Pantoprazole sodium for delayed-release oral suspension is indicated in adults and pediatric patients five years of age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis (EE). For those adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium for delayed-release oral suspension may be considered. Safety of treatment beyond 8 weeks in pediatric patients has not been established.

Pantoprazole sodium for delayed-release oral suspension is indicated for maintenance of healing of EE and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with GERD. Controlled studies did not extend beyond 12 months.

Pantoprazole sodium for delayed-release oral suspension is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison (ZE) Syndrome.

Pantoprazole sodium is supplied as delayed-release granules in packets for preparation of oral suspensions. The recommended dosages are outlined in Table 1.

Table 1: Recommended Dosing Schedule for Pantoprazole Sodium for Delayed-Release Oral Suspension

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <colgroup> <col width="100%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td class="Lrule Rrule" valign="top"><span class="Bold">Indication                                                 </span><span class="Bold">Dose                                                 Frequency</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top"><span class="Bold">Short-Term Treatment of Erosive Esophagitis Associated With GERD</span> <br/>Adults                                                       40 mg                                               Once daily for up to 8 weeks<span class="Sup">*</span><span class="Underline"> </span> <br/>Children (5 years and older)<br/>≥ 15 kg to &lt; 40 kg                                    20 mg                                               Once daily for up to 8 weeks<br/>≥ 40 kg                                                     40 mg<span class="Bold"></span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top"><span class="Bold"> Maintenance </span><span class="Bold">of Healing of Erosive Esophagitis</span> <br/>Adults                                                      40 mg                                                Once daily<span class="Sup">***</span> <br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top"><span class="Bold">Pathological </span><span class="Bold">Hypersecretory Conditions Including Zollinger-Ellison Syndrome</span> <br/>Adults                                                      40 mg                                               Twice daily<span class="Sup">**</span> <br/> </td> </tr> </tbody> </table></div>

* For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium for delayed-release oral suspension may be considered.

** Dosage regimens should be adjusted to individual patient needs and should continue for as long as clinically indicated. Doses up to 240 mg daily have been administered.

*** Controlled studies did not extend beyond 12 months

Directions for method of administration for each dosage form are presented in Table 2.

Table 2: Administration Instructions

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <colgroup> <col width="31.16%"/> <col width="18.04%"/> <col width="50.8%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td class="Lrule Rrule" valign="middle"><span class="Bold">Formulation</span> <br/> </td><td class="Rrule" valign="middle"><span class="Bold">          Route</span> <br/> </td><td class="Rrule" valign="middle"><span class="Bold">Instructions</span><span class="Sup">*</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"><span class="Bold">For Delayed-Release Oral </span> <br/> <span class="Bold">Suspension</span> <br/> </td><td align="center" class="Rrule" valign="middle">Oral<br/> </td><td align="justify" class="Rrule" valign="middle">Administered in 1 teaspoonful of applesauce or apple juice approximately 30 minutes prior to a meal<br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="middle"><span class="Bold">For Delayed-Release Oral </span> <br/> <span class="Bold">Suspension</span> <br/> </td><td align="center" class="Rrule" valign="middle">Nasogastric <br/>tube<br/> </td><td class="Rrule" valign="middle">See instructions below<br/> </td> </tr> </tbody> </table></div>

* Do not split, chew, or crush Pantoprazole Sodium For Delayed-Release Oral Suspension.

Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and take the next dose at the regular scheduled time. Do not take 2 doses at the same time.

Administer Pantoprazole Sodium For Delayed-Release Oral Suspension approximately 30 minutes prior to a meal via oral administration in apple juice or applesauce or nasogastric tube in apple juice only. Because proper pH is necessary for stability, do not administer Pantoprazole Sodium For Delayed-Release Oral Suspension in liquids other than apple juice, or foods other than applesauce.

Do not divide the 40 mg Pantoprazole Sodium For Delayed-Release Oral Suspension packet to create a 20 mg dosage for pediatric patients who are unable to take the tablet formulation.

Pantoprazole Sodium For Delayed-Release Oral Suspension - Oral Administration in Applesauce

Pantoprazole Sodium For Delayed-Release Oral Suspension - Oral Administration in Apple Juice

Pantoprazole Sodium For Delayed-Release Oral Suspension - Nasogastric (NG) Tube or Gastrostomy Tube Administration

For patients who have a nasogastric tube or gastrostomy tube in place, Pantoprazole Sodium For Delayed-Release Oral Suspension can be given as follows:

For Delayed-Release Oral Suspension:

{ "type": "p", "children": [], "text": "For Delayed-Release Oral Suspension:" }

{ "type": "ul", "children": [ "40 mg pantoprazole, pale yellowish to yellow, enteric-coated granules in a unit dose packet" ], "text": "" }

{ "type": "ul", "children": [ "Pantoprazole sodium for delayed-release oral suspension is contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions (5.2), Adverse Reactions (6)]. ", " Proton pump inhibitors (PPIs), including pantoprazole sodium for delayed-release oral suspension, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions (7)]." ], "text": "" }

In adults, symptomatic response to therapy with pantoprazole sodium for delayed-release oral suspension does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy.

Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue pantoprazole sodium for delayed-release oral suspension and evaluate patients with suspected acute TIN [see Contraindications (4)].

Published observational studies suggest that PPI therapy like pantoprazole sodium for delayed-release oral suspension may be associated with an increased risk of Clostridium difficile associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.2)].

Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.

Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2), Adverse Reactions (6.2)].

Severe cutaneous adverse reactions, including erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs [see Adverse Reactions (6.2)]. Discontinue pantoprazole sodium for delayed-release oral suspension at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including pantoprazole sodium. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematous cases were CLE.

The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement.

Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported.

Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving pantoprazole sodium for delayed-release oral suspension, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g., ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations.

Generally, daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (Vitamin B-12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, and in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2)].

Consider monitoring magnesium and calcium levels prior to initiation of pantoprazole sodium for delayed-release oral suspension and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium as necessary. If hypocalcemia is refractory to treatment, consider discontinuing the PPI.

Due to the chronic nature of GERD, there may be a potential for prolonged administration of pantoprazole sodium for delayed-release oral suspension. In long-term rodent studies, pantoprazole was carcinogenic and caused rare types of gastrointestinal tumors. The relevance of these findings to tumor development in humans is unknown [see Nonclinical Toxicology (13.1)].

PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated.

Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop pantoprazole sodium for delayed-release oral suspension treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary [see Clinical Pharmacology (12.2)].

There have been reports of false-positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including pantoprazole sodium for delayed-release oral suspension [see Drug Interactions (7)].

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions (7)].

The adverse reaction profiles for Pantoprazole Sodium For Delayed-Release Oral Suspension and PROTONIX Delayed-Release Tablets are similar.

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 clinical practice.

Adults

Safety in nine randomized comparative US clinical trials in patients with GERD included 1,473 patients on oral pantoprazole sodium (20 mg or 40 mg), 299 patients on an H2-receptor antagonist, 46 patients on another PPI, and 82 patients on placebo. The most frequently occurring adverse reactions are listed in Table 3.

