=\"Sup\">™</span>).</li>\n<li>azathioprine (Azasan<span class=\"Sup\">®</span>, Imuran<span class=\"Sup\">®</span>).</li>\n<li>cholestyramine (Questran Light<span class=\"Sup\">®</span>, Questran<span class=\"Sup\">®</span>, Locholest Light, Locholest, Prevalite<span class=\"Sup\">®</span>).</li>\n</ul>\n<p> Know the medicines you take. Keep a list of them to show to your doctor or nurse and pharmacist when you get a new medicine. <span class=\"Bold\">Do not </span>take any new medicine without talking with your doctor.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"> <span class=\"Bold\">How should I take mycophenolate mofetil capsules?</span>\n<ul class=\"Disc\">\n<li>Take mycophenolate mofetil capsules exactly as prescribed.</li>\n<li>\n<span class=\"Bold\">Do not</span> stop taking mycophenolate mofetil capsules or change the dose unless your doctor tells you to.</li>\n<li>If you miss a dose of mycophenolate mofetil capsules, or you are not sure when you took your last dose, take your prescribed dose of mycophenolate mofetil capsules as soon as you remember. If your next dose is less than 2 hours away, skip the missed dose and take your next dose at your normal scheduled time. Do not take 2 doses at the same time. Call your doctor if you are not sure what to do.</li>\n<li>Take mycophenolate mofetil capsules on an empty stomach, unless your doctor tells you otherwise.</li>\n<li>\n<span class=\"Bold\">Do no</span><span class=\"Bold\">t</span> open or crush mycophenolate mofetil capsules.</li>\n<li>If you take too many mycophenolate mofetil capsules, call your doctor or the poison control center right away.</li>\n<li>If you are not able to swallow mycophenolate mofetil capsules, your doctor may prescribe mycophenolate mofetil oral suspension. This is a liquid form of mycophenolate mofetil capsules. Your pharmacist will mix the medicine before you pick it up from a pharmacy.</li>\n<li>\n<span class=\"Bold\">Do not </span>breathe in (inhale) or let mycophenolate mofetil capsules powder come in contact with your skin or mucous membranes.\n <ul class=\"Circle\">\n<li>If you accidentally get the powder on the skin, wash the area well with soap and water.</li>\n<li>If you accidentally get the powder in your eyes or other mucous membranes, flush with plain water.</li>\n</ul>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"> <span class=\"Bold\">What should I avoid while taking </span><span class=\"Bold\">mycophenolate mofetil capsules?</span>\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\"> </span>Avoid becoming pregnant. (See <span class=\"Bold\">“What is the most important information I should know about </span><span class=\"Bold\">mycophenolate mofetil capsules?”).</span>\n</li>\n<li>Limit the amount of time you spend in sunlight. Avoid using tanning beds or sunlamps. People who take mycophenolate mofetil capsules have a higher risk of getting skin cancer (See <span class=\"Bold\">“What is the most important information I should know about </span><span class=\"Bold\">mycophenolate mofetil capsules?”</span>). Wear protective clothing when you are in the sun and use a broad-spectrum sunscreen with a high protection factor. This is especially important if your skin is very fair or if you have a family history of skin cancer. </li>\n<li>You should not donate blood while taking mycophenolate mofetil capsules and for at least 6 weeks after stopping mycophenolate mofetil capsules. </li>\n<li>You should not donate sperm while taking mycophenolate mofetil capsules and for 90 days after stopping mycophenolate mofetil capsules. </li>\n<li>Mycophenolate mofetil capsules may influence your ability to drive and use machines (See<span class=\"Bold\"> “<span class=\"Bold\">What are the possible side effects of </span><span class=\"Bold\">mycophenolate mofetil capsules?</span>”.</span> If you experience drowsiness, confusion, dizziness, tremor, or low blood pressure during treatment with mycophenolate mofetil capsules, you should be cautious about driving or using heavy machines.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">What are the possible side effects of </span><span class=\"Bold\">mycophenolate mofetil capsules?</span>\n<p class=\"First\">\n<span class=\"Bold\">Mycophenolate mofetil capsules may cause serious side effects, including: </span>\n</p>\n<ul class=\"Disc\">\n<li>See <span class=\"Bold\">“What is the most important information I should know about </span><span class=\"Bold\">mycophenolate mofetil capsules?” </span>\n</li>\n<li>\n<span class=\"Bold\">Low blood cell counts. </span>People taking high doses of mycophenolate mofetil capsules each day may have a decrease in blood counts, including:\n <ul class=\"Circle\">\n<li>\n<span class=\"Bold\">white blood cells, especially neutrophils. </span>Neutrophils fight against bacterial infections. You have a higher chance of getting an infection when your white blood cell count is low. This is most common from 1 month to 6 months after your transplant. </li>\n<li>\n<span class=\"Bold\">red blood cells. </span>Red blood cells carry oxygen to your body tissues. You have a higher chance of getting severe anemia when your red blood cell count is low. </li>\n<li>\n<span class=\"Bold\">platelets</span>. Platelets help with blood clotting. Your doctor will do blood tests before you start taking mycophenolate mofetil capsules and during treatment with mycophenolate mofetil capsules to check your blood cell counts. Tell your doctor right away if you have any signs of infection (See <span class=\"Bold\">“What is the most important information I should know about </span><span class=\"Bold\">mycophenolate mofetil capsules?”</span>), including any unexpected bruising or bleeding. Also, tell your doctor if you have unusual tiredness, lack of energy, dizziness or fainting. </li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Stomach problems. </span>Stomach problems including intestinal bleeding, a tear in your intestinal wall (perforation) or stomach ulcers can happen in people who take mycophenolate mofetil capsules. Bleeding can be severe and you may have to be hospitalized for treatment. Call your doctor right away if you have sudden or severe stomach-area pain or stomach-area pain that does not go away, or if you have diarrhea.</li>\n<li>\n<span class=\"Bold\">Inflammatory reactions.</span> Some people taking mycophenolate mofetil capsules may have an inflammatory reaction with fever, joint stiffness, joint pain, and muscle pain. Some of these reactions may require hospitalization. This reaction could happen within weeks to months after your treatment with mycophenolate mofetil capsules starts or if your dose is increased. Call your doctor right away if you experience these symptoms.</li>\n</ul>\n<p>\n<span class=\"Bold\">The most common side effects of </span><span class=\"Bold\">mycophenolate mofetil capsules include:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li> diarrhea</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li> changes in laboratory blood levels, including high levels of blood sugar (hyperglycemia)</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li> blood problems including low white and red blood cell counts </li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li> stomach problems including diarrhea, constipation, nausea and vomiting </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li> infections</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li> rash</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li> blood pressure problems </li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li> nervous system problems such as headache, dizziness and tremor </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li> fast heartbeat</li>\n</ul>\n</td><td class=\"Rrule\"> </td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li> swelling of the lower legs, ankles and feet </li>\n</ul>\n</td><td class=\"Rrule\"> </td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\"> <span class=\"Bold\">Side effects that can happen more often in children than in adults taking </span><span class=\"Bold\">mycophenolate mofetil capsules include</span>:</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li> stomach area pain</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li> vomiting</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li> fever</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li> sore throat</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li> infection</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li> colds (respiratory tract infections)</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li> pain</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li> high blood pressure</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li> blood infection (sepsis)</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li> low white blood cell count</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li> diarrhea</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li> low red blood cell count</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\">\n<p class=\"First\"> These are not all of the possible side effects of mycophenolate mofetil capsules. Tell your doctor about any side effect that bothers you or that does not go away.</p>\n<p>\n<span class=\"Bold\">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088</span>.</p>\n<p>You may also report side effects to Teva at 1-888-838-2872.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"> <span class=\"Bold\">How should I store mycophenolate mofetil capsules?</span>\n<ul class=\"Disc\">\n<li>Store mycophenolate mofetil capsules at room temperature between 68°F to 77°F (20°C to 25°C). Keep the container closed tightly.</li>\n</ul>\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">Keep mycophenolate mofetil capsules and all medicines out of the reach of children.</span>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">General information about the safe and effective use of mycophenolate mofetil capsules.</span>\n<p class=\"First\">Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use mycophenolate mofetil capsules for a condition for which they were not prescribed. Do not give mycophenolate mofetil capsules to other people, even if they have the same symptoms that you have. They may harm them.</p>\n This Medication Guide summarizes the most important information about mycophenolate mofetil capsules. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist about mycophenolate mofetil capsules that is written for health professionals.</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">What are the ingredients in mycophenolate mofetil capsules?</span>\n<p class=\"First\">\n<span class=\"Bold\">Active ingredient: </span>mycophenolate mofetil</p>\n<p>\n<span class=\"Bold\">Inactive ingredients:</span><span class=\"Bold\"> </span>black iron oxide, croscarmellose sodium, D&amp;C red #28, D&amp;C yellow #10, FD&amp;C blue #1, FD&amp;C red #40, gelatin, magnesium stearate, povidone, pregelatinized corn starch, propylene glycol, shellac glaze, and titanium dioxide.</p>\n<p>Brands listed are the trademarks of their respective owners. </p>\n<p>Manufactured In Czech Republic By: <span class=\"Bold\">Teva Czech Industries, s.r.o.</span> Opava-Komarov, Czech Republic</p>\n<p>Manufactured For:<span class=\"Bold\"> Teva Pharmaceuticals,</span> Parsippany, NJ 07054</p>\n<p> For more information, call 1-888-838-2872 </p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Medication Guide has been approved by the U.S. Food and Drug Administration.                                                                                        Rev. N 7/2023

{ "type": "p", "children": [], "text": "This Medication Guide has been approved by the U.S. Food and Drug Administration.                                                                                        Rev. N 7/2023" }

NDC 0093-7334-01 

{ "type": "p", "children": [], "text": "NDC 0093-7334-01 " }

Mycophenolate Mofetil Capsules, USP

{ "type": "p", "children": [], "text": "\nMycophenolate Mofetil Capsules, USP\n" }

250 mg

{ "type": "p", "children": [], "text": "250 mg" }

PHARMACIST: Dispense the accompanying Medication Guide to each patient.

{ "type": "p", "children": [], "text": "PHARMACIST: Dispense the accompanying Medication Guide to each patient." }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

100 Capsules 

{ "type": "p", "children": [], "text": "100 Capsules " }

CELLCEPT [mycophenolate mofetil (MMF)] is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney [see Clinical Studies (14.1)], heart [see Clinical Studies (14.2)] or liver transplants [see Clinical Studies (14.3)], in combination with other immunosuppressants.

{ "type": "p", "children": [], "text": "CELLCEPT [mycophenolate mofetil (MMF)] is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney [see Clinical Studies (14.1)], heart [see Clinical Studies (14.2)] or liver transplants [see Clinical Studies (14.3)], in combination with other immunosuppressants. " }

CELLCEPT should not be used without the supervision of a physician with experience in immunosuppressive therapy.

CELLCEPT Capsules, Tablets and Oral Suspension

CELLCEPT oral dosage forms (capsules, tablets or oral suspension) should not be used interchangeably with mycophenolic acid delayed-release tablets without supervision of a physician with experience in immunosuppressive therapy because the rates of absorption following the administration of CELLCEPT oral dosage forms and mycophenolic acid delayed-release tablets are not equivalent.

CELLCEPT tablets should not be crushed and CELLCEPT capsules should not be opened or crushed. Patients should avoid inhalation or contact of the skin or mucous membranes with the powder contained in CELLCEPT capsules and oral suspension. If such contact occurs, they must wash the area of contact thoroughly with soap and water. In case of ocular contact, rinse eyes with plain water.

The initial oral dose of CELLCEPT should be given as soon as possible following kidney, heart or liver transplant. It is recommended that CELLCEPT be administered on an empty stomach. In stable transplant patients, however, CELLCEPT may be administered with food if necessary [see Clinical Pharmacology (12.3)]. Once reconstituted, CELLCEPT Oral Suspension must not be mixed with any liquids prior to dose administration. If needed, CELLCEPT Oral Suspension can be administered via a nasogastric tube with a minimum size of 8 French (minimum 1.7 mm interior diameter).

Patients should be instructed to take a missed dose as soon as they remember, except if it is closer than 2 hours to the next scheduled dose; in this case, they should continue to take CELLCEPT at the usual times.

CELLCEPT Intravenous

CELLCEPT Intravenous is recommended for patients unable to take oral CELLCEPT. CELLCEPT Intravenous should be administered within 24 hours following transplant. CELLCEPT Intravenous can be administered for up to 14 days; however, patients should be switched to oral CELLCEPT as soon as they can tolerate oral medication.

CELLCEPT Intravenous must be reconstituted before use [see Dosage and Administration (2.6)]. CELLCEPT Intravenous is incompatible with other intravenous infusion solutions and should not be mixed or administered concurrently via the same infusion catheter with other intravenous drugs or infusion admixtures.

CELLCEPT Intravenous must not be administered as a bolus. Following reconstitution, CELLCEPT Intravenous must be administered by slow intravenous infusion over a period of no less than 2 hours by either peripheral or central vein, as rapid infusion increases the risk of local adverse reactions such as phlebitis and thrombosis [see Adverse Reactions (6.1)].

Adults

The recommended dosage for adult kidney transplant patients is 1 g orally or intravenously infused over no less than 2 hours, twice daily (total daily dose of 2 g).

Pediatrics (3 months and older)

Pediatric dosing is based on body surface area (BSA). The recommended dosage of CELLCEPT oral suspension for pediatric kidney transplant patients 3 months and older is 600 mg/m2, administered twice daily (maximum total daily dose of 2 g or 10 mL of the oral suspension). Pediatric patients with BSA ≥ 1.25 m2 may be dosed with capsules or tablets as follows:

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 1 Pediatric Kidney Transplant: Dosage Using Capsules or Tablets</span> </caption> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="75%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">Body Surface Area</th><th align="left" class="Rrule">Dosage</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">1.25 m<span class="Sup">2</span> to &lt;1.5 m<span class="Sup">2</span></td><td align="left" class="Rrule">CELLCEPT capsule 750 mg twice daily (1.5 g total daily dose)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">≥ 1.5 m<span class="Sup">2</span></td><td align="left" class="Rrule">CELLCEPT capsules or tablets 1 g twice daily (2 g total daily dose)</td> </tr> </tbody> </table></div>

Adults

The recommended dosage of CELLCEPT for adult heart transplant patients is 1.5 g orally or intravenously infused over no less than 2 hours administered twice daily (total daily dose of 3 g).

Pediatrics (3 months and older)

The recommended starting dosage of CELLCEPT oral suspension for pediatric heart transplant patients 3 months and older is 600 mg/m2, administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m2 twice daily (maximum total daily dose of 3 g or 15 mL of the oral suspension). The dose may be individualized based on clinical assessment.

Pediatric patients with BSA ≥1.25 m2 may be started on therapy with capsules or tablets as follows:

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 2 Pediatric Heart Transplant: Pediatric Starting Dosage Using Capsules or Tablets</span> </caption> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="75%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">Body Surface Area</th><th align="left" class="Rrule">Starting Dosage<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Maximum maintenance dose: 3 g total daily.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">1.25 m<span class="Sup">2</span> to &lt;1.5 m<span class="Sup">2</span></td><td align="left" class="Rrule">CELLCEPT capsule 750 mg twice daily (1.5 g total daily dose)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">≥ 1.5 m<span class="Sup">2</span></td><td align="left" class="Rrule">CELLCEPT capsules or tablets 1 g twice daily (2 g total daily dose)</td> </tr> </tbody> </table></div>

Adults

The recommended dosage of CELLCEPT for adult liver transplant patients is 1.5 g administered orally twice daily (total daily dose of 3 g) or 1 g infused intravenously over no less than 2 hours, twice daily (total daily dose of 2 g).

Pediatrics (3 months and older)

The recommended starting dosage of CELLCEPT oral suspension for pediatric liver transplant patients 3 months of age and older is 600 mg/m2, administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m2 twice daily (maximum total daily dose of 3 g or 15 mL of the oral suspension). The dose may be individualized based on clinical assessment.

Pediatric patients with BSA ≥1.25 m2 may be started on therapy with capsules or tablets as follows:

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 3 Pediatric Liver Transplant: Pediatric Starting Dosage Using Capsules or Tablets</span> </caption> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="75%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">Body Surface Area</th><th align="left" class="Rrule">Starting Dosage<a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>Maximum maintenance dose: 3 g total daily.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">1.25 m<span class="Sup">2</span> to &lt;1.5 m<span class="Sup">2</span></td><td align="left" class="Rrule">CELLCEPT capsule 750 mg twice daily (1.5 g total daily dose)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">≥ 1.5 m<span class="Sup">2</span></td><td align="left" class="Rrule">CELLCEPT capsules or tablets 1 g twice daily (2 g total daily dose)</td> </tr> </tbody> </table></div>

Renal Impairment

No dosage modifications are needed in kidney transplant patients with delayed graft function postoperatively [see Clinical Pharmacology (12.3)]. In kidney transplant patients with severe chronic impairment of the graft (GFR <25 mL/min/1.73 m2), do not administer doses of CELLCEPT greater than 1 g twice a day. These patients should be carefully monitored [see Clinical Pharmacology (12.3)].

Neutropenia

If neutropenia develops (ANC <1.3 × 103/µL), dosing with CELLCEPT should be interrupted or reduced, appropriate diagnostic tests performed, and the patient managed appropriately [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)].

General Preparation Instructions Before Handling the Formulations

Mycophenolate mofetil (MMF) has demonstrated teratogenic effects in humans. Follow applicable special handling and disposal procedures1 [see Warnings and Precautions (5.1), Adverse Reactions (6.2), Use in Specific Populations (8.1, 8.3), How Supplied/Storage and Handling (16.1)].

Care should be taken to avoid inhalation or direct contact with skin or mucous membranes of the dry powder or the constituted suspension because MMF has demonstrated teratogenic effects in humans. Wearing disposable gloves is recommended during reconstitution and when wiping the outer surface of the bottle/cap and the table surface after reconstitution. If such contact occurs, wash hands thoroughly with soap and water; rinse eyes with water.

Alert patients that they and others should also avoid inhalation or contact of the skin or mucous membranes with the oral suspension. Advise them to wash the area thoroughly with soap and water if such contact occurs; if ocular contact occurs, rinse eyes with plain water.

CELLCEPT Oral Suspension

CELLCEPT Oral Suspension must be reconstituted by the pharmacist prior to dispensing to the patient. CELLCEPT Oral Suspension should not be mixed with any other medication. After reconstitution, the oral suspension contains 200 mg/mL MMF.

Before proceeding with the reconstitution steps read the general preparation instructions above [see General Preparation Instructions Before Handling the Formulations]. The following are the steps for reconstitution:

Store reconstituted suspension at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Storage in a refrigerator at 2°C to 8°C (36°F to 46°F) is acceptable. Do not freeze. Discard any unused portion 60 days after constitution.

CELLCEPT Intravenous

Before proceeding with the preparation steps for CELLCEPT Intravenous read the general preparation instructions [see General Preparation Instructions Before Handling the Formulations] and note the following:

CELLCEPT Intravenous must be reconstituted and further diluted. A detailed description of the preparation is given below.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 4 Preparation Instructions of CELLCEPT Intravenous for Pharmacists</span> </caption> <col align="center" valign="middle" width="20%"/> <col align="left" valign="middle" width="80%"/> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">Preparation of the <span class="Bold">1g dose</span></td><td align="left" class="Rrule"> <ol class="Arabic"> <li> <span class="Underline">Reconstitute</span> two (2) vials of CELLCEPT Intravenous by injecting 14 mL of 5% Dextrose Injection USP into each vial. </li> <li>Gently shake the vial to dissolve the drug.</li> <li>Inspect the resulting slightly yellow solution for particulate matter and discoloration prior to further dilution. Discard the vials if particulate matter or discoloration is observed.</li> <li> <span class="Underline">Dilute</span> the contents of the two reconstituted vials (approximately 2 × 15 mL) into 140 mL of 5% Dextrose Injection USP.</li> <li>Inspect the resulting infusion solution and discard if particulate matter or discoloration is observed.</li> </ol> </td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">Preparation of the <span class="Bold">1.5 g dose</span></td><td align="left" class="Rrule"> <ol class="Arabic"> <li> <span class="Underline">Reconstitute</span> three (3) vials of CELLCEPT Intravenous by injecting 14 mL of 5% Dextrose Injection USP into each vial. </li> <li>Gently shake the vial to dissolve the drug.</li> <li>Inspect the resulting slightly yellow solution for particulate matter and discoloration prior to further dilution. Discard the vials if particulate matter or discoloration is observed.</li> <li> <span class="Underline">Dilute</span> the contents of the three reconstituted vials (approximately 3 × 15 mL) into 210 mL of 5% Dextrose Injection USP.</li> <li>Inspect the resulting infusion solution and discard if particulate matter or discoloration is observed.</li> </ol> </td> </tr> </tbody> </table></div>

The administration of the infusion should be initiated within 4 hours of reconstitution and dilution of the drug product. Keep solutions at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Discard unused portion of the reconstituted solutions.

CELLCEPT Injection should not be mixed or administered concurrently via the same infusion catheter with other intravenous drugs or infusion admixtures.

CELLCEPT is available in the following dosage forms and strengths:

{ "type": "p", "children": [], "text": "CELLCEPT is available in the following dosage forms and strengths:" }

<div class="scrollingtable"><table width="75%"> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="80%"/> <tbody class="Headless"> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Capsules</td><td align="left" class="Rrule">250 mg mycophenolate mofetil, two-piece hard gelatin capsules, blue-brown, "CELLCEPT 250" printed in black on the blue cap and "Roche" on the brown body</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Tablets</td><td align="left" class="Rrule">500 mg mycophenolate mofetil, lavender-colored, caplet-shaped, film-coated tablets engraved with "CELLCEPT 500" on one side and "Roche" on the other</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">For oral suspension</td><td align="left" class="Rrule">35 g mycophenolate mofetil white to off-white powder for reconstitution (200 mg/mL upon reconstitution)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">For injection</td><td align="left" class="Rrule">500 mg mycophenolate mofetil white to off-white lyophilized powder, in a single-dose vial for reconstitution</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"75%\">\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<col align=\"left\" valign=\"top\" width=\"80%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\">Capsules</td><td align=\"left\" class=\"Rrule\">250 mg mycophenolate mofetil, two-piece hard gelatin capsules, blue-brown, \"CELLCEPT 250\" printed in black on the blue cap and \"Roche\" on the brown body</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Tablets</td><td align=\"left\" class=\"Rrule\">500 mg mycophenolate mofetil, lavender-colored, caplet-shaped, film-coated tablets engraved with \"CELLCEPT 500\" on one side and \"Roche\" on the other</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">For oral suspension</td><td align=\"left\" class=\"Rrule\">35 g mycophenolate mofetil white to off-white powder for reconstitution (200 mg/mL upon reconstitution)</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\">For injection</td><td align=\"left\" class=\"Rrule\">500 mg mycophenolate mofetil white to off-white lyophilized powder, in a single-dose vial for reconstitution</td>\n</tr>\n</tbody>\n</table></div>" }

CELLCEPT is contraindicated in patients with a history of hypersensitivity, including anaphylaxis, to mycophenolate mofetil (MMF), mycophenolic acid (MPA) or any component of the drug product [see Warnings and Precautions (5.8)]. CELLCEPT Intravenous is contraindicated in patients who are allergic to Polysorbate 80 (TWEEN).

{ "type": "p", "children": [], "text": "CELLCEPT is contraindicated in patients with a history of hypersensitivity, including anaphylaxis, to mycophenolate mofetil (MMF), mycophenolic acid (MPA) or any component of the drug product [see Warnings and Precautions (5.8)]. CELLCEPT Intravenous is contraindicated in patients who are allergic to Polysorbate 80 (TWEEN)." }

Use of MMF during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney and nervous system. Females of reproductive potential must be made aware of these risks and must be counseled regarding pregnancy prevention and planning. Avoid use of MMF during pregnancy if safer treatment options are available [see Use in Specific Populations (8.1, 8.3)].

Patients receiving immunosuppressants, including CELLCEPT, are at increased risk of developing lymphomas and other malignancies, particularly of the skin [see Adverse Reactions (6.1)]. The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. For patients with increased risk for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen with a high protection factor.

Post-transplant lymphoproliferative disorder (PTLD) developed in 0.4% to 1% of patients receiving CELLCEPT (2 g or 3 g) with other immunosuppressive agents in controlled clinical trials of kidney, heart and liver transplant patients [see Adverse Reactions (6.1)]. The majority of PTLD cases appear to be related to Epstein Barr Virus (EBV) infection. The risk of PTLD appears greatest in those individuals who are EBV seronegative, a population which includes many young children. In pediatric patients, no other malignancies besides PTLD were observed in clinical trials [see Adverse Reactions (6.1)].

Patients receiving immunosuppressants, including CELLCEPT, are at increased risk of developing bacterial, fungal, protozoal and new or reactivated viral infections, including opportunistic infections. The risk increases with the total immunosuppressive load. These infections may lead to serious outcomes, including hospitalizations and death [see Adverse Reactions (6.1, 6.2)].

Serious viral infections reported include:

Consider dose reduction or discontinuation of CELLCEPT in patients who develop new infections or reactivate viral infections, weighing the risk that reduced immunosuppression represents to the functioning allograft.

PVAN, especially due to BK virus infection, is associated with serious outcomes, including deteriorating renal function and renal graft loss [see Adverse Reactions (6.2)]. Patient monitoring may help detect patients at risk for PVAN.

PML, which is sometimes fatal, commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia [see Adverse Reactions (6.2)]. In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms.

The risk of CMV viremia and CMV disease is highest among transplant recipients seronegative for CMV at time of transplant who receive a graft from a CMV seropositive donor. Therapeutic approaches to limiting CMV disease exist and should be routinely provided. Patient monitoring may help detect patients at risk for CMV disease.

Viral reactivation has been reported in patients infected with HBV or HCV. Monitoring infected patients for clinical and laboratory signs of active HBV or HCV infection is recommended.

Severe neutropenia [absolute neutrophil count (ANC) <0.5 × 103/µL] developed in transplant patients receiving CELLCEPT 3 g daily [see Adverse Reactions (6.1)]. Patients receiving CELLCEPT should be monitored for neutropenia. Neutropenia has been observed most frequently in the period from 31 to 180 days post-transplant in patients treated for prevention of kidney, heart and liver rejection. The development of neutropenia may be related to CELLCEPT itself, concomitant medications, viral infections, or a combination of these causes. If neutropenia develops (ANC <1.3 × 103/µL), dosing with CELLCEPT should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately [see Dosage and Administration (2.5)].

Patients receiving CELLCEPT should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression.

Consider monitoring with complete blood counts weekly for the first month, twice monthly for the second and third months, and monthly for the remainder of the first year.

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with CELLCEPT in combination with other immunosuppressive agents. In some cases, PRCA was found to be reversible with dose reduction or cessation of CELLCEPT therapy. In transplant patients, however, reduced immunosuppression may place the graft at risk.

Gastrointestinal bleeding requiring hospitalization, ulceration and perforations were observed in clinical trials. Physicians should be aware of these serious adverse effects particularly when administering CELLCEPT to patients with a gastrointestinal disease.

CELLCEPT is an inosine monophosphate dehydrogenase (IMPDH) inhibitor; therefore it should be avoided in patients with hereditary deficiencies of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndromes because it may cause an exacerbation of disease symptoms characterized by the overproduction and accumulation of uric acid leading to symptoms associated with gout such as acute arthritis, tophi, nephrolithiasis or urolithiasis and renal disease including renal failure.

Acute inflammatory syndrome (AIS) has been reported with the use of MMF and mycophenolate products, and some cases have resulted in hospitalization. AIS is a paradoxical pro-inflammatory reaction characterized by fever, arthralgias, arthritis, muscle pain and elevated inflammatory markers including, C-reactive protein and erythrocyte sedimentation rate, without evidence of infection or underlying disease recurrence. Symptoms occur within weeks to months of initiation of treatment or a dose increase. After discontinuation, improvement of symptoms and inflammatory markers are usually observed within 24 to 48 hours.

Monitor patients for symptoms and laboratory parameters of AIS when starting treatment with mycophenolate products or when increasing the dosage. Discontinue treatment and consider other treatment alternatives based on the risk and benefit for the patient.

Postmarketing cases of hypersensitivity reactions, including angioedema and anaphylaxis, have been reported with CELLCEPT. These reactions generally occurred within hours to the next day after initiating CELLCEPT. If signs or symptoms of hypersensitivity reaction occur, discontinue CELLCEPT; treat and monitor until symptoms resolve [see Contraindications (4)].

During treatment with CELLCEPT, the use of live attenuated vaccines should be avoided (e.g., intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) and patients should be advised that vaccinations may be less effective. Advise patients to discuss with the physician before seeking any immunizations.

CELLCEPT Intravenous solution must not be administered by rapid or bolus intravenous injection as rapid infusion increases the risk of local adverse reactions such as phlebitis and thrombosis [see Adverse Reactions (6.1)].

Phenylalanine can be harmful to patients with phenylketonuria (PKU). CELLCEPT Oral Suspension contains aspartame, a source of phenylalanine (0.56 mg phenylalanine/mL suspension). Before prescribing CELLCEPT Oral Suspension to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including CELLCEPT.

Patients should not donate blood during therapy and for at least 6 weeks following discontinuation of CELLCEPT because their blood or blood products might be administered to a female of reproductive potential or a pregnant woman.

Based on animal data, men should not donate semen during therapy and for 90 days following discontinuation of CELLCEPT [see Use In Specific Populations (8.3)].

A variety of drugs have potential to alter systemic MPA exposure when co-administered with CELLCEPT. Therefore, determination of MPA concentrations in plasma before and after making any changes to immunosuppressive therapy, or when adding or discontinuing concomitant medications, may be appropriate to ensure MPA concentrations remain stable.

CELLCEPT may impact the ability to drive and use machines. Patients should avoid driving or using machines if they experience somnolence, confusion, dizziness, tremor, or hypotension during treatment with CELLCEPT [see Adverse Reactions (6.1)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

An estimated total of 1557 adult patients received CELLCEPT during pivotal clinical trials in the prevention of acute organ rejection. Of these, 991 were included in the three renal studies, 277 were included in one hepatic study, and 289 were included in one cardiac study. Patients in all study arms also received cyclosporine and corticosteroids.

The data described below primarily derive from five randomized, active-controlled double-blind 12-month trials of CELLCEPT in de novo kidney (3) heart (1) and liver (1) transplant patients [see Clinical Studies (14.1, 14.2, and 14.3)].

CELLCEPT Oral

The incidence of adverse reactions for CELLCEPT was determined in five randomized, comparative, double-blind trials in the prevention of rejection in kidney, heart and liver transplant patients (two active- and one placebo-controlled trials, one active-controlled trial, and one active-controlled trial, respectively) [see Clinical Studies (14.1, 14.2 and 14.3)].

The three de novo kidney studies with 12-month duration compared two dose levels of oral CELLCEPT (1 g twice daily and 1.5 g twice daily) with azathioprine (2 studies) or placebo (1 study) when administered in combination with cyclosporine (Sandimmune®) and corticosteroids to prevent acute rejection episodes. One study also included anti-thymocyte globulin (ATGAM®) induction therapy.

In the de novo heart transplantation study with 12-month duration, patients received CELLCEPT 1.5 g twice daily (n=289) or azathioprine 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune® or Neoral®) and corticosteroids as maintenance immunosuppressive therapy.

In the de novo liver transplantation study with 12-month duration, patients received CELLCEPT 1 g twice daily intravenously for up to 14 days followed by CELLCEPT 1.5 g twice daily orally or azathioprine 1 to 2 mg/kg/day intravenously followed by azathioprine 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral®) and corticosteroids as maintenance immunosuppressive therapy. The total number of patients enrolled was 565.

Approximately 53% of the kidney transplant patients, 65% of the heart transplant patients, and 48% of the liver transplant patients were treated for more than 1 year. Adverse reactions reported in ≥ 20% of patients in the CELLCEPT treatment groups are presented below. The safety data of three kidney transplantation studies are pooled together.

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 5 Adverse Reactions in Controlled Studies of De Novo Kidney, Heart or Liver Transplantation Reported in ≥20% of Patients in the CELLCEPT Group</span> </caption> <col align="left" valign="top" width="30%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <thead> <tr class="First"> <th align="left" class="Lrule Rrule" rowspan="2" valign="middle">Adverse drug reaction</th><th align="center" class="Botrule Rrule" colspan="3">Kidney Studies</th><th align="center" class="Botrule Rrule" colspan="2">Heart Study</th><th align="center" class="Botrule Rrule" colspan="2">Liver Study</th> </tr> <tr> <th align="center" class="Botrule Rrule">CellCept 2g/day (n=501) or 3g/day (n=490)</th><th align="center" class="Botrule Rrule">AZA 1 to 2 mg/kg/day or 100 to 150 mg/day</th><th align="center" class="Botrule Rrule">Placebo</th><th align="center" class="Botrule Rrule">CellCept 3g/day</th><th align="center" class="Botrule Rrule">AZA 1.5 to 3 mg/kg/day</th><th align="center" class="Botrule Rrule">CellCept 3g/day</th><th align="center" class="Botrule Rrule" valign="bottom">AZA 1 to 2 mg/kg/day</th> </tr> <tr> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule">(n=991)</th><th align="center" class="Botrule Rrule">(n=326)</th><th align="center" class="Botrule Rrule">(n=166)</th><th align="center" class="Botrule Rrule">(n=289)</th><th align="center" class="Botrule Rrule">(n=289)</th><th align="center" class="Botrule Rrule">(n=277)</th><th align="center" class="Botrule Rrule">(n=287)</th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule">System Organ Class</th><th align="center" class="Botrule Rrule">%</th><th align="center" class="Botrule Rrule">%</th><th align="center" class="Botrule Rrule">%</th><th align="center" class="Botrule Rrule">%</th><th align="center" class="Botrule Rrule">%</th><th align="center" class="Botrule Rrule">%</th><th align="center" class="Botrule Rrule">%</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="8"> <dl class="Footnote"> <dt> <a href="#footnote-reference-3" name="footnote-3">*</a> </dt> <dd>"-" Indicates that the incidence was below the cutoff value of 20% for inclusion in the table. </dd> <dt> <a href="#footnote-reference-4" name="footnote-4">†</a> </dt> <dd>"Edema" includes peripheral edema, facial edema, scrotal edema.</dd> <dt> <a href="#footnote-reference-5" name="footnote-5">‡</a> </dt> <dd>"Pain" includes musculoskeletal pain (myalgia, neck pain, back pain).</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="8"><span class="Bold">Infections and infestations</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Bacterial infections</td><td align="center" class="Rrule">39.9</td><td align="center" class="Rrule">33.7</td><td align="center" class="Rrule">37.3</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">27.4</td><td align="center" class="Rrule">26.5</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Viral infections</td><td align="center" class="Rrule">- <a class="Sup" href="#footnote-3" name="footnote-reference-3">*</a></td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">31.1</td><td align="center" class="Rrule">24.9</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="8"><span class="Bold">Blood and lymphatic system disorders</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Anemia</td><td align="center" class="Rrule">20.0</td><td align="center" class="Rrule">23.6</td><td align="center" class="Rrule">2.4</td><td align="center" class="Rrule">45.0</td><td align="center" class="Rrule">47.1</td><td align="center" class="Rrule">43.0</td><td align="center" class="Rrule">53.0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Ecchymosis</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">20.1</td><td align="center" class="Rrule">9.7</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Leukocytosis</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">42.6</td><td align="center" class="Rrule">37.4</td><td align="center" class="Rrule">22.4</td><td align="center" class="Rrule">21.3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Leukopenia</td><td align="center" class="Rrule">28.6</td><td align="center" class="Rrule">24.8</td><td align="center" class="Rrule">4.2</td><td align="center" class="Rrule">34.3</td><td align="center" class="Rrule">43.3</td><td align="center" class="Rrule">45.8</td><td align="center" class="Rrule">39.0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Thrombocytopenia</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">24.2</td><td align="center" class="Rrule">28.0</td><td align="center" class="Rrule">38.3</td><td align="center" class="Rrule">42.2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="8"><span class="Bold">Metabolism and nutrition disorders </span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Hypercholesterolemia</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">46.0</td><td align="center" class="Rrule">43.9</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Hyperglycemia</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">48.4</td><td align="center" class="Rrule">53.3</td><td align="center" class="Rrule">43.7</td><td align="center" class="Rrule">48.8</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Hyperkalemia</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">22.0</td><td align="center" class="Rrule">23.7</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Hypocalcemia</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">30.0</td><td align="center" class="Rrule">30.0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Hypokalemia</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">32.5</td><td align="center" class="Rrule">26.3</td><td align="center" class="Rrule">37.2</td><td align="center" class="Rrule">41.1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Hypomagnesemia</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">20.1</td><td align="center" class="Rrule">14.2</td><td align="center" class="Rrule">39.0</td><td align="center" class="Rrule">37.6</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="8"><span class="Bold">Psychiatric disorders</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Depression</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">20.1</td><td align="center" class="Rrule">15.2</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Insomnia</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">43.3</td><td align="center" class="Rrule">39.8</td><td align="center" class="Rrule">52.3</td><td align="center" class="Rrule">47.0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="8"><span class="Bold">Nervous system disorders</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Dizziness</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">34.3</td><td align="center" class="Rrule">33.9</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Headache</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">58.5</td><td align="center" class="Rrule">55.4</td><td align="center" class="Rrule">53.8</td><td align="center" class="Rrule">49.1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Tremor</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">26.3</td><td align="center" class="Rrule">25.6</td><td align="center" class="Rrule">33.9</td><td align="center" class="Rrule">35.5</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="8"><span class="Bold">Cardiac disorders</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Tachycardia</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">22.8</td><td align="center" class="Rrule">21.8</td><td align="center" class="Rrule">22.0</td><td align="center" class="Rrule">15.7</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="8"><span class="Bold">Vascular disorders</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Hypertension</td><td align="center" class="Rrule">27.5</td><td align="center" class="Rrule">32.2</td><td align="center" class="Rrule">19.3</td><td align="center" class="Rrule">78.9</td><td align="center" class="Rrule">74.0</td><td align="center" class="Rrule">62.1</td><td align="center" class="Rrule">59.6</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Hypotension</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">34.3</td><td align="center" class="Rrule">40.1</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="8"><span class="Bold">Respiratory, thoracic and mediastinal disorders</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Cough</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">40.5</td><td align="center" class="Rrule">32.2</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Dyspnea</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">44.3</td><td align="center" class="Rrule">44.3</td><td align="center" class="Rrule">31.0</td><td align="center" class="Rrule">30.3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pleural effusion</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">34.3</td><td align="center" class="Rrule">35.9</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="8"><span class="Bold">Gastrointestinal disorders</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Abdominal pain</td><td align="center" class="Rrule">22.4</td><td align="center" class="Rrule">23.0</td><td align="center" class="Rrule">11.4</td><td align="center" class="Rrule">41.9</td><td align="center" class="Rrule">39.4</td><td align="center" class="Rrule">62.5</td><td align="center" class="Rrule">51.2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Constipation</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">43.6</td><td align="center" class="Rrule">38.8</td><td align="center" class="Rrule">37.9</td><td align="center" class="Rrule">38.3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Decreased appetite</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">25.3</td><td align="center" class="Rrule">17.1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Diarrhea</td><td align="center" class="Rrule">30.4</td><td align="center" class="Rrule">20.9</td><td align="center" class="Rrule">13.9</td><td align="center" class="Rrule">52.6</td><td align="center" class="Rrule">39.4</td><td align="center" class="Rrule">51.3</td><td align="center" class="Rrule">49.8</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Dyspepsia</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">22.1</td><td align="center" class="Rrule">22.1</td><td align="center" class="Rrule">22.4</td><td align="center" class="Rrule">20.9</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Nausea</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">56.1</td><td align="center" class="Rrule">60.2</td><td align="center" class="Rrule">54.5</td><td align="center" class="Rrule">51.2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Vomiting</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">39.1</td><td align="center" class="Rrule">34.6</td><td align="center" class="Rrule">32.9</td><td align="center" class="Rrule">33.4</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="8"><span class="Bold">Hepatobiliary disorders</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="middle">Blood lactate dehydrogenase increased</td><td align="center" class="Rrule" valign="middle">-</td><td align="center" class="Rrule" valign="middle">-</td><td align="center" class="Rrule" valign="middle">-</td><td align="center" class="Rrule" valign="middle">23.5</td><td align="center" class="Rrule" valign="middle">18.3</td><td align="center" class="Rrule" valign="middle">-</td><td align="center" class="Rrule" valign="middle">-</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="middle">Hepatic enzyme increased</td><td align="center" class="Rrule" valign="middle">-</td><td align="center" class="Rrule" valign="middle">-</td><td align="center" class="Rrule" valign="middle">-</td><td align="center" class="Rrule" valign="middle">-</td><td align="center" class="Rrule" valign="middle">-</td><td align="center" class="Rrule" valign="middle">24.9</td><td align="center" class="Rrule" valign="middle">19.2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="8"><span class="Bold">Skin and subcutaneous tissues disorders</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Rash</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">26.0</td><td align="center" class="Rrule">20.8</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="8"><span class="Bold">Renal and urinary disorders</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="middle">Blood creatinine increased</td><td align="center" class="Rrule" valign="middle">-</td><td align="center" class="Rrule" valign="middle">-</td><td align="center" class="Rrule" valign="middle">-</td><td align="center" class="Rrule" valign="middle">42.2</td><td align="center" class="Rrule" valign="middle">39.8</td><td align="center" class="Rrule" valign="middle">-</td><td align="center" class="Rrule" valign="middle">-</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Blood urea increased</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">36.7</td><td align="center" class="Rrule">34.3</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="8"><span class="Bold">General disorders and administration site conditions</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Asthenia</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">49.1</td><td align="center" class="Rrule">41.2</td><td align="center" class="Rrule">35.4</td><td align="center" class="Rrule">33.8</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Edema <a class="Sup" href="#footnote-4" name="footnote-reference-4">†</a></td><td align="center" class="Rrule">21.0</td><td align="center" class="Rrule">28.2</td><td align="center" class="Rrule">8.4</td><td align="center" class="Rrule">67.5</td><td align="center" class="Rrule">55.7</td><td align="center" class="Rrule">48.4</td><td align="center" class="Rrule">47.7</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pain <a class="Sup" href="#footnote-5" name="footnote-reference-5">‡</a></td><td align="center" class="Rrule">24.8</td><td align="center" class="Rrule">32.2</td><td align="center" class="Rrule">9.6</td><td align="center" class="Rrule">79.2</td><td align="center" class="Rrule">77.5</td><td align="center" class="Rrule">74.0</td><td align="center" class="Rrule">77.5</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Pyrexia</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">-</td><td align="center" class="Rrule">56.4</td><td align="center" class="Rrule">53.6</td><td align="center" class="Rrule">52.3</td><td align="center" class="Rrule">56.1</td> </tr> </tbody> </table></div>

In the three de novo kidney studies, patients receiving 2 g/day of CELLCEPT had an overall better safety profile than did patients receiving 3 g/day of CELLCEPT.

Post-transplant lymphoproliferative disease (PTLD, pseudolymphoma) developed in 0.4% to 1% of patients receiving CELLCEPT (2 g or 3 g daily) with other immunosuppressive agents in controlled clinical trials of kidney, heart and liver transplant patients followed for at least 1 year [see Warnings and Precautions (5.2)]. Non-melanoma skin carcinomas occurred in 1.6% to 4.2% of patients, other types of malignancy in 0.7% to 2.1% of patients. Three-year safety data in kidney and heart transplant patients did not reveal any unexpected changes in incidence of malignancy compared to the 1-year data. In pediatric patients, PTLD was observed in 1.35% (2/148) by 12 months post-transplant.

Cytopenias, including leukopenia, anemia, thrombocytopenia and pancytopenia are a known risk associated with mycophenolate and may lead or contribute to the occurrence of infections and hemorrhages [see Warnings and Precautions (5.3)]. Severe neutropenia (ANC <0.5 × 103/µL) developed in up to 2% of kidney transplant patients, up to 2.8% of heart transplant patients and up to 3.6% of liver transplant patients receiving CELLCEPT 3 g daily [see Warnings and Precautions (5.4) and Dosage and Administration (2.5)].

The most common opportunistic infections in patients receiving CELLCEPT with other immunosuppressants were mucocutaneous candida, CMV viremia/syndrome, and herpes simplex. The proportion of patients with CMV viremia/syndrome was 13.5%. In patients receiving CELLCEPT (2 g or 3 g) in controlled studies for prevention of kidney, heart or liver rejection, fatal infection/sepsis occurred in approximately 2% of kidney and heart patients and in 5% of liver patients [see Warnings and Precautions (5.3)].

The most serious gastrointestinal disorders reported were ulceration and hemorrhage, which are known risks associated with CELLCEPT. Mouth, esophageal, gastric, duodenal, and intestinal ulcers often complicated by hemorrhage, as well as hematemesis, melena, and hemorrhagic forms of gastritis and colitis were commonly reported during the pivotal clinical trials, while the most common gastrointestinal disorders were diarrhea, nausea and vomiting. Endoscopic investigation of patients with CELLCEPT-related diarrhea revealed isolated cases of intestinal villous atrophy [see Warnings and Precautions (5.5)].

The following adverse reactions were reported with 3% to <20% incidence in kidney, heart, and liver transplant patients treated with CELLCEPT, in combination with cyclosporine and corticosteroids.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 6 Adverse Reactions in Controlled Studies of De Novo Kidney, Heart or Liver Transplantation Reported in 3% to &lt;20% of Patients Treated with CELLCEPT in Combination with Cyclosporine and Corticosteroids</span> </caption> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="80%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">System Organ Class</th><th align="left" class="Rrule">Adverse Reactions</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Body as a Whole</td><td align="left" class="Rrule">cellulitis, chills, hernia, malaise</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Infections and Infestations</td><td align="left" class="Rrule">fungal infections</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Hematologic and Lymphatic</td><td align="left" class="Rrule">coagulation disorder, ecchymosis, pancytopenia</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Urogenital</td><td align="left" class="Rrule">hematuria</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Cardiovascular</td><td align="left" class="Rrule">hypotension</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Metabolic and Nutritional</td><td align="left" class="Rrule">acidosis, alkaline phosphatase increased, hyperlipemia, hypophosphatemia, weight loss</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Digestive</td><td align="left" class="Rrule">esophagitis, flatulence, gastritis, gastrointestinal hemorrhage, hepatitis, ileus, nausea and vomiting, stomach ulcer, stomatitis</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Neoplasm benign, malignant and unspecified</td><td align="left" class="Rrule">neoplasm</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Skin and Appendages</td><td align="left" class="Rrule">skin benign neoplasm, skin carcinoma</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Psychiatric</td><td align="left" class="Rrule">confusional state</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Nervous</td><td align="left" class="Rrule">hypertonia, paresthesia, somnolence</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Musculoskeletal</td><td align="left" class="Rrule">arthralgia, myasthenia</td> </tr> </tbody> </table></div>

Pediatrics

The type and frequency of adverse events in a clinical study for prevention of kidney allograft rejection in 100 pediatric patients 3 months to 18 years of age dosed with CELLCEPT oral suspension 600 mg/m2 twice daily (up to 1 g twice daily) were generally similar to those observed in adult patients dosed with CELLCEPT capsules at a dose of 1 g twice daily with the exception of abdominal pain, fever, infection, pain, sepsis, diarrhea, vomiting, pharyngitis, respiratory tract infection, hypertension, leukopenia, and anemia, which were observed in a higher proportion in pediatric patients.

Safety information in pediatric heart transplant or pediatric liver transplant patients treated with CELLCEPT is supported by an open-label study in pediatric liver transplant patients and publications; the type and frequency of the reported adverse reactions are consistent with those observed in pediatric patients following renal transplant and in adults.

Geriatrics

Geriatric patients (≥65 years), particularly those who are receiving CELLCEPT as part of a combination immunosuppressive regimen, may be at increased risk of certain infections (including cytomegalovirus [CMV] tissue invasive disease) and possibly gastrointestinal hemorrhage and pulmonary edema, compared to younger individuals [see Warnings and Precautions (5.3) and Adverse Reactions (6.1)].

CELLCEPT Intravenous

The safety profile of CELLCEPT Intravenous was determined from a single, double-blind, controlled comparative study of the safety of 2 g/day of intravenous and oral CELLCEPT in kidney transplant patients in the immediate post-transplant period (administered for the first 5 days). The potential venous irritation of CELLCEPT Intravenous was evaluated by comparing the adverse reactions attributable to peripheral venous infusion of CELLCEPT Intravenous with those observed in the intravenous placebo group; patients in the placebo group received active medication by the oral route.

Adverse reactions attributable to peripheral venous infusion were phlebitis and thrombosis, both observed at 4% in patients treated with CELLCEPT Intravenous.

The following adverse reactions have been identified during post-approval use of CELLCEPT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 7 Drug Interactions with CELLCEPT that Affect Mycophenolic Acid (MPA) Exposure </span> </caption> <col align="right" valign="middle" width="25%"/> <col align="left" valign="middle" width="75%"/> <tbody class="Headless"> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Antacids with Magnesium or Aluminum Hydroxide</span></td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">Concomitant use with an antacid containing magnesium or aluminum hydroxide decreases MPA systemic exposure <span class="Italics">[see <a href="#S12.3">Clinical Pharmacology (12.3)</a>]</span>, which may reduce CELLCEPT efficacy. </td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Prevention or Management</span></td><td align="left" class="Rrule">Administer magnesium or aluminum hydroxide containing antacids at least 2h after CELLCEPT administration.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Proton Pump Inhibitors (PPIs)</span></td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">Concomitant use with PPIs decreases MPA systemic exposure <span class="Italics">[see <a href="#S12.3">Clinical Pharmacology (12.3)</a>]</span>, which may reduce CELLCEPT efficacy.</td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Prevention or Management</span></td><td align="left" class="Rrule">Monitor patients for alterations in efficacy when PPIs are co-administered with CELLCEPT.</td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Examples</span></td><td align="left" class="Rrule">Lansoprazole, pantoprazole </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Drugs that Interfere with Enterohepatic Recirculation</span></td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">Concomitant use with drugs that directly interfere with enterohepatic recirculation, or indirectly interfere with enterohepatic recirculation by altering the gastrointestinal flora, can decrease MPA systemic exposure <span class="Italics">[see <a href="#S12.3">Clinical Pharmacology (12.3)</a>]</span>, which may reduce CELLCEPT efficacy.</td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Prevention or Management</span></td><td align="left" class="Rrule">Monitor patients for alterations in efficacy or CELLCEPT related adverse reactions when these drugs are co-administered with CELLCEPT.</td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Examples</span></td><td align="left" class="Rrule">Cyclosporine A, trimethoprim/sulfamethoxazole, bile acid sequestrants (cholestyramine), rifampin as well as aminoglycoside, cephalosporin, fluoroquinolone and penicillin classes of antimicrobials </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Drugs Modulating Glucuronidation</span></td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">Concomitant use with drugs inducing glucuronidation decreases MPA systemic exposure, potentially reducing CELLCEPT efficacy, while use with drugs inhibiting glucuronidation increases MPA systemic exposure <span class="Italics">[see <a href="#S12.3">Clinical Pharmacology (12.3)</a>]</span>, which may increase the risk of CELLCEPT related adverse reactions.</td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Prevention or Management</span></td><td align="left" class="Rrule">Monitor patients for alterations in efficacy or CELLCEPT related adverse reactions when these drugs are co-administered with CELLCEPT.</td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Examples</span></td><td align="left" class="Rrule">Telmisartan (induces glucuronidation); isavuconazole (inhibits glucuronidation).</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Calcium Free Phosphate Binders</span></td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">Concomitant use with calcium free phosphate binders decrease MPA systemic exposure <span class="Italics">[see <a href="#S12.3">Clinical Pharmacology (12.3)</a>]</span>, which may reduce CELLCEPT efficacy.</td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Prevention or Management</span></td><td align="left" class="Rrule">Administer calcium free phosphate binders at least 2 hours after CELLCEPT.</td> </tr> <tr class="Botrule Last"> <td align="right" class="Lrule Rrule"><span class="Italics">Examples</span></td><td align="left" class="Rrule">Sevelamer</td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 8 Drug Interactions with CELLCEPT that Affect Other Drugs</span> </caption> <col align="right" valign="middle" width="25%"/> <col align="left" valign="middle" width="75%"/> <tbody class="Headless"> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Drugs that Undergo Renal Tubular Secretion</span></td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">When concomitantly used with CELLCEPT, its metabolite MPAG, may compete with drugs eliminated by renal tubular secretion which may increase plasma concentrations and/or adverse reactions associated with these drugs.</td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Prevention or Management</span></td><td align="left" class="Rrule">Monitor for drug-related adverse reactions in patients with renal impairment.</td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule" valign="bottom"><span class="Italics">Examples</span></td><td align="left" class="Rrule">Acyclovir, ganciclovir, probenecid, valacyclovir, valganciclovir</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Combination Oral Contraceptives</span></td> </tr> <tr class="Botrule"> <td align="right" class="Lrule Rrule"><span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">Concomitant use with CELLCEPT decreased the systemic exposure to levonorgestrel, but did not affect the systemic exposure to ethinylestradiol <span class="Italics">[see <a href="#S12.3">Clinical Pharmacology (12.3)</a>]</span>, which may result in reduced combination oral contraceptive effectiveness.</td> </tr> <tr class="Last"> <td align="right" class="Lrule Rrule"><span class="Italics">Prevention or Management</span></td><td align="left" class="Rrule">Use additional barrier contraceptive methods.</td> </tr> </tbody> </table></div>

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to mycophenolate during pregnancy and those becoming pregnant within 6 weeks of discontinuing CELLCEPT treatment. To report a pregnancy or obtain information about the registry, visit www.mycophenolateREMS.com or call 1-800-617-8191.

Risk Summary

Use of mycophenolate mofetil (MMF) during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of multiple congenital malformations in multiple organ systems [see Human Data]. Oral administration of mycophenolate to rats and rabbits during the period of organogenesis produced congenital malformations and pregnancy loss at doses less than the recommended clinical dose (0.01 to 0.05 times the recommended clinical doses in kidney and heart transplant patients) [see Animal Data].

Consider alternative immunosuppressants with less potential for embryofetal toxicity. Risks and benefits of CELLCEPT should be discussed with the pregnant woman.

The estimated background risk of pregnancy loss and congenital malformations in organ transplant populations is not clear. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

A spectrum of congenital malformations (including multiple malformations in individual newborns) has been reported in 23 to 27% of live births in MMF exposed pregnancies, based on published data from pregnancy registries. Malformations that have been documented include external ear, eye, and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system.

Based on published data from pregnancy registries, the risk of first trimester pregnancy loss has been reported at 45 to 49% following MMF exposure.