Table 3: Adverse Reactions Reported in Clinical Trials of Adult Patients with GERD at a Frequency of >2%

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <colgroup> <col width="24.6%"/> <col width="25.8%"/> <col width="25.8%"/> <col width="23.8%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" valign="middle"></td><td align="center" class="Rrule" valign="middle">Pantoprazole sodium <br/>for delayed-release oral suspension<br/>(n=1473) <br/>%<br/> </td><td align="center" class="Rrule" valign="middle">Comparators <br/>(n=345) <br/>%<br/> </td><td align="center" class="Rrule" valign="middle">Placebo <br/>(n=82) <br/>%<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Headache<br/> </td><td align="center" class="Rrule" valign="middle">12.2<br/> </td><td align="center" class="Rrule" valign="middle">12.8<br/> </td><td align="center" class="Rrule" valign="middle">8.5<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Diarrhea<br/> </td><td align="center" class="Rrule" valign="middle">8.8<br/> </td><td align="center" class="Rrule" valign="middle">9.6<br/> </td><td align="center" class="Rrule" valign="middle">4.9<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Nausea<br/> </td><td align="center" class="Rrule" valign="middle">7.0<br/> </td><td align="center" class="Rrule" valign="middle">5.2<br/> </td><td align="center" class="Rrule" valign="middle">9.8<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Abdominal pain<br/> </td><td align="center" class="Rrule" valign="middle">6.2<br/> </td><td align="center" class="Rrule" valign="middle">4.1<br/> </td><td align="center" class="Rrule" valign="middle">6.1<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Vomiting<br/> </td><td align="center" class="Rrule" valign="middle">4.3<br/> </td><td align="center" class="Rrule" valign="middle">3.5<br/> </td><td align="center" class="Rrule" valign="middle">2.4<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Flatulence<br/> </td><td align="center" class="Rrule" valign="middle">3.9<br/> </td><td align="center" class="Rrule" valign="middle">2.9<br/> </td><td align="center" class="Rrule" valign="middle">3.7<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Dizziness<br/> </td><td align="center" class="Rrule" valign="middle">3.0<br/> </td><td align="center" class="Rrule" valign="middle">2.9<br/> </td><td align="center" class="Rrule" valign="middle">1.2<br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="middle">Arthralgia<br/> </td><td align="center" class="Rrule" valign="middle">2.8<br/> </td><td align="center" class="Rrule" valign="middle">1.4<br/> </td><td align="center" class="Rrule" valign="middle">1.2<br/> </td> </tr> </tbody> </table></div>

Additional adverse reactions that were reported for pantoprazole sodium for delayed-release oral suspension in clinical trials with a frequency of ≤2% are listed below by body system:

Body as a Whole: allergic reaction, pyrexia, photosensitivity reaction, facial edema

Gastrointestinal: constipation, dry mouth, hepatitis

Hematologic: leukopenia, thrombocytopenia

Metabolic/Nutritional: elevated CK (creatine kinase), generalized edema, elevated triglycerides, liver enzymes elevated

Musculoskeletal: myalgia

Nervous: depression, vertigo

Skin and Appendages: urticaria, rash, pruritus

Special Senses: blurred vision

Pediatric Patients

Safety of pantoprazole sodium for delayed-release oral suspension in the treatment of EE associated with GERD was evaluated in pediatric patients ages 1 year through 16 years in three clinical trials. Safety trials involved pediatric patients with EE; however, as EE is uncommon in the pediatric population, 249 pediatric patients with endoscopically-proven or symptomatic GERD were also evaluated. All adult adverse reactions to pantoprazole sodium for delayed-release oral suspension are considered relevant to pediatric patients. In patients ages 1 year through 16 years, the most commonly reported (>4%) adverse reactions include: URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain.

For safety information in patients less than 1 year of age see Use in Specific Populations (8.4).

Additional adverse reactions that were reported for pantoprazole sodium for delayed-release oral suspension in pediatric patients in clinical trials with a frequency of ≤4% are listed below by body system:

Body as a Whole: allergic reaction, facial edema

Gastrointestinal: constipation, flatulence, nausea

Metabolic/Nutritional: elevated triglycerides, elevated liver enzymes, elevated CK (creatine kinase)

Musculoskeletal: arthralgia, myalgia

Nervous: dizziness, vertigo

Skin and Appendages: urticaria

The following adverse reactions seen in adults in clinical trials were not reported in pediatric patients in clinical trials, but are considered relevant to pediatric patients: photosensitivity reaction, dry mouth, hepatitis, thrombocytopenia, generalized edema, depression, pruritus, leukopenia, and blurred vision.

Zollinger-Ellison (ZE) Syndrome

In clinical studies of ZE Syndrome, adverse reactions reported in 35 patients taking pantoprazole sodium for delayed-release oral suspension 80 mg/day to 240 mg/day for up to 2 years were similar to those reported in adult patients with GERD.

The following adverse reactions have been identified during postapproval use of pantoprazole sodium for delayed-release oral suspension. 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.

These adverse reactions are listed below by body system:

Gastrointestinal Disorders: fundic gland polyps

General Disorders and Administration Conditions: asthenia, fatigue, malaise

Hematologic: pancytopenia, agranulocytosis

Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure

Immune System Disorders: anaphylaxis (including anaphylactic shock), systemic lupus erythematosus

Infections and Infestations: Clostridium difficile associated diarrhea

Investigations: weight changes

Metabolism and Nutritional Disorders: hypomagnesemia, hypocalcemia, hypokalemia, hyponatremia

Musculoskeletal Disorders: rhabdomyolysis, bone fracture

Nervous: ageusia, dysgeusia

Psychiatric Disorders: hallucination, confusion, insomnia, somnolence

Renal and Genitourinary Disorders: acute tubulointerstitial nephritis, erectile dysfunction

Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions (some fatal), including erythema multiforme, SJS/TEN, DRESS, AGEP, angioedema (Quincke’s edema) and cutaneous lupus erythematosus

Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with pantoprazole sodium for delayed-release oral suspension and instructions for preventing or managing them.

{ "type": "p", "children": [], "text": "Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with pantoprazole sodium for delayed-release oral suspension and instructions for preventing or managing them. " }

Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.

{ "type": "p", "children": [], "text": "Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. " }

Table 4: Clinically Relevant Interactions Affecting Drugs Co-Administered with Pantoprazole Sodium for Delayed-Release Oral Suspension and Interactions with Diagnostics

{ "type": "p", "children": [], "text": "\nTable 4: Clinically Relevant Interactions Affecting Drugs Co-Administered with Pantoprazole Sodium for Delayed-Release Oral Suspension and Interactions with Diagnostics \n" }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <colgroup> <col width="18.94%"/> <col width="81.06%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td class="Lrule Rrule" colspan="2" valign="middle"><span class="Bold">Antiretrovirals</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact:</span> <br/> </td><td class="Rrule" valign="middle">The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known.<br/> <ul class="Disc"> <li>Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with pantoprazole may reduce antiviral effect and promote the development of drug resistance.</li> <li>Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with pantoprazole may increase toxicity of the antiretroviral drugs.</li> <li>There are other antiretroviral drugs which do not result in clinically relevant interactions with pantoprazole.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top"><span class="Italics">Intervention:</span> <br/> <br/> </td><td class="Rrule" valign="middle">Rilpivirine-containing products: Concomitant use with pantoprazole sodium for delayed-release oral suspension is contraindicated <span class="Italics">[see <a href="#Section_4">Contraindications (4)</a>]</span>. See prescribing information.<br/>Atazanavir: See prescribing information for atazanavir for dosing information.<br/>Nelfinavir: Avoid concomitant use with pantoprazole sodium for delayed-release oral suspension. See prescribing information for nelfinavir.<br/>Saquinavir: See the prescribing information for saquinavir and monitor for potential saquinavir toxicities.<br/> <br/>Other antiretrovirals: See prescribing information.<br/> <br/> <br/> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"><span class="Bold">Warfarin</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact:</span> <br/> </td><td class="Rrule" valign="middle">Increased INR and prothrombin time in patients receiving PPIs, including pantoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death.<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top"><span class="Italics">Intervention:</span> <br/> </td><td class="Rrule" valign="middle">Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin.<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"><span class="Bold">Clopidogrel</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact:</span> <br/> </td><td class="Rrule" valign="middle">Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition <span class="Italics">[see <a href="#Section_12.3">Clinical Pharmacology (12.3)</a>].</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top"><span class="Italics">Intervention:</span> <br/> </td><td class="Rrule" valign="middle">No dose adjustment of clopidogrel is necessary when administered with an approved dose of pantoprazole sodium for delayed-release oral suspension.<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"><span class="Bold">Methotrexate</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact:</span> <br/> </td><td class="Rrule" valign="middle">Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted <span class="Italics">[see <a href="#Section_5.13">Warnings and Precautions (5.13)</a>].</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top"><span class="Italics">Intervention:</span> <br/> </td><td class="Rrule" valign="middle">A temporary withdrawal of pantoprazole sodium for delayed-release oral suspension may be considered in some patients receiving  high-dose methotrexate.<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"><span class="Bold">Drugs </span><span class="Bold">Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib,  dasatinib,  nilotinib, mycophenolate mofetil, ketoconazole/itraconazole)</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact:</span> <br/> </td><td class="Rrule" valign="middle">Pantoprazole  can  reduce the absorption of other drugs due to its effect on reducing  intragastric acidity.<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top"><span class="Italics">Intervention:</span> <br/> </td><td class="Rrule" valign="middle">Mycophenolate mofetil (MMF): Co-administration of pantoprazole sodium in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH <span class="Italics">[see <a href="#Section_12.3">Clinical Pharmacology (12.3)</a>]</span>. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving pantoprazole sodium for delayed-release oral suspension and MMF. Use pantoprazole sodium for delayed-release oral suspension with caution in transplant patients receiving MMF.<br/> <br/>See the prescribing information for other drugs dependent on gastric pH for absorption.<br/> <br/> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"><span class="Bold">Interactions</span><span class="Bold"> with Investigations of Neuroendocrine Tumors</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact:</span> <br/> </td><td class="Rrule" valign="middle">CgA levels  increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may  cause false positive  results in diagnostic investigations for neuroendocrine tumors <span class="Italics">[see <a href="#Section_5.11">Warnings and Precautions  (5.11),</a>   <a href="#Section_12.2">Clinical Pharmacology (12.2)</a>]</span>.<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top"><span class="Italics">Intervention:</span> <br/> </td><td class="Rrule" valign="middle">Temporarily stop pantoprazole sodium for delayed-release oral suspension treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"><span class="Bold">False Positive Urine Tests for THC</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact:</span> <br/> </td><td class="Rrule" valign="middle">There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs <span class="Italics">[see <a href="#Section_5.12">Warnings and Precautions  (5.12)</a>]</span>.<br/> </td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule" valign="top"><span class="Italics">Intervention:</span> <br/> </td><td class="Rrule" valign="middle">An alternative confirmatory method should be considered to verify positive results.<br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"100%\">\n<colgroup>\n<col width=\"18.94%\"/>\n<col width=\"81.06%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\"><span class=\"Bold\">Antiretrovirals</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Italics\">Clinical Impact:</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\">The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known.<br/>\n<ul class=\"Disc\">\n<li>Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with pantoprazole may reduce antiviral effect and promote the development of drug resistance.</li>\n<li>Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with pantoprazole may increase toxicity of the antiretroviral drugs.</li>\n<li>There are other antiretroviral drugs which do not result in clinically relevant interactions with pantoprazole.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Italics\">Intervention:</span>\n<br/> <br/>\n</td><td class=\"Rrule\" valign=\"middle\">Rilpivirine-containing products: Concomitant use with pantoprazole sodium for delayed-release oral suspension is contraindicated <span class=\"Italics\">[see <a href=\"#Section_4\">Contraindications (4)</a>]</span>. See prescribing information.<br/>Atazanavir: See prescribing information for atazanavir for dosing information.<br/>Nelfinavir: Avoid concomitant use with pantoprazole sodium for delayed-release oral suspension. See prescribing information for nelfinavir.<br/>Saquinavir: See the prescribing information for saquinavir and monitor for potential saquinavir toxicities.<br/> <br/>Other antiretrovirals: See prescribing information.<br/> <br/> <br/> <br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\"><span class=\"Bold\">Warfarin</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Italics\">Clinical Impact:</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\">Increased INR and prothrombin time in patients receiving PPIs, including pantoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death.<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Italics\">Intervention:</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\">Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin.<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\"><span class=\"Bold\">Clopidogrel</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Italics\">Clinical Impact:</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\">Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition <span class=\"Italics\">[see <a href=\"#Section_12.3\">Clinical Pharmacology (12.3)</a>].</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Italics\">Intervention:</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\">No dose adjustment of clopidogrel is necessary when administered with an approved dose of pantoprazole sodium for delayed-release oral suspension.<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\"><span class=\"Bold\">Methotrexate</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Italics\">Clinical Impact:</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\">Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted <span class=\"Italics\">[see <a href=\"#Section_5.13\">Warnings and Precautions (5.13)</a>].</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Italics\">Intervention:</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\">A temporary withdrawal of pantoprazole sodium for delayed-release oral suspension may be considered in some patients receiving  high-dose methotrexate.<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\"><span class=\"Bold\">Drugs </span><span class=\"Bold\">Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib,  dasatinib,  nilotinib, mycophenolate mofetil, ketoconazole/itraconazole)</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Italics\">Clinical Impact:</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\">Pantoprazole  can  reduce the absorption of other drugs due to its effect on reducing  intragastric acidity.<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Italics\">Intervention:</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\">Mycophenolate mofetil (MMF): Co-administration of pantoprazole sodium in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH <span class=\"Italics\">[see <a href=\"#Section_12.3\">Clinical Pharmacology (12.3)</a>]</span>. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving pantoprazole sodium for delayed-release oral suspension and MMF. Use pantoprazole sodium for delayed-release oral suspension with caution in transplant patients receiving MMF.<br/>\n<br/>See the prescribing information for other drugs dependent on gastric pH for absorption.<br/> <br/> <br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\"><span class=\"Bold\">Interactions</span><span class=\"Bold\"> with Investigations of Neuroendocrine Tumors</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Italics\">Clinical Impact:</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\">CgA levels  increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may  cause false positive  results in diagnostic investigations for neuroendocrine tumors <span class=\"Italics\">[see <a href=\"#Section_5.11\">Warnings and Precautions  (5.11),</a>   <a href=\"#Section_12.2\">Clinical Pharmacology (12.2)</a>]</span>.<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Italics\">Intervention:</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\">Temporarily stop pantoprazole sodium for delayed-release oral suspension treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\"><span class=\"Bold\">False Positive Urine Tests for THC</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Italics\">Clinical Impact:</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\">There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs <span class=\"Italics\">[see <a href=\"#Section_5.12\">Warnings and Precautions  (5.12)</a>]</span>.<br/>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Italics\">Intervention:</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\">An alternative confirmatory method should be considered to verify positive results.<br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Risk Summary

Available data from published observational studies did not demonstrate an association of major malformations or other adverse pregnancy outcomes with pantoprazole.