Animal Data

In animal reproductive toxicology studies, there were increased rates of fetal resorptions and malformations in the absence of maternal toxicity. Oral administration of MMF to pregnant rats from Gestational Day 7 to Day 16 produced increased embryofetal lethality and fetal malformations including anophthalmia, agnathia, and hydrocephaly at doses equivalent to 0.015 and 0.01 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA. Oral administration of MMF to pregnant rabbits from Gestational Day 7 to Day 19 produced increased embryofetal lethality and fetal malformations included ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia at dose equivalents as low as 0.05 and 0.03 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA.

Risk Summary

There are no data on the presence of mycophenolate in human milk, or the effects on milk production. There are limited data in the National Transplantation Pregnancy Registry on the effects of mycophenolate on a breastfed child [see Data]. Studies in rats treated with MMF have shown mycophenolic acid (MPA) to be present in milk. Because available data are limited, it is not possible to exclude potential risks to a breastfeeding infant.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for CELLCEPT and any potential adverse effects on the breastfed infant from CELLCEPT or from the underlying maternal condition.

Data

Limited information is available from the National Transplantation Pregnancy Registry. Of seven infants reported by the National Transplantation Pregnancy Registry to have been breastfed while the mother was taking mycophenolate, all were born at 34-40 weeks gestation, and breastfed for up to 14 months. No adverse events were reported.

Females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning.

Pregnancy Planning

For patients who are considering pregnancy, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible. Risks and benefits of CELLCEPT should be discussed with the patient.

Pregnancy Testing

To prevent unplanned exposure during pregnancy, all females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL immediately before starting CELLCEPT. Another pregnancy test with the same sensitivity should be done 8 to 10 days later. Repeat pregnancy tests should be performed during routine follow-up visits. Results of all pregnancy tests should be discussed with the patient. In the event of a positive pregnancy test, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible.

Contraception

Female Patients

Females of reproductive potential taking CELLCEPT must receive contraceptive counseling and use acceptable contraception (see Table 9 for acceptable contraception methods). Patients must use acceptable birth control during the entire CELLCEPT therapy, and for 6 weeks after stopping CELLCEPT, unless the patient chooses abstinence.

Patients should be aware that CELLCEPT reduces blood levels of the hormones from the oral contraceptive pill and could theoretically reduce its effectiveness [see Drug Interactions (7.2)].

<div class="scrollingtable"><table class="Noautorules" width="75%"> <caption> <span>Table 9 Acceptable Contraception Methods for Females of Reproductive Potential</span> </caption> <col align="left" valign="top" width="15%"/> <col align="left" valign="top" width="37%"/> <col align="left" valign="top" width="11%"/> <col align="left" valign="top" width="37%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left" colspan="4"><span class="Bold">Pick from the following birth control options:</span></td> </tr> <tr> <td align="left" class="Lrule Rrule"><span class="Bold">Option 1</span></td><td align="left" class="Rrule" colspan="3"></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Bold">Methods to Use Alone</span></td><td align="left" class="Rrule" colspan="3"> <ul class="Disc"> <li>Intrauterine devices (IUDs)</li> <li>Tubal sterilization</li> <li>Patient's partner vasectomy</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" colspan="4"><span class="Bold">OR</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Bold">Option 2</span></td><td align="left" class="Rrule"><span class="Bold">Hormone Methods</span> <br/>choose 1</td><td align="left" class="Rrule"></td><td align="left" class="Rrule"><span class="Bold">Barrier Methods</span> <br/>choose 1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Bold">Choose One Hormone Method</span> <span class="Italics">AND</span> <span class="Bold">One Barrier Method</span></td><td align="left" class="Rrule" valign="middle"><span class="Bold">Estrogen and Progesterone</span> <ul class="Disc"> <li>Oral Contraceptive Pill</li> <li>Transdermal patch</li> <li>Vaginal ring</li> </ul> <span class="Bold">Progesterone-only</span> <ul class="Disc"> <li>Injection</li> <li>Implant</li> </ul> </td><td align="left" class="Rrule" valign="middle"><span class="Italics">AND</span></td><td align="left" class="Rrule" valign="middle"> <ul class="Disc"> <li>Diaphragm with spermicide</li> <li>Cervical cap with spermicide</li> <li>Contraceptive sponge</li> <li>Male condom</li> <li>Female condom</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" colspan="4"><span class="Bold">OR</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Bold">Option 3</span></td><td align="left" class="Rrule"><span class="Bold">Barrier Methods</span> <br/>choose 1</td><td align="left" class="Rrule"></td><td align="left" class="Rrule"><span class="Bold">Barrier Methods</span> <br/>choose 1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Bold">Choose One Barrier Method from each column</span> <span class="Italics">(must choose two methods)</span></td><td align="left" class="Rrule" valign="middle"> <ul class="Disc"> <li>Diaphragm with spermicide</li> <li>Cervical cap with spermicide</li> <li>Contraceptive sponge</li> </ul> </td><td align="left" class="Rrule" valign="middle"><span class="Italics">AND</span></td><td align="left" class="Rrule" valign="middle"> <ul class="Disc"> <li>Male condom</li> <li>Female condom</li> </ul> </td> </tr> </tbody> </table></div>

Male Patients

Genotoxic effects have been observed in animal studies at exposures exceeding the human therapeutic exposures by approximately 1.25 times. Thus, the risk of genotoxic effects on sperm cells cannot be excluded. Based on this potential risk, sexually active male patients and/or their female partners are recommended to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment. Also, based on the potential risk of genotoxic effects, male patients should not donate sperm during treatment with CELLCEPT and for at least 90 days after cessation of treatment [see Use in Special Populations (8.1), Nonclinical Toxicology (13.1), Patient Counseling Information (17.9)].

Safety and effectiveness have been established in pediatric patients 3 months and older for the prophylaxis of organ rejection of allogenic kidney, heart or liver transplants.

Kidney Transplant

Use of CELLCEPT in this population is supported by evidence from adequate and well-controlled studies of CELLCEPT in adults with additional data from one open-label, pharmacokinetic and safety study of CELLCEPT in pediatric patients after receiving allogeneic kidney transplant (100 patients, 3 months to 18 years of age) [see Dosage and Administration (2.2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.1)].

Heart Transplant and Liver Transplant

Use of CELLCEPT in pediatric heart transplant and liver transplant patients is supported by adequate and well-controlled studies and pharmacokinetic data in adult heart transplant and liver transplant patients. Additional supportive data include pharmacokinetic data in pediatric kidney transplant and pediatric liver transplant patients (8 liver transplant patients, 9 months to 5 years of age, in an open-label, pharmacokinetic and safety study) and published evidence of clinical efficacy and safety in pediatric heart transplant and pediatric liver transplant patients [see Dosage and Administration (2.3, 2.4), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.1)].

Clinical studies of CELLCEPT did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between geriatric and younger patients. In general, dose selection for a geriatric patient should take into consideration the presence of decreased hepatic, renal or cardiac function and of concomitant drug therapies [see Adverse Reactions (6.1), Drug Interactions (7)].

Patients with Kidney Transplant

No dosage adjustments are needed in kidney transplant patients experiencing delayed graft function postoperatively but patients should be carefully monitored [see Clinical Pharmacology (12.3)]. In kidney transplant patients with severe chronic impairment of the graft (GFR <25 mL/min/1.73 m2), no dose adjustments are necessary; however, doses greater than 1 g administered twice a day should be avoided.

Patients with Heart and Liver Transplant

No data are available for heart or liver transplant patients with severe chronic renal impairment. CELLCEPT may be used for heart or liver transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks.

Patients with Kidney Transplant

No dosage adjustments are recommended for kidney transplant patients with severe hepatic parenchymal disease. However, it is not known whether dosage adjustments are needed for hepatic disease with other etiologies [see Clinical Pharmacology (12.3)].

Patients with Heart Transplant

No data are available for heart transplant patients with severe hepatic parenchymal disease.

Treatment and Management

MPA and the phenolic glucuronide metabolite of MPA (MPAG) are usually not removed by hemodialysis. However, at high MPAG plasma concentrations (>100 µg/mL), small amounts of MPAG are removed. By increasing excretion of the drug, MPA can be removed by bile acid sequestrants, such as cholestyramine [see Clinical Pharmacology (12.3)].

CELLCEPT (mycophenolate mofetil) is an antimetabolite immunosuppressant. It is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine monophosphate dehydrogenase (IMPDH) inhibitor.

{ "type": "p", "children": [], "text": "CELLCEPT (mycophenolate mofetil) is an antimetabolite immunosuppressant. It is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine monophosphate dehydrogenase (IMPDH) inhibitor." }

The chemical name for mycophenolate mofetil (MMF) is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate. It has an empirical formula of C23H31NO7, a molecular weight of 433.50, and the following structural formula:

{ "type": "p", "children": [], "text": "The chemical name for mycophenolate mofetil (MMF) is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate. It has an empirical formula of C23H31NO7, a molecular weight of 433.50, and the following structural formula:" }

MMF is a white to off-white crystalline powder. It is slightly soluble in water (43 µg/mL at pH 7.4); the solubility increases in acidic medium (4.27 mg/mL at pH 3.6). It is freely soluble in acetone, soluble in methanol, and sparingly soluble in ethanol. The apparent partition coefficient in 1-octanol/water (pH 7.4) buffer solution is 238. The pKa values for MMF are 5.6 for the morpholino group and 8.5 for the phenolic group.

{ "type": "p", "children": [], "text": "MMF is a white to off-white crystalline powder. It is slightly soluble in water (43 µg/mL at pH 7.4); the solubility increases in acidic medium (4.27 mg/mL at pH 3.6). It is freely soluble in acetone, soluble in methanol, and sparingly soluble in ethanol. The apparent partition coefficient in 1-octanol/water (pH 7.4) buffer solution is 238. The pKa values for MMF are 5.6 for the morpholino group and 8.5 for the phenolic group." }

MMF hydrochloride has a solubility of 65.8 mg/mL in 5% Dextrose Injection USP (D5W). The pH of the reconstituted solution is 2.4 to 4.1.

{ "type": "p", "children": [], "text": "MMF hydrochloride has a solubility of 65.8 mg/mL in 5% Dextrose Injection USP (D5W). The pH of the reconstituted solution is 2.4 to 4.1." }

CELLCEPT is available for oral administration as capsules containing 250 mg of MMF, tablets containing 500 mg of MMF, and as a powder for oral suspension which, when reconstituted, contains 200 mg/mL of MMF.

{ "type": "p", "children": [], "text": "CELLCEPT is available for oral administration as capsules containing 250 mg of MMF, tablets containing 500 mg of MMF, and as a powder for oral suspension which, when reconstituted, contains 200 mg/mL of MMF." }

Inactive ingredients in CELLCEPT 250 mg capsules include croscarmellose sodium, magnesium stearate, povidone (K-90) and pregelatinized starch. The capsule shells contain black iron oxide, FD&C blue #2, gelatin, red iron oxide, silicon dioxide, sodium lauryl sulfate, titanium dioxide, and yellow iron oxide.

{ "type": "p", "children": [], "text": "Inactive ingredients in CELLCEPT 250 mg capsules include croscarmellose sodium, magnesium stearate, povidone (K-90) and pregelatinized starch. The capsule shells contain black iron oxide, FD&C blue #2, gelatin, red iron oxide, silicon dioxide, sodium lauryl sulfate, titanium dioxide, and yellow iron oxide." }

Inactive ingredients in CELLCEPT 500 mg tablets include croscarmellose sodium, magnesium stearate, microcrystalline cellulose, povidone (K-90), and Opadry® lavender Y-5R-10272-A (hydroxypropyl methylcellulose, hydroxypropyl cellulose, titanium dioxide, polyethylene glycol 400, FD&C Blue No. 2 aluminum lake [indigo carmine aluminum lake], and red iron oxide).

{ "type": "p", "children": [], "text": "Inactive ingredients in CELLCEPT 500 mg tablets include croscarmellose sodium, magnesium stearate, microcrystalline cellulose, povidone (K-90), and Opadry® lavender Y-5R-10272-A (hydroxypropyl methylcellulose, hydroxypropyl cellulose, titanium dioxide, polyethylene glycol 400, FD&C Blue No. 2 aluminum lake [indigo carmine aluminum lake], and red iron oxide)." }

Inactive ingredients in CELLCEPT Oral Suspension include aspartame, citric acid anhydrous, colloidal silicon dioxide, methylparaben, mixed fruit flavor, sodium citrate dihydrate, sorbitol, soybean lecithin, and xanthan gum.

{ "type": "p", "children": [], "text": "Inactive ingredients in CELLCEPT Oral Suspension include aspartame, citric acid anhydrous, colloidal silicon dioxide, methylparaben, mixed fruit flavor, sodium citrate dihydrate, sorbitol, soybean lecithin, and xanthan gum." }

CELLCEPT Intravenous is the hydrochloride salt of MMF. The chemical name for the hydrochloride salt of MMF is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate hydrochloride. It has an empirical formula of C23H31NO7 HCl and a molecular weight of 469.96.

{ "type": "p", "children": [], "text": "CELLCEPT Intravenous is the hydrochloride salt of MMF. The chemical name for the hydrochloride salt of MMF is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate hydrochloride. It has an empirical formula of C23H31NO7 HCl and a molecular weight of 469.96." }

CELLCEPT Intravenous is available as a sterile white to off-white lyophilized powder in single-dose vials containing MMF hydrochloride for administration by intravenous infusion only. Each vial contains 500 mg of mycophenolate mofetil equivalent to 542 mg of mycophenolate mofetil hydrochloride. The inactive ingredients are polysorbate 80, 25 mg, and citric acid, 5 mg. Sodium hydroxide or hydrochloric acid may have been used in the manufacture of CELLCEPT Intravenous to adjust the pH. Reconstitution and dilution with 5% Dextrose Injection USP yields a slightly yellow solution of MMF, 6 mg/mL [see Dosage and Administration (2.6)].

{ "type": "p", "children": [], "text": "CELLCEPT Intravenous is available as a sterile white to off-white lyophilized powder in single-dose vials containing MMF hydrochloride for administration by intravenous infusion only. Each vial contains 500 mg of mycophenolate mofetil equivalent to 542 mg of mycophenolate mofetil hydrochloride. The inactive ingredients are polysorbate 80, 25 mg, and citric acid, 5 mg. Sodium hydroxide or hydrochloric acid may have been used in the manufacture of CELLCEPT Intravenous to adjust the pH. Reconstitution and dilution with 5% Dextrose Injection USP yields a slightly yellow solution of MMF, 6 mg/mL [see Dosage and Administration (2.6)].\n" }

Mycophenolate mofetil (MMF) is absorbed following oral administration and hydrolyzed to mycophenolic acid (MPA), the active metabolite. MPA is a selective uncompetitive inhibitor of the two isoforms (type I and type II) of inosine monophosphate dehydrogenase (IMPDH) leading to inhibition of the de novo pathway of guanosine nucleotide synthesis and blocks DNA synthesis. The mechanism of action of MPA is multifaceted and includes effects on cellular checkpoints responsible for metabolic programming of lymphocytes. MPA shifts transcriptional activities in lymphocytes from a proliferative state to catabolic processes. In vitro studies suggest that MPA modulates transcriptional activities in human CD4+ T-lymphocytes by suppressing the Akt/mTOR and STAT5 pathways that are relevant to metabolism and survival, leading to an anergic state of T-cells whereby the cells become less responsive to antigenic stimulation. Additionally, MPA enhanced the expression of negative co-stimulators such as CD70, PD-1, CTLA-4, and transcription factor FoxP3 as well as decreased the expression of positive co-stimulators CD27 and CD28.

MPA decreases proliferative responses of T- and B-lymphocytes to both mitogenic and allo-antigenic stimulation, antibody responses, as well as the production of cytokines from lymphocytes and monocytes such as GM-CSF, IFN-ɣ, IL-17, and TNF-α. Additionally, MPA prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection.

Overall, the effect of MPA is cytostatic and reversible.

There is a lack of information regarding the pharmacodynamic effects of MMF.

Absorption

Following oral and intravenous administration, MMF undergoes complete conversion to MPA, the active metabolite. In 12 healthy volunteers, the mean absolute bioavailability of oral MMF relative to intravenous MMF was 94%. Two 500 mg CELLCEPT tablets have been shown to be bioequivalent to four 250 mg CELLCEPT capsules. Five mL of the 200 mg/mL constituted CELLCEPT oral suspension have been shown to be bioequivalent to four 250 mg capsules.

The mean (±SD) pharmacokinetic parameters estimates for MPA following the administration of MMF given as single doses to healthy volunteers, and multiple doses to kidney, heart, and liver transplant patients, are shown in Table 10. The area under the plasma-concentration time curve (AUC) for MPA appears to increase in a dose-proportional fashion in kidney transplant patients receiving multiple oral doses of MMF up to a daily dose of 3 g (1.5g twice daily) (see Table 10).

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 10 Pharmacokinetic Parameters for MPA [mean (±SD)] Following Administration of MMF to Healthy Volunteers (Single Dose), and Kidney, Heart, and Liver Transplant Patients (Multiple Doses)</span> </caption> <col align="left" valign="top" width="25%"/> <col align="center" valign="top" width="16%"/> <col align="center" valign="top" width="17%"/> <col align="center" valign="top" width="17%"/> <col align="center" valign="top" width="25%"/> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-6" name="footnote-6">*</a> </dt> <dd>AUC(0-12h) values quoted are extrapolated from data from samples collected over 4 hours.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" valign="middle"><span class="Bold">Healthy Volunteers</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">Dose/Route</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">T<span class="Sub">max</span> <br/>(h)</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">C<span class="Sub">max</span> <br/>(mcg/mL)</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">Total AUC<br/>(mcg∙h/mL)</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Single dose</td><td align="center" class="Rrule">1 g/oral</td><td align="center" class="Rrule">0.80<br/>(±0.36)<br/>(n=129)</td><td align="center" class="Rrule">24.5<br/>(±9.5)<br/>(n=129)</td><td align="center" class="Rrule">63.9<br/>(±16.2)<br/>(n=117)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="middle"><span class="Bold">Kidney Transplant Patients (twice daily dosing) Time After Transplantation</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">Dose/Route</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">T<span class="Sub">max</span> <br/>(h)</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">C<span class="Sub">max</span> <br/>(mcg/mL)</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">Interdosing Interval AUC(0-12h)<br/>(mcg∙h/mL)</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">5 days</td><td align="center" class="Rrule">1 g/iv</td><td align="center" class="Rrule">1.58<br/>(±0.46)<br/>(n=31)</td><td align="center" class="Rrule">12.0<br/>(±3.82)<br/>(n=31)</td><td align="center" class="Rrule">40.8<br/>(±11.4)<br/>(n=31)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">6 days</td><td align="center" class="Rrule">1 g/oral</td><td align="center" class="Rrule">1.33<br/>(±1.05)<br/>(n=31) </td><td align="center" class="Rrule">10.7<br/>(±4.83)<br/>(n=31) </td><td align="center" class="Rrule">32.9<br/>(±15.0)<br/>(n=31)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Early (Less than 40 days)</td><td align="center" class="Rrule">1 g/oral</td><td align="center" class="Rrule">1.31<br/>(±0.76)<br/>(n=25)</td><td align="center" class="Rrule">8.16<br/>(±4.50)<br/>(n=25)</td><td align="center" class="Rrule">27.3<br/>(±10.9)<br/>(n=25)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Early (Less than 40 days)</td><td align="center" class="Rrule">1.5 g/oral</td><td align="center" class="Rrule">1.21<br/>(±0.81)<br/>(n=27)</td><td align="center" class="Rrule">13.5<br/>(±8.18)<br/>(n=27)</td><td align="center" class="Rrule">38.4<br/>(±15.4)<br/>(n=27)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Late (Greater than 3 months)</td><td align="center" class="Rrule">1.5 g/oral</td><td align="center" class="Rrule">0.90<br/>(±0.24)<br/>(n=23)</td><td align="center" class="Rrule">24.1<br/>(±12.1)<br/>(n=23)</td><td align="center" class="Rrule">65.3<br/>(±35.4)<br/>(n=23)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="middle"><span class="Bold">Heart transplant Patients (twice daily dosing) Time After Transplantation</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">Dose/Route</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">T<span class="Sub">max</span> <br/>(h)</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">C<span class="Sub">max</span> <br/>(mcg/mL)</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">Interdosing Interval AUC(0-12h)<br/>(mcg∙h/mL)</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Early (Day before discharge)</td><td align="center" class="Rrule">1.5 g/oral</td><td align="center" class="Rrule">1.8<br/>(±1.3)<br/>(n=11)</td><td align="center" class="Rrule">11.5<br/>(±6.8)<br/>(n=11)</td><td align="center" class="Rrule">43.3<br/>(±20.8)<br/>(n=9)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Late (Greater than 6 months)</td><td align="center" class="Rrule">1.5 g/oral</td><td align="center" class="Rrule">1.1<br/>(±0.7)<br/>(n=52)</td><td align="center" class="Rrule">20.0<br/>(±9.4)<br/>(n=52)</td><td align="center" class="Rrule">54.1<a class="Sup" href="#footnote-6" name="footnote-reference-6">*</a> <br/>(±20.4)<br/>(n=49)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="middle"><span class="Bold">Liver transplant Patients (twice daily dosing) Time After Transplantation</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">Dose/Route</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">T<span class="Sub">max</span> <br/>(h)</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">C<span class="Sub">max</span> <br/>(mcg/mL)</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">Interdosing Interval AUC(0-12h)<br/>(mcg∙h/mL)</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">4 to 9 days</td><td align="center" class="Rrule">1 g/iv</td><td align="center" class="Rrule">1.50<br/>(±0.517)<br/>(n=22) </td><td align="center" class="Rrule">17.0<br/>(±12.7)<br/>(n=22)</td><td align="center" class="Rrule">34.0<br/>(±17.4)<br/>(n=22)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Early (5 to 8 days)</td><td align="center" class="Rrule">1.5 g/oral</td><td align="center" class="Rrule">1.15<br/>(±0.432)<br/>(n=20)</td><td align="center" class="Rrule">13.1<br/>(±6.76)<br/>(n=20)</td><td align="center" class="Rrule">29.2<br/>(±11.9)<br/>(n=20)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Late (Greater than 6 months)</td><td align="center" class="Rrule">1.5 g/oral</td><td align="center" class="Rrule">1.54<br/>(±0.51)<br/>(n=6)</td><td align="center" class="Rrule">19.3<br/>(±11.7)<br/>(n=6)</td><td align="center" class="Rrule">49.3<br/>(±14.8)<br/>(n=6)</td> </tr> </tbody> </table></div>

In the early post-transplant period (less than 40 days post-transplant), kidney, heart, and liver transplant patients had mean MPA AUCs approximately 20% to 41% lower and mean Cmax approximately 32% to 44% lower compared to the late transplant period (i.e., 3 to 6 months post-transplant) (non-stationarity in MPA pharmacokinetics).

Mean MPA AUC values following administration of 1 g twice daily intravenous CELLCEPT over 2 hours to kidney transplant patients for 5 days were about 24% higher than those observed after oral administration of a similar dose in the immediate post-transplant phase.

In liver transplant patients, administration of 1 g twice daily intravenous CELLCEPT followed by 1.5 g twice daily oral CELLCEPT resulted in mean MPA AUC estimates similar to those found in kidney transplant patients administered 1 g CELLCEPT twice daily.

Effect of Food

Food (27 g fat, 650 calories) had no effect on the extent of absorption (MPA AUC) of MMF when administered at doses of 1.5 g twice daily to kidney transplant patients. However, MPA Cmax was decreased by 40% in the presence of food [see Dosage and Administration (2.1)].

Distribution

The mean (±SD) apparent volume of distribution of MPA in 12 healthy volunteers was approximately 3.6 (±1.5) L/kg. At clinically relevant concentrations, MPA is 97% bound to plasma albumin. The phenolic glucuronide metabolite of MPA (MPAG) is 82% bound to plasma albumin at MPAG concentration ranges that are normally seen in stable kidney transplant patients; however, at higher MPAG concentrations (observed in patients with kidney impairment or delayed kidney graft function), the binding of MPA may be reduced as a result of competition between MPAG and MPA for protein binding. Mean blood to plasma ratio of radioactivity concentrations was approximately 0.6 indicating that MPA and MPAG do not extensively distribute into the cellular fractions of blood.

In vitro studies to evaluate the effect of other agents on the binding of MPA to human serum albumin (HSA) or plasma proteins showed that salicylate (at 25 mg/dL with human serum albumin) and MPAG (at ≥ 460 mcg/mL with plasma proteins) increased the free fraction of MPA. MPA at concentrations as high as 100 mcg/mL had little effect on the binding of warfarin, digoxin or propranolol, but decreased the binding of theophylline from 53% to 45% and phenytoin from 90% to 87%.

Elimination

Mean (±SD) apparent half-life and plasma clearance of MPA are 17.9 (±6.5) hours and 193 (±48) mL/min following oral administration and 16.6 (±5.8) hours and 177 (±31) mL/min following intravenous administration, respectively.

Metabolism

The parent drug, MMF, can be measured systemically during the intravenous infusion; however, approximately 5 minutes after the infusion is stopped or after oral administration, MMF concentrations are below the limit of quantitation (0.4 mcg/mL).

Metabolism to MPA occurs pre-systemically after oral dosing. MPA is metabolized principally by glucuronyl transferase to form MPAG, which is not pharmacologically active. In vivo, MPAG is converted to MPA during enterohepatic recirculation. The following metabolites of the 2-hydroxyethyl-morpholino moiety are also recovered in the urine following oral administration of MMF to healthy subjects: N-(2-carboxymethyl)-morpholine, N-(2-hydroxyethyl)-morpholine, and the N-oxide of N-(2-hydroxyethyl)-morpholine.

Due to the enterohepatic recirculation of MPAG/MPA, secondary peaks in the plasma MPA concentration-time profile are usually observed 6 to 12 hours post-dose. Bile sequestrants, such as cholestyramine, reduce MPA AUC by interfering with this enterohepatic recirculation of the drug [see Overdosage (10) and Drug Interaction Studies below].

Excretion

Negligible amount of drug is excreted as MPA (less than 1% of dose) in the urine. Orally administered radiolabeled MMF resulted in complete recovery of the administered dose, with 93% of the administered dose recovered in the urine and 6% recovered in feces. Most (about 87%) of the administered dose is excreted in the urine as MPAG. At clinically encountered concentrations, MPA and MPAG are usually not removed by hemodialysis. However, at high MPAG plasma concentrations (> 100 mcg/mL), small amounts of MPAG are removed.

Increased plasma concentrations of MMF metabolites (MPA 50% increase and MPAG about a 3-fold to 6-fold increase) are observed in patients with renal insufficiency [see Specific Populations].

Specific Populations

Patients with Renal Impairment

The mean (±SD) pharmacokinetic parameters for MPA following the administration of oral MMF given as single doses to non-transplant subjects with renal impairment are presented in Table 11.

In a single-dose study, MMF was administered as a capsule or as an intravenous infusion over 40 minutes. Plasma MPA AUC observed after oral dosing to volunteers with severe chronic renal impairment (GFR < 25 mL/min/1.73 m2) was about 75% higher relative to that observed in healthy volunteers (GFR > 80 mL/min/1.73 m2). In addition, the single-dose plasma MPAG AUC was 3-fold to 6-fold higher in volunteers with severe renal impairment than in volunteers with mild renal impairment or healthy volunteers, consistent with the known renal elimination of MPAG. No data are available on the safety of long-term exposure to this level of MPAG.

Plasma MPA AUC observed after single-dose (1 g) intravenous dosing to volunteers (n=4) with severe chronic renal impairment (GFR < 25 mL/min/1.73 m2) was 62.4 mcg∙h/mL (±19.3). Multiple dosing of MMF in patients with severe chronic renal impairment has not been studied.

Patients with Delayed Graft Function or Nonfunction

In patients with delayed renal graft function post-transplant, mean MPA AUC(0-12h) was comparable to that seen in post-transplant patients without delayed renal graft function. There is a potential for a transient increase in the free fraction and concentration of plasma MPA in patients with delayed renal graft function. However, dose adjustment does not appear to be necessary in patients with delayed renal graft function. Mean plasma MPAG AUC(0-12h) was 2-fold to 3-fold higher than in post-transplant patients without delayed renal graft function [see Dosage and Administration (2.5)].

In eight patients with primary graft non-function following kidney transplantation, plasma concentrations of MPAG accumulated about 6-fold to 8-fold after multiple dosing for 28 days. Accumulation of MPA was about 1-fold to 2-fold.

The pharmacokinetics of MMF are not altered by hemodialysis. Hemodialysis usually does not remove MPA or MPAG. At high concentrations of MPAG (> 100 mcg/mL), hemodialysis removes only small amounts of MPAG.

Patients with Hepatic Impairment

The mean (± SD) pharmacokinetic parameters for MPA following the administration of oral MMF given as single doses to non-transplant subjects with hepatic impairment is presented in Table 11.

In a single-dose (1 g oral) study of 18 volunteers with alcoholic cirrhosis and 6 healthy volunteers, hepatic MPA glucuronidation processes appeared to be relatively unaffected by hepatic parenchymal disease when pharmacokinetic parameters of healthy volunteers and alcoholic cirrhosis patients within this study were compared. However, it should be noted that for unexplained reasons, the healthy volunteers in this study had about a 50% lower AUC as compared to healthy volunteers in other studies, thus making comparisons between volunteers with alcoholic cirrhosis and healthy volunteers difficult. In a single-dose (1 g intravenous) study of 6 volunteers with severe hepatic impairment (aminopyrine breath test less than 0.2% of dose) due to alcoholic cirrhosis, MMF was rapidly converted to MPA. MPA AUC was 44.1 mcg∙h/mL (±15.5).

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 11 Pharmacokinetic Parameters for MPA [mean (±SD)] Following Single Doses of MMF Capsules in Chronic Renal and Hepatic Impairment</span> </caption> <col align="left" valign="top" width="40%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="15%"/> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="5"><span class="Bold">Pharmacokinetic Parameters for Renal Impairment</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"></td><td align="center" class="Rrule" valign="middle"><span class="Bold">Dose</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">T<span class="Sub">max</span> <br/>(h)</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">C<span class="Sub">max</span> <br/>(mcg/mL)</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">AUC(0-96h)<br/>(mcg∙h/mL)</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Healthy Volunteers<br/>  GFR greater than 80 mL/min/1.73 m<span class="Sup">2</span> <br/>  (n=6)</td><td align="center" class="Rrule">1 g</td><td align="center" class="Rrule">0.75<br/>(±0.27)</td><td align="center" class="Rrule">25.3<br/>(±7.99)</td><td align="center" class="Rrule">45.0<br/>(±22.6)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Mild Renal Impairment<br/>  GFR 50 to 80 mL/min/1.73 m<span class="Sup">2</span> <br/>  (n=6)</td><td align="center" class="Rrule">1 g</td><td align="center" class="Rrule">0.75<br/>(±0.27)</td><td align="center" class="Rrule">26.0<br/>(±3.82)</td><td align="center" class="Rrule">59.9<br/>(±12.9)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Moderate Renal Impairment<br/>  GFR 25 to 49 mL/min/1.73 m<span class="Sup">2</span> <br/>  (n=6)</td><td align="center" class="Rrule">1 g</td><td align="center" class="Rrule">0.75<br/>(±0.27)</td><td align="center" class="Rrule">19.0<br/>(±13.2)</td><td align="center" class="Rrule">52.9<br/>(±25.5)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Severe Renal Impairment<br/>  GFR less than 25 mL/min/1.73 m<span class="Sup">2</span> <br/>  (n=7)</td><td align="center" class="Rrule">1 g</td><td align="center" class="Rrule">1.00<br/>(±0.41)</td><td align="center" class="Rrule">16.3<br/>(±10.8)</td><td align="center" class="Rrule">78.6<br/>(±46.4)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" colspan="5"><span class="Bold">Pharmacokinetic Parameters for Hepatic Impairment</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"></td><td align="center" class="Rrule" valign="middle"><span class="Bold">Dose</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">T<span class="Sub">max</span> <br/>(h)</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">C<span class="Sub">max</span> <br/>(mcg/mL)</span></td><td align="center" class="Rrule" valign="middle"><span class="Bold">AUC(0-48h)<br/>(mcg∙h/mL)</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Healthy Volunteers<br/>  (n=6)</td><td align="center" class="Rrule">1 g</td><td align="center" class="Rrule">0.63<br/>(±0.14)</td><td align="center" class="Rrule">24.3<br/>(±5.73)</td><td align="center" class="Rrule">29.0<br/>(±5.78)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Alcoholic Cirrhosis<br/>  (n=18)</td><td align="center" class="Rrule">1 g</td><td align="center" class="Rrule">0.85<br/>(±0.58)</td><td align="center" class="Rrule">22.4<br/>(±10.1)</td><td align="center" class="Rrule">29.8<br/>(±10.7)</td> </tr> </tbody> </table></div>

Pediatric Patients

The pharmacokinetic parameters of MPA and MPAG have been evaluated in 55 pediatric patients (ranging from 1 year to 18 years of age) receiving CELLCEPT oral suspension at a dose of 600 mg/m2 twice daily (up to a maximum of 1 g twice daily) after allogeneic kidney transplantation. The pharmacokinetic data for MPA is provided in Table 12.

<div class="scrollingtable"><table width="95%"> <caption> <span>Table 12 Mean (±SD) Computed Pharmacokinetic Parameters for MPA by Age and Time after Allogeneic Kidney Transplantation</span> </caption> <col align="left" valign="top" width="18%"/> <col align="left" valign="top" width="5%"/> <col align="center" valign="top" width="17%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule" valign="middle">Age Group</th><th align="left" class="Rrule" valign="middle">(n)</th><th align="center" class="Rrule" valign="middle">Time</th><th align="center" class="Rrule" colspan="2" valign="middle">T<span class="Sub">max</span> <br/>(h)</th><th align="center" class="Rrule" colspan="2" valign="middle">Dose Adjusted<a class="Sup" href="#footnote-7" name="footnote-reference-7">*</a> C<span class="Sub">max</span> <br/>(mcg/mL)</th><th align="center" class="Rrule" colspan="2" valign="middle">Dose Adjusted<a class="Sup" href="#footnote-7">*</a> AUC<span class="Sub">0-12</span> <br/>(mcg∙h/mL)</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="9"> <dl class="Footnote"> <dt> <a href="#footnote-reference-7" name="footnote-7">*</a> </dt> <dd>adjusted to a dose of 600 mg/m<span class="Sup">2</span> </dd> <dt> <a href="#footnote-reference-8" name="footnote-8">†</a> </dt> <dd>a subset of 1 to &lt;6 yr</dd> <dt> <a href="#footnote-reference-9" name="footnote-9">‡</a> </dt> <dd>n=20</dd> <dt> <a href="#footnote-reference-10" name="footnote-10">§</a> </dt> <dd>n=16</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td align="left" class="Lrule"></td><td align="left" class="Rrule"></td><td align="center" class="Rrule">Early (Day 7)</td><td align="center"></td><td align="center" class="Rrule"></td><td align="center"></td><td align="center" class="Rrule"></td><td align="center"></td><td align="center" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule">1 to less than 2 yr</td><td align="left" class="Rrule">(6)<a class="Sup" href="#footnote-8" name="footnote-reference-8">†</a></td><td align="center" class="Rrule"></td><td align="center">3.03</td><td align="center" class="Rrule">(4.70)</td><td align="center">10.3</td><td align="center" class="Rrule">(5.80)</td><td align="center">22.5</td><td align="center" class="Rrule">(6.66)</td> </tr> <tr> <td align="left" class="Lrule">1 to less than 6 yr</td><td align="left" class="Rrule">(17)</td><td align="center" class="Rrule"></td><td align="center">1.63</td><td align="center" class="Rrule">(2.85)</td><td align="center">13.2</td><td align="center" class="Rrule">(7.16)</td><td align="center">27.4</td><td align="center" class="Rrule">(9.54)</td> </tr> <tr> <td align="left" class="Lrule">6 to less than 12 yr</td><td align="left" class="Rrule">(16)</td><td align="center" class="Rrule"></td><td align="center">0.940</td><td align="center" class="Rrule">(0.546)</td><td align="center">13.1</td><td align="center" class="Rrule">(6.30)</td><td align="center">33.2</td><td align="center" class="Rrule">(12.1)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule">12 to 18 yr</td><td align="left" class="Rrule">(21)</td><td align="center" class="Rrule"></td><td align="center">1.16</td><td align="center" class="Rrule">(0.830)</td><td align="center">11.7</td><td align="center" class="Rrule">(10.7)</td><td align="center">26.3</td><td align="center" class="Rrule">(9.14)<a class="Sup" href="#footnote-9" name="footnote-reference-9">‡</a></td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" class="Rrule"></td><td align="center" class="Rrule">Late (Month 3)</td><td align="center"></td><td align="center" class="Rrule"></td><td align="center"></td><td align="center" class="Rrule"></td><td align="center"></td><td align="center" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule">1 to less than 2 yr</td><td align="left" class="Rrule">(4)<a class="Sup" href="#footnote-8">†</a></td><td align="center" class="Rrule"></td><td align="center">0.725</td><td align="center" class="Rrule">(0.276)</td><td align="center">23.8</td><td align="center" class="Rrule">(13.4)</td><td align="center">47.4</td><td align="center" class="Rrule">(14.7)</td> </tr> <tr> <td align="left" class="Lrule">1 to less than 6 yr</td><td align="left" class="Rrule">(15)</td><td align="center" class="Rrule"></td><td align="center">0.989</td><td align="center" class="Rrule">(0.511)</td><td align="center">22.7</td><td align="center" class="Rrule">(10.1)</td><td align="center">49.7</td><td align="center" class="Rrule">(18.2)</td> </tr> <tr> <td align="left" class="Lrule">6 to less than 12 yr</td><td align="left" class="Rrule">(14)</td><td align="center" class="Rrule"></td><td align="center">1.21</td><td align="center" class="Rrule">(0.532)</td><td align="center">27.8</td><td align="center" class="Rrule">(14.3)</td><td align="center">61.9</td><td align="center" class="Rrule">(19.6)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule">12 to 18 yr</td><td align="left" class="Rrule">(17)</td><td align="center" class="Rrule"></td><td align="center">0.978</td><td align="center" class="Rrule">(0.484)</td><td align="center">17.9</td><td align="center" class="Rrule">(9.57)</td><td align="center">53.6</td><td align="center" class="Rrule">(20.3)<a class="Sup" href="#footnote-10" name="footnote-reference-10">§</a></td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" class="Rrule"></td><td align="center" class="Rrule">Late (Month 9)</td><td align="center"></td><td align="center" class="Rrule"></td><td align="center"></td><td align="center" class="Rrule"></td><td align="center"></td><td align="center" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule">1 to less than 2 yr</td><td align="left" class="Rrule">(4)<a class="Sup" href="#footnote-8">†</a></td><td align="center" class="Rrule"></td><td align="center">0.604</td><td align="center" class="Rrule">(0.208)</td><td align="center">25.6</td><td align="center" class="Rrule">(4.25)</td><td align="center">55.8</td><td align="center" class="Rrule">(11.6)</td> </tr> <tr> <td align="left" class="Lrule">1 to less than 6 yr</td><td align="left" class="Rrule">(12)</td><td align="center" class="Rrule"></td><td align="center">0.869</td><td align="center" class="Rrule">(0.479)</td><td align="center">30.4</td><td align="center" class="Rrule">(9.16)</td><td align="center">61.0</td><td align="center" class="Rrule">(10.7)</td> </tr> <tr> <td align="left" class="Lrule">6 to less than 12 yr</td><td align="left" class="Rrule">(11)</td><td align="center" class="Rrule"></td><td align="center">1.12</td><td align="center" class="Rrule">(0.462)</td><td align="center">29.2</td><td align="center" class="Rrule">(12.6)</td><td align="center">66.8</td><td align="center" class="Rrule">(21.2)</td> </tr> <tr class="Last"> <td align="left" class="Lrule">12 to 18 yr</td><td align="left" class="Rrule">(14)</td><td align="center" class="Rrule"></td><td align="center">1.09</td><td align="center" class="Rrule">(0.518)</td><td align="center">18.1</td><td align="center" class="Rrule">(7.29)</td><td align="center">56.7</td><td align="center" class="Rrule">(14.0)</td> </tr> </tbody> </table></div>

The CELLCEPT oral suspension dose of 600 mg/m2 twice daily (up to a maximum of 1 g twice daily) achieved mean MPA AUC values in pediatric patients similar to those seen in adult kidney transplant patients receiving CELLCEPT capsules at a dose of 1 g twice daily in the early post-transplant period. There was wide variability in the data. As observed in adults, early post-transplant MPA AUC values were approximately 45% to 53% lower than those observed in the later post-transplant period (>3 months). MPA AUC values were similar in the early and late post-transplant period across the 1 to 18-year age range.

A comparison of dose-normalized (to 600 mg/m2) MPA AUC values in 12 pediatric kidney transplant patients less than 6 years of age at 9 months post-transplant with those values in 7 pediatric liver transplant patients [median age 17 months (range: 10 – 60 months)] and at 6 months and beyond post-transplant revealed that, at the same dose, there were on average 23% lower AUC values in the pediatric liver compared to pediatric kidney patients. This is consistent with the need for higher dosing in adult liver transplant patients compared to kidney transplant patients to achieve the same exposure.

In adult transplant patients administered the same dosage of CELLCEPT, there is similar MPA exposure among kidney transplant and heart transplant patients. Based on the established similarity in MPA exposure between pediatric kidney transplant and adult kidney transplant patients at their respective approved doses, it is expected that MPA exposure at the recommended dosage will be similar in pediatric heart transplant and adult heart transplant patients.

Male and Female Patients

Data obtained from several studies were pooled to look at any gender-related differences in the pharmacokinetics of MPA (data were adjusted to 1 g oral dose). Mean (±SD) MPA AUC (0-12h) for males (n=79) was 32.0 (±14.5) and for females (n=41) was 36.5 (±18.8) mcg∙h/mL while mean (±SD) MPA Cmax was 9.96 (±6.19) in the males and 10.6 (±5.64) mcg/mL in the females. These differences are not of clinical significance.

Geriatric Patients

The pharmacokinetics of mycophenolate mofetil and its metabolites have not been found to be altered in geriatric transplant patients when compared to younger transplant patients.

Drug Interaction Studies

Acyclovir

Coadministration of MMF (1 g) and acyclovir (800 mg) to 12 healthy volunteers resulted in no significant change in MPA AUC and Cmax. However, MPAG and acyclovir plasma AUCs were increased 10.6% and 21.9%, respectively.

Antacids with Magnesium and Aluminum Hydroxides

Absorption of a single dose of MMF (2 g) was decreased when administered to 10 rheumatoid arthritis patients also taking Maalox® TC (10 mL qid). The Cmax and AUC(0-24h) for MPA were 33% and 17% lower, respectively, than when MMF was administered alone under fasting conditions.

Proton Pump Inhibitors (PPIs)

Coadministration of PPIs (e.g., lansoprazole, pantoprazole) in single doses to healthy volunteers and multiple doses to transplant patients receiving CELLCEPT has been reported to reduce the exposure to MPA. An approximate reduction of 30 to 70% in the Cmax and 25% to 35% in the AUC of MPA has been observed, possibly due to a decrease in MPA solubility at an increased gastric pH.

Cholestyramine

Following single-dose administration of 1.5 g MMF to 12 healthy volunteers pretreated with 4 g three times a day of cholestyramine for 4 days, MPA AUC decreased approximately 40%. This decrease is consistent with interruption of enterohepatic recirculation which may be due to binding of recirculating MPAG with cholestyramine in the intestine.

Cyclosporine

Cyclosporine (Sandimmune®) pharmacokinetics (at doses of 275 to 415 mg/day) were unaffected by single and multiple doses of 1.5 g twice daily of MMF in 10 stable kidney transplant patients. The mean (±SD) AUC(0-12h) and Cmax of cyclosporine after 14 days of multiple doses of MMF were 3290 (±822) ng∙h/mL and 753 (±161) ng/mL, respectively, compared to 3245 (±1088) ng∙h/mL and 700 (±246) ng/mL, respectively, 1 week before administration of MMF.

Cyclosporine A interferes with MPA enterohepatic recirculation. In kidney transplant patients, mean MPA exposure (AUC(0-12h)) was approximately 30-50% greater when MMF was administered without cyclosporine compared with when MMF was coadministered with cyclosporine. This interaction is due to cyclosporine inhibition of multidrug-resistance-associated protein 2 (MRP-2) transporter in the biliary tract, thereby preventing the excretion of MPAG into the bile that would lead to enterohepatic recirculation of MPA. This information should be taken into consideration when MMF is used without cyclosporine.

Drugs Affecting Glucuronidation

Concomitant administration of drugs inhibiting glucuronidation of MPA may increase MPA exposure (e.g., increase of MPA AUC (0-∞) by 35% was observed with concomitant administration of isavuconazole).

Concomitant administration of telmisartan and CELLCEPT resulted in an approximately 30% decrease in MPA concentrations. Telmisartan changes MPA's elimination by enhancing PPAR gamma (peroxisome proliferator-activated receptor gamma) expression, which in turn results in an enhanced UGT1A9 expression and glucuronidation activity.

Ganciclovir

Following single-dose administration to 12 stable kidney transplant patients, no pharmacokinetic interaction was observed between MMF (1.5 g) and intravenous ganciclovir (5 mg/kg). Mean (±SD) ganciclovir AUC and Cmax (n=10) were 54.3 (±19.0) mcg∙h/mL and 11.5 (±1.8) mcg/mL, respectively, after coadministration of the two drugs, compared to 51.0 (±17.0) mcg∙h/mL and 10.6 (±2.0) mcg/mL, respectively, after administration of intravenous ganciclovir alone. The mean (±SD) AUC and Cmax of MPA (n=12) after coadministration were 80.9 (±21.6) mcg∙h/mL and 27.8 (±13.9) mcg/mL, respectively, compared to values of 80.3 (±16.4) µg∙h/mL and 30.9 (±11.2) mcg/mL, respectively, after administration of MMF alone.

Oral Contraceptives

A study of coadministration of CELLCEPT (1 g twice daily) and combined oral contraceptives containing ethinylestradiol (0.02 mg to 0.04 mg) and levonorgestrel (0.05 mg to 0.20 mg), desogestrel (0.15 mg) or gestodene (0.05 mg to 0.10 mg) was conducted in 18 women with psoriasis over 3 consecutive menstrual cycles. Mean serum levels of LH, FSH and progesterone were not significantly affected. Mean AUC(0-24h) was similar for ethinylestradiol and 3-keto desogestrel; however, mean levonorgestrel AUC(0-24h) significantly decreased by about 15%. There was large inter-patient variability (%CV in the range of 60% to 70%) in the data, especially for ethinylestradiol.

Sevelamer

Concomitant administration of sevelamer and MMF in adult and pediatric patients decreased the mean MPA Cmax and AUC (0-12h) by 36% and 26% respectively.

Antimicrobials

Antimicrobials eliminating beta-glucuronidase-producing bacteria in the intestine (e.g. aminoglycoside, cephalosporin, fluoroquinolone, and penicillin classes of antimicrobials) may interfere with the MPAG/MPA enterohepatic recirculation thus leading to reduced systemic MPA exposure. Information concerning antibiotics is as follows:

In a 104-week oral carcinogenicity study in mice, MMF in daily doses up to 180 mg/kg was not tumorigenic. The highest dose tested was 0.2 times the recommended clinical dose (2 g/day) in renal transplant patients and 0.15 times the recommended clinical dose (3 g/day) in cardiac transplant patients when corrected for differences in body surface area (BSA). In a 104-week oral carcinogenicity study in rats, MMF in daily doses up to 15 mg/kg was not tumorigenic. The highest dose was 0.035 times the recommended clinical dose in kidney transplant patients and 0.025 times the recommended clinical dose in heart transplant patients when corrected for BSA. While these animal doses were lower than those given to patients, they were maximal in those species and were considered adequate to evaluate the potential for human risk [see Warnings and Precautions (5.2)].

The genotoxic potential of MMF was determined in five assays. MMF was genotoxic in the mouse lymphoma/thymidine kinase assay and the in vivo mouse micronucleus assay. MMF was not genotoxic in the bacterial mutation assay, the yeast mitotic gene conversion assay or the Chinese hamster ovary cell chromosomal aberration assay.

MMF had no effect on fertility of male rats at oral doses up to 20 mg/kg/day. This dose represents 0.05 times the recommended clinical dose in renal transplant patients and 0.03 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. In a female fertility and reproduction study conducted in rats, oral doses of 4.5 mg/kg/day caused malformations (principally of the head and eyes) in the first generation offspring in the absence of maternal toxicity. This dose was 0.01 times the recommended clinical dose in renal transplant patients and 0.005 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. No effects on fertility or reproductive parameters were evident in the dams or in the subsequent generation.

Adults

The three de novo kidney transplantation studies compared two dose levels of oral CELLCEPT (1 g twice daily and 1.5 g twice daily) with azathioprine (2 studies) or placebo (1 study) to prevent acute rejection episodes. One of the two studies with azathioprine (AZA) control arm also included anti-thymocyte globulin (ATGAM®) induction therapy. The geographic location of the investigational sites of these studies are included in Table 13.

In all three de novo kidney transplantation studies, the primary efficacy endpoint was the proportion of patients in each treatment group who experienced treatment failure within the first 6 months after transplantation. Treatment failure was defined as biopsy-proven acute rejection on treatment or the occurrence of death, graft loss or early termination from the study for any reason without prior biopsy-proven rejection.

CELLCEPT, in combination with corticosteroids and cyclosporine, reduced (statistically significant at 0.05 level) the incidence of treatment failure within the first 6 months following transplantation (Table 13). Patients who prematurely discontinued treatment were followed for the occurrence of death or graft loss, and the cumulative incidence of graft loss and patient death combined are summarized in Table 14. Patients who prematurely discontinued treatment were not followed for the occurrence of acute rejection after termination.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 13 Treatment Failure in De Novo Kidney Transplantation Studies</span> </caption> <col align="left" valign="top" width="30%"/> <col align="center" valign="top" width="23%"/> <col align="center" valign="top" width="23%"/> <col align="center" valign="top" width="24%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="4">*Does not include death and graft loss as reason for early termination. </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="left" class="Lrule Rrule" valign="middle"><span class="Bold">USA Study</span></td><td align="center" class="Rrule"><span class="Bold">CELLCEPT<br/>2 g/day</span></td><td align="center" class="Rrule"><span class="Bold">CELLCEPT<br/>3 g/day</span></td><td align="center" class="Rrule"><span class="Bold">AZA<br/>1 to 2 mg/kg/day</span></td> </tr> <tr> <td align="left" class="Lrule Rrule"><span class="Bold">(N=499 patients)</span></td><td align="center" class="Rrule"><span class="Bold">(n=167 patients)</span></td><td align="center" class="Rrule"><span class="Bold">(n=166 patients)</span></td><td align="center" class="Rrule"><span class="Bold">(n=166 patients)</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"></td><td align="center" class="Rrule Toprule" colspan="3">All 3 groups received anti-thymocyte globulin induction, cyclosporine and corticosteroids</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">All treatment failures</td><td align="center" class="Rrule">31.1%</td><td align="center" class="Rrule">31.3%</td><td align="center" class="Rrule">47.6%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Early termination without prior acute rejection</td><td align="center" class="Rrule">9.6%</td><td align="center" class="Rrule">12.7%</td><td align="center" class="Rrule">6.0%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Biopsy-proven rejection episode on treatment</td><td align="center" class="Rrule">19.8%</td><td align="center" class="Rrule">17.5%</td><td align="center" class="Rrule">38.0%</td> </tr> <tr> <td align="left" class="Lrule Rrule" rowspan="2" valign="middle"><span class="Bold">Europe/Canada/Australia Study<br/>(N=503 patients)</span></td><td align="center" class="Rrule"><span class="Bold">CELLCEPT<br/>2 g/day<br/>(n=173 patients)</span></td><td align="center" class="Rrule"><span class="Bold">CELLCEPT<br/>3 g/day<br/>(n=164 patients)</span></td><td align="center" class="Rrule"><span class="Bold">AZA<br/>100 to 150 mg/day<br/>(n=166 patients)</span></td> </tr> <tr class="Botrule"> <td align="center" class="Rrule Toprule" colspan="3">No induction treatment administered; all 3 groups received cyclosporine and corticosteroids.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule Toprule">All treatment failures</td><td align="center" class="Rrule">38.2%</td><td align="center" class="Rrule">34.8%</td><td align="center" class="Rrule">50.0%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Early termination without prior acute rejection</td><td align="center" class="Rrule">13.9%</td><td align="center" class="Rrule">15.2%</td><td align="center" class="Rrule">10.2%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Biopsy-proven rejection episode on treatment</td><td align="center" class="Rrule">19.7%</td><td align="center" class="Rrule">15.9%</td><td align="center" class="Rrule">35.5%</td> </tr> <tr> <td align="left" class="Lrule Rrule" valign="middle"><span class="Bold">Europe Study</span></td><td align="center" class="Rrule"><span class="Bold">CELLCEPT<br/>2 g/day</span></td><td align="center" class="Rrule"><span class="Bold">CELLCEPT<br/>3 g/day</span></td><td align="center" class="Rrule"><span class="Bold">Placebo</span></td> </tr> <tr> <td align="left" class="Lrule Rrule"><span class="Bold">(N=491 patients)</span></td><td align="center" class="Rrule"><span class="Bold">(n=165 patients)</span></td><td align="center" class="Rrule"><span class="Bold">(n=160 patients)</span></td><td align="center" class="Rrule"><span class="Bold">(n=166 patients)</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"></td><td align="center" class="Rrule Toprule" colspan="3">No induction treatment administered; all 3 groups received cyclosporine and corticosteroids.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">All treatment failures</td><td align="center" class="Rrule">30.3%</td><td align="center" class="Rrule">38.8%</td><td align="center" class="Rrule">56.0%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Early termination without prior acute rejection</td><td align="center" class="Rrule">11.5%</td><td align="center" class="Rrule">22.5%</td><td align="center" class="Rrule">7.2%</td> </tr> <tr class="Botrule Last"> <td align="left" class="Lrule Rrule">Biopsy-proven rejection episode on treatment</td><td align="center" class="Rrule">17.0%</td><td align="center" class="Rrule">13.8%</td><td align="center" class="Rrule">46.4%</td> </tr> </tbody> </table></div>

No advantage of CELLCEPT at 12 months with respect to graft loss or patient death (combined) was established (Table 14). Numerically, patients receiving CELLCEPT 2 g/day and 3 g/day experienced a better outcome than controls in all three studies; patients receiving CELLCEPT 2 g/day experienced a better outcome than CELLCEPT 3 g/day in two of the three studies. Patients in all treatment groups who terminated treatment early were found to have a poor outcome with respect to graft loss or patient death at 1 year.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 14 De Novo Kidney Transplantation Studies Cumulative Incidence of Combined Graft Loss or Patient Death at 12 Months</span> </caption> <col align="left" valign="top" width="30%"/> <col align="center" valign="top" width="23%"/> <col align="center" valign="top" width="23%"/> <col align="center" valign="top" width="24%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule" valign="middle">Study</th><th align="center" class="Rrule">CELLCEPT<br/>2 g/day</th><th align="center" class="Rrule">CELLCEPT<br/>3 g/day</th><th align="center" class="Rrule">Control<br/> (AZA or Placebo)</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">USA</td><td align="center" class="Rrule">8.5%</td><td align="center" class="Rrule">11.5%</td><td align="center" class="Rrule">12.2%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Europe/Canada/Australia</td><td align="center" class="Rrule">11.7%</td><td align="center" class="Rrule">11.0%</td><td align="center" class="Rrule">13.6%</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Europe</td><td align="center" class="Rrule">8.5%</td><td align="center" class="Rrule">10.0%</td><td align="center" class="Rrule">11.5%</td> </tr> </tbody> </table></div>

Pediatrics- De Novo Kidney transplantation PK Study with Long Term Follow-Up

One open-label, safety and pharmacokinetic study of CELLCEPT oral suspension 600 mg/m2 twice daily (up to 1 g twice daily) in combination with cyclosporine and corticosteroids was performed at centers in the United States (9), Europe (5) and Australia (1) in 100 pediatric patients (3 months to 18 years of age) for the prevention of renal allograft rejection. CELLCEPT was well tolerated in pediatric patients [see Adverse Reactions (6.1)], and the pharmacokinetics profile was similar to that seen in adult patients dosed with 1 g twice daily CELLCEPT capsules [see Clinical Pharmacology (12.3)]. The rate of biopsy-proven rejection was similar across the age groups (3 months to <6 years, 6 years to <12 years, 12 years to 18 years). The overall biopsy-proven rejection rate at 6 months was comparable to adults. The combined incidence of graft loss (5%) and patient death (2%) at 12 months post-transplant was similar to that observed in adult kidney transplant patients.