In animal reproduction studies, no evidence of adverse development outcomes was observed with pantoprazole. Reproduction studies have been performed in rats at oral doses up to 450 mg/kg/day (about 88 times the recommended human dose) and rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose) with administration of pantoprazole during organogenesis in pregnant animals and have revealed no evidence of harm to the fetus due to pantoprazole in this study (see Data).

A pre-and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. Oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day) were administered to pregnant females from gestation day (GD) 6 through lactation day (LD) 21. Changes in bone morphology were observed in pups exposed to pantoprazole in utero and through milk during the period of lactation as well as by oral dosing from postnatal day (PND) 4 through PND 21 [see Use in Specific Populations (8.4)]. There were no drug-related findings in maternal animals. Advise pregnant women of the potential risk of fetal harm.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

Available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and pantoprazole use. Methodological limitations of these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. In a prospective study by the European Network of Teratology Information Services, outcomes from a group of 53 pregnant women administered median daily doses of 40 mg pantoprazole were compared to a control group of 868 pregnant women who did not take any proton pump inhibitors (PPIs). There was no difference in the rate of major malformations between women exposed to PPIs and the control group, corresponding to a Relative Risk (RR)=0.55, [95% Confidence Interval (CI) 0.08 to 3.95]. In a population-based retrospective cohort study covering all live births in Denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to pantoprazole in 549 live births. A meta-analysis that compared 1,530 pregnant women exposed to PPIs in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to PPIs (for major malformations OR=1.12 ([95% CI 0.86 to 1.45] and for spontaneous abortions OR=1.29 [95% CI 0.84 to 1.97]).

Animal Data

Reproduction studies have been performed in rats at oral pantoprazole doses up to 450 mg/kg/day (about 88 times the recommended human dose based on body surface area) and in rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose based on body surface area) with administration of pantoprazole sodium during organogenesis in pregnant animals. The studies have revealed no evidence of impaired fertility or harm to the fetus due to pantoprazole.

A pre- and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. Oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day on a body surface area basis) were administered to pregnant females from gestation day (GD) 6 through lactation day (LD) 21. On postnatal day (PND 4) through PND 21, the pups were administered oral doses at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (AUC) in humans at a dose of 40 mg). There were no drug-related findings in maternal animals. During the preweaning dosing phase (PND 4 to 21) of the pups, there were increased mortality and/or moribundity and decreased body weight and body weight gain at 5 mg/kg/day (approximately equal exposures (AUC) in humans receiving the 40 mg dose) and higher doses. On PND 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (AUC) in humans at the 40 mg dose) and higher doses. The femur findings included lower total area, bone mineral content and density, periosteal and endosteal circumference, and cross-sectional moment of inertia. There were no microscopic changes in the distal femur, proximal tibia, or stifle joints. Changes in bone parameters were partially reversible following a recovery period, with findings on PND 70 limited to lower femur metaphysis cortical/subcortical bone mineral density in female pups at 5 mg/kg/day (approximately equal exposures (AUC) in humans at the 40 mg dose) and higher doses.

Risk Summary

Pantoprazole has been detected in breast milk of a nursing mother after a single 40 mg oral dose of pantoprazole. There were no effects on the breastfed infant (see Data). There are no data on pantoprazole effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for pantoprazole sodium for delayed-release oral suspension and any potential adverse effects on the breastfed child from pantoprazole or from the underlying maternal condition.

Data

The breast milk of a 42-year-old woman receiving 40 mg of oral pantoprazole, at 10 months postpartum, was studied for 24 hours, to demonstrate low levels of pantoprazole present in the breast milk. Pantoprazole was detectable in milk only 2 and 4 hours after the dose with milk levels of approximately 36 mcg/L and 24 mcg/L, respectively. A milk-to-plasma ratio of 0.022 was observed at 2 hours after drug administration. Pantoprazole was not detectable (<10 mcg/L) in milk at 6, 8 and 24 hours after the dose. The relative dose to the infant was estimated to be 7.3 mcg of pantoprazole, which is equivalent to 0.14% of the weight-adjusted maternal dose. No adverse events in the infant were reported by the mother.

The safety and effectiveness of pantoprazole sodium for delayed-release oral suspension for short-term treatment (up to eight weeks) of EE associated with GERD have been established in pediatric patients 1 year through 16 years of age. Effectiveness for EE has not been demonstrated in patients less than 1 year of age. In addition, for patients less than 5 years of age, there is no appropriate dosage strength in an age-appropriate formulation available. Therefore, pantoprazole sodium for delayed-release oral suspension is indicated for the short-term treatment of EE associated with GERD for patients 5 years and older. The safety and effectiveness of pantoprazole sodium for delayed-release oral suspension for pediatric uses other than EE have not been established.

1 year through 16 years of age

Use of pantoprazole sodium for delayed-release oral suspension in pediatric patients 1 year through 16 years of age for short-term treatment (up to eight weeks) of EE associated with GERD is supported by: a) extrapolation of results from adequate and well-controlled studies that supported the approval of pantoprazole sodium for delayed-release oral suspension for treatment of EE associated with GERD in adults, and b) safety, effectiveness, and pharmacokinetic studies performed in pediatric patients [see Clinical Studies (14.1), Clinical Pharmacology (12.3)].

Safety of pantoprazole sodium for delayed-release oral suspension in the treatment of EE associated with GERD in pediatric patients 1 through 16 years of age was evaluated in three multicenter, randomized, double-blind, parallel-treatment studies, involving 249 pediatric patients, including 8 with EE (4 patients ages 1 year to 5 years and 4 patients 5 years to 11 years). The children ages 1 year to 5 years with endoscopically diagnosed EE (defined as an endoscopic Hetzel-Dent score ≥2) were treated once daily for 8 weeks with one of two dose levels of pantoprazole sodium for delayed-release oral suspension (approximating 0.6 mg/kg or 1.2 mg/kg). All 4 of these patients with EE were healed (Hetzel-Dent score of 0 or 1) at 8 weeks. Because EE is uncommon in the pediatric population, predominantly pediatric patients with endoscopically-proven or symptomatic GERD were also included in these studies. Patients were treated with a range of doses of pantoprazole sodium for delayed-release oral suspension once daily for 8 weeks. For safety findings see Adverse Reactions (6.1).