A double-blind, randomized, comparative, parallel-group, multicenter study in primary de novo heart transplant recipients was performed at centers in the United States (20), in Canada (1), in Europe (5) and in Australia (2). The total number of patients enrolled (ITT population) was 650; 72 never received study drug and 578 received study drug (Safety Population). Patients received CELLCEPT 1.5 g twice daily (n=289) or AZA 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune® or Neoral®) and corticosteroids as maintenance immunosuppressive therapy. The two primary efficacy endpoints were: (1) the proportion of patients who, after transplantation, had at least one endomyocardial biopsy-proven rejection with hemodynamic compromise, or were re-transplanted or died, within the first 6 months, and (2) the proportion of patients who died or were re-transplanted during the first 12 months following transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection for up to 6 months and for the occurrence of death for 1 year.

The analyses of the endpoints showed:

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 15 De Novo Heart Transplantation Study Rejection at 6 Months/Death or Re-transplantation at 1 Year</span> </caption> <col align="left" valign="top" width="34%"/> <col align="center" valign="middle" width="16%"/> <col align="center" valign="middle" width="17%"/> <col align="center" valign="middle" width="16%"/> <col align="center" valign="middle" width="17%"/> <thead> <tr class="First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule" colspan="2">All Patients (ITT)</th><th align="center" class="Botrule Rrule" colspan="2">Treated Patients</th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">AZA<br/>N = 323</th><th align="center" class="Rrule">CELLCEPT<br/>N = 327</th><th align="center" class="Rrule">AZA<br/>N = 289</th><th align="center" class="Rrule">CELLCEPT<br/>N = 289</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-11" name="footnote-11">*</a> </dt> <dd>Hemodynamic compromise occurred if any of the following criteria were met: pulmonary capillary wedge pressure ≥20 mm or a 25% increase; cardiac index &lt;2.0 L/min/m<span class="Sup">2</span> or a 25% decrease; ejection fraction ≤30%; pulmonary artery oxygen saturation ≤60% or a 25% decrease; presence of new S<span class="Sub">3</span> gallop; fractional shortening was ≤20% or a 25% decrease; inotropic support required to manage the clinical condition.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Biopsy-proven rejection with hemodynamic compromise at 6 months<a class="Sup" href="#footnote-11" name="footnote-reference-11">*</a></td><td align="center" class="Rrule">121 (38%)</td><td align="center" class="Rrule">120 (37%)</td><td align="center" class="Rrule">100 (35%)</td><td align="center" class="Rrule">92 (32%)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Death or re-transplantation at 1 year</td><td align="center" class="Rrule">49 (15.2%)</td><td align="center" class="Rrule">42 (12.8%)</td><td align="center" class="Rrule">33 (11.4%)</td><td align="center" class="Rrule">18 (6.2%)</td> </tr> </tbody> </table></div>

A double-blind, randomized, comparative, parallel-group, multicenter study in primary hepatic transplant recipients was performed at centers in the United States (16), in Canada (2), in Europe (4) and in Australia (1). The total number of patients enrolled was 565. Per protocol, patients received CELLCEPT 1 g twice daily intravenously for up to 14 days followed by CELLCEPT 1.5 g twice daily orally or AZA 1 to 2 mg/kg/day intravenously followed by AZA 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral®) and corticosteroids as maintenance immunosuppressive therapy. The actual median oral dose of AZA on study was 1.5 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) initially and 1.26 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) at 12 months. The two primary endpoints were: (1) the proportion of patients who experienced, in the first 6 months post-transplantation, one or more episodes of biopsy-proven and treated rejection or death or re-transplantation, and (2) the proportion of patients who experienced graft loss (death or re-transplantation) during the first 12 months post-transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection and for the occurrence of graft loss (death or re-transplantation) for 1 year.

In combination with corticosteroids and cyclosporine, CELLCEPT demonstrated a lower rate of acute rejection at 6 months and a similar rate of death or re-transplantation at 1 year compared to AZA (Table 16).

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 16 De Novo Liver Transplantation Study Rejection at 6 Months/Death or Retransplantation at 1 Year</span> </caption> <col align="left" valign="middle" width="50%"/> <col align="center" valign="middle" width="25%"/> <col align="center" valign="middle" width="25%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">AZA<br/>N = 287</th><th align="center" class="Rrule">CELLCEPT<br/>N = 278</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Biopsy-proven, treated rejection at 6 months (includes death or re-transplantation)</td><td align="center" class="Rrule">137 (47.7%)</td><td align="center" class="Rrule">107 (38.5%)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Death or re-transplantation at 1 year</td><td align="center" class="Rrule">42 (14.6%)</td><td align="center" class="Rrule">41 (14.7%)</td> </tr> </tbody> </table></div>

1. "OSHA Hazardous Drugs." OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

{ "type": "p", "children": [], "text": "1. \"OSHA Hazardous Drugs.\" OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html\n" }

Mycophenolate mofetil (MMF) has demonstrated teratogenic effects in humans [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. CELLCEPT tablets should not be crushed and CELLCEPT capsules should not be opened or crushed. Wearing disposable gloves is recommended during reconstitution and when wiping the outer surface of the bottle/cap and the table after reconstitution. Avoid inhalation or direct contact with skin or mucous membranes of the powder contained in CELLCEPT capsules, CELLCEPT Oral Suspension (before or after constitution), or CELLCEPT Intravenous (during or after preparation) [see Dosage and Administration (2.6)]. Follow applicable special handling and disposal procedures1.

<div class="scrollingtable"><table width="75%"> <col align="left" valign="top" width="75%"/> <col align="left" valign="top" width="25%"/> <tbody class="Headless"> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="2">Capsules<br/>Blue-brown, two-piece hard gelatin capsules, printed in black with "CELLCEPT 250" on the blue cap and "Roche" on the brown body.</td> </tr> <tr> <td align="left" class="Lrule">Sizes</td><td align="left" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule">Bottle of 100</td><td align="left" class="Rrule">NDC 0004-0259-01</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule">Bottle of 500</td><td align="left" class="Rrule">NDC 0004-0259-43</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="2">Storage<br/>Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)</td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="75%"> <col align="left" valign="top" width="75%"/> <col align="left" valign="top" width="25%"/> <tbody class="Headless"> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="2">Tablets<br/>Lavender-colored, caplet-shaped, film-coated tablets engraved with "CELLCEPT 500" on one side and "Roche" on the other</td> </tr> <tr> <td align="left" class="Lrule">Sizes</td><td align="left" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule">Bottle of 100</td><td align="left" class="Rrule">NDC 0004-0260-01</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule">Bottle of 500</td><td align="left" class="Rrule">NDC 0004-0260-43</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="2">Storage and Dispensing Information: <ul class="Disc"> <li>Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). </li> <li>Dispense in light-resistant containers, such as the manufacturer's original containers.</li> </ul> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="75%"> <col align="left" valign="top" width="75%"/> <col align="left" valign="top" width="25%"/> <tbody class="Headless"> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="2">For oral suspension: 35 g mycophenolate mofetil, white to off-white powder blend for constitution to a white to off-white mixed-fruit flavor suspension</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule">225 mL bottle with bottle adapter and 2 oral dispensers </td><td align="left" class="Rrule">NDC 0004-0261-29</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="2">Storage <ul class="Disc"> <li>Store dry powder at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). </li> <li>Store constituted suspension at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) for up to 60 days. Storage in a refrigerator at 2°C to 8°C (36°F to 46°F) is acceptable. Do not freeze.</li> </ul> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="75%"> <col align="left" valign="top" width="75%"/> <col align="left" valign="top" width="25%"/> <tbody class="Headless"> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="2">For injection: 500 mg mycophenolate mofetil in a 20 mL sterile single-dose vial cartons of 4 vials</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule">Cartons of 4 single-dose vials</td><td align="left" class="Rrule">NDC 0004-0298-09</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="2">Storage <ul class="Disc"> <li>Store powder and reconstituted infusion solution at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).</li> </ul> </td> </tr> </tbody> </table></div>

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Pregnancy loss and malformations

Contraception

Inform patients that they are at increased risk of developing a variety of infections due to immunosuppression. Instruct them to contact their physician if they develop any of the signs and symptoms of infection explained in the Medication Guide [see Warnings and Precautions (5.3)].

Inform patients that they are at increased risk for developing blood adverse effects such as anemia or low white blood cells. Advise patients to immediately contact their healthcare provider if they experience any evidence of infection, unexpected bruising, or bleeding, or any other manifestation of bone marrow suppression [see Warnings and Precautions (5.4)].

Inform patients that CELLCEPT can cause gastrointestinal tract complications including bleeding, intestinal perforations, and gastric or duodenal ulcers. Advise the patient to contact their healthcare provider if they have symptoms of gastrointestinal bleeding, or sudden onset or persistent abdominal pain [see Warnings and Precautions (5.5)].

Inform patients that acute inflammatory reactions have been reported in some patients who received CELLCEPT. Some reactions were severe, requiring hospitalization. Advise patients to contact their physician if they develop fever, joint stiffness, joint pain or muscle pains [see Warnings and Precautions (5.7)].

Inform patients of the potential risk of hypersensitivity reactions. Advise patients to stop taking CELLCEPT and seek immediate medical attention if signs or symptoms of hypersensitivity reaction occur (such as swelling of face, lips, tongue, or throat; difficulty breathing or swallowing) [see Warnings and Precautions (5.8)].

Inform patients that CELLCEPT can interfere with the usual response to immunizations. Before seeking vaccines on their own, advise patients to discuss first with their physician [see Warnings and Precautions (5.9)].

Advise patients not to donate blood during therapy and for at least 6 weeks following discontinuation of CELLCEPT [see Warnings and Precautions (5.12)].

Advise males of childbearing potential not to donate semen during therapy and for 90 days following discontinuation of CELLCEPT [see Warnings and Precautions (5.13)].

Advise patients that CELLCEPT can affect the ability to drive or operate machines. Patients should avoid driving or operating machines if they experience somnolence, confusion, dizziness, tremor or hypotension during treatment with CELLCEPT [see Warnings and Precautions (5.15)].

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Genentech USA, Inc. A Member of the Roche Group1 DNA WaySouth San Francisco, CA 94080-4990

{ "type": "p", "children": [], "text": "\nGenentech USA, Inc.\nA Member of the Roche Group1 DNA WaySouth San Francisco, CA 94080-4990" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="3%"/> <col align="left" valign="top" width="30%"/> <col align="left" valign="top" width="17%"/> <col align="left" valign="top" width="17%"/> <col align="left" valign="top" width="3%"/> <col align="left" valign="top" width="10%"/> <col align="left" valign="top" width="20%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="6">This Medication Guide has been approved by the U.S. Food and Drug Administration.</td><td align="right" colspan="1">Revised: May 2025</td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="7"><span class="Bold">MEDICATION GUIDE</span></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule" colspan="2"><span class="Bold">CELLCEPT<span class="Sup">®</span> [SEL-sept]<br/>(mycophenolate mofetil capsules)<br/>(mycophenolate mofetil tablets)</span></td><td align="center" colspan="2"><span class="Bold">CELLCEPT<span class="Sup">®</span> [SEL-sept]<br/>(mycophenolate mofetil for oral suspension)</span></td><td align="center" class="Rrule" colspan="3"><span class="Bold">CELLCEPT<span class="Sup">®</span> [SEL-sept]<br/>(mycophenolate mofetil for injection)</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7">Read the Medication Guide that comes with CELLCEPT before you start taking it and each time you refill your prescription. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold"><a name="Important"></a>What is the most important information I should know about CELLCEPT?<br/>CELLCEPT can cause serious side effects, including:<br/>Increased risk of loss of a pregnancy (miscarriage) and higher risk of birth defects.</span> Females who take CELLCEPT during pregnancy have a higher risk of miscarriage during the first 3 months (first trimester), and a higher risk that their baby will be born with birth defects. <ul class="Disc"> <li> <span class="Bold">If you are a female who can become pregnant</span>, your doctor must talk with you about acceptable birth control methods (contraceptive counseling) to use while taking CELLCEPT. You should have 1 pregnancy test immediately before starting CELLCEPT and another pregnancy test 8 to 10 days later. Pregnancy tests should be repeated during routine follow-up visits with your doctor. Talk to your doctor about the results of all of your pregnancy tests.<br/>You must use acceptable birth control during your entire CELLCEPT treatment and for 6 weeks after stopping CELLCEPT, unless at any time you choose to avoid sexual intercourse (abstinence) with a man completely. CELLCEPT decreases blood levels of the hormones in birth control pills that you take by mouth. Birth control pills may not work as well while you take CELLCEPT, and you could become pregnant. If you take birth control pills while using CELLCEPT you must also use another form of birth control. Talk to your doctor about other birth control methods that you can use while taking CELLCEPT.</li> <li> <span class="Bold">If you are a sexually active male whose female partner can become pregnant while you are taking CELLCEPT</span>, use effective contraception during treatment and for at least 90 days after stopping CELLCEPT.</li> <li> <span class="Bold">If you plan to become pregnant</span>, talk with your doctor. Your doctor will decide if other medicines to prevent rejection may be right for you.</li> <li> <span class="Bold">If you become pregnant while taking CELLCEPT</span>, <span class="Bold">do not stop taking CELLCEPT. Call your doctor right away.</span> You and your doctor may decide that other medicines to prevent rejection may be right for you. You and your doctor should report your pregnancy to the Mycophenolate Pregnancy Registry either:<ul class="Circle"> <li>By phone at 1-800-617-8191 <span class="Bold">or</span> </li> <li>By visiting the REMS website at: <span class="Bold">www.mycophenolateREMS.com</span> </li> </ul>The purpose of this registry is to gather information about the health of you and your baby.</li> </ul> <span class="Bold">Increased risk of getting certain cancers.</span> People who take CELLCEPT have a higher risk of getting lymphoma, and other cancers, especially skin cancer. Tell your doctor if you have:</td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>unexplained fever, prolonged tiredness, weight loss or lymph node swelling</li> <li>a brown or black skin lesion with uneven borders, or one part of the lesion does not look like the other</li> </ul> </td><td align="left" class="Rrule" colspan="4"> <ul class="Disc"> <li>a change in the size and color of a mole</li> <li>a new skin lesion or bump</li> <li>any other changes to your health</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">Increased risk of getting serious infections.</span> CELLCEPT weakens the body's immune system and affects your ability to fight infections. Serious infections can happen with CELLCEPT and can lead to hospitalizations and death. These serious infections can include:<ul class="Disc"> <li> <span class="Bold">Viral infections.</span> Certain viruses can live in your body and cause active infections when your immune system is weak. Viral infections that can happen with CELLCEPT include:<ul class="Circle"> <li>Shingles, other herpes infections, and cytomegalovirus (CMV). CMV can cause serious tissue and blood infections.</li> <li>BK virus. BK virus can affect how your kidney works and cause your transplanted kidney to fail.</li> <li>Hepatitis B and C viruses. Hepatitis viruses can affect how your liver works. Talk to your doctor about how hepatitis viruses may affect you.</li> <li>COVID-19</li> </ul> </li> <li> <span class="Bold">A brain infection called Progressive Multifocal Leukoencephalopathy (PML).</span> In some patients, CELLCEPT may cause an infection of the brain that may cause death. You are at risk for this brain infection because you have a weakened immune system. Call your doctor right away if you have any of the following symptoms:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Circle"> <li>weakness on one side of the body</li> <li>you do not care about things you usually care about (apathy)</li> </ul> </td><td align="left"></td><td align="left" class="Rrule" colspan="3"> <ul class="Circle"> <li>you are confused or have problems thinking</li> <li>you cannot control your muscles</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="7"> <ul class="Disc"> <li> <span class="Bold">Fungal infections.</span> Yeasts and other types of fungal infections can happen with CELLCEPT and can cause serious tissue and blood infections (See <span class="Bold">"<a href="#Effects">What are the possible side effects of CELLCEPT?</a>"</span>).</li> </ul> <span class="Bold">Call your doctor right away if you have any of the following signs and symptoms of infection:</span></td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>temperature of 100.5°F or greater</li> <li>cold symptoms, such as a runny nose or sore throat</li> <li>flu symptoms, such as an upset stomach, stomach pain, vomiting or diarrhea</li> <li>earache or headache</li> </ul> </td><td align="left" class="Rrule" colspan="4"> <ul class="Disc"> <li>pain during urination</li> <li>white patches in the mouth or throat</li> <li>unexpected bruising or bleeding</li> <li>cuts, scrapes or incisions that are red, warm and oozing pus</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7">See <span class="Bold">"<a href="#Effects">What are the possible side effects of CELLCEPT?</a>"</span> for information about other serious side effects.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">What is CELLCEPT?</span> <ul class="Disc"> <li>CELLCEPT is a prescription medicine to prevent rejection (antirejection medicine) in people who have received a kidney, heart or liver transplant. Rejection is when the body's immune system perceives the new organ as a "foreign" threat and attacks it.</li> <li>CELLCEPT is used with other medicines containing cyclosporine and corticosteroids.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">Who should not take CELLCEPT?<br/>Do not take CELLCEPT if you have a history of allergic reactions to mycophenolate mofetil or any of the ingredients in CELLCEPT.</span> See the end of this Medication Guide for a complete list of ingredients in CELLCEPT.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">What should I tell my doctor before taking CELLCEPT?<br/>Tell your doctor about all of your medical conditions, including if you:</span> <ul class="Disc"> <li>have any digestive problems, such as ulcers.</li> <li>have Phenylketonuria (PKU). CELLCEPT oral suspension contains aspartame (a source of phenylalanine).</li> <li>have Lesch-Nyhan syndrome, Kelley-Seegmiller syndrome, or another rare inherited deficiency hypoxanthine-guanine phosphoribosyl-transferase (HGPRT). You should not take CELLCEPT if you have one of these disorders.</li> <li>plan to receive any vaccines. People taking CELLCEPT should not receive live vaccines. Some vaccines may not work as well during treatment with CELLCEPT.</li> <li>are pregnant or plan to become pregnant. See <span class="Bold">"<a href="#Important">What is the most important information I should know about CELLCEPT?</a>"</span> </li> <li>are breastfeeding or plan to breastfeed. It is not known if CELLCEPT passes into breast milk. You and your doctor will decide if you will take CELLCEPT or breastfeed. </li> </ul> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins and herbal supplements. Some medicines may affect the way CELLCEPT works, and CELLCEPT may affect how some medicines work. <br/>Especially tell your doctor if you take:<ul class="Disc"> <li>birth control pills (oral contraceptives). See <span class="Bold">"<a href="#Important">What is the most important information I should know about CELLCEPT?</a>"</span> </li> <li>sevelamer (Renagel<span class="Sup">®</span>, Renvela™). These products should be taken at least 2 hours after taking CELLCEPT.</li> <li>acyclovir (Zovirax<span class="Sup">®</span>), valacyclovir (Valtrex<span class="Sup">®</span>), ganciclovir (CYTOVENE<span class="Sup">®</span>-IV, Vitrasert<span class="Sup">®</span>), valganciclovir (VALCYTE<span class="Sup">®</span>).</li> <li>rifampin (Rifater<span class="Sup">®</span>, Rifamate<span class="Sup">®</span>, Rimactane<span class="Sup">®</span>, Rifadin<span class="Sup">®</span>).</li> <li>antacids that contain magnesium and aluminum (CELLCEPT and the antacid should not be taken at the same time).</li> <li>proton pump inhibitors (PPIs) (Prevacid<span class="Sup">®</span>, Protonix<span class="Sup">®</span>).</li> <li>sulfamethoxazole/trimethoprim (BACTRIM™, BACTRIM DS™).</li> <li>norfloxacin (Noroxin<span class="Sup">®</span>) and metronidazole (Flagyl<span class="Sup">®</span>, Flagyl<span class="Sup">®</span> ER, Flagyl<span class="Sup">®</span> IV, Metro IV, Helidac<span class="Sup">®</span>, Pylera™).</li> <li>ciprofloxacin (Cipro<span class="Sup">®</span>, Cipro<span class="Sup">®</span> XR, Ciloxan<span class="Sup">®</span>, Proquin<span class="Sup">®</span> XR) and amoxicillin plus clavulanic acid (Augmentin<span class="Sup">®</span>, Augmentin XR™).</li> <li>azathioprine (Azasan<span class="Sup">®</span>, Imuran<span class="Sup">®</span>).</li> <li>cholestyramine (Questran Light<span class="Sup">®</span>, Questran<span class="Sup">®</span>, Locholest Light, Locholest, Prevalite<span class="Sup">®</span>).</li> </ul>Know the medicines you take. Keep a list of them to show to your doctor or nurse and pharmacist when you get a new medicine. <span class="Bold">Do not</span> take any new medicine without talking with your doctor.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">How should I take CELLCEPT?</span> <ul class="Disc"> <li>Take CELLCEPT exactly as prescribed.</li> <li> <span class="Bold">Do not</span> stop taking CELLCEPT or change the dose unless your doctor tells you to.</li> <li>If you miss a dose of CELLCEPT, or you are not sure when you took your last dose, take your prescribed dose of CELLCEPT as soon as you remember. If your next dose is less than 2 hours away, skip the missed dose and take your next dose at your normal scheduled time. <span class="Bold">Do not</span> take 2 doses at the same time. Call your doctor if you are not sure what to do.</li> <li>Take CELLCEPT capsules, tablets and oral suspension on an empty stomach, unless your doctor tells you otherwise. <span class="Bold">Do not</span> crush CELLCEPT tablets.</li> <li> <span class="Bold">Do not</span> open or crush CELLCEPT capsules.</li> <li>If you are not able to swallow CELLCEPT tablets or capsules, your doctor may prescribe CELLCEPT Oral Suspension. This is a liquid form of CELLCEPT. Your pharmacist will mix the medicine before you pick it up from a pharmacy.</li> <li> <span class="Bold">Do not</span> mix CELLCEPT Oral Suspension with any other medicine. CELLCEPT Oral Suspension should not be mixed with any type of liquids before taking the dose. See the <a href="#IFU">Instructions for Use</a> at the end of this Medication Guide for detailed instructions about how to take CELLCEPT Oral Suspension the right way.</li> <li> <span class="Bold">Do not</span> breathe in (inhale) or let CELLCEPT powder or oral suspension come in contact with your skin or mucous membranes.<ul class="Circle"> <li>If you accidentally get the powder or oral suspension on the skin, wash the area well with soap and water.</li> <li>If you accidentally get the powder or oral suspension in your eyes or other mucous membranes, flush with plain water.</li> </ul> </li> <li>If you take too much CELLCEPT, call your doctor or the poison control center right away.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">What should I avoid while taking CELLCEPT?</span> <ul class="Disc"> <li>Avoid becoming pregnant. (See <span class="Bold">"<a href="#Important">What is the most important information I should know about CELLCEPT?</a>").</span> </li> <li>Limit the amount of time you spend in sunlight. Avoid using tanning beds or sunlamps. People who take CELLCEPT have a higher risk of getting skin cancer (See <span class="Bold">"<a href="#Important">What is the most important information I should know about CELLCEPT?</a>"</span>). Wear protective clothing when you are in the sun and use a broad-spectrum sunscreen with a high protection factor. This is especially important if your skin is very fair or if you have a family history of skin cancer.</li> <li>You should not donate blood while taking CELLCEPT and for at least 6 weeks after stopping CELLCEPT.</li> <li>You should not donate sperm while taking CELLCEPT and for 90 days after stopping CELLCEPT.</li> <li>CELLCEPT may influence your ability to drive and use machines (See "<span class="Bold"><a href="#Effects">What are the possible side effects of CELLCEPT?</a></span>". If you experience drowsiness, confusion, dizziness, tremor, or low blood pressure during treatment with CELLCEPT, you should be cautious about driving or using heavy machines.</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold"><a name="Effects"></a>What are the possible side effects of CELLCEPT?<br/>CELLCEPT may cause serious side effects, including:</span> <ul class="Disc"> <li>See <span class="Bold">"<a href="#Important">What is the most important information I should know about CELLCEPT?</a>"</span> </li> <li> <span class="Bold">Low blood cell counts.</span> People taking high doses of CELLCEPT each day may have a decrease in blood counts, including:<ul class="Circle"> <li> <span class="Bold">white blood cells, especially neutrophils.</span> Neutrophils fight against bacterial infections. You have a higher chance of getting an infection when your white blood cell count is low. This is most common from 1 month to 6 months after your transplant.</li> <li> <span class="Bold">red blood cells.</span> Red blood cells carry oxygen to your body tissues. You have a higher chance of getting severe anemia when your red blood cell count is low.</li> <li> <span class="Bold">platelets</span>. Platelets help with blood clotting.</li> </ul>Your doctor will do blood tests before you start taking CELLCEPT and during treatment with CELLCEPT to check your blood cell counts. Tell your doctor right away if you have any signs of infection (See <span class="Bold">"<a href="#Important">What is the most important information I should know about CELLCEPT?</a>"</span>), including any unexpected bruising or bleeding. Also, tell your doctor if you have unusual tiredness, lack of energy, dizziness or fainting.</li> <li> <span class="Bold">Stomach problems.</span> Stomach problems including intestinal bleeding, a tear in your intestinal wall (perforation) or stomach ulcers can happen in people who take CELLCEPT. Bleeding can be severe and you may have to be hospitalized for treatment. Call your doctor right away if you have sudden or severe stomach-area pain or stomach-area pain that does not go away, or if you have diarrhea.</li> <li> <span class="Bold">Inflammatory reactions.</span> Some people taking CELLCEPT may have an inflammatory reaction with fever, joint stiffness, joint pain, and muscle pain. Some of these reactions may require hospitalization. This reaction could happen within weeks to months after your treatment with CELLCEPT starts or if your dose is increased. Call your doctor right away if you experience these symptoms.</li> <li> <span class="Bold">Allergic (hypersensitivity) reactions.</span> Allergic reactions, including a severe allergic reaction called anaphylaxis, can happen after taking CELLCEPT. Stop taking CELLCEPT and get emergency medical help right away if you have any of the following symptoms of an allergic reaction:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>swelling of the face, lips, tongue, or throat</li> <li>rash, hives, or itching</li> <li>fainting, dizziness, feeling lightheaded</li> </ul> </td><td align="left" class="Rrule" colspan="4"> <ul class="Disc"> <li>trouble breathing or swallowing</li> <li>fast heartbeat</li> <li>chest pain</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">The most common side effects of CELLCEPT include:</span></td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>diarrhea</li> <li>blood problems including low white and red blood cell counts</li> <li>infections</li> <li>blood pressure problems</li> <li>fast heartbeat</li> <li>swelling of the lower legs, ankles and feet</li> </ul> </td><td align="left" class="Rrule" colspan="4"> <ul class="Disc"> <li>changes in laboratory blood levels, including high levels of blood sugar (hyperglycemia)</li> <li>stomach problems including diarrhea, constipation, nausea and vomiting</li> <li>rash</li> <li>nervous system problems such as headache, dizziness and tremor</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">Side effects that can happen more often in children than in adults taking CELLCEPT include</span>:</td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>stomach area pain</li> <li>fever</li> <li>infection</li> <li>pain</li> <li>blood infection (sepsis)</li> <li>diarrhea</li> </ul> </td><td align="left" class="Rrule" colspan="4"> <ul class="Disc"> <li>vomiting</li> <li>sore throat</li> <li>colds (respiratory tract infections)</li> <li>high blood pressure</li> <li>low white blood cell count</li> <li>low red blood cell count</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7">These are not all of the possible side effects of CELLCEPT. Tell your doctor about any side effect that bothers you or that does not go away.<br/> <span class="Bold">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088</span>.<br/>You may also report side effects to Genentech at 1-888-835-2555.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">How should I store CELLCEPT?</span> <ul class="Disc"> <li>Store CELLCEPT capsules and tablets at room temperature between 59°F to 86°F (15°C to 30°C).</li> <li>Keep CELLCEPT tablets in the light resistant container that it comes in.</li> <li>Store CELLCEPT Oral Suspension at room temperature between 59°F to 86°F (15°C to 30°C), for up to 60 days. You can also store CELLCEPT Oral Suspension in the refrigerator between 36°F to 46°F (2°C to 8°C). <span class="Bold">Do not</span> freeze<span class="Bold">.</span> </li> </ul> <span class="Bold">Keep CELLCEPT and all medicines out of the reach of children.</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">General information about the safe and effective use of CELLCEPT.</span> <br/>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use CELLCEPT for a condition for which it was not prescribed. Do not give CELLCEPT to other people, even if they have the same symptoms that you have. It may harm them.<br/>This Medication Guide summarizes the most important information about CELLCEPT. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist about CELLCEPT that is written for health professionals. </td> </tr> <tr> <td align="left"></td><td align="left"></td><td align="left"></td><td align="left"></td><td align="left"></td><td align="left"></td><td align="left"></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">What are the ingredients in CELLCEPT?<br/>Active ingredient:</span> mycophenolate mofetil<br/> <span class="Bold">Inactive ingredients: <br/>CELLCEPT 250 mg capsules:</span> croscarmellose sodium, magnesium stearate, povidone (K-90) and pregelatinized starch. The capsule shells contain black iron oxide, FD&amp;C blue #2, gelatin, red iron oxide, silicon dioxide, sodium lauryl sulfate, titanium dioxide, and yellow iron oxide.<br/> <span class="Bold">CELLCEPT 500 mg tablets:</span> croscarmellose sodium, FD&amp;C blue #2 aluminum lake, hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol 400, povidone (K-90), red iron oxide, and titanium dioxide.<br/> <span class="Bold">CELLCEPT Oral Suspension:</span> aspartame, citric acid anhydrous, colloidal silicon dioxide, methylparaben, mixed fruit flavor, sodium citrate dihydrate, sorbitol, soybean lecithin, and xanthan gum.<br/> <span class="Bold">CELLCEPT Intravenous:</span> polysorbate 80, and citric acid. Sodium hydroxide and hydrochloric acid may have been used in the manufacture of CELLCEPT Intravenous to adjust the pH. <br/>Distributed by:<br/> Genentech USA, Inc.<br/>A Member of the Roche Group<br/>1 DNA Way<br/>South San Francisco, CA 94080-4990<br/>CELLCEPT and VALCYTE are registered trademarks of Hoffmann-La Roche Inc. <br/>© 2025 Genentech, Inc. All rights reserved.<br/>For more information, call 1-888-835-2555 or visit www.gene.com/gene/products/information/CELLCEPT. </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"3%\"/>\n<col align=\"left\" valign=\"top\" width=\"30%\"/>\n<col align=\"left\" valign=\"top\" width=\"17%\"/>\n<col align=\"left\" valign=\"top\" width=\"17%\"/>\n<col align=\"left\" valign=\"top\" width=\"3%\"/>\n<col align=\"left\" valign=\"top\" width=\"10%\"/>\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"6\">This Medication Guide has been approved by the U.S. Food and Drug Administration.</td><td align=\"right\" colspan=\"1\">Revised: May 2025</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"7\"><span class=\"Bold\">MEDICATION GUIDE</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule\" colspan=\"2\"><span class=\"Bold\">CELLCEPT<span class=\"Sup\">®</span> [SEL-sept]<br/>(mycophenolate mofetil capsules)<br/>(mycophenolate mofetil tablets)</span></td><td align=\"center\" colspan=\"2\"><span class=\"Bold\">CELLCEPT<span class=\"Sup\">®</span> [SEL-sept]<br/>(mycophenolate mofetil for oral suspension)</span></td><td align=\"center\" class=\"Rrule\" colspan=\"3\"><span class=\"Bold\">CELLCEPT<span class=\"Sup\">®</span> [SEL-sept]<br/>(mycophenolate mofetil for injection)</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\">Read the Medication Guide that comes with CELLCEPT before you start taking it and each time you refill your prescription. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\"><span class=\"Bold\"><a name=\"Important\"></a>What is the most important information I should know about CELLCEPT?<br/>CELLCEPT can cause serious side effects, including:<br/>Increased risk of loss of a pregnancy (miscarriage) and higher risk of birth defects.</span> Females who take CELLCEPT during pregnancy have a higher risk of miscarriage during the first 3 months (first trimester), and a higher risk that their baby will be born with birth defects. <ul class=\"Disc\">\n<li>\n<span class=\"Bold\">If you are a female who can become pregnant</span>, your doctor must talk with you about acceptable birth control methods (contraceptive counseling) to use while taking CELLCEPT. You should have 1 pregnancy test immediately before starting CELLCEPT and another pregnancy test 8 to 10 days later. Pregnancy tests should be repeated during routine follow-up visits with your doctor. Talk to your doctor about the results of all of your pregnancy tests.<br/>You must use acceptable birth control during your entire CELLCEPT treatment and for 6 weeks after stopping CELLCEPT, unless at any time you choose to avoid sexual intercourse (abstinence) with a man completely. CELLCEPT decreases blood levels of the hormones in birth control pills that you take by mouth. Birth control pills may not work as well while you take CELLCEPT, and you could become pregnant. If you take birth control pills while using CELLCEPT you must also use another form of birth control. Talk to your doctor about other birth control methods that you can use while taking CELLCEPT.</li>\n<li>\n<span class=\"Bold\">If you are a sexually active male whose female partner can become pregnant while you are taking CELLCEPT</span>, use effective contraception during treatment and for at least 90 days after stopping CELLCEPT.</li>\n<li>\n<span class=\"Bold\">If you plan to become pregnant</span>, talk with your doctor. Your doctor will decide if other medicines to prevent rejection may be right for you.</li>\n<li>\n<span class=\"Bold\">If you become pregnant while taking CELLCEPT</span>, <span class=\"Bold\">do not stop taking CELLCEPT. Call your doctor right away.</span> You and your doctor may decide that other medicines to prevent rejection may be right for you. You and your doctor should report your pregnancy to the Mycophenolate Pregnancy Registry either:<ul class=\"Circle\">\n<li>By phone at 1-800-617-8191 <span class=\"Bold\">or</span>\n</li>\n<li>By visiting the REMS website at: <span class=\"Bold\">www.mycophenolateREMS.com</span>\n</li>\n</ul>The purpose of this registry is to gather information about the health of you and your baby.</li>\n</ul>\n<span class=\"Bold\">Increased risk of getting certain cancers.</span> People who take CELLCEPT have a higher risk of getting lymphoma, and other cancers, especially skin cancer. Tell your doctor if you have:</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>unexplained fever, prolonged tiredness, weight loss or lymph node swelling</li>\n<li>a brown or black skin lesion with uneven borders, or one part of the lesion does not look like the other</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>a change in the size and color of a mole</li>\n<li>a new skin lesion or bump</li>\n<li>any other changes to your health</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\"><span class=\"Bold\">Increased risk of getting serious infections.</span> CELLCEPT weakens the body's immune system and affects your ability to fight infections. Serious infections can happen with CELLCEPT and can lead to hospitalizations and death. These serious infections can include:<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Viral infections.</span> Certain viruses can live in your body and cause active infections when your immune system is weak. Viral infections that can happen with CELLCEPT include:<ul class=\"Circle\">\n<li>Shingles, other herpes infections, and cytomegalovirus (CMV). CMV can cause serious tissue and blood infections.</li>\n<li>BK virus. BK virus can affect how your kidney works and cause your transplanted kidney to fail.</li>\n<li>Hepatitis B and C viruses. Hepatitis viruses can affect how your liver works. Talk to your doctor about how hepatitis viruses may affect you.</li>\n<li>COVID-19</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">A brain infection called Progressive Multifocal Leukoencephalopathy (PML).</span> In some patients, CELLCEPT may cause an infection of the brain that may cause death. You are at risk for this brain infection because you have a weakened immune system. Call your doctor right away if you have any of the following symptoms:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>weakness on one side of the body</li>\n<li>you do not care about things you usually care about (apathy)</li>\n</ul>\n</td><td align=\"left\"></td><td align=\"left\" class=\"Rrule\" colspan=\"3\">\n<ul class=\"Circle\">\n<li>you are confused or have problems thinking</li>\n<li>you cannot control your muscles</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Fungal infections.</span> Yeasts and other types of fungal infections can happen with CELLCEPT and can cause serious tissue and blood infections (See <span class=\"Bold\">\"<a href=\"#Effects\">What are the possible side effects of CELLCEPT?</a>\"</span>).</li>\n</ul>\n<span class=\"Bold\">Call your doctor right away if you have any of the following signs and symptoms of infection:</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>temperature of 100.5°F or greater</li>\n<li>cold symptoms, such as a runny nose or sore throat</li>\n<li>flu symptoms, such as an upset stomach, stomach pain, vomiting or diarrhea</li>\n<li>earache or headache</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>pain during urination</li>\n<li>white patches in the mouth or throat</li>\n<li>unexpected bruising or bleeding</li>\n<li>cuts, scrapes or incisions that are red, warm and oozing pus</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\">See <span class=\"Bold\">\"<a href=\"#Effects\">What are the possible side effects of CELLCEPT?</a>\"</span> for information about other serious side effects.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\"><span class=\"Bold\">What is CELLCEPT?</span>\n<ul class=\"Disc\">\n<li>CELLCEPT is a prescription medicine to prevent rejection (antirejection medicine) in people who have received a kidney, heart or liver transplant. Rejection is when the body's immune system perceives the new organ as a \"foreign\" threat and attacks it.</li>\n<li>CELLCEPT is used with other medicines containing cyclosporine and corticosteroids.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\"><span class=\"Bold\">Who should not take CELLCEPT?<br/>Do not take CELLCEPT if you have a history of allergic reactions to mycophenolate mofetil or any of the ingredients in CELLCEPT.</span> See the end of this Medication Guide for a complete list of ingredients in CELLCEPT.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\"><span class=\"Bold\">What should I tell my doctor before taking CELLCEPT?<br/>Tell your doctor about all of your medical conditions, including if you:</span>\n<ul class=\"Disc\">\n<li>have any digestive problems, such as ulcers.</li>\n<li>have Phenylketonuria (PKU). CELLCEPT oral suspension contains aspartame (a source of phenylalanine).</li>\n<li>have Lesch-Nyhan syndrome, Kelley-Seegmiller syndrome, or another rare inherited deficiency hypoxanthine-guanine phosphoribosyl-transferase (HGPRT). You should not take CELLCEPT if you have one of these disorders.</li>\n<li>plan to receive any vaccines. People taking CELLCEPT should not receive live vaccines. Some vaccines may not work as well during treatment with CELLCEPT.</li>\n<li>are pregnant or plan to become pregnant. See <span class=\"Bold\">\"<a href=\"#Important\">What is the most important information I should know about CELLCEPT?</a>\"</span>\n</li>\n<li>are breastfeeding or plan to breastfeed. It is not known if CELLCEPT passes into breast milk. You and your doctor will decide if you will take CELLCEPT or breastfeed. </li>\n</ul>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins and herbal supplements. Some medicines may affect the way CELLCEPT works, and CELLCEPT may affect how some medicines work. <br/>Especially tell your doctor if you take:<ul class=\"Disc\">\n<li>birth control pills (oral contraceptives). See <span class=\"Bold\">\"<a href=\"#Important\">What is the most important information I should know about CELLCEPT?</a>\"</span>\n</li>\n<li>sevelamer (Renagel<span class=\"Sup\">®</span>, Renvela™). These products should be taken at least 2 hours after taking CELLCEPT.</li>\n<li>acyclovir (Zovirax<span class=\"Sup\">®</span>), valacyclovir (Valtrex<span class=\"Sup\">®</span>), ganciclovir (CYTOVENE<span class=\"Sup\">®</span>-IV, Vitrasert<span class=\"Sup\">®</span>), valganciclovir (VALCYTE<span class=\"Sup\">®</span>).</li>\n<li>rifampin (Rifater<span class=\"Sup\">®</span>, Rifamate<span class=\"Sup\">®</span>, Rimactane<span class=\"Sup\">®</span>, Rifadin<span class=\"Sup\">®</span>).</li>\n<li>antacids that contain magnesium and aluminum (CELLCEPT and the antacid should not be taken at the same time).</li>\n<li>proton pump inhibitors (PPIs) (Prevacid<span class=\"Sup\">®</span>, Protonix<span class=\"Sup\">®</span>).</li>\n<li>sulfamethoxazole/trimethoprim (BACTRIM™, BACTRIM DS™).</li>\n<li>norfloxacin (Noroxin<span class=\"Sup\">®</span>) and metronidazole (Flagyl<span class=\"Sup\">®</span>, Flagyl<span class=\"Sup\">®</span> ER, Flagyl<span class=\"Sup\">®</span> IV, Metro IV, Helidac<span class=\"Sup\">®</span>, Pylera™).</li>\n<li>ciprofloxacin (Cipro<span class=\"Sup\">®</span>, Cipro<span class=\"Sup\">®</span> XR, Ciloxan<span class=\"Sup\">®</span>, Proquin<span class=\"Sup\">®</span> XR) and amoxicillin plus clavulanic acid (Augmentin<span class=\"Sup\">®</span>, Augmentin XR™).</li>\n<li>azathioprine (Azasan<span class=\"Sup\">®</span>, Imuran<span class=\"Sup\">®</span>).</li>\n<li>cholestyramine (Questran Light<span class=\"Sup\">®</span>, Questran<span class=\"Sup\">®</span>, Locholest Light, Locholest, Prevalite<span class=\"Sup\">®</span>).</li>\n</ul>Know the medicines you take. Keep a list of them to show to your doctor or nurse and pharmacist when you get a new medicine. <span class=\"Bold\">Do not</span> take any new medicine without talking with your doctor.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\"><span class=\"Bold\">How should I take CELLCEPT?</span>\n<ul class=\"Disc\">\n<li>Take CELLCEPT exactly as prescribed.</li>\n<li>\n<span class=\"Bold\">Do not</span> stop taking CELLCEPT or change the dose unless your doctor tells you to.</li>\n<li>If you miss a dose of CELLCEPT, or you are not sure when you took your last dose, take your prescribed dose of CELLCEPT as soon as you remember. If your next dose is less than 2 hours away, skip the missed dose and take your next dose at your normal scheduled time. <span class=\"Bold\">Do not</span> take 2 doses at the same time. Call your doctor if you are not sure what to do.</li>\n<li>Take CELLCEPT capsules, tablets and oral suspension on an empty stomach, unless your doctor tells you otherwise. <span class=\"Bold\">Do not</span> crush CELLCEPT tablets.</li>\n<li>\n<span class=\"Bold\">Do not</span> open or crush CELLCEPT capsules.</li>\n<li>If you are not able to swallow CELLCEPT tablets or capsules, your doctor may prescribe CELLCEPT Oral Suspension. This is a liquid form of CELLCEPT. Your pharmacist will mix the medicine before you pick it up from a pharmacy.</li>\n<li>\n<span class=\"Bold\">Do not</span> mix CELLCEPT Oral Suspension with any other medicine. CELLCEPT Oral Suspension should not be mixed with any type of liquids before taking the dose. See the <a href=\"#IFU\">Instructions for Use</a> at the end of this Medication Guide for detailed instructions about how to take CELLCEPT Oral Suspension the right way.</li>\n<li>\n<span class=\"Bold\">Do not</span> breathe in (inhale) or let CELLCEPT powder or oral suspension come in contact with your skin or mucous membranes.<ul class=\"Circle\">\n<li>If you accidentally get the powder or oral suspension on the skin, wash the area well with soap and water.</li>\n<li>If you accidentally get the powder or oral suspension in your eyes or other mucous membranes, flush with plain water.</li>\n</ul>\n</li>\n<li>If you take too much CELLCEPT, call your doctor or the poison control center right away.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\"><span class=\"Bold\">What should I avoid while taking CELLCEPT?</span>\n<ul class=\"Disc\">\n<li>Avoid becoming pregnant. (See <span class=\"Bold\">\"<a href=\"#Important\">What is the most important information I should know about CELLCEPT?</a>\").</span>\n</li>\n<li>Limit the amount of time you spend in sunlight. Avoid using tanning beds or sunlamps. People who take CELLCEPT have a higher risk of getting skin cancer (See <span class=\"Bold\">\"<a href=\"#Important\">What is the most important information I should know about CELLCEPT?</a>\"</span>). Wear protective clothing when you are in the sun and use a broad-spectrum sunscreen with a high protection factor. This is especially important if your skin is very fair or if you have a family history of skin cancer.</li>\n<li>You should not donate blood while taking CELLCEPT and for at least 6 weeks after stopping CELLCEPT.</li>\n<li>You should not donate sperm while taking CELLCEPT and for 90 days after stopping CELLCEPT.</li>\n<li>CELLCEPT may influence your ability to drive and use machines (See \"<span class=\"Bold\"><a href=\"#Effects\">What are the possible side effects of CELLCEPT?</a></span>\". If you experience drowsiness, confusion, dizziness, tremor, or low blood pressure during treatment with CELLCEPT, you should be cautious about driving or using heavy machines.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\"><span class=\"Bold\"><a name=\"Effects\"></a>What are the possible side effects of CELLCEPT?<br/>CELLCEPT may cause serious side effects, including:</span>\n<ul class=\"Disc\">\n<li>See <span class=\"Bold\">\"<a href=\"#Important\">What is the most important information I should know about CELLCEPT?</a>\"</span>\n</li>\n<li>\n<span class=\"Bold\">Low blood cell counts.</span> People taking high doses of CELLCEPT each day may have a decrease in blood counts, including:<ul class=\"Circle\">\n<li>\n<span class=\"Bold\">white blood cells, especially neutrophils.</span> Neutrophils fight against bacterial infections. You have a higher chance of getting an infection when your white blood cell count is low. This is most common from 1 month to 6 months after your transplant.</li>\n<li>\n<span class=\"Bold\">red blood cells.</span> Red blood cells carry oxygen to your body tissues. You have a higher chance of getting severe anemia when your red blood cell count is low.</li>\n<li>\n<span class=\"Bold\">platelets</span>. Platelets help with blood clotting.</li>\n</ul>Your doctor will do blood tests before you start taking CELLCEPT and during treatment with CELLCEPT to check your blood cell counts. Tell your doctor right away if you have any signs of infection (See <span class=\"Bold\">\"<a href=\"#Important\">What is the most important information I should know about CELLCEPT?</a>\"</span>), including any unexpected bruising or bleeding. Also, tell your doctor if you have unusual tiredness, lack of energy, dizziness or fainting.</li>\n<li>\n<span class=\"Bold\">Stomach problems.</span> Stomach problems including intestinal bleeding, a tear in your intestinal wall (perforation) or stomach ulcers can happen in people who take CELLCEPT. Bleeding can be severe and you may have to be hospitalized for treatment. Call your doctor right away if you have sudden or severe stomach-area pain or stomach-area pain that does not go away, or if you have diarrhea.</li>\n<li>\n<span class=\"Bold\">Inflammatory reactions.</span> Some people taking CELLCEPT may have an inflammatory reaction with fever, joint stiffness, joint pain, and muscle pain. Some of these reactions may require hospitalization. This reaction could happen within weeks to months after your treatment with CELLCEPT starts or if your dose is increased. Call your doctor right away if you experience these symptoms.</li>\n<li>\n<span class=\"Bold\">Allergic (hypersensitivity) reactions.</span> Allergic reactions, including a severe allergic reaction called anaphylaxis, can happen after taking CELLCEPT. Stop taking CELLCEPT and get emergency medical help right away if you have any of the following symptoms of an allergic reaction:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>swelling of the face, lips, tongue, or throat</li>\n<li>rash, hives, or itching</li>\n<li>fainting, dizziness, feeling lightheaded</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>trouble breathing or swallowing</li>\n<li>fast heartbeat</li>\n<li>chest pain</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\"><span class=\"Bold\">The most common side effects of CELLCEPT include:</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>diarrhea</li>\n<li>blood problems including low white and red blood cell counts</li>\n<li>infections</li>\n<li>blood pressure problems</li>\n<li>fast heartbeat</li>\n<li>swelling of the lower legs, ankles and feet</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>changes in laboratory blood levels, including high levels of blood sugar (hyperglycemia)</li>\n<li>stomach problems including diarrhea, constipation, nausea and vomiting</li>\n<li>rash</li>\n<li>nervous system problems such as headache, dizziness and tremor</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\"><span class=\"Bold\">Side effects that can happen more often in children than in adults taking CELLCEPT include</span>:</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>stomach area pain</li>\n<li>fever</li>\n<li>infection</li>\n<li>pain</li>\n<li>blood infection (sepsis)</li>\n<li>diarrhea</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>vomiting</li>\n<li>sore throat</li>\n<li>colds (respiratory tract infections)</li>\n<li>high blood pressure</li>\n<li>low white blood cell count</li>\n<li>low red blood cell count</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\">These are not all of the possible side effects of CELLCEPT. Tell your doctor about any side effect that bothers you or that does not go away.<br/>\n<span class=\"Bold\">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088</span>.<br/>You may also report side effects to Genentech at 1-888-835-2555.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\"><span class=\"Bold\">How should I store CELLCEPT?</span>\n<ul class=\"Disc\">\n<li>Store CELLCEPT capsules and tablets at room temperature between 59°F to 86°F (15°C to 30°C).</li>\n<li>Keep CELLCEPT tablets in the light resistant container that it comes in.</li>\n<li>Store CELLCEPT Oral Suspension at room temperature between 59°F to 86°F (15°C to 30°C), for up to 60 days. You can also store CELLCEPT Oral Suspension in the refrigerator between 36°F to 46°F (2°C to 8°C). <span class=\"Bold\">Do not</span> freeze<span class=\"Bold\">.</span>\n</li>\n</ul>\n<span class=\"Bold\">Keep CELLCEPT and all medicines out of the reach of children.</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\"><span class=\"Bold\">General information about the safe and effective use of CELLCEPT.</span>\n<br/>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use CELLCEPT for a condition for which it was not prescribed. Do not give CELLCEPT to other people, even if they have the same symptoms that you have. It may harm them.<br/>This Medication Guide summarizes the most important information about CELLCEPT. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist about CELLCEPT that is written for health professionals. </td>\n</tr>\n<tr>\n<td align=\"left\"></td><td align=\"left\"></td><td align=\"left\"></td><td align=\"left\"></td><td align=\"left\"></td><td align=\"left\"></td><td align=\"left\"></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"7\"><span class=\"Bold\">What are the ingredients in CELLCEPT?<br/>Active ingredient:</span> mycophenolate mofetil<br/>\n<span class=\"Bold\">Inactive ingredients: <br/>CELLCEPT 250 mg capsules:</span> croscarmellose sodium, magnesium stearate, povidone (K-90) and pregelatinized starch. The capsule shells contain black iron oxide, FD&amp;C blue #2, gelatin, red iron oxide, silicon dioxide, sodium lauryl sulfate, titanium dioxide, and yellow iron oxide.<br/>\n<span class=\"Bold\">CELLCEPT 500 mg tablets:</span> croscarmellose sodium, FD&amp;C blue #2 aluminum lake, hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol 400, povidone (K-90), red iron oxide, and titanium dioxide.<br/>\n<span class=\"Bold\">CELLCEPT Oral Suspension:</span> aspartame, citric acid anhydrous, colloidal silicon dioxide, methylparaben, mixed fruit flavor, sodium citrate dihydrate, sorbitol, soybean lecithin, and xanthan gum.<br/>\n<span class=\"Bold\">CELLCEPT Intravenous:</span> polysorbate 80, and citric acid. Sodium hydroxide and hydrochloric acid may have been used in the manufacture of CELLCEPT Intravenous to adjust the pH. <br/>Distributed by:<br/>\t\t\t\t\t\t\t\t\t\tGenentech USA, Inc.<br/>A Member of the Roche Group<br/>1 DNA Way<br/>South San Francisco, CA 94080-4990<br/>CELLCEPT and VALCYTE are registered trademarks of Hoffmann-La Roche Inc. <br/>© 2025 Genentech, Inc. All rights reserved.<br/>For more information, call 1-888-835-2555 or visit www.gene.com/gene/products/information/CELLCEPT. </td>\n</tr>\n</tbody>\n</table></div>" }

Read this Instructions for Use before you take or give CELLCEPT for the first time and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

{ "type": "p", "children": [], "text": "Read this Instructions for Use before you take or give CELLCEPT for the first time and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment." }

Important:

{ "type": "p", "children": [], "text": "\nImportant: \n" }

{ "type": "ul", "children": [ "Always use the oral dispenser provided with CELLCEPT Oral Suspension to make sure you measure the right amount of medicine. If your CELLCEPT Oral Suspension does not come with the oral dispenser, contact your pharmacist. ", "Call your pharmacist if your oral dispenser is lost or damaged.", "Your pharmacist will write the expiration date on your CELLCEPT Oral Suspension bottle label. Do not use CELLCEPT after the expiration date.", "Ask your doctor or pharmacist if you have any questions or are unsure about how to take or give the right amount of medicine. ", "The CELLCEPT Oral Suspension should not be mixed with any type of liquids before taking or giving the dose.", "\nDo not let the CELLCEPT Oral Suspension come in contact with the skin. If this happens, wash the skin well with soap and water. If the CELLCEPT Oral Suspension gets in the eyes, rinse the eyes with plain water.", "If you spill any CELLCEPT Oral Suspension, wipe it up using paper towels wet with water. Put the child-resistant bottle cap back on the bottle and wipe the outside of the bottle with wet paper towels." ], "text": "" }

Supplies needed to take or give a dose of CELLCEPT Oral Suspension:

{ "type": "p", "children": [], "text": "\nSupplies needed to take or give a dose of CELLCEPT Oral Suspension:" }

To take or give a dose of CELLCEPT Oral Suspension, you will need the bottle of medicine and the oral dispenser provided with the medicine (See Figure 1). Your pharmacist will insert the bottle adapter in the CELLCEPT Oral Suspension bottle. Do not remove the bottle adapter from the bottle.