Because these pediatric trials had no placebo, active comparator, or evidence of a dose response, the trials were inconclusive regarding the clinical benefit of pantoprazole sodium for delayed-release oral suspension for symptomatic GERD in the pediatric population. The effectiveness of pantoprazole sodium for delayed-release oral suspension for treating symptomatic GERD in pediatric patients has not been established.

Although the data from the clinical trials support use of pantoprazole sodium for delayed-release oral suspension for the short-term treatment of EE associated with GERD in pediatric patients 1 year through 5 years, there is no commercially available dosage formulation appropriate for patients less than 5 years of age [see Dosage and Administration (2)].

In a population pharmacokinetic analysis, clearance values in the children 1 to 5 years old with endoscopically proven GERD had a median value of 2.4 L/h. Following a 1.2 mg/kg equivalent dose (15 mg for ≤12.5 kg and 20 mg for >12.5 to <25 kg), the plasma concentrations of pantoprazole were highly variable and the median time to peak plasma concentration was 3 to 6 hours. The estimated AUC for patients 1 to 5 years old was 37% higher than for adults receiving a single 40 mg tablet, with a geometric mean AUC value of 6.8 mcg•hr/mL.

Neonates to less than one year of age

Pantoprazole sodium for delayed-release oral suspension was not found to be effective in a multicenter, randomized, double-blind, placebo-controlled, treatment-withdrawal study of 129 pediatric patients 1 through 11 months of age. Patients were enrolled if they had symptomatic GERD based on medical history and had not responded to non-pharmacologic interventions for GERD for two weeks. Patients received pantoprazole sodium for delayed-release oral suspension daily for four weeks in an open-label phase, then patients were randomized in equal proportion to receive pantoprazole sodium for delayed-release oral suspension treatment or placebo for the subsequent four weeks in a double-blind manner. Efficacy was assessed by observing the time from randomization to study discontinuation due to symptom worsening during the four-week treatment-withdrawal phase. There was no statistically significant difference between pantoprazole sodium for delayed-release oral suspension and placebo in the rate of discontinuation.

In this trial, the adverse reactions that were reported more commonly (difference of ≥4%) in the treated population compared to the placebo population were elevated CK, otitis media, rhinitis, and laryngitis.

In a population pharmacokinetic analysis, the systemic exposure was higher in patients less than 1 year of age with GERD compared to adults who received a single 40 mg dose (geometric mean AUC was 103% higher in preterm infants and neonates receiving single dose of 2.5 mg of pantoprazole sodium for delayed-release oral suspension, and 23% higher in infants 1 through 11 months of age receiving a single dose of approximately 1.2 mg/kg). In these patients, the apparent clearance (CL/F) increased with age (median clearance: 0.6 L/hr, range: 0.03 to 3.2 L/hr).

These doses resulted in pharmacodynamic effects on gastric but not esophageal pH. Following once daily dosing of 2.5 mg of pantoprazole sodium for delayed-release oral suspension in preterm infants and neonates, there was an increase in the mean gastric pH (from 4.3 at baseline to 5.2 at steady-state) and in the mean % time that gastric pH was > 4 (from 60% at baseline to 80% at steady-state). Following once daily dosing of approximately 1.2 mg/kg of pantoprazole sodium for delayed-release oral suspension in infants 1 through 11 months of age, there was an increase in the mean gastric pH (from 3.1 at baseline to 4.2 at steady-state) and in the mean % time that gastric pH was > 4 (from 32% at baseline to 60% at steady-state). However, no significant changes were observed in mean intraesophageal pH or % time that esophageal pH was <4 in either age group.

Because pantoprazole sodium for delayed-release oral suspension was not shown to be effective in the randomized, placebo-controlled study in this age group, the use of pantoprazole sodium for delayed-release oral suspension for treatment of symptomatic GERD in infants less than 1 year of age is not indicated.

Animal Toxicity Data

In a pre- and post-natal development study in rats, the pups were administered oral doses of pantoprazole at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (AUC) in children aged 6 to 11 years at a dose of 40 mg) on postnatal day (PND 4) through PND 21, in addition to lactational exposure through milk. On PND 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (AUC) in children aged 6 to 11 years at the 40 mg dose) and higher doses. Changes in bone parameters were partially reversible following a recovery period.

In neonatal/juvenile animals (rats and dogs) toxicities were similar to those observed in adult animals, including gastric alterations, decreases in red cell mass, increases in lipids, enzyme induction and hepatocellular hypertrophy. An increased incidence of eosinophilic chief cells in adult and neonatal/juvenile rats, and atrophy of chief cells in adult rats and in neonatal/juvenile dogs, was observed in the fundic mucosa of stomachs in repeated-dose studies. Full to partial recovery of these effects were noted in animals of both age groups following a recovery period.

In short-term US clinical trials, EE healing rates in the 107 elderly patients (≥65 years old) treated with pantoprazole sodium for delayed-release oral suspension were similar to those found in patients under the age of 65. The incidence rates of adverse reactions and laboratory abnormalities in patients aged 65 years and older were similar to those associated with patients younger than 65 years of age.

Experience in patients taking very high doses of pantoprazole sodium for delayed-release oral suspension (greater than 240 mg) is limited. Spontaneous post-marketing reports of overdose are generally within the known safety profile of pantoprazole sodium for delayed-release oral suspension.

{ "type": "p", "children": [], "text": "Experience in patients taking very high doses of pantoprazole sodium for delayed-release oral suspension (greater than 240 mg) is limited. Spontaneous post-marketing reports of overdose are generally within the known safety profile of pantoprazole sodium for delayed-release oral suspension. " }

Pantoprazole is not removed by hemodialysis. In case of overdosage, treatment should be symptomatic and supportive.

{ "type": "p", "children": [], "text": "Pantoprazole is not removed by hemodialysis. In case of overdosage, treatment should be symptomatic and supportive. " }

Single oral doses of pantoprazole at 709 mg/kg, 798 mg/kg, and 887 mg/kg were lethal to mice, rats, and dogs, respectively. The symptoms of acute toxicity were hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor.

{ "type": "p", "children": [], "text": "Single oral doses of pantoprazole at 709 mg/kg, 798 mg/kg, and 887 mg/kg were lethal to mice, rats, and dogs, respectively. The symptoms of acute toxicity were hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor. " }

If overexposure to pantoprazole sodium for delayed-release oral suspension occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

{ "type": "p", "children": [], "text": "If overexposure to pantoprazole sodium for delayed-release oral suspension occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage." }

The active ingredient in pantoprazole sodium for delayed-release oral suspension, a PPI, is a substituted benzimidazole, sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl] sulfinyl]-1H-benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its molecular formula is C16H14F2N3NaO4S x 1.5 H2O, with a molecular weight of 432.4. The structural formula is:

{ "type": "p", "children": [], "text": "The active ingredient in pantoprazole sodium for delayed-release oral suspension, a PPI, is a substituted benzimidazole, sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl] sulfinyl]-1H-benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its molecular formula is C16H14F2N3NaO4S x 1.5 H2O, with a molecular weight of 432.4. The structural formula is:" }

Pantoprazole sodium USP is a white to off-white powder and is racemic. Pantoprazole has weakly basic and acidic properties. Pantoprazole sodium USP is freely soluble in water, methanol, dehydrated alcohol, practically insoluble in hexane and dichloromethane.