{ "type": "p", "children": [], "text": "To take or give a dose of CELLCEPT Oral Suspension, you will need the bottle of medicine and the oral dispenser provided with the medicine (See Figure 1). Your pharmacist will insert the bottle adapter in the CELLCEPT Oral Suspension bottle. Do not remove the bottle adapter from the bottle." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="center" valign="top" width="100%"/> <tbody class="Headless"> <tr> <td align="center"><a name="Fig1"></a><img alt="Figure 1" src="/dailymed/image.cfm?name=cellcept-02.jpg&amp;setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40"/></td> </tr> <tr> <td align="center"><span class="Bold">Figure 1</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"center\" valign=\"top\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\"><a name=\"Fig1\"></a><img alt=\"Figure 1\" src=\"/dailymed/image.cfm?name=cellcept-02.jpg&amp;setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40\"/></td>\n</tr>\n<tr>\n<td align=\"center\"><span class=\"Bold\">Figure 1</span></td>\n</tr>\n</tbody>\n</table></div>" }

Taking or giving a dose of CELLCEPT Oral Suspension:

{ "type": "p", "children": [], "text": "\nTaking or giving a dose of CELLCEPT Oral Suspension:\n" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="top" width="7%"/> <col align="left" valign="top" width="93%"/> <tbody class="Headless"> <tr> <td align="left"><span class="Bold">Step 1</span>:</td><td align="left">With the child-resistant cap on the bottle, shake the bottle well for about 5 seconds before each use.</td> </tr> <tr> <td align="left"><span class="Bold">Step 2</span>:</td><td align="left">Open the bottle by firmly pressing down on the child-resistant bottle cap and turning it to the left (counter-clockwise). <span class="Bold">Do not</span> throw away the child-resistant bottle cap.</td> </tr> <tr> <td align="left"><span class="Bold">Step 3</span>:</td><td align="left">Place the bottle on a flat surface. Before inserting the tip of the oral dispenser into the bottle adapter, push the plunger completely down toward the tip of the oral dispenser. Use 1 hand to hold the bottle upright. Insert the oral dispenser tip firmly into the opening of the bottle adapter.</td> </tr> <tr> <td align="left"><span class="Bold">Step 4</span>: </td><td align="left">Carefully turn the bottle upside down with the oral dispenser tip in place. Slowly pull the plunger down to withdraw your prescribed dose. <span class="Bold">Do not</span> pull the plunger out of the oral dispenser (See <span class="Bold"><a href="#Fig2">Figure 2</a></span>).<br/> <a name="Fig2"></a><img alt="Figure 1" src="/dailymed/image.cfm?name=cellcept-03.jpg&amp;setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40"/></td> </tr> <tr> <td align="left"><span class="Bold">Step 5</span>:</td><td align="left">Leave the oral dispenser tip in the bottle and turn the bottle to an upright position. Slowly remove the oral dispenser tip from the bottle.<br/>If there are air bubbles in the oral dispenser or if you have withdrawn the wrong dose, insert the oral dispenser tip back into the bottle adapter while the bottle is in an upright position. Push the plunger gently all the way up so the CELLCEPT Oral Suspension flows back into the bottle. Repeat <span class="Bold">Step 4</span>.</td> </tr> <tr> <td align="left"><span class="Bold">Step 6</span>:</td><td align="left">Place the tip of the oral dispenser in the mouth directed towards the cheek and slowly push the plunger down until the oral dispenser is empty.</td> </tr> <tr> <td align="left"><span class="Bold">Step 7</span>:</td><td align="left">Put the child-resistant bottle cap back on the bottle and turn the cap to the right (clockwise) to close the bottle. Keep the bottle tightly closed after each use.</td> </tr> <tr> <td align="left"><span class="Bold">Step 8</span>:</td><td align="left">Rinse the oral dispenser under running tap water after each use: <ul class="Disc"> <li>Remove the plunger from the oral dispenser.</li> <li>Rinse the oral dispenser and plunger with water only and let them air dry on a paper towel.</li> <li>When the oral dispenser and plunger are dry, put the plunger back in the oral dispenser for the next use. <span class="Bold">Do not</span> throw away the oral dispenser. Store the oral dispenser in a clean, dry place. </li> <li> <span class="Bold">Do not</span> boil the oral dispenser. <span class="Bold">Do not</span> use solvent-containing wipes to clean the oral dispenser. <span class="Bold">Do not</span> use cloths or wipes to dry the oral dispenser.</li> </ul> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"7%\"/>\n<col align=\"left\" valign=\"top\" width=\"93%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\"><span class=\"Bold\">Step 1</span>:</td><td align=\"left\">With the child-resistant cap on the bottle, shake the bottle well for about 5 seconds before each use.</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Step 2</span>:</td><td align=\"left\">Open the bottle by firmly pressing down on the child-resistant bottle cap and turning it to the left (counter-clockwise). <span class=\"Bold\">Do not</span> throw away the child-resistant bottle cap.</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Step 3</span>:</td><td align=\"left\">Place the bottle on a flat surface. Before inserting the tip of the oral dispenser into the bottle adapter, push the plunger completely down toward the tip of the oral dispenser. Use 1 hand to hold the bottle upright. Insert the oral dispenser tip firmly into the opening of the bottle adapter.</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Step 4</span>: </td><td align=\"left\">Carefully turn the bottle upside down with the oral dispenser tip in place. Slowly pull the plunger down to withdraw your prescribed dose. <span class=\"Bold\">Do not</span> pull the plunger out of the oral dispenser (See <span class=\"Bold\"><a href=\"#Fig2\">Figure 2</a></span>).<br/>\n<a name=\"Fig2\"></a><img alt=\"Figure 1\" src=\"/dailymed/image.cfm?name=cellcept-03.jpg&amp;setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40\"/></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Step 5</span>:</td><td align=\"left\">Leave the oral dispenser tip in the bottle and turn the bottle to an upright position. Slowly remove the oral dispenser tip from the bottle.<br/>If there are air bubbles in the oral dispenser or if you have withdrawn the wrong dose, insert the oral dispenser tip back into the bottle adapter while the bottle is in an upright position. Push the plunger gently all the way up so the CELLCEPT Oral Suspension flows back into the bottle. Repeat <span class=\"Bold\">Step 4</span>.</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Step 6</span>:</td><td align=\"left\">Place the tip of the oral dispenser in the mouth directed towards the cheek and slowly push the plunger down until the oral dispenser is empty.</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Step 7</span>:</td><td align=\"left\">Put the child-resistant bottle cap back on the bottle and turn the cap to the right (clockwise) to close the bottle. Keep the bottle tightly closed after each use.</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Step 8</span>:</td><td align=\"left\">Rinse the oral dispenser under running tap water after each use: \t\t\t\t\t\t\t\t\t<ul class=\"Disc\">\n<li>Remove the plunger from the oral dispenser.</li>\n<li>Rinse the oral dispenser and plunger with water only and let them air dry on a paper towel.</li>\n<li>When the oral dispenser and plunger are dry, put the plunger back in the oral dispenser for the next use. <span class=\"Bold\">Do not</span> throw away the oral dispenser. Store the oral dispenser in a clean, dry place. </li>\n<li>\n<span class=\"Bold\">Do not</span> boil the oral dispenser. <span class=\"Bold\">Do not</span> use solvent-containing wipes to clean the oral dispenser. <span class=\"Bold\">Do not</span> use cloths or wipes to dry the oral dispenser.</li>\n</ul>\n</td>\n</tr>\n</tbody>\n</table></div>" }

How should I store CELLCEPT Oral Suspension?

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{ "type": "ul", "children": [ "Store the CELLCEPT Oral Suspension at room temperature between 59°F to 86°F (15°C to 30°C), for up to 60 days. You can also store the CELLCEPT Oral Suspension in the refrigerator between 36°F to 46°F (2°C to 8°C). )", "\nDo not freeze." ], "text": "" }

Keep CELLCEPT Oral Suspension and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep CELLCEPT Oral Suspension and all medicines out of the reach of children.\n" }

Distributed by: Genentech USA, Inc. A Member of the Roche Group1 DNA WaySouth San Francisco, CA 94080-4990 ©2022 Genentech, Inc. All rights reserved.

{ "type": "p", "children": [], "text": "Distributed by:\nGenentech USA, Inc.\nA Member of the Roche Group1 DNA WaySouth San Francisco, CA 94080-4990\n©2022 Genentech, Inc. All rights reserved." }

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration." }

Revised: August 2022

{ "type": "p", "children": [], "text": "Revised: August 2022" }

Representative sample of labeling (see the HOW SUPPLIED section for complete listing):

{ "type": "p", "children": [], "text": "Representative sample of labeling (see the HOW SUPPLIED section for complete listing):" }

NDC 0004-0260-43

{ "type": "p", "children": [], "text": "NDC 0004-0260-43" }

CellCept® (mycophenolate mofetil tablets)

{ "type": "p", "children": [], "text": "CellCept®\n (mycophenolate mofetil tablets)" }

500 mg

{ "type": "p", "children": [], "text": "500 mg" }

Each tablet contains 500 mg mycophenolate mofetil.

{ "type": "p", "children": [], "text": "Each tablet contains 500 mg mycophenolate mofetil." }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

Attention Pharmacist: Dispense the accompanying Medication Guide to each patient. For additional Medication Guides call 1-800-617-8191 or visit www.gene.com/gene/ products/information/cellcept.

{ "type": "p", "children": [], "text": "Attention Pharmacist: Dispense the accompanying Medication Guide to each patient. For additional Medication Guides call 1-800-617-8191 or visit www.gene.com/gene/ products/information/cellcept." }

500 tablets

{ "type": "p", "children": [], "text": "500 tablets" }

Genentech

{ "type": "p", "children": [], "text": "Genentech" }

10235320

{ "type": "p", "children": [], "text": "10235320" }

NDC 0004-0259-43

{ "type": "p", "children": [], "text": "NDC 0004-0259-43" }

CellCept® (mycophenolate mofetil capsules)

{ "type": "p", "children": [], "text": "CellCept®\n (mycophenolate mofetil capsules)" }

250 mg

{ "type": "p", "children": [], "text": "250 mg" }

Each capsule contains 250 mg mycophenolate mofetil.

{ "type": "p", "children": [], "text": "Each capsule contains 250 mg mycophenolate mofetil." }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

Attention Pharmacist: Dispense the accompanying Medication Guide to each patient. For additional Medication Guides call 1-800-617-8191 or visit www.gene.com/gene/ products/information/cellcept.

{ "type": "p", "children": [], "text": "Attention Pharmacist: Dispense the accompanying Medication Guide to each patient. For additional Medication Guides call 1-800-617-8191 or visit www.gene.com/gene/ products/information/cellcept." }

500 capsules

{ "type": "p", "children": [], "text": "500 capsules" }

Genentech

{ "type": "p", "children": [], "text": "Genentech" }

10235316

{ "type": "p", "children": [], "text": "10235316" }

NDC 0004-0298-09

{ "type": "p", "children": [], "text": "NDC 0004-0298-09" }

CellCept® Intravenous (mycophenolate mofetil for injection)

{ "type": "p", "children": [], "text": "CellCept® Intravenous (mycophenolate mofetil for injection)" }

500 mg

{ "type": "p", "children": [], "text": "500 mg" }

FOR INTRAVENOUS INFUSION ONLY.

{ "type": "p", "children": [], "text": "FOR INTRAVENOUS INFUSION ONLY." }

Each single-dose vial contains the equivalent of 500 mg mycophenolate mofetil (equivalent to 542 mg of mycophenolate mofetil hydrochloride), 25 mg polysorbate 80 and 5 mg citric acid. Sodium hydroxide or hydrochloric acid may have been used to adjust pH.

{ "type": "p", "children": [], "text": "Each single-dose vial contains the equivalent of 500 mg mycophenolate mofetil (equivalent to 542 mg of mycophenolate mofetil hydrochloride), 25 mg polysorbate 80 and 5 mg citric acid. Sodium hydroxide or hydrochloric acid may have been used to adjust pH." }

Attention Pharmacist: Dispense the accompanying Medication Guide to each patient. For additional Medication Guides, call 1-800-617-8191 or visit www.gene.com/gene/products/information/cellcept.

{ "type": "p", "children": [], "text": "Attention Pharmacist: Dispense the accompanying Medication Guide to each patient. For additional Medication Guides, call 1-800-617-8191 or visit www.gene.com/gene/products/information/cellcept." }

Rx only 4 Single-Dose Vials

{ "type": "p", "children": [], "text": "Rx only 4 Single-Dose Vials" }

Genentech

{ "type": "p", "children": [], "text": "Genentech" }

10215811

{ "type": "p", "children": [], "text": "10215811" }

NDC 0004-0261-29

{ "type": "p", "children": [], "text": "NDC 0004-0261-29" }

CellCept® Oral Suspension (mycophenolate mofetil for oral suspension)

{ "type": "p", "children": [], "text": "\nCellCept®\nOral Suspension\n(mycophenolate mofetil for oral suspension)" }

200 mg/mL

{ "type": "p", "children": [], "text": "\n200 mg/mL\n" }

Each mL contains 200 mg mycophenolate mofetil after constitution.

{ "type": "p", "children": [], "text": "Each mL contains 200 mg mycophenolate mofetil after constitution." }

Attention Pharmacist: Dispense the accompanyingMedication Guide to each patient. For additionalMedication Guides, call 1-800-617-8191 or visitwww.gene.com/gene/products/information/cellcept.

{ "type": "p", "children": [], "text": "\nAttention Pharmacist: Dispense the accompanyingMedication Guide to each patient. For additionalMedication Guides, call 1-800-617-8191 or visitwww.gene.com/gene/products/information/cellcept.\n" }

Rx only

{ "type": "p", "children": [], "text": "\nRx only\n" }

Genentech

{ "type": "p", "children": [], "text": "\nGenentech\n" }

10225425

{ "type": "p", "children": [], "text": "10225425" }

Mycophenolate mofetil (MMF) is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney [see Clinical Studies (14.1)], heart [see Clinical Studies (14.2)] or liver transplants [see Clinical Studies (14.3)], in combination with other immunosuppressants.

{ "type": "p", "children": [], "text": "\nMycophenolate mofetil (MMF) is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney [see Clinical Studies (14.1)], heart [see Clinical Studies (14.2)] or liver transplants [see Clinical Studies (14.3)], in combination with other immunosuppressants." }

Mycophenolate mofetil should not be used without the supervision of a physician with experience in immunosuppressive therapy.

Mycophenolate Mofetil Capsules and Tablets 

Mycophenolate mofetil oral dosage forms (capsules or tablets) should not be used interchangeably with mycophenolic acid delayed-release tablets without supervision of a physician with experience in immunosuppressive therapy because the rates of absorption following the administration of mycophenolate mofetil oral dosage forms and mycophenolic acid delayed-release tablets are not equivalent.

Mycophenolate mofetil tablets should not be crushed and mycophenolate mofetil capsules should not be opened or crushed. Patients should avoid inhalation or contact of the skin or mucous membranes with the powder contained in mycophenolate mofetil capsules. If such contact occurs, they must wash the area of contact thoroughly with soap and water. In case of ocular contact, rinse eyes with plain water.

The initial oral dose of mycophenolate mofetil should be given as soon as possible following kidney, heart or liver transplant. It is recommended that mycophenolate mofetil be administered on an empty stomach. In stable transplant patients, however, mycophenolate mofetil may be administered with food if necessary [see Clinical Pharmacology (12.3)].

Patients should be instructed to take a missed dose as soon as they remember, except if it is closer than 2 hours to the next scheduled dose; in this case, they should continue to take mycophenolate mofetil at the usual times.

Adults

The recommended dosage for adult kidney transplant patients is 1 g orally, twice daily (total daily dose of 2 g).

Pediatrics (3 months and older)

Pediatric dosing is based on body surface area (BSA). The recommended dosage of mycophenolate mofetil for oral suspension for pediatric kidney transplant patients 3 months and older is 600 mg/m2, administered twice daily (maximum total daily dose of 2 g or 10 mL of the oral suspension). Pediatric patients with BSA ≥ 1.25 m2 may be dosed with capsules or tablets as follows:

<div class="scrollingtable"><table class="Noautorules" width="588"> <caption> <span> Table 1 Pediatric Kidney Transplant: Dosage Using Capsules or Tablets </span> </caption> <col width="147"/> <col width="441"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold"> Body Surface Area</span> <br/> </td><td align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> Dosage</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> 1.25 m<span class="Sup">2</span> to &lt;1.5 m<span class="Sup">2</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Mycophenolate mofetil capsule 750 mg twice daily (1.5 g total daily dose)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> ≥ 1.5 m<span class="Sup">2</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Mycophenolate mofetil capsules or tablets 1 g twice daily (2 g total daily dose)<br/> </td> </tr> </tbody> </table></div>

Adults

The recommended dosage of Mycophenolate mofetil for adult heart transplant patients is 1.5 g orally administered twice daily (total daily dose of 3 g).

Pediatrics (3 months and older)

The recommended starting dosage of Mycophenolate mofetil oral suspension for pediatric heart transplant patients 3 months and older is 600 mg/m2, administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m2 twice daily (maximum total daily dose of 3 g or 15 mL of the oral suspension). The dose may be individualized based on clinical assessment.

Pediatric patients with BSA ≥1.25 m2 may be started on therapy with capsules or tablets as follows:

<div class="scrollingtable"><table class="Noautorules" width="590"> <caption> <span> Table 2 Pediatric Heart Transplant: Pediatric Starting Dosage Using Capsules or Tablets </span> </caption> <col width="155"/> <col width="435"/> <tfoot> <tr> <td align="left" colspan="2"> <p class="First Footnote">*Maximum maintenance dose: 3 g total daily.</p> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold"> Body Surface Area</span> <br/> </td><td align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> Starting Dosage*</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> 1.25 m<span class="Sup">2</span> to &lt;1.5 m<span class="Sup">2</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Mycophenolate mofetil capsule 750 mg twice daily (1.5 g total daily dose)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> ≥ 1.5 m<span class="Sup">2</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Mycophenolate mofetil capsules or tablets 1 g twice daily (2 g total daily dose)<br/> </td> </tr> </tbody> </table></div>

Adults

The recommended dosage of Mycophenolate mofetil for adult liver transplant patients is 1.5 g administered orally twice daily (total daily dose of 3 g).

Pediatrics (3 months and older)

The recommended starting dosage of Mycophenolate mofetil oral suspension for pediatric liver transplant patients 3 months of age and older is 600 mg/m2, administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m2 twice daily (maximum total daily dose of 3 g or 15 mL of the oral suspension). The dose may be individualized based on clinical assessment.

Pediatric patients with BSA ≥1.25 m2 may be started on therapy with capsules or tablets as follows:

<div class="scrollingtable"><table class="Noautorules" width="760"> <caption> <span> Table 3 Pediatric Liver Transplant: Pediatric Starting Dosage Using Capsules or Tablets</span> </caption> <col width="380"/> <col width="380"/> <tfoot> <tr> <td align="left" colspan="2"> <p class="First Footnote">*Maximum maintenance dose: 3 g total daily.</p> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold"> Body Surface Area</span> <br/> </td><td align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> Starting Dosage*</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> 1.25 m<span class="Sup">2</span> to &lt;1.5 m<span class="Sup">2</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Mycophenolate mofetil capsule 750 mg twice daily (1.5 g total daily dose)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> ≥ 1.5 m<span class="Sup">2</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Mycophenolate mofetil capsules or tablets 1 g twice daily (2 g total daily dose)<br/> </td> </tr> </tbody> </table></div>

Renal Impairment

No dosage modifications are needed in kidney transplant patients with delayed graft function postoperatively [see Clinical Pharmacology (12.3)]. In kidney transplant patients with severe chronic impairment of the graft (GFR <25 mL/min/1.73 m2), do not administer doses of mycophenolate mofetil greater than 1 g twice a day. These patients should be carefully monitored [see Clinical Pharmacology (12.3)].

Neutropenia

If neutropenia develops (ANC <1.3 x 103/μL), dosing with mycophenolate mofetil should be interrupted or reduced, appropriate diagnostic tests performed, and the patient managed appropriately [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)].

Mycophenolate mofetil for tablets and capsules are available in the following dosage forms and strengths:

{ "type": "p", "children": [], "text": "\nMycophenolate mofetil for tablets and capsules are available in the following dosage forms and strengths:" }

<div class="scrollingtable"><table width="100%"> <col width="50%"/> <col width="50%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"> Capsules<br/> </td><td align="left" class="Botrule Rrule Toprule" valign="top"> 250 mg mycophenolate mofetil, white to off-white blend of mycophenolate mofetil filled in size "1" hard gelatin capsule with Ivory Cap and Ivory Body, printed "SAL" on cap and "726" on body in black.<br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> Tablets<br/> </td><td align="left" class="Botrule Rrule" valign="top"> 500 mg mycophenolate mofetil, pinkish brown colored, capsule shaped, film coated tablet with "SAL" engraved on one side and engraved "725" on other side. <br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"50%\"/>\n<col width=\"50%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"> Capsules<br/>\n</td><td align=\"left\" class=\"Botrule Rrule Toprule\" valign=\"top\"> 250 mg mycophenolate mofetil, white to off-white blend of mycophenolate mofetil filled in size \"1\" hard gelatin capsule with Ivory Cap and Ivory Body, printed \"SAL\" on cap and \"726\" on body in black.<br/>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\"> Tablets<br/>\n</td><td align=\"left\" class=\"Botrule Rrule\" valign=\"top\"> 500 mg mycophenolate mofetil, pinkish brown colored, capsule shaped, film coated tablet with \"SAL\" engraved on one side and engraved \"725\" on other side. <br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Allergic reactions to mycophenolate mofetil have been observed; therefore, mycophenolate mofetil is contraindicated in patients with a hypersensitivity to mycophenolate mofetil (MMF), mycophenolic acid (MPA) or any component of the drug product.

{ "type": "p", "children": [], "text": "\nAllergic reactions to mycophenolate mofetil have been observed; therefore, mycophenolate mofetil is contraindicated in patients with a hypersensitivity to mycophenolate mofetil (MMF), mycophenolic acid (MPA) or any component of the drug product. " }

Use of MMF during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney and nervous system. Females of reproductive potential must be made aware of these risks and must be counseled regarding pregnancy prevention and planning. Avoid use of MMF during pregnancy if safer treatment options are available [see Use in Specific Populations (8.1, 8.3)].

Patients receiving immunosuppressants, including mycophenolate mofetil, are at increased risk of developing lymphomas and other malignancies, particularly of the skin [see Adverse Reactions (6.1)]. The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. For patients with increased risk for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen with a high protection factor.

Post-transplant lymphoproliferative disorder (PTLD) developed in 0.4% to 1% of patients receiving mycophenolate mofetil (2 g or 3 g) with other immunosuppressive agents in controlled clinical trials of kidney, heart and liver transplant patients [see Adverse Reactions (6.1)]. The majority of PTLD cases appear to be related to Epstein Barr Virus (EBV) infection. The risk of PTLD appears greatest in those individuals who are EBV seronegative, a population which includes many young children. In pediatric patients, no other malignancies besides PTLD were observed in clinical trials [see Adverse Reactions (6.1)].

Patients receiving immunosuppressants, including mycophenolate mofetil, are at increased risk of developing bacterial, fungal, protozoal and new or reactivated viral infections, including opportunistic infections. The risk increases with the total immunosuppressive load. These infections may lead to serious outcomes, including hospitalizations and death [see Adverse Reactions (6.1, 6.2)].

Serious viral infections reported include:

Consider dose reduction or discontinuation of mycophenolate mofetil in patients who develop new infections or reactivate viral infections, weighing the risk that reduced immunosuppression represents to the functioning allograft.

PVAN, especially due to BK virus infection, is associated with serious outcomes, including deteriorating renal function and renal graft loss [see Adverse Reactions (6.2)]. Patient monitoring may help detect patients at risk for PVAN.

PML, which is sometimes fatal, commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia [see Adverse Reactions (6.2)]. In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms.

The risk of CMV viremia and CMV disease is highest among transplant recipients seronegative for CMV at time of transplant who receive a graft from a CMV seropositive donor. Therapeutic approaches to limiting CMV disease exist and should be routinely provided. Patient monitoring may help detect patients at risk for CMV disease.

Viral reactivation has been reported in patients infected with HBV or HCV. Monitoring infected patients for clinical and laboratory signs of active HBV or HCV infection is recommended.

Severe neutropenia [absolute neutrophil count (ANC) <0.5 x 103/μL] developed in transplant patients receiving mycophenolate mofetil 3 g daily [see Adverse Reactions (6.1)]. Patients receiving mycophenolate mofetil should be monitored for neutropenia. Neutropenia has been observed most frequently in the period from 31 to 180 days post-transplant in patients treated for prevention of kidney, heart and liver rejection. The development of neutropenia may be related to mycophenolate mofetil itself, concomitant medications, viral infections, or a combination of these causes. If neutropenia develops (ANC <1.3 x 103/μL), dosing with mycophenolate mofetil should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately [see Dosage and Administration (2.5)].

Patients receiving mycophenolate mofetil should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression.

Consider monitoring with complete blood counts weekly for the first month, twice monthly for the second and third months, and monthly for the remainder of the first year.

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate mofetil in combination with other immunosuppressive agents. In some cases, PRCA was found to be reversible with dose reduction or cessation of mycophenolate mofetil therapy. In transplant patients, however, reduced immunosuppression may place the graft at risk.

Gastrointestinal bleeding requiring hospitalization, ulceration and perforations were observed in clinical trials. Physicians should be aware of these serious adverse effects particularly when administering mycophenolate mofetil to patients with a gastrointestinal disease.

Mycophenolate mofetil is an inosine monophosphate dehydrogenase (IMPDH) inhibitor; therefore it should be avoided in patients with hereditary deficiencies of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndromes because it may cause an exacerbation of disease symptoms characterized by the overproduction and accumulation of uric acid leading to symptoms associated with gout such as acute arthritis, tophi, nephrolithiasis or urolithiasis and renal disease including renal failure.

Acute inflammatory syndrome (AIS) has been reported with the use of MMF and mycophenolate products, and some cases have resulted in hospitalization. AIS is a paradoxical pro-inflammatory reaction characterized by fever, arthralgias, arthritis, muscle pain and elevated inflammatory markers including, C-reactive protein and erythrocyte sedimentation rate, without evidence of infection or underlying disease recurrence. Symptoms occur within weeks to months of initiation of treatment or a dose increase. After discontinuation, improvement of symptoms and inflammatory markers are usually observed within 24 to 48 hours.

Monitor patients for symptoms and laboratory parameters of AIS when starting treatment with mycophenolate products or when increasing the dosage. Discontinue treatment and consider other treatment alternatives based on the risk and benefit for the patient.

During treatment with mycophenolate mofetil, the use of live attenuated vaccines should be avoided (e.g., intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) and patients should be advised that vaccinations may be less effective. Advise patients to discuss with the physician before seeking any immunizations.

Patients should not donate blood during therapy and for at least 6 weeks following discontinuation of mycophenolate mofetil because their blood or blood products might be administered to a female of reproductive potential or a pregnant woman.

Based on animal data, men should not donate semen during therapy and for 90 days following discontinuation of mycophenolate mofetil [see Use In Specific Populations (8.3)].

A variety of drugs have potential to alter systemic MPA exposure when co-administered with mycophenolate mofetil. Therefore, determination of MPA concentrations in plasma before and after making any changes to immunosuppressive therapy, or when adding or discontinuing concomitant medications, may be appropriate to ensure MPA concentrations remain stable.

Mycophenolate mofetil may impact the ability to drive and use machines. Patients should avoid driving or using machines if they experience somnolence, confusion, dizziness, tremor, or hypotension during treatment with mycophenolate mofetil [see Adverse Reactions (6.1)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

An estimated total of 1557 adult patients received mycophenolate mofetil during pivotal clinical trials in the prevention of acute organ rejection. Of these, 991 were included in the three renal studies, 277 were included in one hepatic study, and 289 were included in one cardiac study. Patients in all study arms also received cyclosporine and corticosteroids.

The data described below primarily derive from five randomized, active-controlled double-blind 12-month trials of mycophenolate mofetil in de novo kidney (3) heart (1) and liver (1) transplant patients [see Clinical Studies (14.1, 14.2, and 14.3)].

 Mycophenolate Mofetil Oral

The incidence of adverse reactions for mycophenolate mofetil was determined in five randomized, comparative, double-blind trials in the prevention of rejection in kidney, heart and liver transplant patients (two active- and one placebo-controlled trials, one active-controlled trial, and one active-controlled trial, respectively) [see Clinical Studies (14.1, 14.2 and 14.3)].

The three de novo kidney studies with 12-month duration compared two dose levels of oral mycophenolate mofetil (1 g twice daily and 1.5 g twice daily) with azathioprine (2 studies) or placebo (1 study) when administered in combination with cyclosporine (Sandimmune®) and corticosteroids to prevent acute rejection episodes. One study also included anti-thymocyte globulin (ATGAM®) induction therapy.

In the de novo heart transplantation study with 12-month duration, patients received mycophenolate mofetil 1.5 g twice daily (n=289) or azathioprine 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune® or Neoral®) and corticosteroids as maintenance immunosuppressive therapy.

In the de novo liver transplantation study with 12-month duration, patients received mycophenolate mofetil 1 g twice daily intravenously for up to 14 days followed by mycophenolate mofetil 1.5 g twice daily orally or azathioprine 1 to 2 mg/kg/day intravenously followed by azathioprine 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral®) and corticosteroids as maintenance immunosuppressive therapy. The total number of patients enrolled was 565.

Approximately 53% of the kidney transplant patients, 65% of the heart transplant patients, and 48% of the liver transplant patients were treated for more than 1 year. Adverse reactions reported in ≥ 20% of patients in the mycophenolate mofetil treatment groups are presented below. The safety data of three kidney transplantation studies are pooled together.

<div class="scrollingtable"><table class="Noautorules" width="808"> <caption> <span> Table 5 Adverse Reactions in Controlled Studies of De Novo Kidney, Heart or Liver Transplantation Reported in ≥ 20% of Patients in the Mycophenolate Mofetil Group </span> </caption> <col width="170"/> <col width="104"/> <col width="85"/> <col width="76"/> <col width="106"/> <col width="83"/> <col width="106"/> <col width="78"/> <col width="0"/> <tfoot> <tr> <td align="left" colspan="9"> <p class="First Footnote"> <span class="Sup">a </span>: "-" Indicates that the incidence was below the cutoff value of 20% for inclusion in the table.</p> </td> </tr> <tr> <td align="left" colspan="9"> <p class="First Footnote"> <span class="Sup">b</span> : "Edema" includes peripheral edema, facial edema, scrotal edema.</p> </td> </tr> <tr> <td align="left" colspan="9"> <p class="First Footnote"> <span class="Sup">c</span> : "Pain" includes musculoskeletal pain (myalgia, neck pain, back pain).</p> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Rrule Toprule" colspan="3" valign="top"><span class="Bold"> Kidney Studies</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" colspan="2"><span class="Bold"> Heart Study</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" colspan="2"><span class="Bold"> Liver Study</span> <br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" rowspan="3" valign="top"><span class="Bold"> Adverse drug reaction</span> <br/> <br/> <br/> <br/> <br/> <br/> <span class="Bold"> System Organ Class</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> Mycophenolate mofetil</span> <br/> <span class="Bold"> 2g/day</span> <br/> <span class="Bold"> (n=501)</span> <br/> <span class="Bold"> or 3g/day (n=490)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> AZA</span> <br/> <span class="Bold"> 1 to 2 mg/kg/day or 100 to</span> <br/> <span class="Bold"> 150</span> <br/> <span class="Bold"> mg/day</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> Placebo</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold"> Mycophenolate</span> <br/> <span class="Bold"> mofetil</span> <br/> <span class="Bold"> 3g/day</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold"> AZA</span> <br/> <span class="Bold"> 1.5 to 3 mg/kg/day</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold"> Mycophenolate mofetil</span> <br/> <span class="Bold"> 3g/day</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold"> AZA</span> <br/> <span class="Bold"> 1 to 2 mg/kg/day</span> <br/> </td><td></td> </tr> <tr> <td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> (n=991)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> (n=326)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> (n=166)</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold"> (n=289)</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold"> (n=289)</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold"> (n=277)</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold"> (n=287)</span> <br/> </td><td></td> </tr> <tr> <td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> %</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> %</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> %</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold"> %</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold"> %</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold"> %</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold"> %</span> <br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="8"><span class="Bold"> Infections and infestations</span> <br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Bacterial infections<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 39.9<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 33.7<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 37.3<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> 27.4<br/> </td><td align="center" class="Botrule Rrule"> 26.5<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Viral infections<br/> </td><td align="center" class="Botrule Rrule" valign="top"> - <span class="Sup">a</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 31.1<br/> </td><td align="center" class="Botrule Rrule"> 24.9<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="8"><span class="Bold"> Blood and lymphatic system disorders</span> <br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Anemia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 20.0<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 23.6<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 2.4<br/> </td><td align="center" class="Botrule Rrule"> 45.0<br/> </td><td align="center" class="Botrule Rrule"> 47.1<br/> </td><td align="center" class="Botrule Rrule"> 43.0<br/> </td><td align="center" class="Botrule Rrule"> 53.0<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Ecchymosis<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 20.1<br/> </td><td align="center" class="Botrule Rrule"> 9.7<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Leukocytosis<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 42.6<br/> </td><td align="center" class="Botrule Rrule"> 37.4<br/> </td><td align="center" class="Botrule Rrule"> 22.4<br/> </td><td align="center" class="Botrule Rrule"> 21.3<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Leukopenia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 28.6<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 24.8<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 4.2<br/> </td><td align="center" class="Botrule Rrule"> 34.3<br/> </td><td align="center" class="Botrule Rrule"> 43.3<br/> </td><td align="center" class="Botrule Rrule"> 45.8<br/> </td><td align="center" class="Botrule Rrule"> 39.0<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Thrombocytopenia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 24.2<br/> </td><td align="center" class="Botrule Rrule"> 28.0<br/> </td><td align="center" class="Botrule Rrule"> 38.3<br/> </td><td align="center" class="Botrule Rrule"> 42.2<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="8"><span class="Bold"> Metabolism and nutrition disorders</span> <br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Hypercholesterolemia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 46.0<br/> </td><td align="center" class="Botrule Rrule"> 43.9<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Hyperglycemia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 48.4<br/> </td><td align="center" class="Botrule Rrule"> 53.3<br/> </td><td align="center" class="Botrule Rrule"> 43.7<br/> </td><td align="center" class="Botrule Rrule"> 48.8<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Hyperkalemia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> 22.0<br/> </td><td align="center" class="Botrule Rrule"> 23.7<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Hypocalcemia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> 30.0<br/> </td><td align="center" class="Botrule Rrule"> 30.0<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Hypokalemia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 32.5<br/> </td><td align="center" class="Botrule Rrule"> 26.3<br/> </td><td align="center" class="Botrule Rrule"> 37.2<br/> </td><td align="center" class="Botrule Rrule"> 41.1<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Hypomagnesemia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 20.1<br/> </td><td align="center" class="Botrule Rrule"> 14.2<br/> </td><td align="center" class="Botrule Rrule"> 39.0<br/> </td><td align="center" class="Botrule Rrule"> 37.6<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="8"><span class="Bold"> Psychiatric disorders</span> <br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Depression<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 20.1<br/> </td><td align="center" class="Botrule Rrule"> 15.2<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Insomnia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 43.3<br/> </td><td align="center" class="Botrule Rrule"> 39.8<br/> </td><td align="center" class="Botrule Rrule"> 52.3<br/> </td><td align="center" class="Botrule Rrule"> 47.0<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="8"><span class="Bold"> Nervous system disorders</span> <br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Dizziness<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 34.3<br/> </td><td align="center" class="Botrule Rrule"> 33.9<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Headache<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 58.5<br/> </td><td align="center" class="Botrule Rrule"> 55.4<br/> </td><td align="center" class="Botrule Rrule"> 53.8<br/> </td><td align="center" class="Botrule Rrule"> 49.1<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Tremor<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 26.3<br/> </td><td align="center" class="Botrule Rrule"> 25.6<br/> </td><td align="center" class="Botrule Rrule"> 33.9<br/> </td><td align="center" class="Botrule Rrule"> 35.5<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="8"><span class="Bold"> Cardiac disorders</span> <br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Tachycardia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 22.8<br/> </td><td align="center" class="Botrule Rrule"> 21.8<br/> </td><td align="center" class="Botrule Rrule"> 22.0<br/> </td><td align="center" class="Botrule Rrule"> 15.7<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="8"><span class="Bold"> Vascular disorders</span> <br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Hypertension<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 27.5<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 32.2<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 19.3<br/> </td><td align="center" class="Botrule Rrule"> 78.9<br/> </td><td align="center" class="Botrule Rrule"> 74.0<br/> </td><td align="center" class="Botrule Rrule"> 62.1<br/> </td><td align="center" class="Botrule Rrule"> 59.6<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Hypotension<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 34.3<br/> </td><td align="center" class="Botrule Rrule"> 40.1<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="8"><span class="Bold"> Respiratory, thoracic and mediastinal disorders</span> <br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Cough<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 40.5<br/> </td><td align="center" class="Botrule Rrule"> 32.2<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Dyspnea<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 44.3<br/> </td><td align="center" class="Botrule Rrule"> 44.3<br/> </td><td align="center" class="Botrule Rrule"> 31.0<br/> </td><td align="center" class="Botrule Rrule"> 30.3<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Pleural effusion<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> 34.3<br/> </td><td align="center" class="Botrule Rrule"> 35.9<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="8"><span class="Bold"> Gastrointestinal disorders</span> <br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Abdominal pain<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 22.4<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 23.0<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 11.4<br/> </td><td align="center" class="Botrule Rrule"> 41.9<br/> </td><td align="center" class="Botrule Rrule"> 39.4<br/> </td><td align="center" class="Botrule Rrule"> 62.5<br/> </td><td align="center" class="Botrule Rrule"> 51.2<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Constipation<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 43.6<br/> </td><td align="center" class="Botrule Rrule"> 38.8<br/> </td><td align="center" class="Botrule Rrule"> 37.9<br/> </td><td align="center" class="Botrule Rrule"> 38.3<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Decreased appetite<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> 25.3<br/> </td><td align="center" class="Botrule Rrule"> 17.1<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Diarrhea<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 30.4<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 20.9<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 13.9<br/> </td><td align="center" class="Botrule Rrule"> 52.6<br/> </td><td align="center" class="Botrule Rrule"> 39.4<br/> </td><td align="center" class="Botrule Rrule"> 51.3<br/> </td><td align="center" class="Botrule Rrule"> 49.8<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Dyspepsia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 22.1<br/> </td><td align="center" class="Botrule Rrule"> 22.1<br/> </td><td align="center" class="Botrule Rrule"> 22.4<br/> </td><td align="center" class="Botrule Rrule"> 20.9<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Nausea<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 56.1<br/> </td><td align="center" class="Botrule Rrule"> 60.2<br/> </td><td align="center" class="Botrule Rrule"> 54.5<br/> </td><td align="center" class="Botrule Rrule"> 51.2<br/> </td><td></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Vomiting<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 39.1<br/> </td><td align="center" class="Botrule Rrule"> 34.6<br/> </td><td align="center" class="Botrule Rrule"> 32.9<br/> </td><td align="center" class="Botrule Rrule"> 33.4<br/> </td><td class="Botrule"></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="9"><span class="Bold"> Hepatobiliary disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Blood lactate dehydrogenase<br/> increased<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> 23.5<br/> </td><td align="center" class="Botrule Rrule"> 18.3<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule" colspan="2"> -<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Hepatic enzyme<br/> increased<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> 24.9<br/> </td><td align="center" class="Botrule Rrule" colspan="2"> 19.2<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="9"><span class="Bold"> Skin and subcutaneous tissues disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Rash<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 26.0<br/> </td><td align="center" class="Botrule Rrule"> 20.8<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule" colspan="2"> -<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="9"><span class="Bold"> Renal and urinary disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Blood creatinine<br/> increased<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> 42.2<br/> </td><td align="center" class="Botrule Rrule"> 39.8<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule" colspan="2"> -<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Blood urea increased<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule"> 36.7<br/> </td><td align="center" class="Botrule Rrule"> 34.3<br/> </td><td align="center" class="Botrule Rrule"> -<br/> </td><td align="center" class="Botrule Rrule" colspan="2"> -<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="9"><span class="Bold"> General disorders and administration site conditions</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Asthenia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 49.1<br/> </td><td align="center" class="Botrule Rrule"> 41.2<br/> </td><td align="center" class="Botrule Rrule"> 35.4<br/> </td><td align="center" class="Botrule Rrule" colspan="2"> 33.8<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Edema <span class="Sup">b</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"> 21.0<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 28.2<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 8.4<br/> </td><td align="center" class="Botrule Rrule"> 67.5<br/> </td><td align="center" class="Botrule Rrule"> 55.7<br/> </td><td align="center" class="Botrule Rrule"> 48.4<br/> </td><td align="center" class="Botrule Rrule" colspan="2"> 47.7<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Pain <span class="Sup">c</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"> 24.8<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 32.2<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 9.6<br/> </td><td align="center" class="Botrule Rrule"> 79.2<br/> </td><td align="center" class="Botrule Rrule"> 77.5<br/> </td><td align="center" class="Botrule Rrule"> 74.0<br/> </td><td align="center" class="Botrule Rrule" colspan="2"> 77.5<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Pyrexia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule" valign="top"> -<br/> </td><td align="center" class="Botrule Rrule"> 56.4<br/> </td><td align="center" class="Botrule Rrule"> 53.6<br/> </td><td align="center" class="Botrule Rrule"> 52.3<br/> </td><td align="center" class="Botrule Rrule" colspan="2"> 56.1<br/> </td> </tr> </tbody> </table></div>

In the three de novo kidney studies, patients receiving 2 g/day of mycophenolate mofetil had an overall better safety profile than did patients receiving 3 g/day of mycophenolate mofetil. 

Post-transplant lymphoproliferative disease (PTLD, pseudolymphoma) developed in 0.4% to 1% of patients receiving mycophenolate mofetil (2 g or 3 g daily) with other immunosuppressive agents in controlled clinical trials of kidney, heart and liver transplant patients followed for at least 1 year [see Warnings and Precautions (5.2)]. Non-melanoma skin carcinomas occurred in 1.6% to 4.2% of patients, other types of malignancy in 0.7% to 2.1% of patients. Three-year safety data in kidney and heart transplant patients did not reveal any unexpected changes in incidence of malignancy compared to the 1-year data. In pediatric patients, PTLD was observed in 1.35% (2/148) by 12 months post-transplant.

Cytopenias, including leukopenia, anemia, thrombocytopenia and pancytopenia are a known risk associated with mycophenolate and may lead or contribute to the occurrence of infections and hemorrhages [see Warnings and Precautions (5.3)]. Severe neutropenia (ANC <0.5 x103/µL) developed in up to 2% of kidney transplant patients, up to 2.8% of heart transplant patients and up to 3.6% of liver transplant patients receiving mycophenolate mofetil 3 g daily [see Warnings and Precautions (5.4) and Dosage and Administration (2.5)].

The most common opportunistic infections in patients receiving mycophenolate mofetil with other immunosuppressants were mucocutaneous candida, CMV viremia/syndrome, and herpes simplex. The proportion of patients with CMV viremia/syndrome was 13.5%. In patients receiving mycophenolate mofetil (2 g or 3 g) in controlled studies for prevention of kidney, heart or liver rejection, fatal infection/sepsis occurred in approximately 2% of kidney and heart patients and in 5% of liver patients [see Warnings and Precautions (5.3)].

The most serious gastrointestinal disorders reported were ulceration and hemorrhage, which are known risks associated with mycophenolate mofetil. Mouth, esophageal, gastric, duodenal, and intestinal ulcers often complicated by hemorrhage, as well as hematemesis, melena, and hemorrhagic forms of gastritis and colitis were commonly reported during the pivotal clinical trials, while the most common gastrointestinal disorders were diarrhea, nausea and vomiting. Endoscopic investigation of patients with mycophenolate mofetil-related diarrhea revealed isolated cases of intestinal villous atrophy [see Warnings and Precautions (5.5)].

The following adverse reactions were reported with 3% to <20% incidence in kidney, heart, and liver transplant patients treated with mycophenolate mofetil, in combination with cyclosporine and corticosteroids.

<div class="scrollingtable"><table class="Noautorules" width="583"> <caption> <span> Table 6 Adverse Reactions in Controlled Studies of De Novo Kidney, Heart or Liver Transplantation Reported in 3% to &lt;20% of Patients Treated with Mycophenolate Mofetil in Combination with Cyclosporine and Corticosteroids </span> </caption> <col width="121"/> <col width="462"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold"> System Organ Class</span> <br/> </td><td align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> Adverse Reactions</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Body as a Whole<br/> </td><td align="left" class="Botrule Rrule" valign="top"> cellulitis, chills, hernia, malaise<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Infections and Infestations<br/> </td><td align="left" class="Botrule Rrule" valign="top"> fungal infections<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Hematologic and Lymphatic<br/> </td><td align="left" class="Botrule Rrule" valign="top"> coagulation disorder, ecchymosis, pancytopenia<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Urogenital<br/> </td><td align="left" class="Botrule Rrule" valign="top"> hematuria<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Cardiovascular<br/> </td><td align="left" class="Botrule Rrule" valign="top"> hypotension<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Metabolic and Nutritional<br/> </td><td align="left" class="Botrule Rrule" valign="top"> acidosis, alkaline phosphatase increased, hyperlipemia, hypophosphatemia, weight loss<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Digestive<br/> </td><td align="left" class="Botrule Rrule" valign="top"> esophagitis, flatulence, gastritis, gastrointestinal hemorrhage, hepatitis, ileus, nausea and vomiting, stomach ulcer, stomatitis<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Neoplasm benign, malignant and unspecified<br/> </td><td align="left" class="Botrule Rrule" valign="top"> neoplasm<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Skin and Appendages<br/> </td><td align="left" class="Botrule Rrule" valign="top"> skin benign neoplasm, skin carcinoma<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Psychiatric<br/> </td><td align="left" class="Botrule Rrule" valign="top"> confusional state<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Nervous<br/> </td><td align="left" class="Botrule Rrule" valign="top"> hypertonia, paresthesia, somnolence     <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Musculoskeletal<br/> </td><td align="left" class="Botrule Rrule" valign="top"> arthralgia, myasthenia<br/> </td> </tr> </tbody> </table></div>

Pediatrics

The type and frequency of adverse events in a clinical study for prevention of  kidney allograft rejection in 100 pediatric patients 3 months to 18 years of age dosed with mycophenolate mofetil oral suspension 600 mg/m2 twice daily (up to 1 g twice daily) were generally similar to those observed in adult patients dosed with mycophenolate mofetil capsules at a dose of 1 g twice daily with the exception of abdominal pain, fever, infection, pain, sepsis, diarrhea, vomiting, pharyngitis, respiratory tract infection, hypertension, leukopenia, and anemia, which were observed in a higher proportion in pediatric patients.

Safety information in pediatric heart transplant or pediatric liver transplant patients treated with mycophenolate mofetil is supported by an open-label study in pediatric liver transplant patients and publications; the type and frequency of the reported adverse reactions are consistent with those observed in pediatric patients following renal transplant and in adults.

Geriatrics

Geriatric patients (≥65 years), particularly those who are receiving mycophenolate mofetil as part of a combination immunosuppressive regimen, may be at increased risk of certain infections (including cytomegalovirus [CMV] tissue invasive disease) and possibly gastrointestinal hemorrhage and pulmonary edema, compared to younger individuals [see Warnings and Precautions (5.3) and Adverse Reactions (6.1)].

The following adverse reactions have been identified during post-approval use of mycophenolate mofetil. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

<div class="scrollingtable"><table class="Noautorules" width="62%"> <caption> <span> Table 7 Drug Interactions with Mycophenolate Mofetil that Affect Mycophenolic Acid (MPA) Exposure </span> </caption> <col width="29%"/> <col width="70%"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">  Antacids with Magnesium or Aluminum Hydroxide</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Clinical Impact</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Concomitant use with an antacid containing magnesium or aluminum hydroxide decreases MPA systemic exposure <span class="Italics">[see Clinical Pharmacology (12.3)]</span> , which may reduce mycophenolate mofetil efficacy.<br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Prevention or Management</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Administer magnesium or aluminum hydroxide containing antacids at least 2h after mycophenolate mofetil administration.<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="2" valign="top"><span class="Bold">  Proton Pump Inhibitors (PPIs)</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Clinical Impact</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top">  Concomitant use with PPIs decreases MPA systemic exposure <span class="Italics">[see Clinical Pharmacology (12.3)]</span> , which may reduce mycophenolate mofetil efficacy.<br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Prevention or Management</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Monitor patients for alterations in efficacy when PPIs are co-administered with mycophenolate mofetil.<br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Examples</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Lansoprazole, pantoprazole<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="2" valign="top"><span class="Bold">  Drugs that Interfere with Enterohepatic Recirculation</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Clinical Impact</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top">  Concomitant use with drugs that directly interfere with enterohepatic recirculation, or indirectly interfere with enterohepatic recirculation by altering the gastrointestinal flora, can decrease MPA systemic exposure <span class="Italics">[see Clinical Pharmacology (12.3)]</span> , which may reduce mycophenolate mofetil efficacy.<br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Prevention or Management</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Monitor patients for alterations in efficacy or mycophenolate mofetil related adverse reactions when these drugs are co-administered with mycophenolate mofetil.<br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Examples</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Cyclosporine A, trimethoprim/sulfamethoxazole, bile acid sequestrants (cholestyramine), rifampin as well as aminoglycoside, cephalosporin, fluoroquinolone and penicillin classes of antimicrobials<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="2" valign="top"><span class="Bold">  Drugs Modulating Glucuronidation</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Clinical Impact</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top">  Concomitant use with drugs inducing glucuronidation decreases MPA systemic exposure, potentially reducing mycophenolate mofetil efficacy, while use with drugs inhibiting glucuronidation increases MPA systemic exposure <span class="Italics">[see Clinical Pharmacology (12.3)]</span> , which may increase the risk of mycophenolate mofetil related adverse reactions.  <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Prevention or Management</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Monitor patients for alterations in efficacy or mycophenolate mofetil related adverse reactions when these drugs are co-administered with mycophenolate mofetil.<br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Examples</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Telmisartan (induces glucuronidation); isavuconazole (inhibits glucuronidation).<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="2" valign="top"><span class="Bold">  Calcium Free Phosphate Binders</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Clinical Impact</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top">  Concomitant use with calcium free phosphate binders decrease MPA systemic exposure <span class="Italics">[see Clinical Pharmacology (12.3)]</span> , which may reduce mycophenolate mofetil efficacy.<br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Prevention or Management</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Administer calcium free phosphate binders at least 2 hours after mycophenolate mofetil.<br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Examples</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Sevelamer<br/> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table class="Noautorules" width="59%"> <caption> <span> Table 8 Drug Interactions with Mycophenolate Mofetil that Affect Other Drugs</span> </caption> <col width="46%"/> <col width="53%"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">  Drugs that Undergo Renal Tubular Secretion</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Clinical Impact</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> When concomitantly used with mycophenolate mofetil, its metabolite MPAG, may compete with drugs eliminated by renal tubular secretion which may increase plasma concentrations and/or adverse reactions associated with these drugs.<br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Prevention or</span> <br/> <span class="Italics">Management</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Monitor for drug-related adverse reactions in patients with renal impairment.<br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Examples</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Acyclovir, ganciclovir, probenecid, valacyclovir, valganciclovir<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="2" valign="top"><span class="Bold">  Combination Oral Contraceptives</span> <br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Clinical Impact</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top">  Concomitant use with mycophenolate mofetil decreased the systemic exposure to levonorgestrel, but did not affect the systemic exposure to ethinylestradiol <span class="Italics">[see Clinical Pharmacology (12.3)]</span> , which may result in reduced combination oral contraceptive effectiveness.<br/> </td> </tr> <tr> <td align="right" class="Botrule Lrule Rrule"><span class="Italics">Prevention or</span> <br/> <span class="Italics">Management</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Use additional barrier contraceptive methods.<br/> </td> </tr> </tbody> </table></div>

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to mycophenolate during pregnancy and those becoming pregnant within 6 weeks of discontinuing mycophenolate mofetil treatment. To report a pregnancy or obtain information about the registry, visit www.mycophenolateREMS.com or call 1-800-617-8191.

Risk Summary

Use of mycophenolate mofetil (MMF) during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of multiple congenital malformations in multiple organ systems [see Human Data]. Oral administration of mycophenolate to rats and rabbits during the period of organogenesis produced congenital malformations and pregnancy loss at doses less than the recommended clinical dose (0.01 to 0.05 times the recommended clinical doses in kidney and heart transplant patients) [see Animal Data].

Consider alternative immunosuppressants with less potential for embryofetal toxicity. Risks and benefits of mycophenolate mofetil should be discussed with the pregnant woman.

The estimated background risk of pregnancy loss and congenital malformations in organ transplant populations is not clear. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

A spectrum of congenital malformations (including multiple malformations in individual newborns) has been reported in 23 to 27% of live births in MMF exposed pregnancies, based on published data from pregnancy registries. Malformations that have been documented include external ear, eye, and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system.

Based on published data from pregnancy registries, the risk of first trimester pregnancy loss has been reported at 45 to 49% following MMF exposure.

Animal Data

In animal reproductive toxicology studies, there were increased rates of fetal resorptions and malformations in the absence of maternal toxicity. Oral administration of MMF to pregnant rats from Gestational Day 7 to Day 16 produced increased embryofetal lethality and fetal malformations including anophthalmia, agnathia, and hydrocephaly at doses equivalent to 0.015 and 0.01 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA. Oral administration of MMF to pregnant rabbits from Gestational Day 7 to Day 19 produced increased embryofetal lethality and fetal malformations included ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia at dose equivalents as low as 0.05 and 0.03 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA.

Risk Summary

There are no data on the presence of mycophenolate in human milk, or the effects on milk production. There are limited data in the National Transplantation Pregnancy Registry on the effects of mycophenolate on a breastfed child [see Data]. Studies in rats treated with MMF have shown mycophenolic acid (MPA) to be present in milk. Because available data are limited, it is not possible to exclude potential risks to a breastfeeding infant.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for mycophenolate mofetil and any potential adverse effects on the breastfed infant from mycophenolate mofetil or from the underlying maternal condition.

Data

Limited information is available from the National Transplantation Pregnancy Registry. Of seven infants reported by the National Transplantation Pregnancy Registry to have been breastfed while the mother was taking mycophenolate, all were born at 34-40 weeks gestation, and breastfed for up to 14 months. No adverse events were reported.

Females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning.

Pregnancy Planning

For patients who are considering pregnancy, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible. Risks and benefits of mycophenolate mofetil should be discussed with the patient.

Pregnancy Testing

To prevent unplanned exposure during pregnancy, all females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL immediately before starting mycophenolate mofetil. Another pregnancy test with the same sensitivity should be done 8 to 10 days later. Repeat pregnancy tests should be performed during routine follow-up visits. Results of all pregnancy tests should be discussed with the patient. In the event of a positive pregnancy test, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible.

Contraception

Female Patients

Females of reproductive potential taking mycophenolate mofetil must receive contraceptive counseling and use acceptable contraception (see Table 9 for acceptable contraception methods). Patients must use acceptable birth control during the entire mycophenolate mofetil therapy, and for 6 weeks after stopping mycophenolate mofetil, unless the patient chooses abstinence.

Patients should be aware that mycophenolate mofetil reduces blood levels of the hormones from the oral contraceptive pill and could theoretically reduce its effectiveness [see Drug Interactions (7.2)].

<div class="scrollingtable"><table class="Noautorules" width="93%"> <caption> <span> Table 9 Acceptable Contraception Methods for Females of Reproductive Potential</span> </caption> <col width="21%"/> <col width="34%"/> <col width="9%"/> <col width="34%"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule" colspan="4" valign="top"><span class="Bold"> Pick from the following birth control options:</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold"> Option 1</span> <br/> <span class="Bold">  Methods to Use Alone</span> <br/> </td><td class="Botrule Rrule" colspan="3" valign="top"> <ul class="Disc"> <li>Intrauterine devices (IUDs)</li> <li>Tubal sterilization</li> <li>Patient's partner vasectomy</li> </ul> </td> </tr> <tr> <td align="left" class="Botrule" colspan="4" valign="top"><span class="Bold"> OR</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold"> Option 2</span> <br/> <br/> </td><td align="left" class="Botrule Rrule" valign="top"><span class="Bold">  Hormone Methods</span> <br/>  choose 1<br/> </td><td class="Botrule Rrule" valign="top"></td><td align="left" class="Botrule Rrule" valign="top">  <span class="Bold"> Barrier Methods</span> <br/>  choose 1<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold">  Choose One Hormone Method </span><span class="Italics">AND</span><span class="Bold"> One Barrier Method</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"><span class="Bold"> Estrogen and Progesterone</span> <br/> <ul class="Disc"> <li>Oral Contraceptive Pill</li> <li>Transdermal patch</li> <li>Vaginal ring</li> </ul> <span class="Bold"> Progesterone-only</span> <br/> <ul class="Disc"> <li>Injection</li> <li>Implant</li> </ul> </td><td align="center" class="Botrule Rrule"><span class="Italics">AND</span> <br/> </td><td class="Botrule Rrule" valign="top"> <ul class="Disc"> <li>Diaphragm with spermicide</li> <li>Cervical cap with spermicide</li> <li>Contraceptive sponge</li> <li>Male condom</li> <li>Female condom</li> </ul> </td> </tr> <tr> <td align="left" class="Botrule" colspan="4" valign="top"><span class="Bold"> OR</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold"> Option 3</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top">  <span class="Bold"> Barrier Methods</span> <br/>  choose 1<br/> </td><td class="Botrule Rrule" valign="top"></td><td align="left" class="Botrule Rrule" valign="top">  <span class="Bold"> Barrier Methods</span> <br/>  choose 1<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top">  <span class="Bold"> Choose One Barrier Method from each column </span><span class="Italics">(must choose two methods)</span> <br/> </td><td class="Botrule Rrule" valign="top"> <ul class="Disc"> <li>Diaphragm with spermicide</li> <li>Cervical cap with spermicide</li> <li>Contraceptive sponge</li> </ul> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Italics">AND</span> <br/> </td><td class="Botrule Rrule" valign="top"> <ul class="Disc"> <li>Male condom</li> <li>Female condom</li> </ul> </td> </tr> </tbody> </table></div>

Male Patients

Genotoxic effects have been observed in animal studies at exposures exceeding the human therapeutic exposures by approximately 1.25 times. Thus, the risk of genotoxic effects on sperm cells cannot be excluded. Based on this potential risk, sexually active male patients and/or their female partners are recommended to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment. Also, based on the potential risk of genotoxic effects, male patients should not donate sperm during treatment with mycophenolate mofetil and for at least 90 days after cessation of treatment [see Use in Special Populations (8.1), Nonclinical Toxicology (13.1), Patient Counseling Information (17.9)].

Safety and effectiveness have been established in pediatric patients 3 months and older for the prophylaxis of organ rejection of allogenic kidney, heart or liver transplants.

Kidney Transplant

Use of mycophenolate mofetil in this population is supported by evidence from adequate and well-controlled studies of mycophenolate mofetil in adults with additional data from one open-label, pharmacokinetic and safety study of mycophenolate mofetil in pediatric patients after receiving allogeneic kidney transplant (100 patients, 3 months to 18 years of age) [see Dosage and Administration (2.2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.1)].

Heart Transplant and Liver Transplant

Use of mycophenolate mofetil in pediatric heart transplant and liver transplant patients is supported by adequate and well-controlled studies and pharmacokinetic data in adult heart transplant and liver transplant patients. Additional supportive data include pharmacokinetic data in pediatric kidney transplant and pediatric liver transplant patients (8 liver transplant patients, 9 months to 5 years of age, in an open-label, pharmacokinetic and safety study) and published evidence of clinical efficacy and safety in pediatric heart transplant and pediatric liver transplant patients [see Dosage and Administration (2.3, 2.4), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.1)].

Clinical studies of mycophenolate mofetil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between geriatric and younger patients. In general, dose selection for a geriatric patient should take into consideration the presence of decreased hepatic, renal or cardiac function and of concomitant drug therapies [see Adverse Reactions (6.1), Drug Interactions (7)].

Patients with Kidney Transplant

No dosage adjustments are needed in kidney transplant patients experiencing delayed graft function postoperatively but patients should be carefully monitored [see Clinical Pharmacology (12.3)]. In kidney transplant patients with severe chronic impairment of the graft (GFR <25 mL/min/1.73 m2), no dose adjustments are necessary; however, doses greater than 1 g administered twice a day should be avoided.

Patients with Heart and Liver Transplant

No data are available for heart or liver transplant patients with severe chronic renal impairment. Mycophenolate mofetil may be used for heart or liver transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks.

Patients with Kidney Transplant

 No dosage adjustments are recommended for kidney transplant patients with severe hepatic parenchymal disease. However, it is not known whether dosage adjustments are needed for hepatic disease with other etiologies [see Clinical Pharmacology (12.3)].

Patients with Heart Transplant

No data are available for heart transplant patients with severe hepatic parenchymal disease.

Possible signs and symptoms of acute overdose include hematological abnormalities such as leukopenia and neutropenia, and gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, and dyspepsia.

{ "type": "p", "children": [], "text": "\nPossible signs and symptoms of acute overdose include hematological abnormalities such as leukopenia and neutropenia, and gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, and dyspepsia." }

 The experience with overdose of mycophenolate mofetil in humans is limited. The reported effects associated with overdose fall within the known safety profile of the drug. The highest dose administered to kidney transplant patients in clinical trials has been 4 g/day. In limited experience with heart and liver transplant patients in clinical trials, the highest doses used were 4 g/day or 5 g/day. At doses of 4 g/day or 5 g/day, there appears to be a higher rate, compared to the use of 3 g/day or less, of gastrointestinal intolerance (nausea, vomiting, and/or diarrhea), and occasional hematologic abnormalities, particularly neutropenia [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": " The experience with overdose of mycophenolate mofetil in humans is limited. The reported effects associated with overdose fall within the known safety profile of the drug. The highest dose administered to kidney transplant patients in clinical trials has been 4 g/day. In limited experience with heart and liver transplant patients in clinical trials, the highest doses used were 4 g/day or 5 g/day. At doses of 4 g/day or 5 g/day, there appears to be a higher rate, compared to the use of 3 g/day or less, of gastrointestinal intolerance (nausea, vomiting, and/or diarrhea), and occasional hematologic abnormalities, particularly neutropenia [see Warnings and Precautions (5.4)]. " }

Treatment and Management

{ "type": "p", "children": [], "text": "\nTreatment and Management\n" }

MPA and the phenolic glucuronide metabolite of MPA (MPAG) are usually not removed by hemodialysis. However, at high MPAG plasma concentrations (>100 μg/mL), small amounts of MPAG are removed. By increasing excretion of the drug, MPA can be removed by bile acid sequestrants, such as cholestyramine [see Clinical Pharmacology (12.3)].

{ "type": "p", "children": [], "text": "MPA and the phenolic glucuronide metabolite of MPA (MPAG) are usually not removed by hemodialysis. However, at high MPAG plasma concentrations (>100 μg/mL), small amounts of MPAG are removed. By increasing excretion of the drug, MPA can be removed by bile acid sequestrants, such as cholestyramine [see Clinical Pharmacology (12.3)].\n" }

Mycophenolate mofetil is an antimetabolite immunosuppressant. It is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine monophosphate dehydrogenase (IMPDH) inhibitor.

{ "type": "p", "children": [], "text": "\nMycophenolate mofetil is an antimetabolite immunosuppressant. It is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine monophosphate dehydrogenase (IMPDH) inhibitor." }

The chemical name for mycophenolate mofetil (MMF) is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate. It has an empirical formula of C23H31NO7, a molecular weight of 433.50, and the following structural formula:

{ "type": "p", "children": [], "text": "The chemical name for mycophenolate mofetil (MMF) is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate. It has an empirical formula of C23H31NO7, a molecular weight of 433.50, and the following structural formula: " }

MMF is a white to off-white crystalline powder. It is slightly soluble in water (43 µg/mL at pH 7.4); the solubility increases in acidic medium (4.27 mg/mL at pH 3.6). It is freely soluble in acetone, soluble in methanol, and sparingly soluble in ethanol. The apparent partition coefficient in 1-octanol/water (pH 7.4) buffer solution is 238. The pKa values for MMF are 5.6 for the morpholino group and 8.5 for the phenolic group.

{ "type": "p", "children": [], "text": "\nMMF is a white to off-white crystalline powder. It is slightly soluble in water (43 µg/mL at pH 7.4); the solubility increases in acidic medium (4.27 mg/mL at pH 3.6). It is freely soluble in acetone, soluble in methanol, and sparingly soluble in ethanol. The apparent partition coefficient in 1-octanol/water (pH 7.4) buffer solution is 238. The pKa values for MMF are 5.6 for the morpholino group and 8.5 for the phenolic group." }

MMF hydrochloride has a solubility of 65.8 mg/mL in 5% Dextrose Injection USP (D5W). The pH of the reconstituted solution is 2.4 to 4.1.

{ "type": "p", "children": [], "text": "MMF hydrochloride has a solubility of 65.8 mg/mL in 5% Dextrose Injection USP (D5W). The pH of the reconstituted solution is 2.4 to 4.1." }

Mycophenolate mofetil is available for oral administration as capsules containing 250 mg of MMF, tablets containing 500 mg of MMF.

{ "type": "p", "children": [], "text": "Mycophenolate mofetil is available for oral administration as capsules containing 250 mg of MMF, tablets containing 500 mg of MMF." }

Inactive ingredients in mycophenolate mofetil capsules, USP 250 mg include croscarmellose sodium, magnesium stearate, microcrystalline cellulose, povidone (K-30). The capsule shells contain FD&C red # 3, gelatin, sodium lauryl sulfate, titanium dioxide and yellow iron oxide.

{ "type": "p", "children": [], "text": "Inactive ingredients in mycophenolate mofetil capsules, USP 250 mg include croscarmellose sodium, magnesium stearate, microcrystalline cellulose, povidone (K-30). The capsule shells contain FD&C red # 3, gelatin, sodium lauryl sulfate, titanium dioxide and yellow iron oxide." }

Inactive ingredients in mycophenolate mofetil tablets, USP 500 mg include croscarmellose sodium, magnesium stearate (Vegetable), microcrystalline cellulose, opadry brown, povidone [K-30].

{ "type": "p", "children": [], "text": "Inactive ingredients in mycophenolate mofetil tablets, USP 500 mg include croscarmellose sodium, magnesium stearate (Vegetable), microcrystalline cellulose, opadry brown, povidone [K-30]." }

The opadry brown contains FD&C blue #1 aluminum lake, FD&C red #40 aluminum lake, hypromellose, iron oxide red, polyethylene glycol and titanium dioxide.

{ "type": "p", "children": [], "text": "The opadry brown contains FD&C blue #1 aluminum lake, FD&C red #40 aluminum lake, hypromellose, iron oxide red, polyethylene glycol and titanium dioxide." }

Mycophenolate mofetil (MMF) is absorbed following oral administration and hydrolyzed to mycophenolic acid (MPA), the active metabolite. MPA is a selective uncompetitive inhibitor of the two isoforms (type I and type II) of inosine monophosphate dehydrogenase (IMPDH) leading to inhibition of the de novo pathway of guanosine nucleotide synthesis and blocks DNA synthesis. The mechanism of action of MPA is multifaceted and includes effects on cellular checkpoints responsible for metabolic programming of lymphocytes. MPA shifts transcriptional activities in lymphocytes from a proliferative state to catabolic processes. In vitro studies suggest that MPA modulates transcriptional activities in human CD4+ T-lymphocytes by suppressing the Akt/mTOR and STAT5 pathways that are relevant to metabolism and survival, leading to an anergic state of T-cells whereby the cells become less responsive to antigenic stimulation. Additionally, MPA enhanced the expression of negative co-stimulators such as CD70, PD-1, CTLA-4, and transcription factor FoxP3 as well as decreased the expression of positive co-stimulators CD27 and CD28.

MPA decreases proliferative responses of T- and B-lymphocytes to both mitogenic and allo-antigenic stimulation, antibody responses, as well as the production of cytokines from lymphocytes and monocytes such as GM-CSF, IFN-Ɣ, IL-17, and TNF-α. Additionally, MPA prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection.

Overall, the effect of MPA is cytostatic and reversible.

There is a lack of information regarding the pharmacodynamic effects of MMF.

Absorption

Following oral and intravenous administration, MMF undergoes complete conversion to MPA, the active metabolite. In 12 healthy volunteers, the mean absolute bioavailability of oral MMF relative to intravenous MMF was 94%. Two 500 mg mycophenolate mofetil tablets have been shown to be bioequivalent to four 250 mg mycophenolate mofetil capsules. Five mL of the 200 mg/mL constituted mycophenolate mofetil oral suspension have been shown to be bioequivalent to four 250 mg capsules.

The mean (±SD) pharmacokinetic parameters estimates for MPA following the administration of MMF given as single doses to healthy volunteers, and multiple doses to kidney, heart, and liver transplant patients, are shown in Table 10. The area under the plasma-concentration time curve (AUC) for MPA appears to increase in a dose-proportional fashion in kidney transplant patients receiving multiple oral doses of MMF up to a daily dose of 3 g (1.5g twice daily) (see Table 10).

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>    Table 10 Pharmacokinetic Parameters for MPA [mean (±SD)] Following Administration of MMF to Healthy Volunteers (Single Dose), and Kidney, Heart, and Liver Transplant Patients (Multiple Doses)</span> </caption> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tfoot> <tr> <td align="left" colspan="5"> <p class="First Footnote"> <span class="Sup">a</span>AUC<span class="Sub">(0-12h)</span> values quoted are extrapolated from data from samples collected over 4 hours.</p> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">  Healthy Volunteers</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">  Dose/Route</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">  T<span class="Sub">max (</span>h)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">  C<span class="Sub">max</span> (mcg/mL)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">  Total AUC (mcg•h/mL)</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Single dose<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1 g/oral<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 0.80<br/>  (±0.36) (n=129)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 24.5<br/>  (±9.5)<br/>   (n=129)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 63.9<br/>  (±16.2) (n=117)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold">  Kidney Transplant Patients (twice daily dosing) Time After Transplantation</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  Dose/Route</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  T<span class="Sub">max</span> (h)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  C<span class="Sub">max</span> (mcg/mL)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  Interdosing Interval AUC </span> <br/> <span class="Bold">  (0-12h)</span> <br/> <span class="Bold">  (mcg•h/mL)</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> 5 days<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1 g/iv<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.58<br/>  (±0.46)<br/>  (n=31)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 12.0<br/>  (±3.82)<br/>   (n=31)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 40.8<br/>  (±11.4)<br/>   (n=31)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> 6 days<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1 g/oral<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.33<br/>  (±1.05)<br/>  (n=31)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 10.7<br/>  (±4.83)<br/>   (n=31)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 32.9<br/>  (±15.0)<br/>   (n=31)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Early (Less than 40 days)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1 g/oral<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.31<br/>  (±0.76)<br/>  (n=25)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 8.16<br/>  (±4.50)<br/>   (n=25)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 27.3<br/>  (±10.9)<br/>   (n=25)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Early (Less than 40 days)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.5 g/oral<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.21<br/>  (±0.81)<br/>  (n=27)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 13.5<br/>  (±8.18)<br/>   (n=27)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 38.4<br/>  (±15.4) <br/>  (n=27)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Late (Greater than 3 months)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.5 g/oral<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 0.90<br/>  (±0.24)<br/>  (n=23)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 24.1<br/>  (±12.1)<br/>   (n=23)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 65.3<br/>  (±35.4) <br/>  (n=23)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold">  Heart transplant Patients (twice daily dosing) Time After Transplantation</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  Dose/Route</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  T<span class="Sub">max</span> (h)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  C<span class="Sub">max</span> (mcg/mL)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  Interdosing Interval</span> <br/> <span class="Bold">  AUC</span> <br/> <span class="Bold">  (0-12h)</span> <br/> <span class="Bold">  (mcg•h/mL)</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Early<br/>  (Day before discharge)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.5 g/oral<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.8<br/>  (±1.3) <br/>  (n=11)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 11.5<br/>  (±6.8)<br/>   (n=11)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 43.3<br/>  (±20.8)<br/>   (n=9)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Late (Greater than 6 months)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.5 g/oral<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.1<br/>  (±0.7) <br/>  (n=52)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 20.0<br/>  (±9.4)<br/>   (n=52)<br/> </td><td align="center" class="Botrule Rrule" valign="top">  54.1<span class="Sup">a</span> <br/>  (±20.4) <br/>  (n=49)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold">  Liver transplant Patients (twice daily dosing) Time After Transplantation</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  Dose/Route</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  T<span class="Sub">max</span> (h)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  C<span class="Sub">max</span> (mcg/mL)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  Interdosing Interval AUC </span> <br/> <span class="Bold">  (0-12h)</span> <br/> <span class="Bold">  (mcg•h/mL)</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> 4 to 9 days<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1 g/iv<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.50<br/>  (±0.517)<br/>  (n=22)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 17.0<br/>  (±12.7)<br/>   (n=22)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 34.0<br/>  (±17.4)<br/>   (n=22)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Early (5 to 8 days)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.5 g/oral<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.15<br/>  (±0.432)<br/>  (n=20)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 13.1<br/>  (±6.76)<br/>   (n=20)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 29.2<br/>  (±11.9)<br/>   (n=20)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Late (Greater than 6 months)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.5 g/oral<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.54<br/>  (±0.51)<br/>   (n=6)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 19.3<br/>  (±11.7)<br/>   (n=6)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 49.3<br/>  (±14.8)<br/>   (n=6)<br/> </td> </tr> </tbody> </table></div>

In the early post-transplant period (less than 40 days post-transplant), kidney, heart, and liver transplant patients had mean MPA AUCs approximately 20% to 41% lower and mean Cmax approximately 32% to 44% lower compared to the late transplant period (i.e., 3 to 6 months post-transplant) (non-stationarity in MPA pharmacokinetics).

Mean MPA AUC values following administration of 1 g twice daily intravenous mycophenolate mofetil over 2 hours to kidney transplant patients for 5 days were about 24% higher than those observed after oral administration of a similar dose in the immediate post-transplant phase.

In liver transplant patients, administration of 1 g twice daily intravenous mycophenolate mofetil followed by 1.5 g twice daily oral mycophenolate mofetil resulted in mean MPA AUC estimates similar to those found in kidney transplant patients administered 1 g mycophenolate mofetil twice daily.

Effect of Food

Food (27 g fat, 650 calories) had no effect on the extent of absorption (MPA AUC) of MMF when administered at doses of 1.5 g twice daily to kidney transplant patients. However, MPA Cmax was decreased by 40% in the presence of food [see Dosage and Administration (2.1)].

Distribution

The mean (±SD) apparent volume of distribution of MPA in 12 healthy volunteers was approximately 3.6 (±1.5) L/kg. At clinically relevant concentrations, MPA is 97% bound to plasma albumin. The phenolic glucuronide metabolite of MPA (MPAG) is 82% bound to plasma albumin at MPAG concentration ranges that are normally seen in stable kidney transplant patients; however, at higher MPAG concentrations (observed in patients with kidney impairment or delayed kidney graft function), the binding of MPA may be reduced as a result of competition between MPAG and MPA for protein binding. Mean blood to plasma ratio of radioactivity concentrations was approximately 0.6 indicating that MPA and MPAG do not extensively distribute into the cellular fractions of blood.

In vitro studies to evaluate the effect of other agents on the binding of MPA to human serum albumin (HSA) or plasma proteins showed that salicylate (at 25 mg/dL with human serum albumin) and MPAG (at ≥ 460 mcg/mL with plasma proteins) increased the free fraction of MPA. MPA at concentrations as high as 100 mcg/mL had little effect on the binding of warfarin, digoxin or propranolol, but decreased the binding of theophylline from 53% to 45% and phenytoin from 90% to 87%.

Elimination

Mean (±SD) apparent half-life and plasma clearance of MPA are 17.9 (±6.5) hours and 193 (±48) mL/min following oral administration, respectively.

Metabolism

The parent drug, MMF, can be measured systemically during the intravenous infusion; however, approximately 5 minutes after the infusion is stopped or after oral administration, MMF concentrations are below the limit of quantitation (0.4 mcg/mL).

Metabolism to MPA occurs pre-systemically after oral dosing. MPA is metabolized principally by glucuronyl transferase to form MPAG, which is not pharmacologically active. In vivo, MPAG is converted to MPA during enterohepatic recirculation. The following metabolites of the 2-hydroxyethyl-morpholino moiety are also recovered in the urine following oral administration of MMF to healthy subjects: N-(2-carboxymethyl)-morpholine, N-(2-hydroxyethyl)-morpholine, and the N-oxide of N-(2-hydroxyethyl)-morpholine.

Due to the enterohepatic recirculation of MPAG/MPA, secondary peaks in the plasma MPA concentration-time profile are usually observed 6 to 12 hours post-dose. Bile sequestrants, such as cholestyramine, reduce MPA AUC by interfering with this enterohepatic recirculation of the drug [see Overdosage (10) and Drug Interaction Studies below].

Excretion

Negligible amount of drug is excreted as MPA (less than 1% of dose) in the urine. Orally administered radiolabeled MMF resulted in complete recovery of the administered dose, with 93% of the administered dose recovered in the urine and 6% recovered in feces. Most (about 87%) of the administered dose is excreted in the urine as MPAG. At clinically encountered concentrations, MPA and MPAG are usually not removed by hemodialysis. However, at high MPAG plasma concentrations (> 100 mcg/mL), small amounts of MPAG are removed.

Increased plasma concentrations of MMF metabolites (MPA 50% increase and MPAG about a 3-fold to 6-fold increase) are observed in patients with renal insufficiency [see Specific Populations].

Specific Populations

Patients with Renal Impairment

The mean (±SD) pharmacokinetic parameters for MPA following the administration of oral MMF given as single doses to non-transplant subjects with renal impairment are presented in Table 11.

In a single-dose study, MMF was administered as a capsule or as an intravenous infusion over 40 minutes. Plasma MPA AUC observed after oral dosing to volunteers with severe chronic renal impairment (GFR < 25 mL/min/1.73 m2) was about 75% higher relative to that observed in healthy volunteers (GFR > 80 mL/min/1.73 m2). In addition, the single-dose plasma MPAG AUC was 3-fold to 6-fold higher in volunteers with severe renal impairment than in volunteers with mild renal impairment or healthy volunteers, consistent with the known renal elimination of MPAG. No data are available on the safety of long-term exposure to this level of MPAG.

Patients with Delayed Graft Function or Nonfunction

In patients with delayed renal graft function post-transplant, mean MPA AUC(0-12h) was comparable to that seen in post-transplant patients without delayed renal graft function. There is a potential for a transient increase in the free fraction and concentration of plasma MPA in patients with delayed renal graft function. However, dose adjustment does not appear to be necessary in patients with delayed renal graft function. Mean plasma MPAG AUC(0-12h) was 2-fold to 3-fold higher than in post-transplant patients without delayed renal graft function [see Dosage and Administration (2.5)].

In eight patients with primary graft non-function following kidney transplantation, plasma concentrations of MPAG accumulated about 6-fold to 8-fold after multiple dosing for 28 days. Accumulation of MPA was about 1-fold to 2-fold.

The pharmacokinetics of MMF are not altered by hemodialysis. Hemodialysis usually does not remove MPA or MPAG. At high concentrations of MPAG (> 100 mcg/mL), hemodialysis removes only small amounts of MPAG.

Patients with Hepatic Impairment

The mean (± SD) pharmacokinetic parameters for MPA following the administration of oral MMF given as single doses to non-transplant subjects with hepatic impairment is presented in Table 11.

In a single-dose (1 g oral) study of 18 volunteers with alcoholic cirrhosis and 6 healthy volunteers, hepatic MPA glucuronidation processes appeared to be relatively unaffected by hepatic parenchymal disease when pharmacokinetic parameters of healthy volunteers and alcoholic cirrhosis patients within this study were compared. However, it should be noted that for unexplained reasons, the healthy volunteers in this study had about a 50% lower AUC as compared to healthy volunteers in other studies, thus making comparisons between volunteers with alcoholic cirrhosis and healthy volunteers difficult.

<div class="scrollingtable"><table class="Noautorules" width="96%"> <caption> <span> Table 11 Pharmacokinetic Parameters for MPA [mean (±SD)] Following Single Doses of MMF Capsules in Chronic Renal and Hepatic Impairment</span> </caption> <col width="26%"/> <col width="13%"/> <col width="13%"/> <col width="21%"/> <col width="25%"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="5" valign="top"><span class="Bold"> Pharmacokinetic Parameters for Renal Impairment</span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> Dose</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> T<span class="Sub">max</span></span><span class="Bold"> (h)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> C<span class="Sub">max</span></span><span class="Bold"> (mcg/mL)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> AUC(0-96h)</span> <br/> <span class="Bold"> (mcg•h/mL)</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Healthy Volunteers<br/> GFR greater than 80 mL/min/1.73 m<span class="Sup">2</span> (n=6)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1 g<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 0.75<br/>  (±0.27)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 25.3<br/>  (±7.99)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 45.0<br/>  (±22.6)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Mild Renal Impairment<br/> GFR 50 to 80 mL/min/1.73 m<span class="Sup">2</span> (n=6)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1 g<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 0.75<br/>  (±0.27)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 26.0<br/>  (±3.82)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 59.9<br/>  (±12.9)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Moderate Renal Impairment<br/> GFR 25 to 49 mL/min/1.73 m<span class="Sup">2</span> (n=6)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1 g<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 0.75 <br/> (±0.27)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 19.0<br/>  (±13.2)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 52.9<br/>  (±25.5)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Severe Renal Impairment<br/> GFR less than 25 mL/min/1.73 m<span class="Sup">2</span> (n=7)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1 g<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.00<br/>  (±0.41)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 16.3<br/>  (±10.8)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 78.6 <br/> (±46.4)<br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="5" valign="top"><span class="Bold"> Pharmacokinetic Parameters for Hepatic Impairment</span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> Dose</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> T<span class="Sub">max</span></span><span class="Bold"> (h)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> C<span class="Sub">max</span></span> <br/> <span class="Bold">  (mcg/mL)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> AUC(0-48h)</span> <br/> <span class="Bold"> (mcg•h/mL)</span> <br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule" valign="top"> Healthy Volunteers<br/> </td><td align="center" class="Botrule Rrule" rowspan="2" valign="top"> 1 g<br/> </td><td align="center" class="Rrule" valign="top"> 0.63<br/> </td><td align="center" class="Rrule" valign="top"> 24.3<br/> </td><td align="center" class="Rrule" valign="top"> 29.0<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> (n=6)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (±0.14)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (±5.73)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (±5.78)<br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule" valign="top"> Alcoholic Cirrhosis<br/> </td><td align="center" class="Botrule Rrule" rowspan="2" valign="top"> 1 g<br/> </td><td align="center" class="Rrule" valign="top"> 0.85<br/> </td><td align="center" class="Rrule" valign="top"> 22.4<br/> </td><td align="center" class="Rrule" valign="top"> 29.8<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> (n=18)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (±0.58)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (±10.1)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (±10.7)<br/> </td> </tr> </tbody> </table></div>

Pediatric Patients

The pharmacokinetic parameters of MPA and MPAG have been evaluated in 55 pediatric patients (ranging from 1 year to 18 years of age) receiving mycophenolate mofetil oral suspension at a dose of 600 mg/m2 twice daily (up to a maximum of 1 g twice daily) after allogeneic kidney transplantation. The pharmacokinetic data for MPA is provided in Table 12.

<div class="scrollingtable"><table class="Noautorules" width="1049"> <caption> <span> Table 12 Mean (±SD) Computed Pharmacokinetic Parameters for MPA by Age and Time after Allogeneic Kidney Transplantation</span> </caption> <col width="153"/> <col width="153"/> <col width="161"/> <col width="87"/> <col width="99"/> <col width="82"/> <col width="98"/> <col width="86"/> <col width="130"/> <tfoot> <tr> <td align="left" colspan="9"> <p class="First Footnote"> <span class="Sup">a</span>adjusted to a dose of 600 mg/m<span class="Sup">2</span> </p> </td> </tr> <tr> <td align="left" colspan="9"> <p class="First Footnote"> <span class="Sup">b</span>n=20</p> </td> </tr> <tr> <td align="left" colspan="9"> <p class="First Footnote"> <span class="Sup">c</span>n=16</p> </td> </tr> <tr> <td align="left" colspan="9"> <p class="First Footnote"> <span class="Sup">d</span>a subset of 1 to &lt;6 yr</p> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold"> Age Group</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold"> (n)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold"> Time</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" colspan="2"><span class="Bold"> T<span class="Sub">max</span> (h)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" colspan="2"><span class="Bold"> Dose Adjusted<span class="Sup">a</span> C<span class="Sub">max</span></span> <br/> <span class="Bold"> (mcg/mL)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" colspan="2"><span class="Bold"> Dose Adjusted<span class="Sup">a</span> AUC<span class="Sub">0-12</span></span> <br/> <span class="Bold"> (mcg•h/mL)</span> <br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule"> 1 to less than 2 yr<br/> </td><td align="center" class="Rrule"> (6)<span class="Sup">d</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="4" valign="top"> Early (Day 7)<br/> </td><td align="center" valign="top"> 3.03<br/> </td><td align="center" class="Rrule" valign="top"> (4.70)<br/> </td><td align="center"> 10.3<br/> </td><td align="center" class="Rrule" valign="top"> (5.80)<br/> </td><td align="center" valign="top"> 22.5<br/> </td><td align="center" class="Rrule" valign="top"> (6.66)<br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule"> 1 to less than 6 yr<br/> </td><td align="center" class="Rrule"> (17)<br/> </td><td align="center" valign="top"> 1.63<br/> </td><td align="center" class="Rrule" valign="top"> (2.85)<br/> </td><td align="center"> 13.2<br/> </td><td align="center" class="Rrule" valign="top"> (7.16)<br/> </td><td align="center" valign="top"> 27.4<br/> </td><td align="center" class="Rrule" valign="top"> (9.54)<br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule"> 6 to less than 12 yr<br/> </td><td align="center" class="Rrule"> (16)<br/> </td><td align="center" valign="top"> 0.940<br/> </td><td align="center" class="Rrule" valign="top"> (0.546)<br/> </td><td align="center"> 13.1<br/> </td><td align="center" class="Rrule" valign="top"> (6.30)<br/> </td><td align="center" valign="top"> 33.2<br/> </td><td align="center" class="Rrule" valign="top"> (12.1)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> 12 to 18 yr<br/> </td><td align="center" class="Botrule Rrule"> (21)<br/> </td><td align="center" class="Botrule" valign="top"> 1.16<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (0.830)<br/> </td><td align="center" class="Botrule"> 11.7<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (10.7)<br/> </td><td align="center" class="Botrule" valign="top"> 26.3<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (9.14)<span class="Sup">b</span> <br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule"> 1 to less than 2 yr<br/> </td><td align="center" class="Rrule"> (4)<span class="Sup">d</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="4" valign="top"> Late (Month 3)<br/> </td><td align="center" valign="top"> 0.725<br/> </td><td align="center" class="Rrule" valign="top"> (0.276)<br/> </td><td align="center" valign="top"> 23.8<br/> </td><td align="center" class="Rrule" valign="top"> (13.4)<br/> </td><td align="center" valign="top"> 47.4<br/> </td><td align="center" class="Rrule" valign="top"> (14.7)<br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule"> 1 to less than 6 yr<br/> </td><td align="center" class="Rrule"> (15)<br/> </td><td align="center" valign="top"> 0.989<br/> </td><td align="center" class="Rrule" valign="top"> (0.511)<br/> </td><td align="center" valign="top"> 22.7<br/> </td><td align="center" class="Rrule" valign="top"> (10.1)<br/> </td><td align="center" valign="top"> 49.7<br/> </td><td align="center" class="Rrule" valign="top"> (18.2)<br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule"> 6 to less than 12 yr<br/> </td><td align="center" class="Rrule"> (14)<br/> </td><td align="center" valign="top"> 1.21<br/> </td><td align="center" class="Rrule" valign="top"> (0.532)<br/> </td><td align="center" valign="top"> 27.8<br/> </td><td align="center" class="Rrule" valign="top"> (14.3)<br/> </td><td align="center" valign="top"> 61.9<br/> </td><td align="center" class="Rrule" valign="top"> (19.6)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> 12 to 18 yr<br/> </td><td align="center" class="Botrule Rrule"> (17)<br/> </td><td align="center" class="Botrule" valign="top"> 0.978<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (0.484)<br/> </td><td align="center" class="Botrule" valign="top"> 17.9<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (9.57)<br/> </td><td align="center" class="Botrule" valign="top"> 53.6<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (20.3)<span class="Sup">c</span> <br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule"> 1 to less than 2 yr<br/> </td><td align="center" class="Rrule"> (4)<span class="Sup">d</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="4" valign="top"> Late (Month 9)<br/> </td><td align="center" valign="top"> 0.604<br/> </td><td align="center" class="Rrule" valign="top"> (0.208)<br/> </td><td align="center" valign="top"> 25.6<br/> </td><td align="center" class="Rrule" valign="top"> (4.25)<br/> </td><td align="center" valign="top"> 55.8<br/> </td><td align="center" class="Rrule" valign="top"> (11.6)<br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule"> 1 to less than 6 yr<br/> </td><td align="center" class="Rrule"> (12)<br/> </td><td align="center" valign="top"> 0.869<br/> </td><td align="center" class="Rrule" valign="top"> (0.479)<br/> </td><td align="center" valign="top"> 30.4<br/> </td><td align="center" class="Rrule" valign="top"> (9.16)<br/> </td><td align="center" valign="top"> 61.0<br/> </td><td align="center" class="Rrule" valign="top"> (10.7)<br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule"> 6 to less than 12 yr<br/> </td><td align="center" class="Rrule"> (11)<br/> </td><td align="center" valign="top"> 1.12<br/> </td><td align="center" class="Rrule" valign="top"> (0.462)<br/> </td><td align="center" valign="top"> 29.2<br/> </td><td align="center" class="Rrule" valign="top"> (12.6)<br/> </td><td align="center" valign="top"> 66.8<br/> </td><td align="center" class="Rrule" valign="top"> (21.2)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> 12 to 18 yr<br/> </td><td align="center" class="Botrule Rrule"> (14)<br/> </td><td align="center" class="Botrule" valign="top"> 1.09<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (0.518)<br/> </td><td align="center" class="Botrule" valign="top"> 18.1<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (7.29)<br/> </td><td align="center" class="Botrule" valign="top"> 56.7<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (14.0)<br/> </td> </tr> </tbody> </table></div>

The mycophenolate mofetil oral suspension dose of 600 mg/m2 twice daily (up to a maximum of 1 g twice daily) achieved mean MPA AUC values in pediatric patients similar to those seen in adult kidney transplant patients receiving mycophenolate mofetil capsules at a dose of 1 g twice daily in the early post-transplant period. There was wide variability in the data. As observed in adults, early post-transplant MPA AUC values were approximately 45% to 53% lower than those observed in the later post-transplant period (>3 months). MPA AUC values were similar in the early and late post-transplant period across the 1 to 18-year age range.

A comparison of dose-normalized (to 600 mg/m2) MPA AUC values in 12 pediatric kidney transplant patients less than 6 years of age at 9 months post-transplant with those values in 7 pediatric liver transplant patients [median age 17 months (range: 10 – 60 months)] and at 6 months and beyond post-transplant revealed that, at the same dose, there were on average 23% lower AUC values in the pediatric liver compared to pediatric kidney patients. This is consistent with the need for higher dosing in adult liver transplant patients compared to kidney transplant patients to achieve the same exposure.

In adult transplant patients administered the same dosage of mycophenolate mofetil, there is similar MPA exposure among kidney transplant and heart transplant patients. Based on the established similarity in MPA exposure between pediatric kidney transplant and adult kidney transplant patients at their respective approved doses, it is expected that MPA exposure at the  recommended dosage will be similar in pediatric heart transplant and adult heart transplant patients.

Male and Female Patients

Data obtained from several studies were pooled to look at any gender-related differences in the pharmacokinetics of MPA (data were adjusted to 1 g oral dose). Mean (±SD) MPA AUC (0-12h) for males (n=79) was 32.0 (±14.5) and for females (n=41) was 36.5 (±18.8) mcg•h/mL while mean (±SD) MPA Cmax was 9.96 (±6.19) in the males and 10.6 (±5.64) mcg/mL in the females. These differences are not of clinical significance.

Geriatric Patients

The pharmacokinetics of mycophenolate mofetil and its metabolites have not been found to be altered in geriatric transplant patients when compared to younger transplant patients.

Drug Interaction Studies

Acyclovir

Coadministration of MMF (1 g) and acyclovir (800 mg) to 12 healthy volunteers resulted in no significant change in MPA AUC and Cmax. However, MPAG and acyclovir plasma AUCs were increased 10.6% and 21.9%, respectively.

Antacids with Magnesium and Aluminum Hydroxides

Absorption of a single dose of MMF (2 g) was decreased when administered to 10 rheumatoid arthritis patients also taking Maalox® TC (10 mL qid). The Cmax and AUC(0-24h) for MPA were 33% and 17% lower, respectively, than when MMF was administered alone under fasting conditions.

Proton Pump Inhibitors (PPIs)

Coadministration of PPIs (e.g., lansoprazole, pantoprazole) in single doses to healthy volunteers and multiple doses to transplant patients receiving mycophenolate mofetil has been reported to reduce the exposure to MPA. An approximate reduction of 30 to 70% in the Cmax and 25% to 35% in the AUC of MPA has been observed, possibly due to a decrease in MPA solubility at an increased gastric pH.

Cholestyramine

Following single-dose administration of 1.5 g MMF to 12 healthy volunteers pretreated with 4 g three times a day of cholestyramine for 4 days, MPA AUC decreased approximately 40%. This decrease is consistent with interruption of enterohepatic recirculation which may be due to binding of recirculating MPAG with cholestyramine in the intestine.

Cyclosporine

Cyclosporine (Sandimmune®) pharmacokinetics (at doses of 275 to 415 mg/day) were unaffected by single and multiple doses of 1.5 g twice daily of MMF in 10 stable kidney transplant patients. The mean (±SD) AUC(0-12h) and Cmax of cyclosporine after 14 days of multiple doses of MMF were 3290 (±822) ng•h/mL and 753 (±161) ng/mL, respectively, compared to 3245 (±1088) ng•h/mL and 700 (±246) ng/mL, respectively, 1 week before administration of MMF.

Cyclosporine A interferes with MPA enterohepatic recirculation. In kidney transplant patients, mean MPA exposure (AUC(0-12h)) was approximately 30-50% greater when MMF was administered without cyclosporine compared with when MMF was coadministered with cyclosporine. This interaction is due to cyclosporine inhibition of multidrug-resistance-associated protein 2 (MRP-2) transporter in the biliary tract, thereby preventing the excretion of MPAG into the bile that would lead to enterohepatic recirculation of MPA. This information should be taken into consideration when MMF is used without cyclosporine.

Drugs Affecting Glucuronidation

Concomitant administration of drugs inhibiting glucuronidation of MPA may increase MPA exposure (e.g., increase of MPA AUC(0-∞) by 35% was observed with concomitant administration of isavuconazole).

Concomitant administration of telmisartan and mycophenolate mofetil resulted in an approximately 30% decrease in MPA concentrations. Telmisartan changes MPA's elimination by enhancing PPAR gamma (peroxisome proliferator-activated receptor gamma) expression, which in turn results in an enhanced UGT1A9 expression and glucuronidation activity.

Ganciclovir

Following single-dose administration to 12 stable kidney transplant patients, no pharmacokinetic interaction was observed between MMF (1.5 g) and intravenous ganciclovir (5 mg/kg). Mean (±SD) ganciclovir AUC and Cmax  (n=10) were 54.3 (±19.0) mcg•h/mL and 11.5 (±1.8) mcg/mL, respectively, after coadministration of the two drugs, compared to 51.0 (±17.0) mcg•h/mL and 10.6 (±2.0) mcg/mL, respectively, after administration of intravenous ganciclovir alone. The mean (±SD) AUC and Cmax of MPA (n=12) after coadministration were 80.9 (±21.6) mcg•h/mL and 27.8 (±13.9) mcg/mL, respectively, compared to values of 80.3 (±16.4) μg•h/mL and 30.9 (±11.2) mcg/mL, respectively, after administration of MMF alone.

Oral Contraceptives

A study of coadministration of mycophenolate mofetil (1 g twice daily) and combined oral contraceptives containing ethinylestradiol (0.02 mg to 0.04 mg) and levonorgestrel (0.05 mg to 0.20 mg), desogestrel (0.15 mg) or gestodene (0.05 mg to 0.10 mg) was conducted in 18 women with psoriasis over 3 consecutive menstrual cycles. Mean serum levels of LH, FSH and progesterone were not significantly affected. Mean AUC(0-24h) was similar for ethinylestradiol and 3-keto desogestrel; however, mean levonorgestrel AUC(0-24h) significantly decreased by about 15%. There was large inter-patient variability (%CV in the range of 60% to 70%) in the data, especially for ethinylestradiol.

Sevelamer

Concomitant administration of sevelamer and MMF in adult and pediatric patients decreased the mean MPA Cmax and AUC (0-12h) by 36% and 26% respectively.

Antimicrobials

Antimicrobials eliminating beta-glucuronidase-producing bacteria in the intestine (e.g. aminoglycoside, cephalosporin, fluoroquinolone, and penicillin classes of antimicrobials) may interfere with the MPAG/MPA enterohepatic recirculation thus leading to reduced systemic MPA exposure. Information concerning antibiotics is as follows:

In a 104-week oral carcinogenicity study in mice, MMF in daily doses up to 180 mg/kg was not tumorigenic. The highest dose tested was 0.2 times the recommended clinical dose (2 g/day) in renal transplant patients and 0.15 times the recommended clinical dose (3 g/day) in cardiac transplant patients when corrected for differences in body surface area (BSA). In a 104-week oral carcinogenicity study in rats, MMF in daily doses up to 15 mg/kg was not tumorigenic. The highest dose was 0.035 times the recommended clinical dose in kidney transplant patients and 0.025 times the recommended clinical dose in heart transplant patients when corrected for BSA. While these animal doses were lower than those given to patients, they were maximal in those species and were considered adequate to evaluate the potential for human risk [see Warnings and Precautions (5.2)]. 

The genotoxic potential of MMF was determined in five assays. MMF was genotoxic in the mouse lymphoma/thymidine kinase assay and the in vivo mouse micronucleus assay. MMF was not genotoxic in the bacterial mutation assay, the yeast mitotic gene conversion assay or the Chinese hamster ovary cell chromosomal aberration assay.

MMF had no effect on fertility of male rats at oral doses up to 20 mg/kg/day. This dose represents 0.05 times the recommended clinical dose in renal transplant patients and 0.03 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. In a female fertility and reproduction study conducted in rats, oral doses of 4.5 mg/kg/day caused malformations (principally of the head and eyes) in the first generation offspring in the absence of maternal toxicity. This dose was 0.01 times the recommended clinical dose in renal transplant patients and 0.005 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. No effects on fertility or reproductive parameters were evident in the dams or in the subsequent generation.

Adults

The three de novo kidney transplantation studies compared two dose levels of oral mycophenolate mofetil (1 g twice daily and 1.5 g twice daily) with azathioprine (2 studies) or placebo (1 study) to prevent acute rejection episodes. One of the two studies with azathioprine (AZA) control arm also included anti-thymocyte globulin (ATGAM®) induction therapy. The geographic location of the investigational sites of these studies are included in Table 13.

In all three de novo kidney transplantation studies, the primary efficacy endpoint was the proportion of patients in each treatment group who experienced treatment failure within the first 6 months after transplantation. Treatment failure was defined as biopsy-proven acute rejection on treatment or the occurrence of death, graft loss or early termination from the study for any reason without prior biopsy-proven rejection.

Mycophenolate mofetil, in combination with corticosteroids and cyclosporine, reduced (statistically significant at 0.05 level) the incidence of treatment failure within the first 6 months following transplantation (Table 13). Patients who prematurely discontinued treatment were followed for the occurrence of death or graft loss, and the cumulative incidence of graft loss and patient death combined are summarized in Table 14. Patients who prematurely discontinued treatment were not followed for the occurrence of acute rejection after termination.

<div class="scrollingtable"><table class="Noautorules" width="98%"> <caption> <span> Table 13 Treatment Failure in De Novo Kidney Transplantation Studies</span> </caption> <col width="27%"/> <col width="26%"/> <col width="26%"/> <col width="19%"/> <tfoot> <tr> <td align="left" colspan="4"> <p class="First Footnote">*Does not include death and graft loss as reason for early termination. </p> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="top"><span class="Bold">  USA Study </span> <br/> <span class="Bold"> (N=499 patients)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">  Mycophenolate mofetil </span> <br/> <span class="Bold"> 2 g/day </span> <br/> <span class="Bold"> (n=167 patients)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">  Mycophenolate mofetil </span> <br/> <span class="Bold"> 3 g/day </span> <br/> <span class="Bold"> (n=166 patients)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">  AZA</span> <br/> <span class="Bold">  1 to 2 mg/kg/day </span> <br/> <span class="Bold"> (n=166 patients)</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Rrule" colspan="3" valign="top"> All 3 groups received anti-thymocyte globulin induction,<br/>  cyclosporine and corticosteroids<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> All treatment failures<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 31.1%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 31.3%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 47.6%<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top">  Early termination without prior acute rejection<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 9.6%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 12.7%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 6.0%<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Biopsy-proven rejection episode on treatment<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 19.8%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 17.5%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 38.0%<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" rowspan="2" valign="top"><span class="Bold">  Europe/Canada/ Australia Study </span> <br/> <span class="Bold"> (N=503 patients)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  Mycophenolate mofetil </span> <br/> <span class="Bold"> 2 g/day </span> <br/> <span class="Bold"> (n=173 patients)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  Mycophenolate mofetil </span> <br/> <span class="Bold"> 3 g/day </span> <br/> <span class="Bold"> (n=164 patients)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  AZA</span> <br/> <span class="Bold">  100 to 150 mg/day </span> <br/> <span class="Bold"> (n=166 patients)</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Rrule" colspan="3" valign="top"> No induction treatment administered; all 3 groups received cyclosporine and corticosteroids.<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> All treatment failures<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 38.2%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 34.8%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 50.0%<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top">  Early termination without prior acute rejection<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 13.9%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 15.2%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 10.2%<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Biopsy-proven rejection episode on treatment<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 19.7%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 15.9%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 35.5%<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" rowspan="2" valign="top"><span class="Bold">  Europe Study </span> <br/> <span class="Bold"> (N=491 patients)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  Mycophenolate mofetil </span> <br/> <span class="Bold"> 2 g/day </span> <br/> <span class="Bold"> (n=165 patients)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  Mycophenolate mofetil </span> <br/> <span class="Bold"> 3 g/day </span> <br/> <span class="Bold"> (n=160 patients)</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  Placebo</span> <br/> <span class="Bold">  (n=166 patients)</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Rrule" colspan="3" valign="top"> No induction treatment administered; all 3 groups received cyclosporine and corticosteroids.<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> All treatment failures<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 30.3%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 38.8%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 56.0%<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top">  Early termination without prior acute rejection<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 11.5%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 22.5%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 7.2%<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Biopsy-proven rejection episode on treatment<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 17.0%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 13.8%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 46.4%<br/> </td> </tr> </tbody> </table></div>

No advantage of mycophenolate mofetil at 12 months with respect to graft loss or patient death (combined) was established (Table 14). Numerically, patients receiving mycophenolate mofetil 2 g/day and 3 g/day experienced a better outcome than controls in all three studies; patients receiving mycophenolate mofetil 2 g/day experienced a better outcome than mycophenolate mofetil 3 g/day in two of the three studies. Patients in all treatment groups who terminated treatment early were found to have a poor outcome with respect to graft loss or patient death at 1 year.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>    Table 14 De Novo Kidney Transplantation Studies Cumulative Incidence of Combined Graft Loss or Patient Death at 12 Months</span> </caption> <col width="25%"/> <col width="25%"/> <col width="25%"/> <col width="25%"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">  Study</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">  Mycophenolate mofetil </span> <br/> <span class="Bold"> 2 g/day</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">  Mycophenolate mofetil </span> <br/> <span class="Bold"> 3 g/day</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">  Control </span> <br/> <span class="Bold"> (AZA or Placebo)</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> USA<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 8.5%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 11.5%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 12.2%<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Europe/Canada/Australia<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 11.7%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 11.0%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 13.6%<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Europe<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 8.5%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 10.0%<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 11.5%<br/> </td> </tr> </tbody> </table></div>

Pediatrics- De Novo Kidney transplantation PK Study with Long Term Follow-Up

One open-label, safety and pharmacokinetic study of mycophenolate mofetil oral suspension 600 mg/m2 twice daily (up to 1 g twice daily) in combination with cyclosporine and corticosteroids was performed at centers in the United States (9), Europe (5) and Australia (1) in 100 pediatric patients (3 months to 18 years of age) for the prevention of renal allograft rejection. Mycophenolate mofetil was well tolerated in pediatric patients [see Adverse Reactions (6.1)], and the pharmacokinetics profile was similar to that seen in adult patients dosed with 1 g twice daily mycophenolate mofetil capsules [see Clinical Pharmacology (12.3)]. The rate of biopsy-proven rejection was similar across the age groups (3 months to <6 years, 6 years to <12 years, 12 years to 18 years). The overall biopsy-proven rejection rate at 6 months was comparable to adults. The combined incidence of graft loss (5%) and patient death (2%) at 12 months post-transplant was similar to that observed in adult kidney transplant patients.

A double-blind, randomized, comparative, parallel-group, multicenter study in primary de novo heart transplant recipients was performed at centers in the United States (20), in Canada (1), in Europe (5) and in Australia (2). The total number of patients enrolled (ITT population) was 650; 72 never received study drug and 578 received study drug (Safety Population). Patients received mycophenolate mofetil 1.5 g twice daily (n=289) or AZA 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune® or Neoral®) and corticosteroids as maintenance immunosuppressive therapy. The two primary efficacy endpoints were: (1) the proportion of patients who, after transplantation, had at least one endomyocardial biopsy-proven rejection with hemodynamic compromise, or were re-transplanted or died, within the first 6 months, and (2) the proportion of patients who died or were re-transplanted during the first 12 months following transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection for up to 6 months and for the occurrence of death for 1 year.

The analyses of the endpoints showed:

<div class="scrollingtable"><table class="Noautorules" width="94%"> <caption> <span>    Table 15 De Novo Heart Transplantation Study Rejection at 6 Months/Death or Re-transplantation at 1 Year</span> </caption> <col width="23%"/> <col width="13%"/> <col width="24%"/> <col width="13%"/> <col width="24%"/> <tfoot> <tr> <td align="left" colspan="5"> <p class="First Footnote"> <span class="Sup">a</span>Hemodynamic compromise occurred if any of the following criteria were met: pulmonary capillary wedge pressure ≥20 mm or a 25% increase; cardiac index &lt;2.0 L/min/m<span class="Sup">2</span> or a 25% decrease; ejection fraction ≤30%; pulmonary artery oxygen saturation ≤60% or a 25% decrease; presence of new S<span class="Sub">3</span> gallop; fractional shortening was ≤20% or a 25% decrease; inotropic support required to manage the clinical condition.</p> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2" valign="top"></td><td align="center" class="Botrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">  All Patients (ITT)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">  Treated Patients</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  AZA</span> <br/> <span class="Bold">  N = 323</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  Mycophenolate    mofetil</span> <br/> <span class="Bold">  N = 327</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  AZA </span> <br/> <span class="Bold">  N = 289</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold">  Mycophenolate mofetil</span> <br/> <span class="Bold">  N = 289</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top">  Biopsy-proven rejection with hemodynamic compromise at 6 months<span class="Sup">a</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"> 121 (38%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 120 (37%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 100 (35%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 92 (32%)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Death or re-transplantation at 1 year<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 49 (15.2%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 42 (12.8%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 33 (11.4%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 18 (6.2%)<br/> </td> </tr> </tbody> </table></div>

A double-blind, randomized, comparative, parallel-group, multicenter study in primary hepatic transplant recipients was performed at centers in the United States (16), in Canada (2), in Europe (4) and in Australia (1). The total number of patients enrolled was 565. Per protocol, patients received mycophenolate mofetil 1 g twice daily intravenously for up to 14 days followed by mycophenolate mofetil 1.5 g twice daily orally or AZA 1 to 2 mg/kg/day intravenously followed by AZA 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral®) and corticosteroids as maintenance immunosuppressive therapy. The actual median oral dose of AZA on study was 1.5 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) initially and 1.26 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) at 12 months. The two primary endpoints were: (1) the proportion of patients who experienced, in the first 6 months post-transplantation, one or more episodes of biopsy-proven and treated rejection or death or re-transplantation, and (2) the proportion of patients who experienced graft loss (death or re-transplantation) during the first 12 months post-transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection and for the occurrence of graft loss (death or re-transplantation) for 1 year.