{ "type": "p", "children": [], "text": "Pantoprazole sodium USP is a white to off-white powder and is racemic. Pantoprazole has weakly basic and acidic properties. Pantoprazole sodium USP is freely soluble in water, methanol, dehydrated alcohol, practically insoluble in hexane and dichloromethane." }

The stability of the compound in aqueous solution is pH-dependent. The rate of degradation increases with decreasing pH. At ambient temperature, the degradation half-life is approximately 2.8 hours at pH 5 and approximately 220 hours at pH 7.8.

{ "type": "p", "children": [], "text": "The stability of the compound in aqueous solution is pH-dependent. The rate of degradation increases with decreasing pH. At ambient temperature, the degradation half-life is approximately 2.8 hours at pH 5 and approximately 220 hours at pH 7.8. " }

Pantoprazole sodium is supplied as a for delayed-release oral suspension in unit dose packets, available in one strength 40 mg pantoprazole, (equivalent to 45.1 mg of pantoprazole sodium USP).

{ "type": "p", "children": [], "text": "Pantoprazole sodium is supplied as a for delayed-release oral suspension in unit dose packets, available in one strength 40 mg pantoprazole, (equivalent to 45.1 mg of pantoprazole sodium USP)." }

Pantoprazole sodium for delayed-release oral suspension contains the following inactive ingredients: crospovidone, hypromellose, methacrylic acid and ethyl acrylate copolymer dispersion (contains copolymer based on ethyl acrylate and methacrylic acid, polysorbate 80 and sodium lauryl sulfate), microcrystalline cellulose, polysorbate 80, sodium carbonate (anhydrous), sodium lauryl sulfate, talc, titanium dioxide, triethyl citrate, and yellow iron oxide.

{ "type": "p", "children": [], "text": "Pantoprazole sodium for delayed-release oral suspension contains the following inactive ingredients: crospovidone, hypromellose, methacrylic acid and ethyl acrylate copolymer dispersion (contains copolymer based on ethyl acrylate and methacrylic acid, polysorbate 80 and sodium lauryl sulfate), microcrystalline cellulose, polysorbate 80, sodium carbonate (anhydrous), sodium lauryl sulfate, talc, titanium dioxide, triethyl citrate, and yellow iron oxide. " }

Pantoprazole is a PPI that suppresses the final step in gastric acid production by covalently binding to the (H+, K+)-ATPase enzyme system at the secretory surface of the gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. The binding to the (H+, K+)-ATPase results in a duration of antisecretory effect that persists longer than 24 hours for all doses tested (20 mg to 120 mg).

Pantoprazole Sodium For Delayed-Release Oral Suspension, 40 mg has been shown to be comparable to PROTONIX Delayed-Release Tablets in suppressing pentagastrin-stimulated MAO in patients (n = 49) with GERD and a history of EE. In this multicenter, pharmacodynamic crossover study, a 40 mg oral dose of Pantoprazole Sodium For Delayed-Release Oral Suspension administered in a teaspoonful of applesauce was compared with a 40 mg oral dose of PROTONIX Delayed-Release Tablets after administration of each formulation once daily for 7 days. Both medications were administered thirty minutes before breakfast. Pentagastrin-stimulated (MAO) was assessed from hour 23 to 24 at steady state.

Antisecretory Activity

Under maximal acid stimulatory conditions using pentagastrin, a dose-dependent decrease in gastric acid output occurs after a single dose of oral (20 to 80 mg) or a single dose of intravenous (20 to 120 mg) pantoprazole in healthy subjects. Pantoprazole given once daily results in increasing inhibition of gastric acid secretion. Following the initial oral dose of 40 mg pantoprazole, a 51% mean inhibition was achieved by 2.5 hours. With once-a-day dosing for 7 days, the mean inhibition was increased to 85%. Pantoprazole suppressed acid secretion in excess of 95% in half of the subjects. Acid secretion had returned to normal within a week after the last dose of pantoprazole; there was no evidence of rebound hypersecretion.

In a series of dose-response studies, pantoprazole, at oral doses ranging from 20 to 120 mg, caused dose-related increases in median basal gastric pH and in the percent of time gastric pH was >3 and >4. Treatment with 40 mg of pantoprazole produced significantly greater increases in gastric pH than the 20 mg dose. Doses higher than 40 mg (60, 80, 120 mg) did not result in further significant increases in median gastric pH. The effects of pantoprazole on median pH from one double-blind crossover study are shown in Table 5.

Table 5: Effect of Single Daily Doses of Oral Pantoprazole on Intragastric pH

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <colgroup> <col width="29.7%"/> <col width="17.82%"/> <col width="17.82%"/> <col width="17.82%"/> <col width="16.84%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="5" valign="middle"><span class="Bold">                                               –––––––––—––––––Median pH on day 7—–––––––––––––––––</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">Time<br/> </td><td align="center" class="Rrule" valign="middle">Placebo<br/> </td><td align="center" class="Rrule" valign="middle">20 mg<br/> </td><td align="center" class="Rrule" valign="middle">40 mg<br/> </td><td align="center" class="Rrule" valign="middle">80 mg<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">8 a.m. to 8 a.m. (24 hours)<br/> </td><td align="center" class="Rrule" valign="middle">1.3<br/> </td><td align="center" class="Rrule" valign="middle">2.9*<br/> </td><td align="center" class="Rrule" valign="middle">3.8*#<br/> </td><td align="center" class="Rrule" valign="middle">3.9*#<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">8 a.m. to 10 p.m. (Daytime)<br/> </td><td align="center" class="Rrule" valign="middle">1.6<br/> </td><td align="center" class="Rrule" valign="middle">3.2*<br/> </td><td align="center" class="Rrule" valign="middle">4.4*#<br/> </td><td align="center" class="Rrule" valign="middle">4.8*#<br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="middle">10 p.m. to 8 a.m. (Nighttime)<br/> </td><td align="center" class="Rrule" valign="middle">1.2<br/> </td><td align="center" class="Rrule" valign="middle">2.1*<br/> </td><td align="center" class="Rrule" valign="middle">3.0*<br/> </td><td align="center" class="Rrule" valign="middle">2.6*<br/> </td> </tr> </tbody> </table></div>

* Significantly different from placebo

# Significantly different from 20 mg

Serum Gastrin Effects

Fasting serum gastrin levels were assessed in two double-blind studies of the acute healing of EE in which 682 patients with gastroesophageal reflux disease (GERD) received 10, 20, or    40 mg of pantoprazole sodium for delayed-release suspension for up to 8 weeks. At 4 weeks of treatment there was an increase in mean gastrin levels of 7%, 35%, and 72% over pretreatment values in the 10, 20, and 40 mg treatment groups, respectively. A similar increase in serum gastrin levels was noted at the 8-week visit with mean increases of 3%, 26%, and 84% for the three pantoprazole dose groups. Median serum gastrin levels remained within normal limits during maintenance therapy with PROTONIX Delayed-Release Tablets.

In long-term international studies involving over 800 patients, a 2- to 3-fold mean increase from the pretreatment fasting serum gastrin level was observed in the initial months of treatment with pantoprazole at doses of 40 mg per day during GERD maintenance studies and 40 mg or higher per day in patients with refractory GERD. Fasting serum gastrin levels generally remained at approximately 2 to 3 times baseline for up to 4 years of periodic follow-up in clinical trials.

Following short-term treatment with pantoprazole sodium for delayed-release oral suspension, elevated gastrin levels return to normal by at least 3 months.

Enterochromaffin-Like (ECL) Cell Effects

In 39 patients treated with oral pantoprazole 40 mg to 240 mg daily (majority receiving 40 mg to 80 mg) for up to 5 years, there was a moderate increase in ECL-cell density, starting after the first year of use, which appeared to plateau after 4 years.

In a nonclinical study in Sprague-Dawley rats, lifetime exposure (24 months) to pantoprazole at doses of 0.5 to 200 mg/kg/day resulted in dose-related increases in gastric ECL-cell proliferation and gastric neuroendocrine (NE)-cell tumors. Gastric NE-cell tumors in rats may result from chronic elevation of serum gastrin concentrations. The high density of ECL cells in the rat stomach makes this species highly susceptible to the proliferative effects of elevated gastrin concentrations produced by PPIs. However, there were no observed elevations in serum gastrin following the administration of pantoprazole at a dose of 0.5 mg/kg/day. In a separate study, a gastric NE-cell tumor without concomitant ECL-cell proliferative changes was observed in 1 female rat following 12 months of dosing with pantoprazole at 5 mg/kg/day and a 9 month off-dose recovery [see Nonclinical Toxicology (13.1)].

Endocrine Effects

In a clinical pharmacology study, pantoprazole sodium for delayed-release oral suspension 40 mg given once daily for 2 weeks had no effect on the levels of the following hormones: cortisol, testosterone, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), thyronine-binding protein, parathyroid hormone, insulin, glucagon, renin, aldosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, and growth hormone.

In a 1-year study of GERD patients treated with pantoprazole sodium for delayed-release oral suspension 40 mg or 20 mg, there were no changes from baseline in overall levels of T3, T4, and TSH.

PROTONIX Delayed-Release Tablets are prepared as enteric-coated tablets so that absorption of pantoprazole begins only after the tablet leaves the stomach. Peak serum concentration (Cmax) and area under the serum concentration time curve (AUC) increase in a manner proportional to oral and intravenous doses from 10 mg to 80 mg. Pantoprazole does not accumulate, and its pharmacokinetics are unaltered with multiple daily dosing. Following oral or intravenous administration, the serum concentration of pantoprazole declines biexponentially, with a terminal elimination half-life of approximately one hour.

In extensive metabolizers with normal liver function receiving an oral dose of the enteric-coated 40 mg pantoprazole tablet, the peak concentration (Cmax) is 2.5 mcg/mL; the time to reach the peak concentration (tmax) is 2.5 h, and the mean total area under the plasma concentration versus time curve (AUC) is 4.8 mcg•h/mL (range 1.4 to 13.3 mcg•h/mL). Following intravenous administration of pantoprazole to extensive metabolizers, its total clearance is 7.6 to 14.0 L/h, and its apparent volume of distribution is 11.0 to 23.6 L.

A single oral dose of Pantoprazole Sodium For Delayed-Release Oral Suspension, 40 mg, was shown to be bioequivalent when administered to healthy subjects (N = 22) as granules sprinkled over a teaspoonful of applesauce, as granules mixed with apple juice, or mixed with apple juice followed by administration through a nasogastric tube. The plasma pharmacokinetic parameters from a crossover study in healthy subjects are summarized in Table 6.

Table 6: Pharmacokinetics Parameters (mean ± SD) of Pantoprazole Sodium For Delayed-Release Oral Suspension at 40 mg

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <colgroup> <col width="19.84%"/> <col width="24.8%"/> <col width="24.8%"/> <col width="30.56%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td class="Lrule Rrule" valign="top"><span class="Bold">   Pharmacokinetic    Parameters</span> <br/> </td><td class="Rrule" valign="middle"><span class="Bold">Granules in Applesauce</span> <br/> </td><td class="Rrule" valign="middle"><span class="Bold">Granules in Apple Juice</span> <br/> </td><td class="Rrule" valign="middle"><span class="Bold">Granules in Nasogastric Tube</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">  AUC (mcg•hr/mL)<br/> </td><td class="Rrule" valign="top">4.0 ± 1.5<br/> </td><td class="Rrule" valign="top">4.0 ± 1.5<br/> </td><td class="Rrule" valign="top">4.1 ± 1.7<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">  C<span class="Sub">max</span>(mcg/mL)<br/> </td><td class="Rrule" valign="top">2.0 ± 0.7<br/> </td><td class="Rrule" valign="top">1.9 ± 0.5<br/> </td><td class="Rrule" valign="top">2.2 ± 0.7<br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top">  T<span class="Sub">max</span>(hr)<span class="Sup">a</span> <br/> </td><td class="Rrule" valign="top">2.0<br/> </td><td class="Rrule" valign="top">2.5<br/> </td><td class="Rrule" valign="top">2.0<br/> </td> </tr> </tbody> </table></div>

a Median values are reported for Tmax.

Absorption

After administration of a single or multiple oral 40 mg doses of PROTONIX Delayed-Release Tablets, the peak plasma concentration of pantoprazole was achieved in approximately 2.5 hours, and Cmax was 2.5 μg/mL. Pantoprazole undergoes little first-pass metabolism, resulting in an absolute bioavailability of approximately 77%. Pantoprazole absorption is not affected by concomitant administration of antacids.

Administration of PROTONIX Delayed-Release Tablets with food may delay its absorption up to 2 hours or longer; however, the Cmax and the extent of pantoprazole absorption (AUC) are not altered. Thus, PROTONIX Delayed-Release Tablets may be taken without regard to timing of meals.

Administration of pantoprazole granules, 40 mg, with a high-fat meal delayed median time to peak plasma concentration by 2 hours. With a concomitant high-fat meal, the Cmax and AUC of pantoprazole granules, 40 mg, sprinkled on applesauce decreased by 51% and 29%, respectively. Thus, Pantoprazole Sodium For Delayed-Release Oral Suspension should be taken approximately 30 minutes before a meal.

Distribution

The apparent volume of distribution of pantoprazole is approximately 11 to 23.6 L, distributing mainly in extracellular fluid. The serum protein binding of pantoprazole is about 98%, primarily to albumin.

Elimination

Metabolism

Pantoprazole is extensively metabolized in the liver through the cytochrome P450 (CYP) system. Pantoprazole metabolism is independent of the route of administration (intravenous or oral). The main metabolic pathway is demethylation, by CYP2C19, with subsequent sulfation; other metabolic pathways include oxidation by CYP3A4. There is no evidence that any of the pantoprazole metabolites have significant pharmacologic activity.

Excretion

After a single oral or intravenous dose of 14C-labeled pantoprazole to healthy, normal metabolizer subjects, approximately 71% of the dose was excreted in the urine, with 18% excreted in the feces through biliary excretion. There was no renal excretion of unchanged pantoprazole.