In combination with corticosteroids and cyclosporine, mycophenolate mofetil demonstrated a lower rate of acute rejection at 6 months and a similar rate of death or re-transplantation at 1 year compared to AZA (Table 16).

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span> Table16 De Novo Liver Transplantation Study Rejection at 6 Months/Death or Retransplantation at 1 Year</span> </caption> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tbody class="Headless"> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">  AZA </span> <br/> <span class="Bold"> N = 287</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">  Mycophenolate Mofetil</span> <br/> <span class="Bold">  N = 278</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Biopsy-proven, treated rejection at 6 months (includes death or re-transplantation)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 137 (47.7%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 107 (38.5%)<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Death or re-transplantation at 1 year<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 42 (14.6%)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 41 (14.7%)<br/> </td> </tr> </tbody> </table></div>

1. "OSHA Hazardous Drugs." OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

{ "type": "p", "children": [], "text": "\n1. \"OSHA Hazardous Drugs.\" OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html\n" }

Mycophenolate mofetil (MMF) has demonstrated teratogenic effects in humans [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. Mycophenolate mofetil tablets should not be crushed and mycophenolate mofetil capsules should not be opened or crushed. Avoid inhalation or direct contact with skin or mucous membranes of the powder contained in mycophenolate mofetil capsules [see Dosage and Administration (2.6)]. Follow applicable special handling and disposal procedures1.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="100%"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"> Capsules<br/> White to off-white blend of mycophenolate mofetil filled in size "1" hard gelatin capsule with Ivory Cap and Ivory Body, printed "SAL" on cap and "726" on body in black.<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Sizes<br/> Bottles of 100 ……………. NDC 64380-726-06<br/> Bottles of 500 ……………. NDC 64380-726-07<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Storage <br/> • Store at 20° to 25°C (68° to 77°F), [See USP controlled room temperature]. Dispense in light-resistant containers, such as the manufacturer's original containers.<br/> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="100%"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"> Tablets<br/> Pinkish brown colored, capsule shaped, film coated tablet with "SAL" engraved on one side and engraved "725" on other side.<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Sizes<br/> Bottle of 100……………………………… NDC 64380-725-06<br/> Bottle of 500……………………………… NDC 64380-725-07<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Storage:<br/> • Store at 20° to 25°C (68° to 77°F). [See USP controlled room temperature]. Dispense in light-resistant containers, such as the manufacturer's original containers.<br/> </td> </tr> </tbody> </table></div>

Pregnancy loss and malformations

Contraception

Inform patients that they are at increased risk of developing a variety of infections due to immunosuppression. Instruct them to contact their physician if they develop any of the signs and symptoms of infection explained in the Medication Guide [see Warnings and Precautions (5.3)].

Inform patients that they are at increased risk for developing blood adverse effects such as anemia or low white blood cells. Advise patients to immediately contact their healthcare provider if they experience any evidence of infection, unexpected bruising, or bleeding, or any other manifestation of bone marrow suppression [see Warnings and Precautions (5.4)].

Inform patients that mycophenolate mofetil can cause gastrointestinal tract complications including bleeding, intestinal perforations, and gastric or duodenal ulcers. Advise the patient to contact their healthcare provider if they have symptoms of gastrointestinal bleeding, or sudden onset or persistent abdominal pain [see Warnings and Precautions (5.5)].

Inform patients that acute inflammatory reactions have been reported in some patients who received mycophenolate mofetil. Some reactions were severe, requiring hospitalization. Advise patients to contact their physician if they develop fever, joint stiffness, joint pain or muscle pains [see Warnings and Precautions (5.7)].

Inform patients that mycophenolate mofetil can interfere with the usual response to immunizations. Before seeking vaccines on their own, advise patients to discuss first with their physician [see Warnings and Precautions (5.8)].

Advise patients not to donate blood during therapy and for at least 6 weeks following discontinuation of mycophenolate mofetil [see Warnings and Precautions (5.11)].

Advise males of childbearing potential not to donate semen during therapy and for 90 days following discontinuation of mycophenolate mofetil [see Warnings and Precautions (5.12)].

Advise patients that mycophenolate mofetil can affect the ability to drive or operate machines. Patients should avoid driving or operating machines if they experience somnolence, confusion, dizziness, tremor or hypotension during treatment with mycophenolate mofetil [see Warnings and Precautions (5.14)].

Distributed by:

Strides Pharma Inc.

East Brunswick, NJ 08816

Revised: 03/2025

Medication Guide available at:

For Capsules: www.strides.com/mmf-caps/

For Tablets: www.strides.com/mmf-tabs/

<div class="scrollingtable"><table class="Noautorules" width="99%"> <col width="354"/> <col width="6"/> <col width="8"/> <col width="337"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="4" valign="top"><span class="Bold">  MEDICATION GUIDE</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="4" valign="top"><span class="Bold"> Mycophenolate Mofetil Capsules, USP and </span> <br/> <span class="Bold"> Mycophenolate Mofetil Tablets, USP</span> <br/> <span class="Bold"> (mye'' koe fen' oh late moe' fe til)</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="4" valign="top"> Read the Medication Guide that comes with mycophenolate mofetil tablets and capsules before you start taking it and each time you refill your prescription. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment.<br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4" valign="top"><span class="Bold">  What is the most important information I should know about mycophenolate mofetil?</span> <br/> <span class="Bold">  Mycophenolate mofetil can cause serious side effects, including:</span> <br/> <span class="Bold">  Increased risk of loss of a pregnancy (miscarriage) and higher risk of birth defects. </span>  Females who take mycophenolate mofetil during pregnancy have a higher risk of miscarriage during the first 3 months (first trimester), and a higher risk that their baby will be born with birth defects.<br/> <ul class="Disc"> <li> <span class="Bold"> If you are a female who can become </span><span class="Bold"> pregnant,</span> your doctor must talk with you about acceptable birth control methods (contraceptive counseling) to use while taking mycophenolate mofetil. You should have 1 pregnancy test immediately before starting mycophenolate mofetil and another pregnancy test 8 to 10 days later. Pregnancy tests should be repeated during routine follow-up visits with your doctor. Talk to your doctor about the results of all of your pregnancy tests.</li> </ul> You must use acceptable birth control during your entire mycophenolate mofetil treatment and for 6 weeks after stopping mycophenolate mofetil, unless at any time you choose to avoid sexual intercourse (abstinence) with a man completely. Mycophenolate mofetil decreases blood levels of the hormones in birth control pills that you take by mouth. Birth control pills may not work as well while you take mycophenolate mofetil, and you could become pregnant. If you take birth control pills while using mycophenolate mofetil you must also use another form of birth control. Talk to your doctor about other birth control methods that you can use while taking mycophenolate mofetil.  <br/> <ul class="Disc"> <li> <span class="Bold"> If you are a sexually active male whose female partner can become pregnant while you are taking mycophenolate mofetil,</span> use effective contraception during treatment and for at least 90 days after stopping mycophenolate mofetil. </li> <li> <span class="Bold"> If you plan to become pregnant</span> , talk with your doctor. Your doctor will decide if other medicines to prevent rejection may be right for you. </li> <li> <span class="Bold"> If you become pregnant while taking mycophenolate mofetil, do not stop taking mycophenolate mofetil. Call your doctor right away. </span>  You and your doctor may decide that other medicines to prevent rejection may be right for you. You and your doctor should report your pregnancy to the Mycophenolate Pregnancy Registry either: <ul class="Circle"> <li>By phone at 1-800-617-8191 <span class="Bold"> or</span> </li> <li>By visiting the REMS website at: <span class="Bold">  www.mycophenolateREMS.com</span> </li> </ul> </li> </ul> The purpose of this registry is to gather information about the health of you and your baby.<br/> <span class="Bold">  Increased risk of getting certain cancers. </span>  People who take mycophenolate mofetil have a higher risk of getting lymphoma, and other cancers, especially skin cancer. Tell your doctor if you have:<br/> </td> </tr> <tr> <td class="Lrule" colspan="3" valign="top"> <ul class="Disc"> <li>unexplained fever, prolonged tiredness, weight loss or lymph node swelling</li> </ul> </td><td class="Rrule" valign="top"> <ul class="Disc"> <li>a change in the size and color of a mole</li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="3" valign="top"> <ul class="Disc"> <li>a brown or black skin lesion with uneven borders, or one part of the lesion does not look like the other</li> </ul> </td><td class="Rrule" valign="top"> <ul class="Disc"> <li>a new skin lesion or bump</li> <li>any other changes to your health</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4" valign="top">  Increased risk of getting serious infections.  Mycophenolate mofetil weakens the body's immune system and affects your ability to fight infections. Serious infections can happen with mycophenolate mofetil and can lead to hospitalizations and death. These serious infections can include:<br/> <ul class="Disc"> <li>Viral infections.  Certain viruses can live in your body and cause active infections when your immune system is weak. Viral infections that can happen with mycophenolate mofetil include: <ul class="Circle"> <li>Shingles, other herpes infections, and cytomegalovirus (CMV). CMV can cause serious tissue and blood infections. </li> <li>BK virus. BK virus can affect how your kidney works and cause your transplanted kidney to fail</li> <li>Hepatitis B and C viruses. Hepatitis viruses can affect how your liver works. Talk to your doctor about how hepatitis viruses may affect you. </li> <li>COVID-19</li> </ul> </li> </ul> <ul class="Disc"> <li>A brain infection called Progressive Multifocal Leukoencephalopathy (PML).  In some patients, mycophenolate mofetil may cause an infection of the brain that may cause death. You are at risk for this brain infection because you have a weakened immune system. Call your doctor right away if you have any of the following symptoms:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> o    weakness on one side of the body<br/> o    you do not care about things you usually care about (apathy)<br/> </td><td align="left" class="Rrule" colspan="3" valign="top"> o    you are confused or have problems thinking<br/> o    you cannot control your muscles<br/> </td> </tr> <tr> <td class="Lrule Rrule" colspan="4" valign="top"> <ul class="Disc"> <li>Fungal infections.  Yeasts and other types of fungal infections can happen with mycophenolate mofetil and can cause serious tissue and blood infections (See "What are the possible side effects of mycophenolate mofetil?").</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4" valign="top"><span class="Bold">  Call your doctor right away if you have any of the following signs and symptoms of infection:</span> <br/> </td> </tr> <tr> <td class="Lrule" colspan="2" valign="top"> <ul class="Disc"> <li>temperature of 100.5°F or greater                            </li> </ul> </td><td class="Rrule" colspan="2" valign="top"> <ul class="Disc"> <li>pain during urination</li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="2" valign="top"> <ul class="Disc"> <li>cold symptoms, such as a runny nose or sore throat       </li> </ul> </td><td class="Rrule" colspan="2" valign="top"> <ul class="Disc"> <li>white patches in the mouth or throat                             </li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="2" valign="top"> <ul class="Disc"> <li>flu symptoms, such as an upset stomach, stomach pain, vomiting or diarrhea  </li> </ul> </td><td class="Rrule" colspan="2" valign="top"> <ul class="Disc"> <li>unexpected bruising or bleeding</li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="2" valign="top"> <ul class="Disc"> <li>earache or headache</li> </ul> </td><td class="Rrule" colspan="2" valign="top"> <ul class="Disc"> <li>cuts, scrapes or incisions that are red, warm and oozing pus</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4" valign="top"> See<span class="Bold"> "What are the possible side effects of mycophenolate mofetil?" </span>  for information about other serious side effects.<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="4" valign="top"><span class="Bold">  What is mycophenolate mofetil?</span> <br/>  •  Mycophenolate mofetil is a prescription medicine to prevent rejection (antirejection medicine) in people who have received a kidney, heart or liver transplant. Rejection is when the body's immune system perceives the new organ as a "foreign" threat and attacks it.<br/>  •  Mycophenolate mofetil is used with other medicines containing cyclosporine and corticosteroids.<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="4" valign="top"><span class="Bold"> Who should not take mycophenolate mofetil?</span> <br/> <span class="Bold"> Do not take mycophenolate mofetil if you are allergic to mycophenolate mofetil or any of the ingredients in mycophenolate mofetil capsules and tablets. </span> See the end of this Medication Guide for a complete list of ingredients in mycophenolate mofetil capsules and tablets.<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="4" valign="top"><span class="Bold">  What should I tell my doctor before taking mycophenolate mofetil?</span> <br/> <span class="Bold">  Tell your doctor about all of your medical conditions, including if you</span> :<br/>  •  have any digestive problems, such as ulcers.<br/>  •   have Lesch-Nyhan syndrome, Kelley-Seegmiller syndrome, or another rare inherited deficiency hypoxanthine-guanine phosphoribosyl-transferase (HGPRT). You should not take mycophenolate mofetil if you have one of these disorders.<br/>  •  plan to receive any vaccines. People taking mycophenolate mofetil should not receive live vaccines. Some vaccines may not work as well during treatment with mycophenolate mofetil.<br/>  •  are pregnant or plan to become pregnant. See<span class="Bold"> "What is the most important information I should know about mycophenolate mofetil?"</span> <br/>  •  are breastfeeding or plan to breastfeed. It is not known if mycophenolate mofetil passes into breast milk. You and your doctor will decide if you will take mycophenolate mofetil or breastfeed.<br/> <span class="Bold">  Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins and herbal supplements. Some medicines may affect the way mycophenolate mofetil works, and mycophenolate mofetil may affect how some medicines work.<br/>  Especially tell your doctor if you take: <br/>  •  birth control pills (oral contraceptives). See <span class="Bold"> "What is the most important information I should know about mycophenolate mofetil?"</span> <br/>  •  sevelamer (Renagel<span class="Sup">®</span>, Renvela<span class="Sup">TM</span>). These products should be taken at least 2 hours after taking mycophenolate mofetil.<br/>  •  acyclovir (Zovirax<span class="Sup">®</span>), valacyclovir (Valtrex<span class="Sup">®</span>), ganciclovir (CYTOVENE<span class="Sup">®</span>-IV, Vitrasert<span class="Sup">®</span>), valganciclovir (VALCYTE<span class="Sup">®</span>).<br/>  •  rifampin (Rifater<span class="Sup">®</span>, Rifamate<span class="Sup">®</span>, Rimactane<span class="Sup">®</span>, Rifadin<span class="Sup">®</span>). <br/>  •  antacids that contain magnesium and aluminum (mycophenolate mofetil and the antacid should not be taken at the same time).<br/>  •  proton pump inhibitors (PPIs) (Prevacid<span class="Sup">®</span>, Protonix<span class="Sup">®</span>).<br/>  •  sulfamethoxazole/trimethoprim (BACTRIM<span class="Sup">TM</span>, BACTRIM DS<span class="Sup">TM</span>).<br/>  •  norfloxacin (Noroxin<span class="Sup">®</span>) and metronidazole (Flagyl<span class="Sup">®</span>, Flagyl<span class="Sup">®</span> ER, Flagyl<span class="Sup">®</span> IV, Metro IV, Helidac<span class="Sup">®</span>, Pylera<span class="Sup">TM</span>).<br/>  •  ciprofloxacin (Cipro<span class="Sup">®</span>, Cipro<span class="Sup">®</span> XR, Ciloxan<span class="Sup">®</span>, Proquin<span class="Sup">®</span> XR) and amoxicillin plus clavulanic acid (Augmentin<span class="Sup">®</span>, Augmentin XR<span class="Sup">TM</span>).  <br/>  •  azathioprine (Azasan<span class="Sup">®</span>, Imuran<span class="Sup">®</span>).<br/>  •  cholestyramine (Questran Light<span class="Sup">®</span>, Questran<span class="Sup">®</span>, Locholest Light, Locholest, Prevalite<span class="Sup">®</span>).<br/>  Know the medicines you take. Keep a list of them to show to your doctor or nurse and pharmacist when you get a new medicine. <span class="Bold"> Do not</span> take any new medicine without talking with your doctor.<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="4" valign="top"><span class="Bold"> How should I take mycophenolate mofetil?</span> <br/> <ul class="Disc"> <li>Take mycophenolate mofetil exactly as prescribed.</li> <li> <span class="Bold"> Do not</span> stop taking mycophenolate mofetil or change the dose unless your doctor tells you to.</li> <li>If you miss a dose of mycophenolate mofetil, or you are not sure when you took your last dose, take your prescribed dose of mycophenolate mofetil as soon as you remember. If your next dose is less than 2 hours away, skip the missed dose and take your next dose at your normal scheduled time. <span class="Bold"> Do not</span> take 2 doses at the same time. Call your doctor if you are not sure what to do.</li> <li>Take mycophenolate mofetil capsules and tablets on an empty stomach, unless your doctor tells you otherwise. <span class="Bold"> Do not</span> crush mycophenolate mofetil tablets.</li> <li> <span class="Bold"> Do not</span> open or crush mycophenolate mofetil capsules.</li> <li>If you are not able to swallow mycophenolate mofetil tablets or capsules, your doctor may prescribe mycophenolate mofetil oral suspension. This is a liquid form of mycophenolate mofetil. Your pharmacist will mix the medicine before you pick it up from a pharmacy. </li> <li> <span class="Bold"> Do not </span> breathe in (inhale) or let mycophenolate mofetil powder or oral suspension come in contact with your skin or mucous membranes. <ul class="Circle"> <li>If you accidentally get the powder or oral suspension on the skin, wash the area well with soap and water.</li> <li>If you accidentally get the powder or oral suspension in your eyes or other mucous membranes, flush with plain water.</li> </ul> </li> <li>If you take too much mycophenolate mofetil, call your doctor or the poison control center right away.</li> </ul> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="4" valign="top"><span class="Bold">  What should I avoid while taking mycophenolate mofetil?</span> <br/>  •  Avoid becoming pregnant. (See "<span class="Bold"> What is the most important information I should know about mycophenolate mofetil?"</span> ).<br/>  •  Limit the amount of time you spend in sunlight. Avoid using tanning beds or sunlamps. People who take mycophenolate mofetil have a higher risk of getting skin cancer (See "<span class="Bold"> What is the most important information I should know about mycophenolate mofetil?"</span> ). Wear protective clothing when you are in the sun and use a broad-spectrum sunscreen with a high protection factor. This is especially important if your skin is very fair or if you have a family history of skin cancer.<br/>  •  You should not donate blood while taking mycophenolate mofetil and for at least 6 weeks after stopping mycophenolate mofetil. <br/>  •  You should not donate sperm while taking mycophenolate mofetil and for 90 days after stopping mycophenolate mofetil. <br/>  •  Mycophenolate mofetil may influence your ability to drive and use machines (See<span class="Bold"> "What are the possible side effects of mycophenolate mofetil?".</span>   If you experience drowsiness, confusion, dizziness, tremor, or low blood pressure during treatment with mycophenolate mofetil, you should be cautious about driving or using heavy machines.<br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4" valign="top"><span class="Bold">  What are the possible side effects of mycophenolate mofetil? </span> <br/> <span class="Bold">  Mycophenolate mofetil can cause serious side effects, including:</span> <br/> <ul class="Disc"> <li>See<span class="Bold"> "What is the most important information I should know about mycophenolate mofetil?"</span> </li> <li> <span class="Bold"> Low blood cell counts. </span>  People taking high doses of mycophenolate mofetil each day may have a decrease in blood counts, including: <ul class="Circle"> <li> <span class="Bold"> white blood cells, especially neutrophils. </span>  Neutrophils fight against bacterial infections. You have a higher chance of getting an infection when your white blood cell count is low. This is most common from 1 month to 6 months after your transplant.</li> <li> <span class="Bold"> red blood cells. </span>  Red blood cells carry oxygen to your body tissues. You have a higher chance of getting severe anemia when your red blood cell count is low.</li> <li> <span class="Bold"> platelets. </span>  Platelets help with blood clotting.</li> </ul> </li> </ul> Your doctor will do blood tests before you start taking mycophenolate mofetil and during treatment with mycophenolate mofetil to check your blood cell counts. Tell your doctor right away if you have any signs of infection (See<span class="Bold"> "What is the most important information I should know about mycophenolate mofetil?"</span> ), including any unexpected bruising or bleeding. Also, tell your doctor if you have unusual tiredness, lack of energy, dizziness or fainting.<br/> <ul class="Disc"> <li> <span class="Bold"> Stomach problems. </span>  Stomach problems including intestinal bleeding, a tear in your intestinal wall (perforation) or stomach ulcers can happen in people who take mycophenolate mofetil. Bleeding can be severe and you may have to be hospitalized for treatment. Call your doctor right away if you have sudden or severe stomach-area pain or stomach-area pain that does not go away, or if you have diarrhea. </li> <li> <span class="Bold"> Inflammatory reactions.</span> Some people taking mycophenolate mofetil may have an inflammatory reaction with fever, joint stiffness, joint pain, and muscle pain. Some of these reactions may require hospitalization. This reaction could happen within weeks to months after your treatment with mycophenolate mofetil starts or if your dose is increased. Call your doctor right away if you experience these symptoms.</li> </ul> <span class="Bold">  The most common side effects of mycophenolate mofetil include:</span> <br/> </td> </tr> <tr> <td class="Lrule" colspan="3" valign="top"> <ul class="Disc"> <li>diarrhea  </li> </ul> </td><td class="Rrule" valign="top"> <ul class="Disc"> <li>changes in laboratory blood levels, including high levels of blood sugar (hyperglycemia)</li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="3" valign="top"> <ul class="Disc"> <li>blood problems including low white and red blood cell counts     </li> </ul> </td><td class="Rrule" valign="top"> <ul class="Disc"> <li>stomach problems including diarrhea, constipation, nausea and vomiting</li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="3" valign="top"> <ul class="Disc"> <li>infections</li> </ul> </td><td class="Rrule" valign="top"> <ul class="Disc"> <li>rash</li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="3" valign="top"> <ul class="Disc"> <li>blood pressure problems</li> </ul> </td><td class="Rrule" valign="top"> <ul class="Disc"> <li>nervous system problems such as headache, dizziness and tremor</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="4" valign="top"> <ul class="Disc"> <li>fast heart beat</li> <li>swelling of the lower legs, ankles and feet</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4" valign="top"><span class="Bold"> Side effects that can happen more often in children than in adults taking mycophenolate mofetil include</span> :<br/> </td> </tr> <tr> <td class="Lrule" colspan="3" valign="top"> <ul class="Disc"> <li>stomach area pain </li> </ul> </td><td class="Rrule" valign="top"> <ul class="Disc"> <li>vomiting </li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="3" valign="top"> <ul class="Disc"> <li>fever </li> </ul> </td><td class="Rrule" valign="top"> <ul class="Disc"> <li>sore throat </li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="3" valign="top"> <ul class="Disc"> <li>infection </li> </ul> </td><td class="Rrule" valign="top"> <ul class="Disc"> <li>colds (respiratory tract infections) </li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="3" valign="top"> <ul class="Disc"> <li>pain </li> </ul> </td><td class="Rrule" valign="top"> <ul class="Disc"> <li>high blood pressure </li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="3" valign="top"> <ul class="Disc"> <li>blood infection (sepsis) </li> </ul> </td><td class="Rrule" valign="top"> <ul class="Disc"> <li>low white blood cell count </li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="3" valign="top"> <ul class="Disc"> <li>diarrhea</li> </ul> </td><td class="Rrule" valign="top"> <ul class="Disc"> <li>low red blood cell count</li> </ul> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="4" valign="top"> These are not all of the possible side effects of mycophenolate mofetil. Tell your doctor about any side effect that bothers you or that does not go away.<br/> <span class="Bold">  Call your doctor for medical advice about side effects.  You may report side effects to FDA at 1-800-FDA-1088. </span> You may also report side effects to Strides Pharma Inc. at 1-877-244-9825 or go to www.strides.com.<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="4" valign="top"><span class="Bold">  How should I store mycophenolate mofetil capsules and tablets?</span> <br/> <ul class="Disc"> <li>Store mycophenolate mofetil capsules and tablets at room temperature between 20° to 25°C (68° to 77°F).</li> </ul> <ul class="Disc"> <li>Keep mycophenolate mofetil tablets in the light resistant container that it comes in.</li> </ul> <span class="Bold">   Keep mycophenolate mofetil and all medicines out of the reach of children.</span> <br/> <br/> <span class="Bold"> General Information about the safe and effective use of mycophenolate mofetil.</span> <br/> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use mycophenolate mofetil for a condition for which it was not prescribed. Do not give mycophenolate mofetil to other people, even if they have the same symptoms that you have. It may harm them.  <br/> This Medication Guide summarizes the most important information about mycophenolate mofetil. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist about mycophenolate mofetil that is written for health professionals.<br/> <span class="Bold"> What are the ingredients in mycophenolate mofetil capsules and tablets?</span> <br/> <span class="Bold"> Active Ingredient: </span> mycophenolate mofetil <br/> <span class="Bold"> Inactive Ingredients:</span> <br/> <span class="Bold"> Mycophenolate mofetil 250 mg capsules: </span> croscarmellose sodium, magnesium stearate, microcrystalline cellulose, povidone (K-30). The capsule shells contain FD&amp;C red # 3, gelatin, sodium lauryl sulfate, titanium dioxide and yellow iron oxide.<br/> <span class="Bold"> Mycophenolate mofetil 500 mg tablets: </span> croscarmellose sodium, magnesium stearate (Vegetable), microcrystalline cellulose, opadry brown, povidone [K-30]. <br/> The opadry brown contains FD&amp;C blue #1 aluminum lake, FD&amp;C red #40 aluminum lake, hypromellose, iron oxide red, polyethylene glycol and titanium dioxide.<br/> Distributed by:<br/> <span class="Bold"> Strides Pharma Inc.</span> <br/> East Brunswick, NJ 08816<br/> Revised: 05/2025<br/> This Medication Guide has been approved by the U.S. Food and Drug Administration.<br/> <br/> <span class="Bold">  Medication Guide available at:</span> <br/> <span class="Bold"> Tablets: www.strides.com/mmf-tabs/</span> <br/> <span class="Bold"> Capsules: www.strides.com/mmf-caps/</span> <br/> <br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"99%\">\n<col width=\"354\"/>\n<col width=\"6\"/>\n<col width=\"8\"/>\n<col width=\"337\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"4\" valign=\"top\"><span class=\"Bold\">  MEDICATION GUIDE</span>\n<br/>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\"><span class=\"Bold\"> Mycophenolate Mofetil Capsules, USP and </span>\n<br/>\n<span class=\"Bold\"> Mycophenolate Mofetil Tablets, USP</span>\n<br/>\n<span class=\"Bold\"> (mye'' koe fen' oh late moe' fe til)</span>\n<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\"> Read the Medication Guide that comes with mycophenolate mofetil tablets and capsules before you start taking it and each time you refill your prescription. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment.<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\" valign=\"top\"><span class=\"Bold\">  What is the most important information I should know about mycophenolate mofetil?</span>\n<br/>\n<span class=\"Bold\">  Mycophenolate mofetil can cause serious side effects, including:</span>\n<br/>\n<span class=\"Bold\">  Increased risk of loss of a pregnancy (miscarriage) and higher risk of birth defects. </span>  Females who take mycophenolate mofetil during pregnancy have a higher risk of miscarriage during the first 3 months (first trimester), and a higher risk that their baby will be born with birth defects.<br/>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\"> If you are a female who can become </span><span class=\"Bold\"> pregnant,</span> your doctor must talk with you about acceptable birth control methods (contraceptive counseling) to use while taking mycophenolate mofetil. You should have 1 pregnancy test immediately before starting mycophenolate mofetil and another pregnancy test 8 to 10 days later. Pregnancy tests should be repeated during routine follow-up visits with your doctor. Talk to your doctor about the results of all of your pregnancy tests.</li>\n</ul>\n You must use acceptable birth control during your entire mycophenolate mofetil treatment and for 6 weeks after stopping mycophenolate mofetil, unless at any time you choose to avoid sexual intercourse (abstinence) with a man completely. Mycophenolate mofetil decreases blood levels of the hormones in birth control pills that you take by mouth. Birth control pills may not work as well while you take mycophenolate mofetil, and you could become pregnant. If you take birth control pills while using mycophenolate mofetil you must also use another form of birth control. Talk to your doctor about other birth control methods that you can use while taking mycophenolate mofetil.  <br/>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\"> If you are a sexually active male whose female partner can become pregnant while you are taking mycophenolate mofetil,</span> use effective contraception during treatment and for at least 90 days after stopping mycophenolate mofetil. </li>\n<li>\n<span class=\"Bold\"> If you plan to become pregnant</span> , talk with your doctor. Your doctor will decide if other medicines to prevent rejection may be right for you. </li>\n<li>\n<span class=\"Bold\"> If you become pregnant while taking mycophenolate mofetil, do not stop taking mycophenolate mofetil. Call your doctor right away. </span>  You and your doctor may decide that other medicines to prevent rejection may be right for you. You and your doctor should report your pregnancy to the Mycophenolate Pregnancy Registry either:\n\n<ul class=\"Circle\">\n<li>By phone at 1-800-617-8191 <span class=\"Bold\"> or</span>\n</li>\n<li>By visiting the REMS website at: <span class=\"Bold\">  www.mycophenolateREMS.com</span>\n</li>\n</ul>\n</li>\n</ul>\n The purpose of this registry is to gather information about the health of you and your baby.<br/>\n<span class=\"Bold\">  Increased risk of getting certain cancers. </span>  People who take mycophenolate mofetil have a higher risk of getting lymphoma, and other cancers, especially skin cancer. Tell your doctor if you have:<br/>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\" valign=\"top\">\n<ul class=\"Disc\">\n<li>unexplained fever, prolonged tiredness, weight loss or lymph node swelling</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"top\">\n<ul class=\"Disc\">\n<li>a change in the size and color of a mole</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\" valign=\"top\">\n<ul class=\"Disc\">\n<li>a brown or black skin lesion with uneven borders, or one part of the lesion does not look like the other</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"top\">\n<ul class=\"Disc\">\n<li>a new skin lesion or bump</li>\n<li>any other changes to your health</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\" valign=\"top\">  Increased risk of getting serious infections.  Mycophenolate mofetil weakens the body's immune system and affects your ability to fight infections. Serious infections can happen with mycophenolate mofetil and can lead to hospitalizations and death. These serious infections can include:<br/>\n<ul class=\"Disc\">\n<li>Viral infections.  Certain viruses can live in your body and cause active infections when your immune system is weak. Viral infections that can happen with mycophenolate mofetil include:\n\n<ul class=\"Circle\">\n<li>Shingles, other herpes infections, and cytomegalovirus (CMV). CMV can cause serious tissue and blood infections. </li>\n<li>BK virus. BK virus can affect how your kidney works and cause your transplanted kidney to fail</li>\n<li>Hepatitis B and C viruses. Hepatitis viruses can affect how your liver works. Talk to your doctor about how hepatitis viruses may affect you. </li>\n<li>COVID-19</li>\n</ul>\n</li>\n</ul>\n<ul class=\"Disc\">\n<li>A brain infection called Progressive Multifocal Leukoencephalopathy (PML).  In some patients, mycophenolate mofetil may cause an infection of the brain that may cause death. You are at risk for this brain infection because you have a weakened immune system. Call your doctor right away if you have any of the following symptoms:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> o    weakness on one side of the body<br/> o    you do not care about things you usually care about (apathy)<br/>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"3\" valign=\"top\"> o    you are confused or have problems thinking<br/> o    you cannot control your muscles<br/>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<ul class=\"Disc\">\n<li>Fungal infections.  Yeasts and other types of fungal infections can happen with mycophenolate mofetil and can cause serious tissue and blood infections (See \"What are the possible side effects of mycophenolate mofetil?\").</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\" valign=\"top\"><span class=\"Bold\">  Call your doctor right away if you have any of the following signs and symptoms of infection:</span>\n<br/>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"2\" valign=\"top\">\n<ul class=\"Disc\">\n<li>temperature of 100.5°F or greater                            </li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\" valign=\"top\">\n<ul class=\"Disc\">\n<li>pain during urination</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"2\" valign=\"top\">\n<ul class=\"Disc\">\n<li>cold symptoms, such as a runny nose or sore throat       </li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\" valign=\"top\">\n<ul class=\"Disc\">\n<li>white patches in the mouth or throat                             </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"2\" valign=\"top\">\n<ul class=\"Disc\">\n<li>flu symptoms, such as an upset stomach, stomach pain, vomiting or diarrhea  </li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\" valign=\"top\">\n<ul class=\"Disc\">\n<li>unexpected bruising or bleeding</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"2\" valign=\"top\">\n<ul class=\"Disc\">\n<li>earache or headache</li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\" valign=\"top\">\n<ul class=\"Disc\">\n<li>cuts, scrapes or incisions that are red, warm and oozing pus</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\" valign=\"top\"> See<span class=\"Bold\"> \"What are the possible side effects of mycophenolate mofetil?\" </span>  for information about other serious side effects.<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\"><span class=\"Bold\">  What is mycophenolate mofetil?</span>\n<br/>  •  Mycophenolate mofetil is a prescription medicine to prevent rejection (antirejection medicine) in people who have received a kidney, heart or liver transplant. Rejection is when the body's immune system perceives the new organ as a \"foreign\" threat and attacks it.<br/>  •  Mycophenolate mofetil is used with other medicines containing cyclosporine and corticosteroids.<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\"><span class=\"Bold\"> Who should not take mycophenolate mofetil?</span>\n<br/>\n<span class=\"Bold\"> Do not take mycophenolate mofetil if you are allergic to mycophenolate mofetil or any of the ingredients in mycophenolate mofetil capsules and tablets. </span> See the end of this Medication Guide for a complete list of ingredients in mycophenolate mofetil capsules and tablets.<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\"><span class=\"Bold\">  What should I tell my doctor before taking mycophenolate mofetil?</span>\n<br/>\n<span class=\"Bold\">  Tell your doctor about all of your medical conditions, including if you</span> :<br/>  •  have any digestive problems, such as ulcers.<br/>  •   have Lesch-Nyhan syndrome, Kelley-Seegmiller syndrome, or another rare inherited deficiency hypoxanthine-guanine phosphoribosyl-transferase (HGPRT). You should not take mycophenolate mofetil if you have one of these disorders.<br/>  •  plan to receive any vaccines. People taking mycophenolate mofetil should not receive live vaccines. Some vaccines may not work as well during treatment with mycophenolate mofetil.<br/>  •  are pregnant or plan to become pregnant. See<span class=\"Bold\"> \"What is the most important information I should know about mycophenolate mofetil?\"</span>\n<br/>  •  are breastfeeding or plan to breastfeed. It is not known if mycophenolate mofetil passes into breast milk. You and your doctor will decide if you will take mycophenolate mofetil or breastfeed.<br/>\n<span class=\"Bold\">  Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins and herbal supplements. Some medicines may affect the way mycophenolate mofetil works, and mycophenolate mofetil may affect how some medicines work.<br/>  Especially tell your doctor if you take: <br/>  •  birth control pills (oral contraceptives). See <span class=\"Bold\"> \"What is the most important information I should know about mycophenolate mofetil?\"</span>\n<br/>  •  sevelamer (Renagel<span class=\"Sup\">®</span>, Renvela<span class=\"Sup\">TM</span>). These products should be taken at least 2 hours after taking mycophenolate mofetil.<br/>  •  acyclovir (Zovirax<span class=\"Sup\">®</span>), valacyclovir (Valtrex<span class=\"Sup\">®</span>), ganciclovir (CYTOVENE<span class=\"Sup\">®</span>-IV, Vitrasert<span class=\"Sup\">®</span>), valganciclovir (VALCYTE<span class=\"Sup\">®</span>).<br/>  •  rifampin (Rifater<span class=\"Sup\">®</span>, Rifamate<span class=\"Sup\">®</span>, Rimactane<span class=\"Sup\">®</span>, Rifadin<span class=\"Sup\">®</span>). <br/>  •  antacids that contain magnesium and aluminum (mycophenolate mofetil and the antacid should not be taken at the same time).<br/>  •  proton pump inhibitors (PPIs) (Prevacid<span class=\"Sup\">®</span>, Protonix<span class=\"Sup\">®</span>).<br/>  •  sulfamethoxazole/trimethoprim (BACTRIM<span class=\"Sup\">TM</span>, BACTRIM DS<span class=\"Sup\">TM</span>).<br/>  •  norfloxacin (Noroxin<span class=\"Sup\">®</span>) and metronidazole (Flagyl<span class=\"Sup\">®</span>, Flagyl<span class=\"Sup\">®</span> ER, Flagyl<span class=\"Sup\">®</span> IV, Metro IV, Helidac<span class=\"Sup\">®</span>, Pylera<span class=\"Sup\">TM</span>).<br/>  •  ciprofloxacin (Cipro<span class=\"Sup\">®</span>, Cipro<span class=\"Sup\">®</span> XR, Ciloxan<span class=\"Sup\">®</span>, Proquin<span class=\"Sup\">®</span> XR) and amoxicillin plus clavulanic acid (Augmentin<span class=\"Sup\">®</span>, Augmentin XR<span class=\"Sup\">TM</span>).  <br/>  •  azathioprine (Azasan<span class=\"Sup\">®</span>, Imuran<span class=\"Sup\">®</span>).<br/>  •  cholestyramine (Questran Light<span class=\"Sup\">®</span>, Questran<span class=\"Sup\">®</span>, Locholest Light, Locholest, Prevalite<span class=\"Sup\">®</span>).<br/>  Know the medicines you take. Keep a list of them to show to your doctor or nurse and pharmacist when you get a new medicine. <span class=\"Bold\"> Do not</span> take any new medicine without talking with your doctor.<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\"><span class=\"Bold\"> How should I take mycophenolate mofetil?</span>\n<br/>\n<ul class=\"Disc\">\n<li>Take mycophenolate mofetil exactly as prescribed.</li>\n<li>\n<span class=\"Bold\"> Do not</span> stop taking mycophenolate mofetil or change the dose unless your doctor tells you to.</li>\n<li>If you miss a dose of mycophenolate mofetil, or you are not sure when you took your last dose, take your prescribed dose of mycophenolate mofetil as soon as you remember. If your next dose is less than 2 hours away, skip the missed dose and take your next dose at your normal scheduled time. <span class=\"Bold\"> Do not</span> take 2 doses at the same time. Call your doctor if you are not sure what to do.</li>\n<li>Take mycophenolate mofetil capsules and tablets on an empty stomach, unless your doctor tells you otherwise. <span class=\"Bold\"> Do not</span> crush mycophenolate mofetil tablets.</li>\n<li>\n<span class=\"Bold\"> Do not</span> open or crush mycophenolate mofetil capsules.</li>\n<li>If you are not able to swallow mycophenolate mofetil tablets or capsules, your doctor may prescribe mycophenolate mofetil oral suspension. This is a liquid form of mycophenolate mofetil. Your pharmacist will mix the medicine before you pick it up from a pharmacy. </li>\n<li>\n<span class=\"Bold\"> Do not </span> breathe in (inhale) or let mycophenolate mofetil powder or oral suspension come in contact with your skin or mucous membranes.\n\n<ul class=\"Circle\">\n<li>If you accidentally get the powder or oral suspension on the skin, wash the area well with soap and water.</li>\n<li>If you accidentally get the powder or oral suspension in your eyes or other mucous membranes, flush with plain water.</li>\n</ul>\n</li>\n<li>If you take too much mycophenolate mofetil, call your doctor or the poison control center right away.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\"><span class=\"Bold\">  What should I avoid while taking mycophenolate mofetil?</span>\n<br/>  •  Avoid becoming pregnant. (See \"<span class=\"Bold\"> What is the most important information I should know about mycophenolate mofetil?\"</span> ).<br/>  •  Limit the amount of time you spend in sunlight. Avoid using tanning beds or sunlamps. People who take mycophenolate mofetil have a higher risk of getting skin cancer (See \"<span class=\"Bold\"> What is the most important information I should know about mycophenolate mofetil?\"</span> ). Wear protective clothing when you are in the sun and use a broad-spectrum sunscreen with a high protection factor. This is especially important if your skin is very fair or if you have a family history of skin cancer.<br/>  •  You should not donate blood while taking mycophenolate mofetil and for at least 6 weeks after stopping mycophenolate mofetil. <br/>  •  You should not donate sperm while taking mycophenolate mofetil and for 90 days after stopping mycophenolate mofetil. <br/>  •  Mycophenolate mofetil may influence your ability to drive and use machines (See<span class=\"Bold\"> \"What are the possible side effects of mycophenolate mofetil?\".</span>   If you experience drowsiness, confusion, dizziness, tremor, or low blood pressure during treatment with mycophenolate mofetil, you should be cautious about driving or using heavy machines.<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\" valign=\"top\"><span class=\"Bold\">  What are the possible side effects of mycophenolate mofetil? </span>\n<br/>\n<span class=\"Bold\">  Mycophenolate mofetil can cause serious side effects, including:</span>\n<br/>\n<ul class=\"Disc\">\n<li>See<span class=\"Bold\"> \"What is the most important information I should know about mycophenolate mofetil?\"</span>\n</li>\n<li>\n<span class=\"Bold\"> Low blood cell counts. </span>  People taking high doses of mycophenolate mofetil each day may have a decrease in blood counts, including:\n\n<ul class=\"Circle\">\n<li>\n<span class=\"Bold\"> white blood cells, especially neutrophils. </span>  Neutrophils fight against bacterial infections. You have a higher chance of getting an infection when your white blood cell count is low. This is most common from 1 month to 6 months after your transplant.</li>\n<li>\n<span class=\"Bold\"> red blood cells. </span>  Red blood cells carry oxygen to your body tissues. You have a higher chance of getting severe anemia when your red blood cell count is low.</li>\n<li>\n<span class=\"Bold\"> platelets. </span>  Platelets help with blood clotting.</li>\n</ul>\n</li>\n</ul>\n Your doctor will do blood tests before you start taking mycophenolate mofetil and during treatment with mycophenolate mofetil to check your blood cell counts. Tell your doctor right away if you have any signs of infection (See<span class=\"Bold\"> \"What is the most important information I should know about mycophenolate mofetil?\"</span> ), including any unexpected bruising or bleeding. Also, tell your doctor if you have unusual tiredness, lack of energy, dizziness or fainting.<br/>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\"> Stomach problems. </span>  Stomach problems including intestinal bleeding, a tear in your intestinal wall (perforation) or stomach ulcers can happen in people who take mycophenolate mofetil. Bleeding can be severe and you may have to be hospitalized for treatment. Call your doctor right away if you have sudden or severe stomach-area pain or stomach-area pain that does not go away, or if you have diarrhea. </li>\n<li>\n<span class=\"Bold\"> Inflammatory reactions.</span> Some people taking mycophenolate mofetil may have an inflammatory reaction with fever, joint stiffness, joint pain, and muscle pain. Some of these reactions may require hospitalization. This reaction could happen within weeks to months after your treatment with mycophenolate mofetil starts or if your dose is increased. Call your doctor right away if you experience these symptoms.</li>\n</ul>\n<span class=\"Bold\">  The most common side effects of mycophenolate mofetil include:</span>\n<br/>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\" valign=\"top\">\n<ul class=\"Disc\">\n<li>diarrhea  </li>\n</ul>\n</td><td class=\"Rrule\" valign=\"top\">\n<ul class=\"Disc\">\n<li>changes in laboratory blood levels, including high levels of blood sugar (hyperglycemia)</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\" valign=\"top\">\n<ul class=\"Disc\">\n<li>blood problems including low white and red blood cell counts     </li>\n</ul>\n</td><td class=\"Rrule\" valign=\"top\">\n<ul class=\"Disc\">\n<li>stomach problems including diarrhea, constipation, nausea and vomiting</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\" valign=\"top\">\n<ul class=\"Disc\">\n<li>infections</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"top\">\n<ul class=\"Disc\">\n<li>rash</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\" valign=\"top\">\n<ul class=\"Disc\">\n<li>blood pressure problems</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"top\">\n<ul class=\"Disc\">\n<li>nervous system problems such as headache, dizziness and tremor</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<ul class=\"Disc\">\n<li>fast heart beat</li>\n<li>swelling of the lower legs, ankles and feet</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\" valign=\"top\"><span class=\"Bold\"> Side effects that can happen more often in children than in adults taking mycophenolate mofetil include</span> :<br/>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\" valign=\"top\">\n<ul class=\"Disc\">\n<li>stomach area pain </li>\n</ul>\n</td><td class=\"Rrule\" valign=\"top\">\n<ul class=\"Disc\">\n<li>vomiting </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\" valign=\"top\">\n<ul class=\"Disc\">\n<li>fever </li>\n</ul>\n</td><td class=\"Rrule\" valign=\"top\">\n<ul class=\"Disc\">\n<li>sore throat </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\" valign=\"top\">\n<ul class=\"Disc\">\n<li>infection </li>\n</ul>\n</td><td class=\"Rrule\" valign=\"top\">\n<ul class=\"Disc\">\n<li>colds (respiratory tract infections) </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\" valign=\"top\">\n<ul class=\"Disc\">\n<li>pain </li>\n</ul>\n</td><td class=\"Rrule\" valign=\"top\">\n<ul class=\"Disc\">\n<li>high blood pressure </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\" valign=\"top\">\n<ul class=\"Disc\">\n<li>blood infection (sepsis) </li>\n</ul>\n</td><td class=\"Rrule\" valign=\"top\">\n<ul class=\"Disc\">\n<li>low white blood cell count </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\" valign=\"top\">\n<ul class=\"Disc\">\n<li>diarrhea</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"top\">\n<ul class=\"Disc\">\n<li>low red blood cell count</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\"> These are not all of the possible side effects of mycophenolate mofetil. Tell your doctor about any side effect that bothers you or that does not go away.<br/>\n<span class=\"Bold\">  Call your doctor for medical advice about side effects.  You may report side effects to FDA at 1-800-FDA-1088. </span> You may also report side effects to Strides Pharma Inc. at 1-877-244-9825 or go to www.strides.com.<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\"><span class=\"Bold\">  How should I store mycophenolate mofetil capsules and tablets?</span>\n<br/>\n<ul class=\"Disc\">\n<li>Store mycophenolate mofetil capsules and tablets at room temperature between 20° to 25°C (68° to 77°F).</li>\n</ul>\n<ul class=\"Disc\">\n<li>Keep mycophenolate mofetil tablets in the light resistant container that it comes in.</li>\n</ul>\n<span class=\"Bold\">   Keep mycophenolate mofetil and all medicines out of the reach of children.</span>\n<br/>\n<br/>\n<span class=\"Bold\"> General Information about the safe and effective use of mycophenolate mofetil.</span>\n<br/> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use mycophenolate mofetil for a condition for which it was not prescribed. Do not give mycophenolate mofetil to other people, even if they have the same symptoms that you have. It may harm them.  <br/> This Medication Guide summarizes the most important information about mycophenolate mofetil. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist about mycophenolate mofetil that is written for health professionals.<br/>\n<span class=\"Bold\"> What are the ingredients in mycophenolate mofetil capsules and tablets?</span>\n<br/>\n<span class=\"Bold\"> Active Ingredient: </span> mycophenolate mofetil <br/>\n<span class=\"Bold\"> Inactive Ingredients:</span>\n<br/>\n<span class=\"Bold\"> Mycophenolate mofetil 250 mg capsules: </span> croscarmellose sodium, magnesium stearate, microcrystalline cellulose, povidone (K-30). The capsule shells contain FD&amp;C red # 3, gelatin, sodium lauryl sulfate, titanium dioxide and yellow iron oxide.<br/>\n<span class=\"Bold\"> Mycophenolate mofetil 500 mg tablets: </span> croscarmellose sodium, magnesium stearate (Vegetable), microcrystalline cellulose, opadry brown, povidone [K-30]. <br/> The opadry brown contains FD&amp;C blue #1 aluminum lake, FD&amp;C red #40 aluminum lake, hypromellose, iron oxide red, polyethylene glycol and titanium dioxide.<br/> Distributed by:<br/>\n<span class=\"Bold\"> Strides Pharma Inc.</span>\n<br/> East Brunswick, NJ 08816<br/> Revised: 05/2025<br/> This Medication Guide has been approved by the U.S. Food and Drug Administration.<br/>\n<br/>\n<span class=\"Bold\">  Medication Guide available at:</span>\n<br/>\n<span class=\"Bold\"> Tablets: www.strides.com/mmf-tabs/</span>\n<br/>\n<span class=\"Bold\"> Capsules: www.strides.com/mmf-caps/</span>\n<br/>\n<br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Mycophenolate Mofetil Capsules, USP

{ "type": "p", "children": [], "text": "\nMycophenolate Mofetil Capsules, USP" }

250 mg

{ "type": "p", "children": [], "text": "250 mg" }

Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }

100 Capsules

{ "type": "p", "children": [], "text": "100 Capsules" }

NDC 64380-726-06

{ "type": "p", "children": [], "text": "NDC 64380-726-06" }

Mycophenolate Mofetil Tablets, USP

{ "type": "p", "children": [], "text": "\nMycophenolate Mofetil Tablets, USP" }

500 mg

{ "type": "p", "children": [], "text": "500 mg" }

Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }

100 Tablets

{ "type": "p", "children": [], "text": "100 Tablets" }

NDC 64380-725-06

{ "type": "p", "children": [], "text": "NDC 64380-725-06" }

Mycophenolate mofetil is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney [see Clinical Studies (14.1)], heart [see Clinical Studies (14.2)] or liver transplants [see Clinical Studies (14.3)] , in combination with other immunosuppressants.

{ "type": "p", "children": [], "text": "Mycophenolate mofetil is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney\n \n [see\n \n Clinical Studies (14.1)],\n \n heart\n \n [see\n \n Clinical Studies (14.2)]\n \n or liver transplants\n \n [see\n \n Clinical Studies (14.3)]\n \n , in combination with other immunosuppressants.\n\n " }

Mycophenolate mofetil for injection should not be used without the supervision of a physician with experience in immunosuppressive therapy.

Mycophenolate Mofetil for Injection

Mycophenolate mofetil for injection is recommended for patients unable to take oral mycophenolate mofetil. Mycophenolate mofetil for injection should be administered within 24 hours following transplant. Mycophenolate mofetil for injection can be administered for up to 14 days; however, patients should be switched to oral mycophenolate mofetil as soon as they can tolerate oral medication.

Mycophenolate mofetil for injection must be reconstituted before use [see Dosage and Administration (2.6)] . Mycophenolate mofetil for injection is incompatible with other intravenous infusion solutions and should not be mixed or administered concurrently via the same infusion catheter with other intravenous drugs or infusion admixtures.

Mycophenolate mofetil for injection must not be administered as a bolus. Following reconstitution, mycophenolate mofetil for injection must be administered by slow intravenous infusion over a period of no less than 2 hours by either peripheral or central vein, as rapid infusion increases the risk of local adverse reactions such as phlebitis and thrombosis [see Adverse Reactions (6.1)] .

Adults

The recommended dosage for adult kidney transplant patients is 1 g orally or intravenously infused over no less than 2 hours, twice daily (daily dose of 2 g).

Pediatrics (3 months and older)

Pediatric dosing is based on body surface area (BSA). The recommended dosage of mycophenolate mofetil oral suspension for pediatric kidney transplant patients 3 months and older is 600 mg/m 2, administered twice daily (maximum total daily dose of 2 g or 10 mL of the oral suspension). Pediatric patients with BSA ≥ 1.25 m 2may be dosed with capsules or tablets as follows:

Table 1: Pediatric Kidney Transplant: Dosage Using Capsules or Tablets

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Body Surface Area</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Dosage</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">1.25 m <span class="Sup">2</span>to &lt;1.5 m <span class="Sup">2</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Mycophenolate mofetil capsule 750 mg twice daily (1.5 g total daily dose)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">≥ 1.5 m <span class="Sup">2</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Mycophenolate mofetil capsules or tablets 1 g twice daily (2 g total daily dose)</p> </td> </tr> </tbody> </table></div>

Adults

The recommended dosage of mycophenolate mofetil for adult heart transplant patients is 1.5 g orally or intravenously infused over no less than 2 hours administered twice daily (total daily dose of 3 g).

Pediatrics (3 months and older) The recommended starting dosage of mycophenolate mofetil oral suspension for pediatric heart transplant patients 3 months and older is 600 mg/m 2, administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m 2twice daily (maximum total daily dose of 3 g or 15 mL of the oral suspension). The dose may be individualized based on clinical assessment. Pediatric patients with BSA ≥1.25 m 2may be started on therapy with capsules or tablets as follows:

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 2 Pediatric Heart Transplant: Pediatric Starting Dosage Using Capsules or Tablets </span> </caption> <tbody class="Headless"> <tr class="First"> <td><span class="Bold"> Body Surface Area</span></td><td><span class="Bold"> Starting Dosage*</span></td> </tr> <tr> <td> 1.25 m <span class="Sup">2</span>to &lt;1.5 m <span class="Sup">2</span></td><td> Mycophenolate mofetil capsule 750 mg twice daily (1.5 g total daily dose)</td> </tr> <tr class="Last"> <td> ≥ 1.5 m <span class="Sup">2</span></td><td> Mycophenolate mofetil capsules or tablets 1 g twice daily (2 g total daily dose)</td> </tr> </tbody> </table></div>

 *Maximum maintenance dose: 3 g total daily.

Adults

The recommended dosage of mycophenolate mofetil for adult liver transplant patients is 1.5 g administered orally twice daily (daily dose of 3 g) or 1 g infused intravenously over no less than 2 hours, twice daily (total daily dose of 2 g).

Pediatrics (3 months and older) The recommended starting dosage of mycophenolate mofetil oral suspension for pediatric liver transplant patients 3 months of age and older is 600 mg/m 2, administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m 2twice daily (maximum total daily dose of 3 g or 15 mL of the oral suspension). The dose may be individualized based on clinical assessment. Pediatric patients with BSA ≥ 1.25 m 2may be started on therapy with capsules or tablets as follows:

<div class="scrollingtable"><table width="100%"> <caption> <span> Table 3 Pediatric Liver Transplant: Pediatric Starting Dosage Using Capsules or Tablets</span> </caption> <tbody class="Headless"> <tr class="First"> <td><span class="Bold"> Body Surface Area</span></td><td><span class="Bold"> Starting Dosage*</span></td> </tr> <tr> <td> 1.25 m <span class="Sup">2</span>to &lt;1.5 m <span class="Sup">2</span></td><td> Mycophenolate mofetil capsule 750 mg twice daily (1.5 g total daily dose)</td> </tr> <tr class="Last"> <td> ≥ 1.5 m <span class="Sup">2</span></td><td> Mycophenolate mofetil capsules or tablets 1 g twice daily (2 g total daily dose)</td> </tr> </tbody> </table></div>

 *Maximum maintenance dose: 3 g total daily.

Renal Impairment

No dose modifications are needed in kidney transplant patients with delayed graft function postoperatively [see Clinical Pharmacology (12.3)] . In kidney transplant patients with severe chronic impairment of the graft(GFR < 25 mL/min/1.73 m 2), do not administer doses of mycophenolate mofetil greater than 1 g twice a day. These patients should be carefully monitored [see Clinical Pharmacology (12.3)].

Neutropenia

If neutropenia develops (ANC < 1.3 x 10 3/μL), dosing with mycophenolate mofetil should be interrupted or reduced, appropriate diagnostic tests performed, and the patient managed appropriately [see Warnings and Precautions (5.4)and Adverse Reactions (6.1)].

General Preparation Instructions Before Handling the Formulations

Mycophenolate mofetil (MMF) has demonstrated teratogenic effects in humans. Follow applicable special handling and disposal procedures. 1[see Warnings and Precautions (5.1), Adverse Reactions (6.2), Use in Specific Populations (8.1, 8.3), How Supplied/Storage and Handling (16.1)].

Care should be taken to avoid inhalation or direct contact with skin or mucous membranes of the dry powder contained in mycophenolate mofetil for injection because MMF has demonstrated teratogenic effects in humans .Wearing disposable gloves is recommended during reconstitution of mycophenolate mofetil for injection and when wiping the outer surface of the vial and the table surface after reconstitution. If such contact occurs, wash hands thoroughly with soap and water; rinse eyes with water.

Mycophenolate Mofetil for Injection

Before proceeding with the preparation steps for mycophenolate mofetil for injection read the general preparation instructions [see General Preparation Instructions Before Handling the Formulation]and note the following:

Mycophenolate mofetil for injection must be reconstituted and further diluted. A detailed description of the preparation is given below.

Table 4 Preparation Instructions of Mycophenolate Mofetil for Injection for Pharmacists

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Preparation of the</p> <p> <span class="Bold">1 g dose</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <ol class="Arabic"> <li> <span class="Underline">Reconstitute</span>two (2) vials of mycophenolate mofetil for injection by injecting 14 mL of 5% Dextrose Injection USP into each vial. </li> <li>Gently shake the vial to dissolve the drug.</li> <li>Inspect the resulting slightly yellow solution for particulate matter and discoloration prior to further dilution. Discard the vials if particulate matter or discoloration is observed.</li> <li> <span class="Underline">Dilute</span>the contents of the two reconstituted vials (approximately 2 x 15 mL) into 140 mL of 5% Dextrose Injection USP. </li> <li>Inspect the resulting infusion solution and discard if particulate matter or discoloration is observed.</li> </ol> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Preparation of the</p> <p> <span class="Bold">1.5 g dose</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <ol class="Arabic"> <li> <span class="Underline">Reconstitute</span>three (3) vials of mycophenolate mofetil for injection by injecting 14 mL of 5% Dextrose Injection USP into each vial. </li> <li>Gently shake the vial to dissolve the drug.</li> <li>Inspect the resulting slightly yellow solution for particulate matter and discoloration prior to further dilution. Discard the vials if particulate matter or discoloration is observed.</li> <li> <span class="Underline">Dilute</span>the contents of the three reconstituted vials (approximately 3 x 15 mL) into 210 mL of 5% Dextrose Injection USP. </li> <li>Inspect the resulting infusion solution and discard if particulate matter or discoloration is observed.</li> </ol> </td> </tr> </tbody> </table></div>

The administration of the infusion should be initiated within 4 hours of reconstitution and dilution of the drug product. Keep solutions at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Discard unused portion of the reconstituted solutions.

Mycophenolate mofetil for injection should not be mixed or administered concurrently via the same infusion catheter with other intravenous drugs or infusion admixtures.

Mycophenolate Mofetil for Injection USP, 500 mgis a sterile, white to off-white lyophilized powder, supplied in single-dose vials for reconstitution.

{ "type": "p", "children": [], "text": "Mycophenolate Mofetil for Injection USP,\n \n 500 mgis a sterile, white to off-white lyophilized powder, supplied in single-dose vials for reconstitution.\n\n " }

Allergic reactions to mycophenolate mofetil have been observed; therefore, mycophenolate mofetil for injection is contraindicated in patients with a hypersensitivity to mycophenolate mofetil (MMF), mycophenolic acid (MPA) or any component of the drug product. Mycophenolate mofetil is contraindicated in patients who are allergic to Polysorbate 80 (TWEEN).

{ "type": "p", "children": [], "text": "Allergic reactions to mycophenolate mofetil have been observed; therefore, mycophenolate mofetil for injection is contraindicated in patients with a hypersensitivity to mycophenolate mofetil (MMF), mycophenolic acid (MPA) or any component of the drug product. Mycophenolate mofetil is contraindicated in patients who are allergic to Polysorbate 80 (TWEEN)." }

Use of MMF during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney and nervous system. Females of reproductive potential must be made aware of these risks and must be counseled regarding pregnancy prevention and planning. Avoid use of MMF  during pregnancy if safer treatment options are available [see Use in Specific Populations (8.1, 8.3)].

Patients receiving immunosuppressants, including mycophenolate mofetil, are at increased risk of developing lymphomas and other malignancies, particularly of the skin [see Adverse Reactions (6.1)]. The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. For patients with increased risk for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen with a high protection factor.

Post-transplant lymphoproliferative disorder (PTLD) developed in 0.4% to 1% of patients receiving mycophenolate mofetil (2 g or 3 g) with other immunosuppressive agents in controlled clinical trials of kidney, heart and liver transplant patients [see Adverse Reactions (6.1)]. The majority of PTLD cases appear to be related to Epstein Barr Virus (EBV) infection. The risk of PTLD appears greatest in those individuals who are EBV seronegative, a population which includes many young children. In pediatric patients, no other malignancies besides PTLD were observed in clinical trials [see Adverse Reactions (6.1)].

Patients receiving immunosuppressants, including mycophenolate mofetil, are at increased risk of developing bacterial, fungal, protozoal and new or reactivated viral infections, including opportunistic infections. The risk increases with the total immunosuppressive load. These infections may lead to serious outcomes, including hospitalizations and death [see Adverse Reactions (6.1, 6.2)].

Serious viral infections reported include:

Consider dose reduction or discontinuation of mycophenolate mofetil in patients who develop new infections or reactivate viral infections, weighing the risk that reduced immunosuppression represents to the functioning allograft.

PVAN, especially due to BK virus infection, is associated with serious outcomes, including deteriorating renal function and renal graft loss [see Adverse Reactions (6.2)]. Patient monitoring may help detect patients at risk for PVAN.

PML, which is sometimes fatal, commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia [see Adverse Reactions (6.2)] . In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms.

The risk of CMV viremia and CMV disease is highest among transplant recipients seronegative for CMV at time of transplant who receive a graft from a CMV seropositive donor. Therapeutic approaches to limiting CMV disease exist and should be routinely provided. Patient monitoring may help detect patients at risk for CMV disease.

Viral reactivation has been reported in patients infected with HBV or HCV. Monitoring infected patients for clinical and laboratory signs of active HBV or HCV infection is recommended.

Severe neutropenia [absolute neutrophil count (ANC) < 0.5 x 10 3/μL] developed in transplant patients receiving mycophenolate mofetil 3 g daily [see Adverse Reactions (6.1)]. Patients receiving mycophenolate mofetil should be monitored for neutropenia .Neutropenia has been observed most frequently in the period from 31 to 180 days post-transplant in patients treated for prevention of kidney, heart and liver rejection. The development of neutropenia may be related to mycophenolate mofetil itself, concomitant medications, viral infections, or a combination of these causes. If neutropenia develops (ANC < 1.3 x 10 3/μL), dosing with mycophenolate mofetil should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately [see Dosage and Administration (2.5)].

Patients receiving mycophenolate mofetil should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression.

Consider monitoring with complete blood counts weekly for the first month, twice monthly for the second and third months, and monthly for the remainder of the first year.

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate mofetil in combination with other immunosuppressive agents. In some cases, PRCA was found to be reversible with dose reduction or cessation of mycophenolate mofetil therapy. In transplant patients, however, reduced immunosuppression may place the graft at risk.

Gastrointestinal bleeding requiring hospitalization, ulceration and perforations were observed in clinical trials. Physicians should be aware of these serious adverse effects particularly when administering mycophenolate mofetil to patients with a gastrointestinal disease.

Mycophenolate mofetil is an inosine monophosphate dehydrogenase (IMPDH) inhibitor; therefore it should be avoided in patients with hereditary deficiencies of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndromes because it may cause an exacerbation of disease symptoms characterized by the overproduction and accumulation of uric acid leading to symptoms associated with gout such as acute arthritis, tophi, nephrolithiasis or urolithiasis and renal disease including renal failure.

Acute inflammatory syndrome (AIS) has been reported with the use of Mycophenolate mofetil, and some cases have resulted in hospitalization. AIS is a paradoxical pro-inflammatory reaction characterized by fever, arthralgias, arthritis, muscle pain and elevated inflammatory markers including, C-reactive protein and erythrocyte sedimentation rate, without evidence of infection or underlying disease recurrence. Symptoms occur within weeks to months of initiation of treatment or a dose increase. After discontinuation, improvement of symptoms and inflammatory markers are usually observed within 24 to 48 hours.

Monitor patients for symptoms and laboratory parameters of AIS when starting treatment with mycophenolate products or when increasing the dosage. Discontinue treatment and consider other treatment alternatives based on the risk and benefit for the patient.

During treatment with mycophenolate mofetil, the use of live attenuated vaccines should be avoided (e.g., intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) and patients should be advised that vaccinations may be less effective. Advise patients to discuss with the physician before seeking any immunizations.

Mycophenolate mofetil injection solution must not be administered by rapid or bolus intravenous injection as rapid infusion increases the risk of local adverse reactions such as phlebitis and thrombosis [see Adverse Reactions (6.1)] .

Patients should not donate blood during therapy and for at least 6 weeks following discontinuation of mycophenolate mofetil because their blood or blood products might be administered to a female of reproductive potential or a pregnant woman.

Based on animal data, men should not donate semen during therapy and for 90 days following discontinuation of mycophenolate mofetil [see Use in Specific Populations (8.3)] .

A variety of drugs have potential to alter systemic MPA exposure when co-administered with mycophenolate mofetil. Therefore, determination of MPA concentrations in plasma before and after making any changes to immunosuppressive therapy, or when adding or discontinuing concomitant medications, may be appropriate to ensure MPA concentrations remain stable.

Mycophenolate mofetil may impact the ability to drive and use machines. Patients should avoid driving or using machines if they experience somnolence, confusion, dizziness, tremor, or hypotension during treatment with mycophenolate mofetil [see Adverse Reactions (6.1)] .

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

An estimated total of 1557 adult patients received mycophenolate mofetil during pivotal clinical trials in the prevention of acute organ rejection. Of these, 991 were included in the three renal studies, 277 were included in one hepatic study, and 289 were included in one cardiac study. Patients in all study arms also received cyclosporine and corticosteroids.

The data described below primarily derive from five randomized, active-controlled double-blind 12-month trials of mycophenolate mofetil in de novokidney (3) heart (1) and liver (1) transplant patients [see Clinical Studies (14.1, 14.2 and 14.3)] .

Mycophenolate Mofetil Oral

The incidence of adverse reactions for mycophenolate mofetil was determined in five randomized, comparative, double-blind trials in the prevention of rejection in kidney, heart and liver transplant patients (two active- and one placebo-controlled trials, one active-controlled trial, and one active-controlled trial, respectively) [see Clinical Studies (14.1, 14.2and 14.3)] .

The three de novokidney studies with 12-month duration compared two dose levels of oral mycophenolate mofetil (1 g twice daily and 1.5 g twice daily) with azathioprine (2 studies) or placebo (1 study) when administered in combination with cyclosporine (Sandimmune ®) and corticosteroids to prevent acute rejection episodes. One study also included anti-thymocyte globulin (ATGAM ®) induction therapy.

In the de novoheart transplantation study with 12-month duration, patients received mycophenolate mofetil 1.5 g twice daily (n=289) or azathioprine 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune ®or Neoral ®) and corticosteroids as maintenance immunosuppressive therapy.

In the de novoliver transplantation study with 12-month duration, patients received mycophenolate mofetil 1 g twice daily intravenously for up to 14 days followed by mycophenolate mofetil 1.5 g twice daily orally or azathioprine 1 to 2 mg/kg/day intravenously followed by azathioprine 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral ®) and corticosteroids as maintenance immunosuppressive therapy. The total number of patients enrolled was 565.

Approximately 53% of the kidney transplant patients, 65% of the heart transplant patients, and 48% of the liver transplant patients were treated for more than 1 year. Adverse reactions reported in >20% of patients in the mycophenolate mofetil treatment groups are presented below. The safety data of three kidney transplantation studies are pooled together.

Table 5 Adverse Reactions in Controlled Studies of De NovoKidney, Heart or Liver Transplantation Reported in >20% of Patients in the Mycophenolate Mofetil Group

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First"> <span class="Bold">Adverse drug reaction</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="3"> <p class="First"> <span class="Bold">Kidney Studies</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Heart Study</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Liver Study</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">2 g/day (n=501) or 3g/day (n=490)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AZA</span> </p> <p> <span class="Bold">1 to 2 mg/kg/day or 100 to 150 mg/day</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Placebo</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">3 g/day</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AZA</span> </p> <p> <span class="Bold">1.5 to 3 mg/kg/day</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil 3 g/day</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AZA</span> </p> <p> <span class="Bold">1 to 2 mg/kg/day</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First"> <span class="Bold">System Organ Class</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">(n=991)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">(n=326)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">(n=166)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">(n=289)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">(n=289)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">(n=277)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">(n=287)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">%</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">%</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">%</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">%</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">%</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">%</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">%</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Infections and infestations</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Bacterial infections</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">39.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">33.7</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">37.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">27.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">26.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Viral infections</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">- <span class="Sup">a</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">31.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">24.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Blood and lymphatic system disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Anemia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">20.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">23.6</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">2.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">45.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">47.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">43.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">53.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Ecchymosis</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">20.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">9.7</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Leukocytosis</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">42.6</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">37.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">22.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">21.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Leukopenia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">28.6</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">24.8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">4.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">34.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">43.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">45.8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">39.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Thrombocytopenia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">24.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">28.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">38.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">42.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Metabolism and nutrition disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Hypercholesterolemia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">46.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">43.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Hyperglycemia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">48.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">53.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">43.7</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">48.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Hyperkalemia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">22.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">23.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Hypocalcemia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">30.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">30.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Hypokalemia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">32.5</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">26.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">37.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">41.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Hypomagnesemia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">20.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">14.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">39.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">37.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Psychiatric disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Depression</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">20.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">15.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Insomnia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">43.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">39.8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">52.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">47.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Nervous system disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Dizziness</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">34.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">33.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Headache</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">58.5</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">55.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">53.8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">49.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Tremor</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">26.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">25.6</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">33.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">35.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Cardiac disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Tachycardia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">22.8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">21.8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">22.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">15.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Vascular disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Hypertension</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">27.5</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">32.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">19.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">78.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">74.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">62.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">59.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Hypotension</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">34.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">40.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Respiratory, thoracic and mediastinal disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Cough</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">40.5</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">32.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Dyspnea</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">44.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">44.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">31.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">30.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Pleural effusion</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">34.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">35.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Gastrointestinal disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Abdominal pain</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">22.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">23.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">11.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">41.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">39.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">62.5</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">51.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Constipation</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">43.6</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">38.8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">37.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">38.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Decreased appetite</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">25.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">17.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Diarrhea</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">30.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">20.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">13.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">52.6</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">39.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">51.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">49.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Dyspepsia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">22.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">22.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">22.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">20.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Nausea</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">56.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">60.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">54.5</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">51.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Vomiting</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">39.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">34.6</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">32.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">33.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Hepatobiliary disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Blood lactate dehydrogenase increased</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">23.5</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">18.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Hepatic enzyme increased</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">24.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">19.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Skin and subcutaneous tissues disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Rash</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">26.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">20.8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">Renal and urinary disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Blood creatinine increased</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">42.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">39.8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Blood urea increased</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">36.7</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">34.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First"> <span class="Bold">General disorders and administration site conditions</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Asthenia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">49.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">41.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">35.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">33.8</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Edema <span class="Sup">b</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">21.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">28.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">8.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">67.5</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">55.7</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">48.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">47.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Pain <span class="Sup">c</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">24.8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">32.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">9.6</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">79.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">77.5</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">74.0</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">77.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Pyrexia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">56.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">53.6</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">52.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">56.1</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="8"> <p class="First">a : “-” Indicates that the incidence was below the cutoff value of 20% for inclusion in the table.</p> <p>b : “Edema” includes peripheral edema, facial edema, scrotal edema.</p>c : “Pain” includes musculoskeletal pain (myalgia, neck pain, back pain). </td> </tr> </tbody> </table></div>

In the three de novokidney studies, patients receiving 2 g/day of mycophenolate mofetil had an overall better safety profile than did patients receiving 3 g/day of mycophenolate mofetil.

Post-transplant lymphoproliferative disease (PTLD, pseudolymphoma) developed in 0.4% to 1% of patients receiving mycophenolate mofetil (2 g or 3 g daily) with other immunosuppressive agents in controlled clinical trials of kidney, heart and liver transplant patients followed for at least 1 year [see Warnings and Precautions (5.2)]. Non-melanoma skin carcinomas occurred in 1.6% to 4.2% of patients, other types of malignancy in 0.7% to 2.1% of patients. Three-year safety data in kidney and heart transplant patients did not reveal any unexpected changes in incidence of malignancy compared to the 1-year data. In pediatric patients, PTLD was observed in 1.35% (2/148) by 12 months post-transplant.

Cytopenias, including leukopenia, anemia, thrombocytopenia and pancytopenia are a known risk associated with mycophenolate and may lead or contribute to the occurrence of infections and hemorrhages [see Warnings and Precautions (5.3)] . Severe neutropenia (ANC < 0.5 x 10 3/μL) developed in up to 2% of kidney transplant patients, up to 2.8% of heart transplant patients and up to 3.6% of liver transplant patients receiving mycophenolate mofetil 3 g daily [see Warnings and Precautions (5.4)and Dosage and Administration (2.5)].

The most common opportunistic infections in patients receiving mycophenolate mofetil with other immunosuppressants were mucocutaneous candida, CMV viremia/syndrome, and herpes simplex. The proportion of patients with CMV viremia/syndrome was 13.5%. In patients receiving mycophenolate mofetil (2 g or 3 g) in controlled studies for prevention of kidney, heart or liver rejection, fatal infection/sepsis occurred in approximately 2% of kidney and heart patients and in 5% of liver patients [see Warnings and Precautions (5.3)].

The most serious gastrointestinal disorders reported were ulceration and hemorrhage, which are known risks associated with mycophenolate mofetil. Mouth, esophageal, gastric, duodenal, and intestinal ulcers often complicated by hemorrhage, as well as hematemesis, melena, and hemorrhagic forms of gastritis and colitis were commonly reported during the pivotal clinical trials, while the most common gastrointestinal disorders were diarrhea, nausea and vomiting. Endoscopic investigation of patients with mycophenolate mofetil-related diarrhea revealed isolated cases of intestinal villous atrophy [see Warnings and Precautions (5.5)] .

The following adverse reactions were reported with 3% to < 20% incidence in kidney, heart, and liver transplant patients treated with mycophenolate mofetil, in combination with cyclosporine and corticosteroids.

Table 6 Adverse Reactions in Controlled Studies of De Novo Kidney, Heart or Liver Transplantation Reported in 3% to < 20% of Patients Treated withMycophenolate Mofetil in Combination with Cyclosporine and Corticosteroids

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">System Organ Class</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Adverse Reactions</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Body as a Whole</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">cellulitis, chills, hernia, malaise</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Infections and Infestations</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">fungal infections</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Hematologic and Lymphatic</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">coagulation disorder, ecchymosis, pancytopenia</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Urogenital</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">hematuria</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Cardiovascular</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">hypotension</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Metabolic and Nutritional</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">acidosis, alkaline phosphatase increased, hyperlipemia, hypophosphatemia, weight loss</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Digestive</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">esophagitis, flatulence, gastritis, gastrointestinal hemorrhage, hepatitis, ileus, nausea and vomiting, stomach ulcer, stomatitis</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Neoplasm benign, malignant and unspecified</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">neoplasm</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Skin and Appendages</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">skin benign neoplasm, skin carcinoma</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Psychiatric</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">confusional state</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Nervous</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">hypertonia, paresthesia, somnolence</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Musculoskeletal</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">arthralgia, myasthenia</p> </td> </tr> </tbody> </table></div>

Pediatric Study

The type and frequency of adverse events in a clinical study for prevention of kidney allograft rejection in 100 pediatric patients 3 months to 18 years of age dosed with mycophenolate mofetil oral suspension 600 mg/m 2twice daily (up to 1 g twice daily) were generally similar to those observed in adult patients dosed with mycophenolate mofetil capsules at a dose of 1 g twice daily with the exception of abdominal pain, fever, infection, pain, sepsis, diarrhea, vomiting, pharyngitis, respiratory tract infection, hypertension, leukopenia, and anemia, which were observed in a higher proportion in pediatric patients.

Safety information in pediatric heart transplant or pediatric liver transplant patients treated with mycophenolate mofetil is supported by an open-label study in pediatric liver transplant patients and publications; the type and frequency of the reported adverse reactions are consistent with those observed in pediatric patients following renal transplant and in adults.

Geriatrics

Geriatric patients (≥ 65 years), particularly those who are receiving mycophenolate mofetil as part of a combination immunosuppressive regimen, may be at increased risk of certain infections (including cytomegalovirus [CMV] tissue invasive disease) and possibly gastrointestinal hemorrhage and pulmonary edema, compared to younger individuals [see Warnings and Precautions (5.3)and Adverse Reactions (6.1)].

Mycophenolate Mofetil for Injection

The safety profile of mycophenolate mofetil for injection was determined from a single, double-blind, controlled comparative study of the safety of 2 g/day of intravenous and oral mycophenolate mofetil in kidney transplant patients in the immediate post-transplant period (administered for the first 5 days). The potential venous irritation of mycophenolate mofetil for injection was evaluated by comparing the adverse reactions attributable to peripheral venous infusion of mycophenolate mofetil for injection with those observed in the intravenous placebo group; patients in the placebo group received active medication by the oral route.

Adverse reactions attributable to peripheral venous infusion were phlebitis and thrombosis, both observed at 4% in patients treated with mycophenolate mofetil for injection.

The following adverse reactions have been identified during post-approval use of mycophenolate mofetil. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

- Facial malformations: cleft lip, cleft palate, micrognathia, hypertelorism of the orbits

- Abnormalities of the ear and eye: abnormally formed or absent external/middle ear, coloboma, microphthalmos

- Malformations of the fingers: polydactyly, syndactyly, brachydactyly

- Cardiac abnormalities: atrial and ventricular septal defects

- Esophageal malformations: esophageal atresia

- Nervous system malformations: such as spina bifida .

Table 7 Drug Interactions with Mycophenolate Mofetil that Affect Mycophenolic Acid (MPA) Exposure

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Antacids with Magnesium or Aluminum Hydroxide</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use with an antacid containing magnesium or aluminum hydroxide decreases MPA systemic exposure <span class="Italics">[see <a href="#LINK_40da22ab-9880-419c-aac4-3222230c217b">Clinical Pharmacology (12.3)</a>] </span>, which may reduce mycophenolate mofetil efficacy. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Prevention or Management</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Administer magnesium or aluminum hydroxide containing antacids at least 2h after mycophenolate mofetil administration.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Proton Pump Inhibitors (PPIs)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use with PPIs decreases MPA systemic exposure <span class="Italics">[see <a href="#LINK_40da22ab-9880-419c-aac4-3222230c217b">Clinical Pharmacology (12.3)</a>] </span>, which may reduce mycophenolate mofetil efficacy. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Prevention or Management</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Monitor patients for alterations in efficacy when PPIs are co-administered with mycophenolate mofetil.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Lansoprazole, pantoprazole</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Drugs that Interfere with Enterohepa</span><span class="Bold">tic Recirculation</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use with drugs that directly interfere with enterohepatic recirculation, or indirectly interfere with enterohepatic recirculation by altering the gastrointestinal flora, can decrease MPA systemic exposure <span class="Italics">[see <a href="#LINK_40da22ab-9880-419c-aac4-3222230c217b">Clinical Pharmacology (12.3)</a>] </span>, which may reduce mycophenolate mofetil efficacy. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Prevention or Management</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Monitor patients for alterations in efficacy or mycophenolate mofetil related adverse reactions when these drugs are co-administered with mycophenolate mofetil.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Trimethoprim/sulfamethoxazole, bile acid sequestrants (cholestyramine), rifampin as well as aminoglycoside, cephalosporin, fluoroquinolone and penicillin classes of antimicrobials</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Drugs Modulating Glucuronidation</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use with drugs inducing glucuronidation decreases MPA systemic exposure, potentially reducing mycophenolate mofetil efficacy, while use with drugs inhibiting glucuronidation increases MPA systemic exposure <span class="Italics">[see <a href="#LINK_40da22ab-9880-419c-aac4-3222230c217b">Clinical Pharmacology (12.3)</a>] </span>, which may increase the risk of mycophenolate mofetil related adverse reactions. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Prevention or Management</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Monitor patients for alterations in efficacy or mycophenolate mofetil related adverse reactions when these drugs are co-administered with mycophenolate mofetil.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Telmisartan (induces glucuronidation); isavuconazole (inhibits glucuronidation).</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Calcium Free Phosph</span><span class="Bold">ate Binders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use with calcium free phosphate binders decrease MPA systemic exposure <span class="Italics">[see <a href="#LINK_40da22ab-9880-419c-aac4-3222230c217b">Clinical Pharmacology (12.3)</a>] </span>, which may reduce mycophenolate mofetil efficacy. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Prevention or Management</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Administer calcium free phosphate binders at least 2 hours after mycophenolate mofetil.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Sevelamer</p> </td> </tr> </tbody> </table></div>

Table 8 Drug Interactions with Mycophenolate Mofetil that Affect Other Drugs

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Drugs that Undergo Renal Tubular Secretion</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">When concomitantly used with mycophenolate mofetil, its metabolite MPAG, may compete with drugs eliminated by renal tubular secretion which may increase plasma concentrations and/or adverse reactions associated with these drugs.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Prevention or Management</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Monitor for drug-related adverse reactions in patients with renal impairment.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Acyclovir, ganciclovir, probenecid, valacyclovir, valganciclovir</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Combination Oral Contraceptives</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use with mycophenolate mofetil decreased the systemic exposure to levonorgestrel, but did not affect the systemic exposure to ethinylestradiol <span class="Italics">[see <a href="#LINK_40da22ab-9880-419c-aac4-3222230c217b">Clinical Pharmacology (12.3)</a>] </span>, which may result in reduced combination oral contraceptive effectiveness. </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Prevention or Management</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Use additional barrier contraceptive methods.</p> </td> </tr> </tbody> </table></div>

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to mycophenolate during pregnancy and those becoming pregnant within 6 weeks of discontinuing mycophenolate mofetil treatment. To report a pregnancy or obtain information about the registry, visit www.mycophenolateREMS.comor call 1-800-617-8191.

Risk Summary

Use of mycophenolate mofetil (MMF) during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of multiple congenital malformations in multiple organ systems [see Human Data]. Oral administration of mycophenolate to rats and rabbits during the period of organogenesis produced congenital malformations and pregnancy loss at doses less than the recommended clinical dose (0.01to 0.05 times the recommended clinical doses in kidney and heart transplant patients) [see Animal Data].

Consider alternative immunosuppressants with less potential for embryofetal toxicity. Risks and benefits of mycophenolate mofetil should be discussed with the pregnant woman.

The estimated background risk of pregnancy loss and congenital malformations in organ transplant populations is not clear .In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Human Data

A spectrum of congenital malformations (including multiple malformations in individual newborns) has been reported in 23% to 27% of live births in MMF exposed pregnancies, based on published data from pregnancy registries. Malformations that have been documented include external ear, eye, and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system.

Based on published data from pregnancy registries, the risk of first trimester pregnancy loss has been reported at 45 to 49% following MMF exposure.

Animal Data

In animal reproductive toxicology studies, there were increased rates of fetal resorptions and malformations in the absence of maternal toxicity. Oral administration of MMF to pregnant rats from Gestational Day 7 to Day 16 produced increased embryofetal lethality and fetal malformations including anophthalmia, agnathia, and hydrocephaly at doses equivalent to 0.015 and 0.01 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA. Oral administration of MMF to pregnant rabbits from Gestational Day 7 to Day 19 produced increased embryofetal lethality and fetal malformations included ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia at dose equivalents as low as 0.05 and 0.03 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA.

Risk Summary

There are no data on the presence of mycophenolate in human milk, or the effects on milk production. There are limited data in the National Transplantation Pregnancy Registry on the effects of mycophenolate on a breastfed child [see Data]. Studies in rats treated with MMF have shown mycophenolic acid (MPA) to be present in milk. Because available data are limited, it is not possible to exclude potential risks to a breastfeeding infant.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for mycophenolate mofetil and any potential adverse effects on the breastfed infant from mycophenolate mofetil or from the underlying maternal condition.

Data

Limited information is available from the National Transplantation Pregnancy Registry. Of seven infants reported by the National Transplantation Pregnancy Registry to have been breastfed while the mother was taking mycophenolate, all were born at 34 to 40 weeks gestation, and breastfed for up to 14 months. No adverse events were reported.

Females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning.

Pregnancy Planning

For patients who are considering pregnancy, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible. Risks and benefits of mycophenolate mofetil should be discussed with the patient.

Pregnancy Testing

To prevent unplanned exposure during pregnancy, all females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL immediately before starting mycophenolate mofetil. Another pregnancy test with the same sensitivity should be done 8 to 10 days later. Repeat pregnancy tests should be performed during routine follow-up visits. Results of all pregnancy tests should be discussed with the patient. In the event of a positive pregnancy test, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible.

Contraception

Female Patients

Females of reproductive potential taking mycophenolate mofetil must receive contraceptive counseling and use acceptable contraception (see Table 9 for acceptable contraception methods). Patients must use acceptable birth control during the entire mycophenolate mofetil therapy, and for 6 weeks after stopping mycophenolate mofetil, unless the patient chooses abstinence.

Patients should be aware that mycophenolate mofetil reduces blood levels of the hormones from the oral contraceptive pill and could theoretically reduce its effectiveness [see Drug Interactions (7.2)].

Table 9 Acceptable Contraception Methods for Females Of Reproductive Potential

Pick from the following birth control options:

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First First Last Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Option 1</span> </p> <p> <span class="Bold">Methods to </span><span class="Bold">Use Alone</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li>Intrauterine devices (IUDs)</li> <li>Tubal sterilization</li> <li>Patient’s partner vasectomy</li> </ul> </td> </tr> </tbody> </table></div>

OR

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Option 2</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Hormone Methods</span> </p> <p>choose 1</p> </td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Barrier Methods</span> </p> <p>choose 1</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Choose One Hormone Method</span><span class="Italics">AND</span><span class="Bold">One Barrier Method</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Estrogen and Progesterone</span> </p> <ul class="Disc"> <li>Oral Contraceptive Pill</li> <li>Transdermal patch</li> <li>Vaginal ring</li> </ul> <p> <span class="Bold">Progesterone-only</span> </p> <ul class="Disc"> <li>Injection</li> <li>Implant</li> </ul> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">AND</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li>Diaphragm with spermicide</li> <li>Cervical cap with spermicide</li> <li>Contraceptive sponge</li> <li>Male condom</li> <li>Female condom</li> </ul> </td> </tr> </tbody> </table></div>

OR

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Option 3</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Barrier Methods</span> </p> <p>choose 1</p> </td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Barrier Methods</span> </p> <p>choose 1</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Choose One Barrier Method from each column</span><span class="Italics">(must choose two methods)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li>Diaphragm with spermicide</li> <li>Cervical cap with spermicide</li> <li>Contraceptive sponge</li> </ul> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">AND</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li>Male condom</li> <li>Female condom</li> </ul> </td> </tr> </tbody> </table></div>

Male Patients

Genotoxic effects have been observed in animal studies at exposures exceeding the human therapeutic exposures by approximately 1.25 times. Thus, the risk of genotoxic effects on sperm cells cannot be excluded. Based on this potential risk, sexually active male patients and/or their female partners are recommended to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment. Also, based on the potential risk of genotoxic effects, male patients should not donate sperm during treatment with mycophenolate mofetil and for at least 90 days after cessation of treatment [see Use in Special Populations (8.1), Nonclinical Toxicology (13.1), Patient Counseling Information (17.9)] .

Safety and effectiveness have been established in pediatric patients 3 months and older for the prophylaxis of organ rejection of allogeneic kidney, heart or liver transplants.

Kidney transplant

Use of mycophenolate mofetil in this population is supported by evidence from adequate and well-controlled studies of mycophenolate mofetil in adults with additional data from one open-label, pharmacokinetic and safety study of mycophenolate mofetil in pediatric patients after receiving allogeneic kidney transplant (100 patients, 3 months to 18 years of age)  [see Dosage and Administration (2.2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.1)].

Heart Transplant and Liver Transplant

Use of mycophenolate mofetil in pediatric heart transplant and liver transplant patients is supported by adequate and well-controlled studies and pharmacokinetic data in adult heart transplant and liver transplant patients. Additional supportive data include pharmacokinetic data in pediatric kidney transplant and pediatric liver transplant patients (8 liver transplant patients, 9 months to 5 years of age, in an open-label, pharmacokinetic and safety study) and published evidence of clinical efficacy and safety in pediatric heart transplant and pediatric liver transplant patients  [ see Dosage and Administration( 2.3,2.4), Adverse Reactions( 6.1), ClinicalPharmacology( 12.3), Clinical Studies( 14.1)].

Clinical studies of mycophenolate mofetil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the geriatric and younger patients. In general, dose selection for an geriatric patient should take into consideration the presence of decreased hepatic, renal or cardiac function and of concomitant drug therapies [see Adverse Reactions (6.1), Drug Interactions (7)].

Patients with Kidney Transplant

No dosage adjustments are needed in kidney transplant patients experiencing delayed graft function postoperatively but patients should be carefully monitored [see Clinical Pharmacology (12.3)]. In kidney transplant patients with severe chronic impairment of the graft(GFR < 25 mL/min/1.73 m 2), no dose adjustments are necessary; however, doses greater than 1 g administered twice a day should be avoided.

Patients with Heart and Liver Transplant

No data are available for heart or liver transplant patients with severe chronic renal impairment. Mycophenolate mofetil may be used for heart or liver transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks.

Patients with Kidney Transplant

No dosage adjustments are recommended for kidney transplant patients with severe hepatic parenchymal disease. However, it is not known whether dosage adjustments are needed for hepatic disease with other etiologies [see Clinical Pharmacology (12.3)].

Patients with Heart Transplant

No data are available for heart transplant patients with severe hepatic parenchymal disease.

Possible signs and symptoms of acute overdose include hematological abnormalities such as leukopenia and neutropenia, and gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, and dyspepsia.

{ "type": "p", "children": [], "text": "Possible signs and symptoms of acute overdose include hematological abnormalities such as leukopenia and neutropenia, and gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, and dyspepsia." }

The experience with overdose of mycophenolate mofetil in humans is limited. The reported effects associated with overdose fall within the known safety profile of the drug. The highest dose administered to kidney transplant patients in clinical trials has been 4 g/day. In limited experience with heart and liver transplant patients in clinical trials, the highest doses used were 4 g/day or 5 g/day. At doses of 4 g/day or 5 g/day, there appears to be a higher rate, compared to the use of 3 g/day or less, of gastrointestinal intolerance (nausea, vomiting, and/or diarrhea), and occasional hematologic abnormalities, particularly neutropenia [see Warnings and Precautions (5.4)] .

{ "type": "p", "children": [], "text": "The experience with overdose of mycophenolate mofetil in humans is limited. The reported effects associated with overdose fall within the known safety profile of the drug. The highest dose administered to kidney transplant patients in clinical trials has been 4 g/day. In limited experience with heart and liver transplant patients in clinical trials, the highest doses used were 4 g/day or 5 g/day. At doses of 4 g/day or 5 g/day, there appears to be a higher rate, compared to the use of 3 g/day or less, of gastrointestinal intolerance (nausea, vomiting, and/or diarrhea), and occasional hematologic abnormalities, particularly neutropenia\n \n [see\n \n Warnings and Precautions (5.4)]\n \n .\n\n " }

Treatment and Management

{ "type": "p", "children": [], "text": "\nTreatment and Management\n" }

MPA and the phenolic glucuronide metabolite of MPA (MPAG) are usually not removed by hemodialysis. However, at high MPAG plasma concentrations (> 100 mcg/mL), small amounts of MPAG are removed. By increasing excretion of the drug, MPA can be removed by bile acid sequestrants, such as cholestyramine [see Clinical Pharmacology (12.3)].

{ "type": "p", "children": [], "text": "MPA and the phenolic glucuronide metabolite of MPA (MPAG) are usually not removed by hemodialysis. However, at high MPAG plasma concentrations (> 100 mcg/mL), small amounts of MPAG are removed. By increasing excretion of the drug, MPA can be removed by bile acid sequestrants, such as cholestyramine\n \n [see\n \n Clinical Pharmacology (12.3)].\n \n \n" }

Mycophenolate mofetil is an antimetabolite immunosuppressant. It is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine monophosphate dehydrogenase (IMPDH) inhibitor.

{ "type": "p", "children": [], "text": "Mycophenolate mofetil is an antimetabolite immunosuppressant. It is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine monophosphate dehydrogenase (IMPDH) inhibitor." }

The chemical name for mycophenolate mofetil (MMF) is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate. It has empirical formula of C 23H 31NO 7, a molecular weight of 433.50 and the following structural formula.

{ "type": "p", "children": [], "text": "The chemical name for mycophenolate mofetil (MMF) is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate. It has empirical formula of C\n \n 23H\n \n 31NO\n \n 7, a molecular weight of 433.50 and the following structural formula.\n\n " }

Mycophenolate mofetil, USP is a white to off-white crystalline powder. It is slightly soluble in water (43 µg/mL at pH 7.4); the solubility increases in acidic medium (4.27 mg/mL at pH 3.6). It is freely soluble in acetone, soluble in methanol, and sparingly soluble in ethanol. The apparent partition coefficient in 1-octanol/water (pH 7.4) buffer solution is 238. The pKa values for MMF are 5.6 for the morpholino group and 8.5 for the phenolic group.

{ "type": "p", "children": [], "text": "Mycophenolate mofetil, USP is a white to off-white crystalline powder. It is slightly soluble in water (43 µg/mL at pH 7.4); the solubility increases in acidic medium (4.27 mg/mL at pH 3.6). It is freely soluble in acetone, soluble in methanol, and sparingly soluble in ethanol. The apparent partition coefficient in 1-octanol/water (pH 7.4) buffer solution is 238. The pKa values for MMF are 5.6 for the morpholino group and 8.5 for the phenolic group." }

Mycophenolate mofetil hydrochloride has a solubility of 65.8 mg/mL in 5% Dextrose Injection USP (D5W). The pH of the reconstituted solution is 2.4 to 4.1.

{ "type": "p", "children": [], "text": "Mycophenolate mofetil hydrochloride has a solubility of 65.8 mg/mL in 5% Dextrose Injection USP (D5W). The pH of the reconstituted solution is 2.4 to 4.1." }

Mycophenolate mofetil for injection is the hydrochloride salt of  MMF. The chemical name for the hydrochloride salt of mycophenolate mofetil is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate hydrochloride. It has empirical formula of C 23H 31NO 7HCl and a molecular weight of 469.96.

{ "type": "p", "children": [], "text": "Mycophenolate mofetil for injection is the hydrochloride salt of  MMF. The chemical name for the hydrochloride salt of mycophenolate mofetil is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate hydrochloride. It has empirical formula of C\n \n 23H\n \n 31NO\n \n 7HCl and a molecular weight of 469.96.\n\n " }

Mycophenolate mofetil for injection, USP is available as a sterile, white to off-white lyophilized powder in single-dose vials containing mycophenolate mofetil hydrochloride for administration by intravenous infusion only. Each vial contains 500 mg of mycophenolate mofetil, USP equivalent to 542 mg of mycophenolate mofetil hydrochloride. The inactive ingredients are polysorbate 80, 25 mg and citric acid anhydrous, 5 mg. Sodium hydroxide or hydrochloric acid may have been used in the manufacture of mycophenolate mofetil for injection, USP to adjust the pH. Reconstitution and dilution with 5% Dextrose Injection USP yields a slightly yellow solution of mycophenolate mofetil, 6 mg/mL [see Dosage and Administration (2.6)].

{ "type": "p", "children": [], "text": "Mycophenolate mofetil for injection, USP is available as a sterile, white to off-white lyophilized powder in single-dose vials containing mycophenolate mofetil hydrochloride for administration by intravenous infusion only. Each vial contains 500 mg of mycophenolate mofetil, USP equivalent to 542 mg of mycophenolate mofetil hydrochloride. The inactive ingredients are polysorbate 80, 25 mg and citric acid anhydrous, 5 mg. Sodium hydroxide or hydrochloric acid may have been used in the manufacture of mycophenolate mofetil for injection, USP to adjust the pH. Reconstitution and dilution with 5% Dextrose Injection USP yields a slightly yellow solution of mycophenolate mofetil, 6 mg/mL\n \n [see\n \n Dosage and Administration (2.6)].\n \n \n" }

Mycophenolate mofetil (MMF) is absorbed following oral administration and hydrolyzed to mycophenolic acid (MPA), the active metabolite. MPA is a selective uncompetitive inhibitor of the two isoforms (type I and type II) of inosine monophosphate dehydrogenase (IMPDH) leading to inhibition of the de novo pathway of guanosine nucleotide synthesis and blocks DNA synthesis. The mechanism of action of MPA is multifaceted and includes effects on cellular checkpoints responsible for metabolic programming of lymphocytes. MPA shifts transcriptional activities in lymphocytes from a proliferative state to catabolic processes. In vitro studies suggest that MPA modulates transcriptional activities in human CD4+ T-lymphocytes by suppressing the Akt/mTOR and STAT5 pathways that are relevant to metabolism and survival, leading to an anergic state of T-cells whereby the cells become less responsive to antigenic stimulation. Additionally, MPA enhanced the expression of negative co-stimulators such as CD70, PD-1, CTLA-4, and transcription factor FoxP3 as well as decreased the expression of positive co-stimulators CD27 and CD28. MPA decreases proliferative responses of T- and B-lymphocytes to both mitogenic and allo-antigenic stimulation, antibody responses, as well as the production of cytokines from lymphocytes and monocytes such as GM-CSF, IFN- Ɣ, IL-17, and TNF-α. Additionally, MPA prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection. Overall, the effect of MPA is cytostatic and reversible.

There is a lack of information regarding the pharmacodynamic effects of mycophenolate mofetil (MMF).

Absorption

Following oral and intravenous administration, mycophenolate mofetil (MMF) undergoes complete conversion to MPA, the active metabolite. In 12 healthy volunteers, the mean absolute bioavailability of oral MMF relative to intravenous MMF was 94%.

The mean (±SD) pharmacokinetic parameters estimates for MPA following the administration of mycophenolate mofetil (MMF) given as single-doses to healthy volunteers, and multiple-doses to kidney, heart, and liver transplant patients, are shown in Table 10. The area under the plasma-concentration time curve (AUC) for MPA appears to increase in a dose-proportional fashion in kidney transplant patients receiving multiple oral doses of MMF up to a daily dose of 3 g (1.5 g twice daily) (see Table 10).

Table 10 Pharmacokinetic Parameters for MPA [mean (±SD)] Following Administration of MMF to Healthy Volunteers (Single-Dose), and Kidney, Heart, and Liver Transplant Patients (Multiple-Doses)

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Healthy Volunteers</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Dose/Route</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">T <span class="Sub">max</span></span> </p> <p> <span class="Bold">(h)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">C <span class="Sub">max</span></span> </p> <p> <span class="Bold">(mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Total AUC</span> </p> <p> <span class="Bold">(mcg•h/mL)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Single-dose</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.80 (±0.36) (n=129)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">24.5 (±9.5) <br/> (n=129) </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">63.9 (±16.2) <br/> (n=117) </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Kidney Transplant Patients (twice daily dosing) Time After Transplantation</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Dose/Route</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">T <span class="Sub">max</span></span> </p> <p> <span class="Bold">(h)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">C <span class="Sub">max</span></span> </p> <p> <span class="Bold">(mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Interdosing Interval AUC <span class="Sub">(0-­12h)</span></span> </p> <p> <span class="Bold">(mcg•h/mL)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">5 days</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g/iv</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.58 (±0.46)</p> <p>(n=31)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">12.0 (±3.82)</p> <p>(n=31)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">40.8 (±11.4)</p> <p>(n=31)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">6 days</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.33 (±1.05)</p> <p>(n=31)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">10.7 (±4.83)</p> <p>(n=31)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">32.9 (±15.0)</p> <p>(n=31)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Early (Less than 40 days)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.31 (±0.76)</p> <p>(n=25)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">8.16 (±4.50)</p> <p>(n=25)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">27.3 (±10.9)</p> <p>(n=25)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Early (Less than 40 days)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.5 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.21 (±0.81)</p> <p>(n=27)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">13.5 (±8.18)</p> <p>(n=27)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">38.4 (±15.4)</p> <p>(n=27)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Late (Greater than 3 months)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.5 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.90 (±0.24)</p> <p>(n=23)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">24.1 (±12.1)</p> <p>(n=23)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">65.3 (±35.4)</p> <p>(n=23)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Heart transplant Patients (twice daily dosing) Time After Transplantation</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Dose/Route</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">T <span class="Sub">max</span></span> </p> <p> <span class="Bold">(h)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">C <span class="Sub">max</span></span> </p> <p> <span class="Bold">(mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Interdosing Interval AUC <span class="Sub">(0­-12h)</span></span> </p> <p> <span class="Bold">(mcg•h/mL)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Early (Day before discharge)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.5 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.8 (±1.3)</p> <p>(n=11)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">11.5 (±6.8)</p> <p>(n=11)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">43.3 (±20.8)</p> <p>(n=9)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Late (Greater than 6 months)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.5 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.1 (±0.7)</p> <p>(n=52)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">20.0 (±9.4)</p> <p>(n=52)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">54.1 <span class="Sup">a</span>(±20.4) </p> <p>(n=49)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Liver transplant Patients (twice daily dosing) Time After Transplantation</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Dose/Route</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">T <span class="Sub">max</span></span> </p> <p> <span class="Bold">(h)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">C <span class="Sub">max</span></span> </p> <p> <span class="Bold">(mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Interdosing Interval AUC <span class="Sub">(0-­12h)</span></span> </p> <p> <span class="Bold">(mcg•h/mL)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">4 to 9 days</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g/iv</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.50 (±0.517) (n=22)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">17.0 (±12.7)</p> <p>(n=22)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">34.0 (±17.4)</p> <p>(n=22)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Early (5 to 8 days)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.5 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.15 (±0.432) (n=20)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">13.1 (±6.76)</p> <p>(n=20)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">29.2 (±11.9)</p> <p>(n=20)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Late (Greater than 6 months)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.5 g/oral</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.54 (±0.51)</p> <p>(n=6)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">19.3 (±11.7)</p> <p>(n=6)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">49.3 (±14.8)</p> <p>(n=6)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Sup">a</span>AUC (0-12h) values quoted are extrapolated from data from samples collected over 4 hours. </p> </td> </tr> </tbody> </table></div>

In the early post-transplant period (less than 40 days post-transplant), kidney, heart, and liver transplant patients had mean MPA AUCs approximately 20% to 41% lower and mean C maxapproximately 32% to 44% lower compared to the late transplant period (i.e. 3 to 6 months post-transplant) (non-stationarity in MPA pharmacokinetics).

Mean MPA AUC values following administration of 1 g twice daily intravenous mycophenolate mofetil over 2 hours to kidney transplant patients for 5 days were about 24% higher than those observed after oral administration of a similar dose in the immediate post-transplant phase.

In liver transplant patients, administration of 1 g twice daily intravenous mycophenolate mofetil followed by 1.5 g twice daily oral mycophenolate mofetil resulted in mean MPA AUC estimates similar to those found in kidney transplant patients administered 1 g mycophenolate mofetil twice daily.

Effect of Food

Food (27 g fat, 650 calories) had no effect on the extent of absorption (MPA AUC) of MMF when administered at doses of 1.5 g twice daily to kidney transplant patients. However, MPA C maxwas decreased by 40% in the presence of food [see Dosage and Administration (2.1)].

Distribution

The mean (±SD) apparent volume of distribution of MPA in 12 healthy volunteers was approximately 3.6 (±1.5) L/kg. At clinically relevant concentrations, MPA is 97% bound to plasma albumin. The phenolic glucuronide metabolite of MPA (MPAG) is 82% bound to plasma albumin at MPAG concentration ranges that are normally seen in stable kidney transplant patients; however, at higher MPAG concentrations (observed in patients with kidney impairment or delayed kidney graft function), the binding of MPA may be reduced as a result of competition between MPAG and MPA for protein binding. Mean blood to plasma ratio of radioactivity concentrations was approximately 0.6 indicating that MPA and MPAG do not extensively distribute into the cellular fractions of blood.

In vitrostudies to evaluate the effect of other agents on the binding of MPA to human serum albumin (HSA) or plasma proteins showed that salicylate (at 25 mg/dL with human serum albumin) and MPAG (at ≥ 460 mcg/mL with plasma proteins) increased the free fraction of MPA. MPA at concentrations as high as 100 mcg/mL had little effect on the binding of warfarin, digoxin or propranolol, but decreased the binding of theophylline from 53% to 45% and phenytoin from 90% to 87%.

Elimination

Mean (±SD) apparent half-life and plasma clearance of MPA are 17.9 (±6.5) hours and 193 (±48) mL/min following oral administration and 16.6 (±5.8) hours and 177 (±31) mL/min following intravenous administration, respectively.

Metabolism

The parent drug, MMF, can be measured systemically during the intravenous infusion; however, approximately 5 minutes after the infusion is stopped or after oral administration, MMF concentrations are below the limit of quantitation (0.4 mcg/mL).

Metabolism to MPA occurs pre-systemically after oral dosing. MPA is metabolized principally by glucuronyl transferase to form MPAG, which is not pharmacologically active. In vivo, MPAG is converted to MPA during enterohepatic recirculation. The following metabolites of the 2-hydroxyethyl-morpholino moiety are also recovered in the urine following oral administration of MMF to healthy subjects: N-(2-carboxymethyl)-morpholine, N-(2-hydroxyethyl)-morpholine, and the N-oxide of N-(2-hydroxyethyl)-morpholine.

Due to the enterohepatic recirculation of MPAG/MPA, secondary peaks in the plasma MPA concentration-time profile are usually observed 6 to 12 hours post-dose. Bile sequestrants, such as cholestyramine, reduce MPA AUC by interfering with this enterohepatic recirculation of the drug [see Overdosage (10) and Drug Interaction Studies below].

Excretion

Negligible amount of drug is excreted as MPA (less than 1% of dose) in the urine. Orally administered radiolabeled MMF resulted in complete recovery of the administered dose, with 93% of the administered dose recovered in the urine and 6% recovered in feces. Most (about 87%) of the administered dose is excreted in the urine as MPAG. At clinically encountered concentrations, MPA and MPAG are usually not removed by hemodialysis. However, at high MPAG plasma concentrations (> 100 mcg/mL), small amounts of MPAG are removed.

Increased plasma concentrations of MMF metabolites (MPA 50% increase and MPAG about a 3-fold to 6-fold increase) are observed in patients with renal insufficiency [see Specific Populations].

Specific Populations

Patients with Renal Impairment

The mean (±SD) pharmacokinetic parameters for MPA following the administration of oral MMF given as single-doses to non-transplant subjects with renal impairment are presented in Table 11.

In a single-dose study, MMF was administered as a capsule or as an intravenous infusion over 40 minutes. Plasma MPA AUC observed after oral dosing to volunteers with severe chronic renal impairment (GFR < 25 mL/min/1.73 m 2) was about 75% higher relative to that observed in healthy volunteers (GFR > 80 mL/min/1.73 m 2). In addition, the single-dose plasma MPAG AUC was 3-fold to 6-fold higher in volunteers with severe renal impairment than in volunteers with mild renal impairment or healthy volunteers, consistent with the known renal elimination of MPAG. No data are available on the safety of long-term exposure to this level of MPAG.

Plasma MPA AUC observed after single-dose (1 g) intravenous dosing to volunteers (n=4) with severe chronic renal impairment (GFR < 25 mL/min/1.73 m 2) was 62.4 mcg•h/mL (±19.3). Multiple dosing of MMF in patients with severe chronic renal impairment has not been studied .

Patients with Delayed Graft Function or Nonfunction

In patients with delayed renal graft function post-transplant, mean MPA AUC (0-12h)was comparable to that seen in post-transplant patients without delayed renal graft function. There is a potential for a transient increase in the free fraction and concentration of plasma MPA in patients with delayed renal graft function. However, dose adjustment does not appear to be necessary in patients with delayed renal graft function. Mean plasma MPAG AUC (0-12h)was 2-fold to 3-fold higher than in post-transplant patients without delayed renal graft function [see Dosage and Administration (2.5)].

In eight patients with primary graft non-function following kidney transplantation, plasma concentrations of MPAG accumulated about 6-fold to 8-fold after multiple-dosing for 28 days. Accumulation of MPA was about 1-fold to 2-fold.

The pharmacokinetics of MMF are not altered by hemodialysis. Hemodialysis usually does not remove MPA or MPAG. At high concentrations of MPAG (> 100 mcg/mL), hemodialysis removes only small amounts of MPAG.

Patients with Hepatic Impairment

The mean (± SD) pharmacokinetic parameters for MPA following the administration of oral MMF given as single-doses to non-transplant subjects with hepatic impairment is presented in Table 11.

In a single-dose (1 g oral) study of 18 volunteers with alcoholic cirrhosis and 6 healthy volunteers, hepatic MPA glucuronidation processes appeared to be relatively unaffected by hepatic parenchymal disease when pharmacokinetic parameters of healthy volunteers and alcoholic cirrhosis patients within this study were compared. However, it should be noted that for unexplained reasons, the healthy volunteers in this study had about a 50% lower AUC as compared to healthy volunteers in other studies, thus making comparisons between volunteers with alcoholic cirrhosis and healthy volunteers difficult. In a single-dose (1 g intravenous) study of 6 volunteers with severe hepatic impairment (aminopyrine breath test less than 0.2% of dose) due to alcoholic cirrhosis, MMF was rapidly converted to MPA. MPA AUC was 44.1 mcg•h/mL (±15.5).

Table 11 Pharmacokinetic Parameters for MPA [mean (± SD)] Following Single-Doses of MMF Capsules in Chronic Renal and Hepatic Impairment

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">Pharmacokinetic Parameters for Renal Impairment</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Dose</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">T <span class="Sub">max</span></span> </p> <p> <span class="Bold">(h)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">C <span class="Sub">max</span></span> </p> <p> <span class="Bold">(mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AUC <span class="Sub">(0-96h)</span></span> </p> <p> <span class="Bold">(mcg•h/mL)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Healthy Volunteers</p> <p>GFR greater than 80 mL/min/1.73 m <span class="Sup">2</span> </p> <p>(n=6)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.75 (±0.27)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">25.3 (±7.99)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">45.0 (±22.6)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Mild Renal Impairment</p> <p>GFR 50 to 80 mL/min/1.73 m <span class="Sup">2</span>(n=6) </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.75 (±0.27)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">26.0 (±3.82)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">59.9 (±12.9)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Moderate Renal Impairment</p> <p>GFR 25 to 49 mL/min/1.73 m <span class="Sup">2</span>(n=6) </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.75 (±0.27)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">19.0 (±13.2)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">52.9 (±25.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Severe Renal Impairment</p> <p>GFR less than 25 mL/min/1.73 m <span class="Sup">2</span>(n=7) </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.00 (±0.41)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">16.3 (±10.8)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">78.6 (±46.4)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">Pharmacokinetic Parameters for Hepatic Impairment</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Dose</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">T <span class="Sub">max</span></span> </p> <p> <span class="Bold">(h)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">C <span class="Sub">max</span></span> </p> <p> <span class="Bold">(mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AUC <span class="Sub">(0-48h)</span></span> </p> <p> <span class="Bold">(mcg•h/mL)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Healthy Volunteers</p> <p>(n=6)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.63 (±0.14)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">24.3 (±5.73)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">29.0 (±5.78)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Alcoholic Cirrhosis</p> <p>(n=18)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 g</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.85 (±0.58)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">22.4 (±10.1)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">29.8 (±10.7)</p> </td> </tr> </tbody> </table></div>

Pediatric Patients

The pharmacokinetic parameters of MPA and MPAG have been evaluated in 55 pediatric patients (ranging from 1 year to 18 years of age) receiving mycophenolate mofetil oral suspension at a dose of 600 mg/m 2twice daily (up to a maximum of 1 g twice daily) after allogeneic kidney transplantation. The pharmacokinetic data for MPA is provided in Table 12.

Table 12 Mean (±SD) Computed Pharmacokinetic Parameters for MPA by Age and Time after Allogeneic Kidney Transplantation

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Age Group</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">(n)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Time</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">T <span class="Sub">max</span></span> </p> <p> <span class="Bold">(h)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Dose Adjusted <span class="Sup">a</span></span> </p> <p> <span class="Bold">C <span class="Sub">max</span></span> </p> <p> <span class="Bold">(mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Dose Adjusted <span class="Sup">a</span></span> </p> <p> <span class="Bold">AUC <span class="Sub">(0-12)</span></span> </p> <p> <span class="Bold">(mcg•h/mL)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">1 to less than 2 yr</p> <p>1 to less than 6 yr</p> <p>6 to less than 12 yr</p> <p>12 to 18 yr</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(6) <span class="Sup">d</span> </p> <p>(17)</p> <p>(16)</p> <p>(21)</p> </td><td class="Botrule Lrule Rrule Toprule"> Early (Day 7)</td><td class="Botrule Lrule Rrule Toprule"> <p class="First">3.03</p> <p>1.63</p> <p>0.940</p> <p>1.16</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(4.70)</p> <p>(2.85)</p> <p>(0.546)</p> <p>(0.830)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">10.3</p> <p>13.2</p> <p>13.1</p> <p>11.7</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(5.80)</p> <p>(7.16)</p> <p>(6.30)</p> <p>(10.7)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">22.5</p> <p>27.4</p> <p>33.2</p> <p>26.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(6.66)</p> <p>(9.54)</p> <p>(12.1)</p> <p>(9.14) <span class="Sup">b</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">1 to less than 2 yr</p> <p>1 to less than 6 yr</p> <p>6 to less than 12 yr</p> <p>12 to 18 yr</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(4) <span class="Sup">d</span> </p> <p>(15)</p> <p>(14)</p> <p>(17)</p> </td><td class="Botrule Lrule Rrule Toprule"> Late (Month 3)</td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.725</p> <p>0.989</p> <p>1.21</p> <p>0.978</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(0.276)</p> <p>(0.511)</p> <p>(0.532)</p> <p>(0.484)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">23.8</p> <p>22.7</p> <p>27.8</p> <p>17.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(13.4)</p> <p>(10.1)</p> <p>(14.3)</p> <p>(9.57)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">47.4</p> <p>49.7</p> <p>61.9</p> <p>53.6</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(14.7)</p> <p>(18.2)</p> <p>(19.6)</p> <p>(20.3) <span class="Sup">c</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">1 to less than 2 yr</p> <p>1 to less than 6 yr</p> <p>6 to less than 12 yr</p> <p>12 to 18 yr</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(4) <span class="Sup">d</span> </p> <p>(12)</p> <p>(11)</p> <p>(14)</p> </td><td class="Botrule Lrule Rrule Toprule"> Late (Month 9)</td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.604</p> <p>0.869</p> <p>1.12</p> <p>1.09</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(0.208)</p> <p>(0.479)</p> <p>(0.462)</p> <p>(0.518)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">25.6</p> <p>30.4</p> <p>29.2</p> <p>18.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(4.25)</p> <p>(9.16)</p> <p>(12.6)</p> <p>(7.29)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">55.8</p> <p>61.0</p> <p>66.8</p> <p>56.7</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">(11.6)</p> <p>(10.7)</p> <p>(21.2)</p> <p>(14.0)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="9"> <p class="First"> <span class="Sup">a</span>adjusted to a dose of 600 mg/m <span class="Sup">2</span> </p> <p> <span class="Sup">b</span>n=20 </p> <p> <span class="Sup">c</span>n=16 </p> <p> <span class="Sup">d</span>a subset of 1 to &lt; 6 yr </p> </td> </tr> </tbody> </table></div>

A comparison of dose-normalized (to 600 mg/m 2) MPA AUC values in 12 pediatric kidney transplant patients less than 6 years of age at 9 months post-transplant with those values in 7 pediatric liver transplant patients [median age 17 months (range: 10 – 60 months)] and at 6 months and beyond post-transplant revealed that, at the same dose, there were on average 23% lower AUC values in the pediatric liver compared to pediatric kidney patients. This is consistent with the need for higher dosing in adult liver transplant patients compared to kidney transplant patients to achieve the same exposure.

In adult transplant patients administered the same dosage of mycophenolate mofetil, there is similar MPA exposure among kidney transplant and heart transplant patients. Based on the established similarity in MPA exposure between pediatric kidney transplant and adult kidney transplant patients at their respective approved doses, it is expected that MPA exposure at the recommended dosage will be similar in pediatric heart transplant and adult heart transplant patients.

Male and Female Patients

Data obtained from several studies were pooled to look at any gender-related differences in the pharmacokinetics of MPA (data were adjusted to 1 g oral dose). Mean (±SD) MPA AUC (0-12h) for males (n=79) was 32.0 (±14.5) and for females (n=41) was 36.5 (±18.8) mcg•h/mL while mean (±SD) MPA C maxwas 9.96 (±6.19) in the males and 10.6 (±5.64) mcg/mL in the females. These differences are not of clinical significance.

Geriatric Patients

The pharmacokinetics of mycophenolate mofetil and its metabolites have not been found to be altered in geriatric transplant patients when compared to younger transplant patients.

Drug Interaction Studies

Acyclovir

Co-administration of MMF (1 g) and acyclovir (800 mg) to 12 healthy volunteers resulted in no significant change in MPA AUC and C max. However, MPAG and acyclovir plasma AUCs were increased 10.6% and 21.9%, respectively.

Antacids with Magnesium and Aluminum Hydroxides

Absorption of a single-dose of MMF (2 g) was decreased when administered to 10 rheumatoid arthritis patients also taking Maalox ®TC (10 mL qid). The C maxand AUC (0-24h)for MPA were 33% and 17% lower, respectively, than when mycophenolate mofetil (MMF) was administered alone under fasting conditions.

Proton Pump Inhibitors (PPIs)

Co-administration of PPIs (e.g., lansoprazole, pantoprazole) in single-doses to healthy volunteers and multiple-doses to transplant patients receiving mycophenolate mofetil has been reported to reduce the exposure to MPA. An approximate reduction of 30% to 70% in the C maxand 25% to 35% in the AUC of MPA has been observed, possibly due to a decrease in MPA solubility at an increased gastric pH.

Cholestyramine

Following single-dose administration of 1.5 g MMF to 12 healthy volunteers pretreated with 4 g three times a day of cholestyramine for 4 days, MPA AUC decreased approximately 40%. This decrease is consistent with interruption of enterohepatic recirculation which may be due to binding of recirculating MPAG with cholestyramine in the intestine.

Cyclosporine

Cyclosporine (Sandimmune ®) pharmacokinetics (at doses of 275 to 415 mg/day) were unaffected by single and multiple doses of 1.5 g twice daily of MMF in 10 stable kidney transplant patients. The mean (±SD) AUC (0-12h)and C maxof cyclosporine after 14 days of multiple doses of MMF were 3,290 (±822) ng•h/mL and 753 (±161) ng/mL, respectively, compared to 3,245 (±1,088) ng•h/mL and 700 (±246) ng/mL, respectively, 1 week before administration of MMF.

Cyclosporine A interferes with MPA enterohepatic recirculation. In kidney transplant patients, mean MPA exposure (AUC (0-12h)) was approximately 30% to 50% greater when MMF was administered without cyclosporine compared with when MMF was co-administered with cyclosporine. This interaction is due to cyclosporine inhibition of multidrug-resistance-associated protein 2 (MRP-2) transporter in the biliary tract, thereby preventing the excretion of MPAG into the bile that would lead to enterohepatic recirculation of MPA. This information should be taken into consideration when MMF is used without cyclosporine.

Drugs Affecting Glucuronidation

Concomitant administration of drugs inhibiting glucuronidation of MPA may increase MPA exposure (e.g., increase of MPA AUC (0-∞)by 35% was observed with concomitant administration of isavuconazole).

Concomitant administration of telmisartan and mycophenolate mofetil resulted in an approximately 30% decrease in MPA concentrations. Telmisartan changes MPA’s elimination by enhancing PPAR gamma (peroxisome proliferator-activated receptor gamma) expression, which in turn results in an enhanced UGT1A9 expression and glucuronidation activity.

Ganciclovir

Following single-dose administration to 12 stable kidney transplant patients, no pharmacokinetic interaction was observed between MMF (1.5 g) and intravenous ganciclovir (5 mg/kg). Mean (±SD) ganciclovir AUC and C max(n=10) were 54.3 (±19.0) mcg•h/mL and 11.5 (±1.8) mcg/mL, respectively, after co-administration of the two drugs, compared to 51.0 (±17.0) mcg•h/mL and 10.6 (±2.0) mcg/mL, respectively, after administration of intravenous ganciclovir alone. The mean (±SD) AUC and C maxof MPA (n=12) after co-administration were 80.9 (±21.6) mcg•h/mL and 27.8 (±13.9) mcg/mL, respectively, compared to values of 80.3 (±16.4) μg•h/mL and 30.9 (±11.2) mcg/mL, respectively, after administration of MMF alone.

Oral Contraceptives

A study of co-administration of mycophenolate mofetil (1 g twice daily) and combined oral contraceptives containing ethinylestradiol (0.02 mg to 0.04 mg) and levonorgestrel (0.05 mg to 0.20 mg), desogestrel (0.15 mg) or gestodene (0.05 mg to 0.10 mg) was conducted in 18 women with psoriasis over 3 consecutive menstrual cycles. Mean serum levels of LH, FSH and progesterone were not significantly affected. Mean AUC (0-24h)was similar for ethinylestradiol and 3-keto desogestrel; however, mean levonorgestrel AUC (0-24h)significantly decreased by about 15%. There was large inter-patient variability (%CV in the range of 60% to 70%) in the data, especially for ethinylestradiol.

Sevelamer

Concomitant administration of sevelamer and MMF in adult and pediatric patients decreased the mean MPA C maxand AUC (0-12h)by 36% and 26% respectively.

Antimicrobials

Antimicrobials eliminating beta-glucuronidase-producing bacteria in the intestine (e.g., aminoglycoside, cephalosporin, fluoroquinolone, and penicillin classes of antimicrobials) may interfere with the MPAG/MPA enterohepatic recirculation thus leading to reduced systemic MPA exposure. Information concerning antibiotics is as follows:

In a 104-week oral carcinogenicity study in mice, MMF in daily doses up to 180 mg/kg was not tumorigenic. The highest dose tested was 0.2 times the recommended clinical dose (2 g/day) in renal transplant patients and 0.15 times the recommended clinical dose (3 g/day) in cardiac transplant patients when corrected for differences in body surface area (BSA). In a 104-week oral carcinogenicity study in rats, MMF in daily doses up to 15 mg/kg was not tumorigenic. The highest dose was 0.035 times the recommended clinical dose in kidney transplant patients and 0.025 times the recommended clinical dose in heart transplant patients when corrected for BSA. While these animal doses were lower than those given to patients, they were maximal in those species and were considered adequate to evaluate the potential for human risk [see Warnings and Precautions (5.2)].

The genotoxic potential of MMF was determined in five assays. MMF was genotoxic in the mouse lymphoma/thymidine kinase assay and the in vivomouse micronucleus assay. MMF was not genotoxic in the bacterial mutation assay, the yeast mitotic gene conversion assay or the Chinese hamster ovary cell chromosomal aberration assay.

MMF had no effect on fertility of male rats at oral doses up to 20 mg/kg/day. This dose represents 0.05 times the recommended clinical dose in renal transplant patients and 0.03 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. In a female fertility and reproduction study conducted in rats, oral doses of 4.5 mg/kg/day caused malformations (principally of the head and eyes) in the first generation offspring in the absence of maternal toxicity. This dose was 0.01 times the recommended clinical dose in renal transplant patients and 0.005 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. No effects on fertility or reproductive parameters were evident in the dams or in the subsequent generation.

Adults

The three de novokidney transplantation studies compared two dose levels of oral mycophenolate mofetil (1 g twice daily and 1.5 g twice daily) with azathioprine (2 studies) or placebo (1 study) to prevent acute rejection episodes. One of the two studies with azathioprine (AZA) control arm also included anti-thymocyte globulin (ATGAM ®) induction therapy. The geographic location of the investigational sites of these studies are included in Table 13.

In all three de novokidney transplantation studies, the primary efficacy endpoint was the proportion of patients in each treatment group who experienced treatment failure within the first 6 months after transplantation. Treatment failure was defined as biopsy-proven acute rejection on treatment or the occurrence of death, graft loss or early termination from the study for any reason without prior biopsy-proven rejection.

Mycophenolate mofetil, in combination with corticosteroids and cyclosporine, reduced (statistically significant at 0.05 level) the incidence of treatment failure within the first 6 months following transplantation ( Table 13).Patients who prematurely discontinued treatment were followed for the occurrence of death or graft loss, and the cumulative incidence of graft loss and patient death combined are summarized in Table 14. Patients who prematurely discontinued treatment were not followed for the occurrence of acute rejection after termination.

Table 13 Treatment Failure in De Novo Kidney Transplantation Studies

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First"> <span class="Bold">USA Study</span> </p> <p> <span class="Bold">(N=499 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">2 g/day</span> </p> <p> <span class="Bold">(n=167 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">3 g/day</span> </p> <p> <span class="Bold">(n=166 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AZA</span> </p> <p> <span class="Bold">1 to 2 mg/kg/day</span> </p> <p> <span class="Bold">(n=166 patients)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="3"> <p class="First">All 3 groups received anti-thymocyte globulin induction, cyclosporine and corticosteroids</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">All treatment failures</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">31.1%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">31.3%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">47.6%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Early termination without prior acute rejection</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">9.6%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">12.7%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">6.0%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Biopsy-proven rejection episode on treatment</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">19.8%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">17.5%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">38.0%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First"> <span class="Bold">Europe/Canada/</span> </p> <p> <span class="Bold">Australia Study</span> </p> <p> <span class="Bold">(N=503 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">2 g/day</span> </p> <p> <span class="Bold">(n=173 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">3 g/day</span> </p> <p> <span class="Bold">(n=164 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AZA</span> </p> <p> <span class="Bold">100 to 150 mg/day</span> </p> <p> <span class="Bold">(n=166 patients)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="3"> <p class="First">No induction treatment administered; all 3 groups received cyclosporine and corticosteroids.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">All treatment failures</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">38.2%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">34.8%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">50.0%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Early termination without prior acute rejection</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">13.9%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">15.2%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">10.2%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Biopsy-proven rejection episode on treatment</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">19.7%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">15.9%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">35.5%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First"> <span class="Bold">Europe Study</span> </p> <p> <span class="Bold">(N=491 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">2 g/day</span> </p> <p> <span class="Bold">(n=165 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">3 g/day</span> </p> <p> <span class="Bold">(n=160 patients)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">(n=166 patients)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="3"> <p class="First">No induction treatment administered; all 3 groups received cyclosporine and corticosteroids.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">All treatment failures</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">30.3%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">38.8%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">56.0%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Early termination without prior acute rejection</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">11.5%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">22.5%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">7.2%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Biopsy-proven rejection episode on treatment</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">17.0%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">13.8%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">46.4%</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="4"> <p class="First">*Does not include death and graft loss as reason for early termination.</p> </td> </tr> </tbody> </table></div>

No advantage of mycophenolate mofetil at 12 months with respect to graft loss or patient death (combined) was established ( Table 14). Numerically, patients receiving mycophenolate mofetil 2 g/day and 3 g/day experienced a better outcome than controls in all three studies; patients receiving mycophenolate mofetil 2 g/day experienced a better outcome than mycophenolate mofetil 3 g/day in two of the three studies. Patients in all treatment groups who terminated treatment early were found to have a poor outcome with respect to graft loss or patient death at 1 year.

Table 14 De Novo Kidney Transplantation Studies Cumulative Incidence of Combined Graft Loss or Patient Death at 12 Months

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Study</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">2 g/day</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">3 g/day</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Control</span> </p> <p> <span class="Bold">(AZA or Placebo)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">USA</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">8.5%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">11.5%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">12.2%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Europe/Canada/Australia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">11.7%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">11.0%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">13.6%</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Europe</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">8.5%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">10.0%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">11.5%</p> </td> </tr> </tbody> </table></div>

Pediatrics- De Novo Kidney transplantation PK Study with Long Term Follow-Up

One open-label, safety and pharmacokinetic study of mycophenolate mofetil oral suspension 600 mg/m 2twice daily (up to 1 g twice daily) in combination with cyclosporine and corticosteroids was performed at centers in the United States (9), Europe (5) and Australia (1) in 100 pediatric patients (3 months to 18 years of age) for the prevention of renal allograft rejection. Mycophenolate mofetil was well tolerated in pediatric patients [see Adverse Reactions (6.1)] , and the pharmacokinetics profile was similar to that seen in adult patients dosed with 1 g twice daily mycophenolate mofetil capsules [see Clinical Pharmacology (12.3)]. The rate of biopsy-proven rejection was similar across the age groups (3 months to < 6 years, 6 years to < 12 years, 12 years to 18 years). The overall biopsy-proven rejection rate at 6 months was comparable to adults. The combined incidence of graft loss (5%) and patient death (2%) at 12 months post-transplant was similar to that observed in adult kidney transplant patients.

A double-blind, randomized, comparative, parallel-group, multicenter study in primary de novoheart transplant recipients was performed at centers in the United States (20), in Canada (1), in Europe (5) and in Australia (2). The total number of patients enrolled (ITT population) was 650; 72 never received study drug and 578 received study drug (Safety Population). Patients received mycophenolate mofetil 1.5 g twice daily (n=289) or AZA 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune ®or Neoral ®) and corticosteroids as maintenance immunosuppressive therapy. The two primary efficacy endpoints were: (1) the proportion of patients who, after transplantation, had at least one endomyocardial biopsy-proven rejection with hemodynamic compromise, or were re-transplanted or died, within the first 6 months, and (2) the proportion of patients who died or were re-transplanted during the first 12 months following transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection for up to 6 months and for the occurrence of death for 1 year.

The analyses of the endpoints showed:

Table 15  De Novo Heart Transplantation Study Rejection at 6 Months/Death or Re-transplantation at 1 Year

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" rowspan="2"></td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">All Patients (ITT)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Treated Patients</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AZA</span> </p> <p> <span class="Bold">N = 323</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">N = 327</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AZA</span> </p> <p> <span class="Bold">N = 289</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">N = 289</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Biopsy-proven rejection with hemodynamic compromise at 6 months <span class="Sup">a</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">121 (38%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">120 (37%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">100 (35%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">92 (32%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Death or re-transplantation at 1 year</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">49  (15.2%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">42 (12.8%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">33 (11.4%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">18 (6.2%)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Sup">a</span>Hemodynamic compromise occurred if any of the following criteria were met: pulmonary capillary wedge pressure <span class="Underline">&gt;</span>20 mm or a 25% increase; cardiac index &lt; 2.0 L/min/m <span class="Sup">2</span>or a 25% decrease; ejection fraction <span class="Underline">&lt;</span>30%; pulmonary artery oxygen saturation <span class="Underline">&lt;</span>60% or a 25% decrease; presence of new S <span class="Sub">3</span>gallop; fractional shortening was <span class="Underline">&lt;</span>20% or a 25% decrease; inotropic support required to manage the clinical condition. </p> </td> </tr> </tbody> </table></div>

A double-blind, randomized, comparative, parallel-group, multicenter study in primary hepatic transplant recipients was performed at centers in the United States (16), in Canada (2), in Europe (4) and in Australia (1). The total number of patients enrolled was 565. Per protocol, patients received mycophenolate mofetil 1 g twice daily intravenously for up to 14 days followed by mycophenolate mofetil 1.5 g twice daily orally or AZA 1 to 2 mg/kg/day intravenously followed by AZA 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral ®) and corticosteroids as maintenance immunosuppressive therapy. The actual median oral dose of AZA on study was 1.5 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) initially and 1.26 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) at 12 months. The two primary endpoints were: (1) the proportion of patients who experienced, in the first 6 months post-transplantation, one or more episodes of biopsy-proven and treated rejection or death or re-transplantation, and (2) the proportion of patients who experienced graft loss (death or re-transplantation) during the first 12 months post-transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection and for the occurrence of graft loss (death or re-transplantation) for 1 year.

In combination with corticosteroids and cyclosporine, mycophenolate mofetil demonstrated a lower rate of acute rejection at 6 months and a similar rate of death or re-transplantation at 1 year compared to AZA ( Table 16).

Table 16  De Novo Liver Transplantation Study Rejection at 6 Months/Death or Retransplantation at 1 Year

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">AZA</span> </p> <p> <span class="Bold">N = 287</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Mycophenolate Mofetil</span> </p> <p> <span class="Bold">N = 278</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Biopsy-proven, treated rejection at 6 months (includes death or re-transplantation)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">137 (47.7%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">107 (38.5%)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Death or re-transplantation at 1 year</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">42 (14.6%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">41 (14.7%)</p> </td> </tr> </tbody> </table></div>

1. “OSHA Hazardous Drugs.” OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

{ "type": "p", "children": [], "text": "1. “OSHA Hazardous Drugs.” OSHA.\n \n http://www.osha.gov/SLTC/hazardousdrugs/index.html\n" }

Mycophenolate mofetil (MMF) has demonstrated teratogenic effects in humans [see Warnings and Precautions (5.1)and Use in Specific Populations (8.1)] . Wearing disposable gloves is recommended during reconstitution and when wiping the outer surface of the bottle/cap and the table after reconstitution. Avoid inhalation or direct contact with skin or mucous membranes of the powder contained in mycophenolate mofetil for injection (during or after preparation) [see Dosage and Administration (2.6)]. Follow applicable special handling and disposal procedures 1.

Mycophenolate Mofetil for Injection, USP, supplied in a 20 mL sterile single-dose vial, is a white to off-white lyophilized powder containing equivalent of 500 mg mycophenolate mofetil, USP and is supplied in a cartons of 4 single-dose vials.

500 mg/vial

4 Single-dose Vials in 1 Carton: NDC 83270-000-04

Storage

Store powder and reconstituted infusion solution at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).

Pregnancy loss and malformations

Contraception

Inform patients that they are at increased risk of developing a variety of infections due to immunosuppression. Instruct them to contact their physician if they develop any of the signs and symptoms of infection explained in the Medication Guide [see Warnings and Precautions (5.3)] .

Inform patients that they are at increased risk for developing blood adverse effects such as anemia or low white blood cells. Advise patients to immediately contact their healthcare provider if they experience any evidence of infection, unexpected bruising, or bleeding, or any other manifestation of bone marrow suppression [see Warnings and Precautions (5.4)] .

Inform patients that mycophenolate mofetil can cause gastrointestinal tract complications including bleeding, intestinal perforations, and gastric or duodenal ulcers. Advise the patient to contact their healthcare provider if they have symptoms of gastrointestinal bleeding, or sudden onset or persistent abdominal pain [see Warnings and Precautions (5.5)].

Inform patients that acute inflammatory reactions have been reported in some patients who received mycophenolate mofetil. Some reactions were severe, requiring hospitalization. Advise patients to contact their physician if they develop fever, joint stiffness, joint pain or muscle pains [see Warnings and Precautions (5.7)] .

Inform patients that mycophenolate mofetil can interfere with the usual response to immunizations. Before seeking vaccines on their own, advise patients to discuss first with their physician [see Warnings and Precautions (5.8)] .

Advise patients to take a missed dose as soon as they remember, except if it is closer than 2 hours to the next scheduled dose; in this case they should continue to take mycophenolate mofetil for injection at the usual times.

Advise patients not to donate blood during therapy and for at least 6 weeks following discontinuation of mycophenolate mofetil  [see Warnings and Precautions (5.11)].

Advise males of childbearing potential not to donate semen during therapy and for 90 days following discontinuation of mycophenolate mofetil [see Warnings and Precautions (5.12)] .

Advise patients that mycophenolate mofetil can affect the ability to drive or operate machines. Patients should avoid driving or operating machines if they experience somnolence, confusion, dizziness, tremor or hypotension during treatment with mycophenolate mofetil [see Warnings and Precautions (5.14)] .

Manufactured for:

Steriscience Specialities Pte. Limited

Mfd by:

OneSource Specialty Pharma Limited Bengaluru - 561203, India.

Revised: 10/2024

Mycophenolate Mofetil(mye’’ koe fen’ oh late moe’ fe til) for Injection

{ "type": "p", "children": [], "text": "\nMycophenolate Mofetil(mye’’ koe fen’ oh late moe’ fe til)\n \n for Injection\n" }

Read the Medication Guide that comes with mycophenolate mofetil for injection before you start taking it and each time you refill your prescription. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment.

{ "type": "p", "children": [], "text": "Read the Medication Guide that comes with mycophenolate mofetil for injection before you start taking it and each time you refill your prescription. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment." }

What is the most important information I should know about mycophenolate mofetil for injection?

{ "type": "p", "children": [], "text": "\nWhat is the most important information I should know about mycophenolate mofetil for injection?\n" }

Mycophenolate mofetil for injection can cause serious side effects, including:

{ "type": "p", "children": [], "text": "\nMycophenolate mofetil for injection can cause serious side effects, including:\n" }

Increased risk of loss of a pregnancy (miscarriage) and higher risk of birth defects.Females who take mycophenolate mofetil for injection during pregnancy have a higher risk of miscarriage during the first 3 months (first trimester), and a higher risk that their baby will be born with birth defects.

{ "type": "p", "children": [], "text": "\nIncreased risk of loss of a pregnancy (miscarriage) and higher risk of birth defects.Females who take mycophenolate mofetil for injection during pregnancy have a higher risk of miscarriage during the first 3 months (first trimester), and a higher risk that their baby will be born with birth defects.\n\n " }

{ "type": "ul", "children": [ "\nIf you are a female who can become pregnant, your doctor must talk with you about acceptable birth control methods (contraceptive counseling) to use while taking mycophenolate mofetil for injection. You should have 1 pregnancy test immediately before starting mycophenolate mofetil for injection and another pregnancy test 8 to 10 days later. Pregnancy tests should be repeated during routine follow-up visits with your doctor. Talk to your doctor about the results of all of your pregnancy tests. You must use acceptable birth control during your entire mycophenolate mofetil for injection treatment and for 6 weeks after stopping mycophenolate mofetil for injection, unless at any time you choose to avoid sexual intercourse (abstinence) with a man completely. Mycophenolate mofetil for injection decreases blood levels of the hormones in birth control pills that you take by mouth. Birth control pills may not work as well while you take mycophenolate mofetil for injection, and you could become pregnant. If you take birth control pills while using mycophenolate mofetil for injection you must also use another form of birth control. Talk to your doctor about other birth control methods that you can use while taking mycophenolate mofetil for injection.\n \n ", "\nIf you are a sexually active male whose female partner can become pregnant while you are taking mycophenolate mofetil for injection, use effective contraception during treatment and for at least 90 days after stopping mycophenolate mofetil for injection.\n \n ", "\nIf you plan to become pregnant, talk with your doctor. Your doctor will decide if other medicines to prevent rejection may be right for you.\n \n ", "\nIf you become pregnant while taking mycophenolate mofetil for injection,do not stop taking mycophenolate mofetil for injection. Call your doctor right away.\n" ], "text": "" }

You and your doctor may decide that other medicines to prevent rejection may be right for you. You and your doctor should report your pregnancy to the Mycophenolate Pregnancy Registry either:

{ "type": "p", "children": [], "text": "You and your doctor may decide that other medicines to prevent rejection may be right for you. You and your doctor should report your pregnancy to the Mycophenolate Pregnancy Registry either:" }

{ "type": "ul", "children": [ "By phone at 1-800-617-8191\n \n or\n", "By visiting the REMS website at:\n \n www.mycophenolateREMS.com\n" ], "text": "" }

The purpose of this registry is to gather information about the health of you and your baby.

{ "type": "p", "children": [], "text": "The purpose of this registry is to gather information about the health of you and your baby." }

Increased risk of getting certain cancers.People who take mycophenolate mofetil for injection have a higher risk of getting lymphoma, and other cancers, especially skin cancer. Tell your doctor if you have:

{ "type": "p", "children": [], "text": "\nIncreased risk of getting certain cancers.People who take mycophenolate mofetil for injection have a higher risk of getting lymphoma, and other cancers, especially skin cancer. Tell your doctor if you have:\n\n " }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td> <ul class="Disc"> <li>unexplained fever, prolonged tiredness, weight loss or lymph node swelling</li> </ul> </td><td> <ul class="Disc"> <li>a change in the size and color of a mole</li> </ul> </td> </tr> <tr> <td> <ul class="Disc"> <li>a brown or black skin lesion with uneven borders, or one part of the lesion does not look like the other</li> </ul> </td><td> <ul class="Disc"> <li>a new skin lesion or bump</li> </ul> </td> </tr> <tr class="Last"> <td></td><td> <ul class="Disc"> <li>any other changes to your health</li> </ul> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"100%\">\n<col width=\"17px\"/>\n<col width=\"17px\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<ul class=\"Disc\">\n<li>unexplained fever, prolonged tiredness, weight loss or lymph node swelling</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>a change in the size and color of a mole</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td>\n<ul class=\"Disc\">\n<li>a brown or black skin lesion with uneven borders, or one part of the lesion does not look like the other</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>a new skin lesion or bump</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Last\">\n<td></td><td>\n<ul class=\"Disc\">\n<li>any other changes to your health</li>\n</ul>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Increased risk of getting serious infections.Mycophenolate mofetil for injection weakens the body’s immune system and affects your ability to fight infections. Serious infections can happen with mycophenolate mofetil for injection and can lead to hospitalizations and death. These serious infections can include:

{ "type": "p", "children": [], "text": "\nIncreased risk of getting serious infections.Mycophenolate mofetil for injection weakens the body’s immune system and affects your ability to fight infections. Serious infections can happen with mycophenolate mofetil for injection and can lead to hospitalizations and death. These serious infections can include:\n\n " }

{ "type": "ul", "children": [ "\nViral infections.Certain viruses can live in your body and cause active infections when your immune system is weak. Viral infections that can happen with mycophenolate mofetil for injection include:\n \n \nShingles, other herpes infections, and cytomegalovirus (CMV). CMV can cause serious tissue and blood infections.\nBK virus. BK virus can affect how your kidney works and cause your transplanted kidney to fail.\nHepatitis B and C viruses. Hepatitis viruses can affect how your liver works. Talk to your doctor about how hepatitis viruses may affect you.\nCOVID-19\n\n" ], "text": "" }

{ "type": "ul", "children": [ "\nA brain infection called Progressive Multifocal Leukoencephalopathy (PML).In some patients, mycophenolate mofetil for injection may cause an infection of the brain that may cause death. You are at risk for this brain infection because you have a weakened immune system. Call your doctor right away if you have any of the following symptoms:\n \n " ], "text": "" }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17px"/> <col width="17px"/> <tbody class="Headless"> <tr class="First"> <td> <ul class="Circle"> <li>weakness on one side of the body</li> </ul> </td><td> <ul class="Circle"> <li>you are confused or have problems thinking</li> </ul> </td> </tr> <tr class="Last"> <td> <ul class="Circle"> <li>you do not care about things you usually care about (apathy)</li> </ul> </td><td> <ul class="Circle"> <li>you cannot control your muscles</li> </ul> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"100%\">\n<col width=\"17px\"/>\n<col width=\"17px\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<ul class=\"Circle\">\n<li>weakness on one side of the body</li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>you are confused or have problems thinking</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Last\">\n<td>\n<ul class=\"Circle\">\n<li>you do not care about things you usually care about (apathy)</li>\n</ul>\n</td><td>\n<ul class=\"Circle\">\n<li>you cannot control your muscles</li>\n</ul>\n</td>\n</tr>\n</tbody>\n</table></div>" }

{ "type": "ul", "children": [ "\nFungal infections.Yeasts and other types of fungal infections can happen with mycophenolate mofetil for injection and can cause serious tissue and blood infections (See\n \n “What are the possible side effects of mycophenolate mofetil for injection?”).\n \n " ], "text": "" }

Call your doctor right away if you have any of the following signs and symptoms of infection:

{ "type": "p", "children": [], "text": "\nCall your doctor right away if you have any of the following signs and symptoms of infection:\n" }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="175px"/> <col width="175px"/> <tbody class="Headless"> <tr class="First"> <td> <ul class="Disc"> <li>temperature of 100.5°F or greater</li> </ul> </td><td> <ul class="Disc"> <li>pain during urination</li> </ul> </td> </tr> <tr> <td> <ul class="Disc"> <li>cold symptoms, such as a runny nose or sore throat</li> </ul> </td><td> <ul class="Disc"> <li>white patches in the mouth or throat</li> </ul> </td> </tr> <tr> <td> <ul class="Disc"> <li>flu symptoms, such as an upset stomach, stomach pain, vomiting or diarrhea</li> </ul> </td><td> <ul class="Disc"> <li>unexpected bruising or bleeding</li> </ul> </td> </tr> <tr class="Last"> <td> <ul class="Disc"> <li>earache or headache</li> </ul> </td><td> <ul class="Disc"> <li>cuts, scrapes or incisions that are red, warm and oozing pus</li> </ul> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"100%\">\n<col width=\"175px\"/>\n<col width=\"175px\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<ul class=\"Disc\">\n<li>temperature of 100.5°F or greater</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>pain during urination</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td>\n<ul class=\"Disc\">\n<li>cold symptoms, such as a runny nose or sore throat</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>white patches in the mouth or throat</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td>\n<ul class=\"Disc\">\n<li>flu symptoms, such as an upset stomach, stomach pain, vomiting or diarrhea</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>unexpected bruising or bleeding</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Last\">\n<td>\n<ul class=\"Disc\">\n<li>earache or headache</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>cuts, scrapes or incisions that are red, warm and oozing pus</li>\n</ul>\n</td>\n</tr>\n</tbody>\n</table></div>" }

See “What are the possible side effects of mycophenolate mofetil for injection?”for information about other serious side effects.

{ "type": "p", "children": [], "text": "See\n \n “What are the possible side effects of mycophenolate mofetil for injection?”for information about other serious side effects.\n\n " }

What is mycophenolate mofetil for injection?

{ "type": "p", "children": [], "text": "\nWhat is mycophenolate mofetil for injection?\n" }

{ "type": "ul", "children": [ "Mycophenolate mofetil for injection is a prescription medicine to prevent rejection (antirejection medicine) in people who have received a kidney, heart or liver transplant. Rejection is when the body’s immune system perceives the new organ as a “foreign” threat and attacks it.", "Mycophenolate mofetil for injection is used with other medicines containing cyclosporine and corticosteroids." ], "text": "" }

Who should not take mycophenolate mofetil for injection?

{ "type": "p", "children": [], "text": "\nWho should not take mycophenolate mofetil for injection?\n" }

Do not take mycophenolate mofetil for injection if you are allergic to mycophenolate mofetil or any of the ingredients in mycophenolate mofetil for injection.

{ "type": "p", "children": [], "text": "\nDo not take mycophenolate mofetil for injection if you are allergic to mycophenolate mofetil or any of the ingredients in mycophenolate mofetil for injection.\n" }

See the end of this Medication Guide for a complete list of ingredients in mycophenolate mofetil for injection.

{ "type": "p", "children": [], "text": "See the end of this Medication Guide for a complete list of ingredients in mycophenolate mofetil for injection." }

What should I tell my doctor before taking mycophenolate mofetil for injection?

{ "type": "p", "children": [], "text": "\nWhat should I tell my doctor before taking mycophenolate mofetil for injection?\n" }

Tell your doctor about all of your medical conditions, including if you:

{ "type": "p", "children": [], "text": "\nTell your doctor about all of your medical conditions, including if you:\n\n " }

{ "type": "ul", "children": [ "have any digestive problems, such as ulcers.", "have Lesch-Nyhan syndrome, Kelley-Seegmiller syndrome, or another rare inherited deficiency hypoxanthine-guanine phosphoribosyl-transferase (HGPRT). You should not take mycophenolate mofetil for injection if you have one of these disorders.", "plan to receive any vaccines. People taking mycophenolate mofetil for injection should not receive live vaccines. Some vaccines may not work as well during treatment with mycophenolate mofetil for injection.", "are pregnant or plan to become pregnant. See\n \n “What is the most important information I should know about mycophenolate mofetil for injection?”\n", "are breastfeeding or plan to breastfeed. It is not known if mycophenolate mofetil passes into breast milk. You and your doctor will decide if you will take mycophenolate mofetil for injection or breastfeed." ], "text": "" }

Tell your healthcare provider about all the medicines you take,including prescription and over-the-counter medicines, vitamins and herbal supplements. Some medicines may affect the way mycophenolate mofetil for injection works, and mycophenolate mofetil for injection may affect how some medicines work.

{ "type": "p", "children": [], "text": "\nTell your healthcare provider about all the medicines you take,including prescription and over-the-counter medicines, vitamins and herbal supplements. Some medicines may affect the way mycophenolate mofetil for injection works, and mycophenolate mofetil for injection may affect how some medicines work.\n\n " }

Especially tell your doctor if you take:

{ "type": "p", "children": [], "text": "Especially tell your doctor if you take:" }

{ "type": "ul", "children": [ "birth control pills (oral contraceptives). See\n \n “What is the most important information I should know about mycophenolate mofetil for injection?”\n", "sevelamer (Renagel\n \n ®, Renvela™). These products should be taken at least 2 hours after taking mycophenolate mofetil for injection.\n \n ", "acyclovir (Zovirax\n \n ®), valacyclovir (Valtrex\n \n ®), ganciclovir (CYTOVENE\n \n ®-IV, Vitrasert\n \n ®), valganciclovir (VALCYTE\n \n ®).\n \n ", "rifampin (Rifater\n \n ®, Rifamate\n \n ®, Rimactane\n \n ®, Rifadin\n \n ®).\n \n ", "antacids that contain magnesium and aluminum (mycophenolate mofetil for injection and the antacid should not be taken at the same time).", "proton pump inhibitors (PPIs) (Prevacid\n \n ®, Protonix\n \n ®).\n \n ", "sulfamethoxazole/trimethoprim (BACTRIM™, BACTRIM DS™).", "norfloxacin (Noroxin\n \n ®) and metronidazole (Flagyl\n \n ®, Flagyl\n \n ®ER, Flagyl\n \n ®IV, Metro IV, Helidac\n \n ®, Pylera™).\n \n ", "ciprofloxacin (Cipro\n \n ®, Cipro\n \n ®XR, Ciloxan\n \n ®, Proquin\n \n ®XR) and amoxicillin plus clavulanic acid (Augmentin\n \n ®, Augmentin XR™).\n \n ", "azathioprine (Azasan\n \n ®, Imuran\n \n ®).\n \n ", "cholestyramine (Questran Light\n \n ®, Questran\n \n ®, Locholest Light, Locholest, Prevalite\n \n ®).\n \n " ], "text": "" }

Know the medicines you take. Keep a list of them to show to your doctor or nurse and pharmacist when you get a new medicine. Do nottake any new medicine without talking with your doctor.

{ "type": "p", "children": [], "text": "Know the medicines you take. Keep a list of them to show to your doctor or nurse and pharmacist when you get a new medicine.\n \n Do nottake any new medicine without talking with your doctor.\n\n " }

How should I take mycophenolate mofetil for injection?

{ "type": "p", "children": [], "text": "\nHow should I take mycophenolate mofetil for injection?\n" }

{ "type": "ul", "children": [ "Take mycophenolate mofetil for injection exactly as prescribed.", "\nDo notstop taking mycophenolate mofetil for injection or change the dose unless your doctor tells you to.\n \n ", "If you miss a dose of mycophenolate mofetil for injection, or you are not sure when you took your last dose, take your prescribed dose of mycophenolate mofetil for injection as soon as you remember. If your next dose is less than 2 hours away, skip the missed dose and take your next dose at your normal scheduled time.\n \n Do nottake 2 doses at the same time. Call your doctor if you are not sure what to do.\n \n ", "If you take too much mycophenolate mofetil for injection, call your doctor or the poison control center right away." ], "text": "" }

What should I avoid while taking mycophenolate mofetil for injection?

{ "type": "p", "children": [], "text": "\nWhat should I avoid while taking mycophenolate mofetil for injection?\n" }

{ "type": "ul", "children": [ "Avoid becoming pregnant. See\n \n “What is the most important information I should know about mycophenolate mofetil for injection?”\n", "Limit the amount of time you spend in sunlight. Avoid using tanning beds or sunlamps. People who take mycophenolate mofetil for injection have a higher risk of getting skin cancer (See\n \n “What is the most important information I should know about mycophenolate mofetil for injection?”). Wear protective clothing when you are in the sun and use a broad-spectrum sunscreen with a high protection factor. This is especially important if your skin is very fair or if you have a family history of skin cancer.\n \n ", "You should not donate blood while taking mycophenolate mofetil for injection and for at least 6 weeks after stopping mycophenolate mofetil for injection.", "You should not donate sperm while taking mycophenolate mofetil for injection and for 90 days after stopping mycophenolate mofetil for injection.", "Mycophenolate mofetil for injection may influence your ability to drive and use machines (see “\n \n What are the possible side effects of mycophenolate mofetil for injection?”). If you experience drowsiness, confusion, dizziness, tremor, or low blood pressure during treatment with mycophenolate mofetil for injection, you should be cautious about driving or using heavy machines.\n \n " ], "text": "" }

What are the possible side effects of mycophenolate mofetil for injection?

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects of mycophenolate mofetil for injection?\n" }

Mycophenolate mofetil for injection may cause serious side effects, including:

{ "type": "p", "children": [], "text": "\nMycophenolate mofetil for injection may cause serious side effects, including:\n" }

{ "type": "ul", "children": [ "See\n \n “What is the most important information I should know about mycophenolate mofetil for injection?”\n", "\nLow blood cell counts.People taking high doses of mycophenolate mofetil for injection each day may have a decrease in blood counts, including:\n \n \n\nwhite blood cells, especially neutrophils.Neutrophils fight against bacterial infections. You have a higher chance of getting an infection when your white blood cell count is low. This is most common from 1 month to 6 months after your transplant.\n \n \n\nred blood cells.Red blood cells carry oxygen to your body tissues. You have a higher chance of getting severe anemia when your red blood cell count is low.\n \n \n\nplatelets. Platelets help with blood clotting.\n \n \n\n" ], "text": "" }

Your doctor will do blood tests before you start taking mycophenolate mofetil for injection and during treatment with mycophenolate mofetil for injection to check your blood cell counts. Tell your doctor right away if you have any signs of infection (See “What is the most important information I should know about mycophenolate mofetil for injection?”), including any unexpected bruising or bleeding. Also, tell your doctor if you have unusual tiredness, lack of energy, dizziness or fainting.

{ "type": "p", "children": [], "text": "Your doctor will do blood tests before you start taking mycophenolate mofetil for injection and during treatment with mycophenolate mofetil for injection to check your blood cell counts. Tell your doctor right away if you have any signs of infection (See\n \n “What is the most important information I should know about mycophenolate mofetil for injection?”), including any unexpected bruising or bleeding. Also, tell your doctor if you have unusual tiredness, lack of energy, dizziness or fainting.\n\n " }

{ "type": "ul", "children": [ "\nStomach problems.Stomach problems including intestinal bleeding, a tear in your intestinal wall (perforation) or stomach ulcers can happen in people who take mycophenolate mofetil for injection. Bleeding can be severe and you may have to be hospitalized for treatment. Call your doctor right away if you have sudden or severe stomach-area pain or stomach-area pain that does not go away, or if you have diarrhea.\n \n ", "\nInflammatory reactions.Some people taking Mycophenolate mofetil for injection may have an inflammatory reaction with fever, joint stiffness, joint pain, and muscle pain. Some of these reactions may require hospitalization. This reaction could happen within weeks to months after your treatment with Mycophenolate mofetil for injection starts or if your dose is increased. Call your doctor right away if you experience these symptoms.\n \n " ], "text": "" }

The most common side effects of mycophenolate mofetil for injection include:

{ "type": "p", "children": [], "text": "\nThe most common side effects of mycophenolate mofetil for injection include:\n" }

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="100%"> <col width="50.84%"/> <col width="49.16%"/> <tbody class="Headless"> <tr class="First"> <td> <ul class="Disc"> <li>diarrhea</li> </ul> </td><td> <ul class="Disc"> <li>changes in laboratory blood levels, including high levels of blood sugar (hyperglycemia)</li> </ul> </td> </tr> <tr> <td> <ul class="Disc"> <li>blood problems including low white and red blood cell counts</li> </ul> </td><td> <ul class="Disc"> <li>stomach problems including diarrhea, constipation, nausea and vomiting</li> </ul> </td> </tr> <tr> <td> <ul class="Disc"> <li>infections</li> </ul> </td><td> <ul class="Disc"> <li>rash</li> </ul> </td> </tr> <tr> <td> <ul class="Disc"> <li>blood pressure problems</li> </ul> </td><td> <ul class="Disc"> <li>nervous system problems such as headache, dizziness and tremor</li> </ul> </td> </tr> <tr> <td> <ul class="Disc"> <li>fast heartbeat</li> </ul> </td><td></td> </tr> <tr class="Last"> <td class="Botrule"> <ul class="Disc"> <li>swelling of the lower legs, ankles and feet</li> </ul> </td><td class="Botrule"></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"0\" cellspacing=\"0\" width=\"100%\">\n<col width=\"50.84%\"/>\n<col width=\"49.16%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<ul class=\"Disc\">\n<li>diarrhea</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>changes in laboratory blood levels, including high levels of blood sugar (hyperglycemia)</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td>\n<ul class=\"Disc\">\n<li>blood problems including low white and red blood cell counts</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>stomach problems including diarrhea, constipation, nausea and vomiting</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td>\n<ul class=\"Disc\">\n<li>infections</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>rash</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td>\n<ul class=\"Disc\">\n<li>blood pressure problems</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>nervous system problems such as headache, dizziness and tremor</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td>\n<ul class=\"Disc\">\n<li>fast heartbeat</li>\n</ul>\n</td><td></td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule\">\n<ul class=\"Disc\">\n<li>swelling of the lower legs, ankles and feet</li>\n</ul>\n</td><td class=\"Botrule\"></td>\n</tr>\n</tbody>\n</table></div>" }

Side effects that can happen more often in children than in adults taking mycophenolate mofetil for injection include:

{ "type": "p", "children": [], "text": "\nSide effects that can happen more often in children than in adults taking mycophenolate mofetil for injection include:\n\n " }

<div class="scrollingtable"><table cellpadding="0" cellspacing="0"> <col width="269.6pt"/> <col width="269.65pt"/> <tbody class="Headless"> <tr class="First"> <td> <ul class="Disc"> <li>stomach area pain</li> </ul> </td><td> <ul class="Disc"> <li>vomiting</li> </ul> </td> </tr> <tr> <td> <ul class="Disc"> <li>fever</li> </ul> </td><td> <ul class="Disc"> <li>sore throat</li> </ul> </td> </tr> <tr> <td> <ul class="Disc"> <li>infection</li> </ul> </td><td> <ul class="Disc"> <li>colds (respiratory tract infections)</li> </ul> </td> </tr> <tr> <td> <ul class="Disc"> <li>pain</li> </ul> </td><td> <ul class="Disc"> <li>high blood pressure</li> </ul> </td> </tr> <tr> <td> <ul class="Disc"> <li>blood infection (sepsis)</li> </ul> </td><td> <ul class="Disc"> <li>low white blood cell count</li> </ul> </td> </tr> <tr class="Last"> <td class="Botrule"> <ul class="Disc"> <li>diarrhea</li> </ul> </td><td class="Botrule"> <ul class="Disc"> <li>low red blood cell count</li> </ul> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"0\" cellspacing=\"0\">\n<col width=\"269.6pt\"/>\n<col width=\"269.65pt\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<ul class=\"Disc\">\n<li>stomach area pain</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>vomiting</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td>\n<ul class=\"Disc\">\n<li>fever</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>sore throat</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td>\n<ul class=\"Disc\">\n<li>infection</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>colds (respiratory tract infections)</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td>\n<ul class=\"Disc\">\n<li>pain</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>high blood pressure</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td>\n<ul class=\"Disc\">\n<li>blood infection (sepsis)</li>\n</ul>\n</td><td>\n<ul class=\"Disc\">\n<li>low white blood cell count</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule\">\n<ul class=\"Disc\">\n<li>diarrhea</li>\n</ul>\n</td><td class=\"Botrule\">\n<ul class=\"Disc\">\n<li>low red blood cell count</li>\n</ul>\n</td>\n</tr>\n</tbody>\n</table></div>" }

These are not all of the possible side effects of mycophenolate mofetil for injection. Tell your doctor about any side effect that bothers you or that does not go away.

{ "type": "p", "children": [], "text": "These are not all of the possible side effects of mycophenolate mofetil for injection. Tell your doctor about any side effect that bothers you or that does not go away." }

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Steriscience at 1-888-278-1784

{ "type": "p", "children": [], "text": "\nCall your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Steriscience at 1-888-278-1784\n\n " }

How should I store mycophenolate mofetil for injection?

{ "type": "p", "children": [], "text": "\nHow should I store mycophenolate mofetil for injection?\n" }

Keep mycophenolate mofetil for injection and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep mycophenolate mofetil for injection and all medicines out of the reach of children.\n" }

General information about the safe and effective use of mycophenolate mofetil for injection.

{ "type": "p", "children": [], "text": "\nGeneral information about the safe and effective use of mycophenolate mofetil for injection.\n" }

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use mycophenolate mofetil for injection for a condition for which it was not prescribed. Do not give mycophenolate mofetil for injection to other people, even if they have the same symptoms that you have. It may harm them.

{ "type": "p", "children": [], "text": "Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use mycophenolate mofetil for injection for a condition for which it was not prescribed. Do not give mycophenolate mofetil for injection to other people, even if they have the same symptoms that you have. It may harm them." }

This Medication Guide summarizes the most important information about mycophenolate mofetil for injection. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist about mycophenolate mofetil for injection that is written for health professionals.

{ "type": "p", "children": [], "text": "This Medication Guide summarizes the most important information about mycophenolate mofetil for injection. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist about mycophenolate mofetil for injection that is written for health professionals." }

What are the ingredients in mycophenolate mofetil for injection?

{ "type": "p", "children": [], "text": "\nWhat are the ingredients in mycophenolate mofetil for injection?\n" }

Active ingredient:mycophenolate mofetil, USP

{ "type": "p", "children": [], "text": "\nActive ingredient:mycophenolate mofetil, USP\n\n " }

Inactive ingredients:polysorbate 80, 25 mg; and citric acid, 5 mg. Sodium hydroxide and hydrochloric acid may have been used in the manufacture of mycophenolate mofetil for injection to adjust the pH.

{ "type": "p", "children": [], "text": "\nInactive ingredients:polysorbate 80, 25 mg; and citric acid, 5 mg. Sodium hydroxide and hydrochloric acid may have been used in the manufacture of mycophenolate mofetil for injection to adjust the pH.\n\n " }

Manufactured for:

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Steriscience Specialities Pte. Limited

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Mfd by:

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OneSource Specialty Pharma Limited

{ "type": "p", "children": [], "text": "OneSource Specialty Pharma Limited" }

Bengaluru - 561203, India.

{ "type": "p", "children": [], "text": "Bengaluru - 561203, India." }

This Medication Guide has been approved by the U.S. Food and Drug Administration

{ "type": "p", "children": [], "text": "This Medication Guide has been approved by the U.S. Food and Drug Administration" }

Revised: 10/2024

{ "type": "p", "children": [], "text": "Revised: 10/2024" }

NDC 83270-000-01 Rx only Mycophenolate Mofetil for Injection USP, 500 mg/mL

{ "type": "p", "children": [], "text": "\nNDC 83270-000-01 Rx only \n \n Mycophenolate Mofetil for Injection USP, 500 mg/mL\n \n" }

For Intravenous Infusion Only

{ "type": "p", "children": [], "text": "\nFor Intravenous Infusion Only\n" }

Attention Pharmacist: Dispense the accompanying Medication Gide to each patient.

{ "type": "p", "children": [], "text": "Attention Pharmacist: Dispense the accompanying Medication Gide to each patient." }

Steriscience 

{ "type": "p", "children": [], "text": "\nSteriscience \n" }

NDC 83270-000-04 Rx only

{ "type": "p", "children": [], "text": "\nNDC 83270-000-04 Rx only\n" }

Mycophenolate Mofetil for Injection USP, 500 mg/mL

{ "type": "p", "children": [], "text": "\nMycophenolate Mofetil for Injection USP, 500 mg/mL\n" }

For Intravenous Infusion Only

{ "type": "p", "children": [], "text": "\nFor Intravenous Infusion Only\n" }

Attention Pharmacist: Dispense the accompanying Medication Gide to each patient.

{ "type": "p", "children": [], "text": "Attention Pharmacist: Dispense the accompanying Medication Gide to each patient." }

4 Single Dose-Vials.

{ "type": "p", "children": [], "text": "\n4 Single Dose-Vials.\n" }

Discard unused portion.

{ "type": "p", "children": [], "text": "\nDiscard unused portion.\n" }

Steriscience Armas Pharmaceuticals

{ "type": "p", "children": [], "text": "\nSteriscience Armas Pharmaceuticals\n" }