Specific Populations

Geriatric Patients

Only slight to moderate increases in the AUC (43%) and Cmax (26%) of pantoprazole were found in elderly subjects (64 to 76 years of age) after repeated oral administration, compared with younger subjects [see Use in Specific Populations (8.5)].

Pediatric Patients

The pharmacokinetics of pantoprazole were studied in children less than 16 years of age in four randomized, open-label clinical trials in pediatric patients with presumed/proven GERD. A pediatric granule formulation was studied in children through 5 years of age, and PROTONIX Delayed-Release Tablets were studied in children older than 5 years.

In a population PK analysis, total clearance increased with increasing bodyweight in a non-linear fashion. The total clearance also increased with increasing age only in children under 3 years of age.

Neonate through 5 Years of Age [see Use in Specific Populations (8.4)]

Children and Adolescents 6 through 16 Years of Age

The pharmacokinetics of PROTONIX Delayed-Release Tablets were evaluated in children ages 6 through 16 years with a clinical diagnosis of GERD. The PK parameters following a single oral dose of 20 mg or 40 mg of PROTONIX Delayed-Release Tablets in children ages 6 through 16 years were highly variable (%CV ranges 40 to 80%). The geometric mean AUC estimated from population PK analysis after a 40 mg Pantoprazole Sodium delayed-release tablet in pediatric patients was about 39% and 10% higher respectively in 6 to 11 and 12 to 16 year-old children, compared to that of adults (Table 7).

Table 7: PK Parameters in Children and Adolescents 6 through 16 years with GERD receiving 40 mg PROTONIX Delayed-Release Tablets

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <colgroup> <col width="32.1%"/> <col width="33.08%"/> <col width="34.82%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" valign="middle"> <br/> </td><td align="left" class="Rrule" valign="middle"><span class="Bold"> 6 to 11 </span><span class="Bold">years (n=12)</span> <br/> </td><td align="left" class="Rrule" valign="middle"><span class="Bold">12 to 16 </span><span class="Bold">years (n=11)</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">C<span class="Sub">max</span>(mcg/mL)<span class="Sup">a</span> <br/> </td><td align="left" class="Rrule" valign="middle">1.8<br/> </td><td align="left" class="Rrule" valign="middle">1.8<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">t<span class="Sub">max</span>(h)<span class="Sup">b</span> <br/> </td><td align="left" class="Rrule" valign="middle">2.0<br/> </td><td align="left" class="Rrule" valign="middle">2.0<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">AUC (mcg•h/mL)<span class="Sup"> a</span> <br/> </td><td align="left" class="Rrule" valign="middle">6.9<br/> </td><td align="left" class="Rrule" valign="middle">5.5<br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="middle">CL/F (L/h)<span class="Sup"> b</span> <br/> </td><td align="left" class="Rrule" valign="middle">6.6<br/> </td><td align="left" class="Rrule" valign="middle">6.8<br/> </td> </tr> </tbody> </table></div>

a Geometric mean values

b Median values

Male and Female Patients

There is a modest increase in pantoprazole AUC and Cmax in women compared to men. However, weight-normalized clearance values are similar in women and men.

In pediatric patients ages 1 through 16 years there were no clinically relevant effects of gender on clearance of pantoprazole, as shown by population pharmacokinetic analysis.

Patients with Renal Impairment

In patients with severe renal impairment, pharmacokinetic parameters for pantoprazole were similar to those of healthy subjects.

Patients with Hepatic Impairment

In patients with mild to severe hepatic impairment (Child-Pugh A to C cirrhosis), maximum pantoprazole concentrations increased only slightly (1.5-fold) relative to healthy subjects. Although serum half-life values increased to 7 to 9 hours and AUC values increased by 5- to 7-fold in hepatic-impaired patients, these increases were no greater than those observed in CYP2C19 poor metabolizers, where no dosage adjustment is warranted. These pharmacokinetic changes in hepatic-impaired patients result in minimal drug accumulation following once-daily, multiple-dose administration. Doses higher than 40 mg/day have not been studied in hepatically impaired patients.

Drug Interaction Studies

Effect of Other Drugs on Pantoprazole

Pantoprazole is metabolized mainly by CYP2C19 and to minor extents by CYPs 3A4, 2D6, and 2C9. In in vivo drug-drug interaction studies with CYP2C19 substrates (diazepam [also a CYP3A4 substrate] and phenytoin [also a CYP3A4 inducer] and clopidogrel), nifedipine, midazolam, and clarithromycin (CYP3A4 substrates), metoprolol (a CYP2D6 substrate), diclofenac, naproxen and piroxicam (CYP2C9 substrates), and theophylline (a CYP1A2 substrate) in healthy subjects, the pharmacokinetics of pantoprazole were not significantly altered.

Effect of Pantoprazole on Other Drugs

Clopidogrel  

Clopidogrel is metabolized to its active metabolite in part by CYP2C19. In a crossover clinical study, 66 healthy subjects were administered clopidogrel (300 mg loading dose followed by 75 mg per day) alone and with pantoprazole (80 mg at the same time as clopidogrel) for 5 days. On Day 5, the mean AUC of the active metabolite of clopidogrel was reduced by approximately 14% (geometric mean ratio was 86%, with 90% CI of 79 to 93%) when pantoprazole was coadministered with clopidogrel as compared to clopidogrel administered alone. Pharmacodynamic parameters were also measured and demonstrated that the change in inhibition of platelet aggregation (induced by 5 μM ADP) was correlated with the change in the exposure to clopidogrel active metabolite. The clinical significance of this finding is not clear.

Mycophenolate Mofetil (MMF)

Administration of pantoprazole 40 mg twice daily for 4 days and a single 1000 mg dose of MMF approximately one hour after the last dose of pantoprazole to 12 healthy subjects in a cross-over study resulted in a 57% reduction in the Cmax and 27% reduction in the AUC of MPA. Transplant patients receiving approximately 2000 mg per day of MMF (n=12) were compared to transplant patients receiving approximately the same dose of MMF and pantoprazole 40 mg per day (n=21). There was a 78% reduction in the Cmax and a 45% reduction in the AUC of MPA in patients receiving both pantoprazole and MMF [see Drug Interactions (7)].

Other Drugs

In vivo studies also suggest that pantoprazole does not significantly affect the kinetics of the following drugs (cisapride, theophylline, diazepam [and its active metabolite, desmethyldiazepam], phenytoin, metoprolol, nifedipine, carbamazepine, midazolam, clarithromycin, diclofenac, naproxen, piroxicam, and oral contraceptives [levonorgestrel/ethinyl estradiol]). In other in vivo studies, digoxin, ethanol, glyburide, antipyrine, caffeine, metronidazole, and amoxicillin had no clinically relevant interactions with pantoprazole.

Although no significant drug-drug interactions have been observed in clinical studies, the potential for significant drug-drug interactions with more than once-daily dosing with high doses of pantoprazole has not been studied in poor metabolizers or individuals who are hepatically impaired.

Antacids

There was also no interaction with concomitantly administered antacids.

CYP2C19 displays a known genetic polymorphism due to its deficiency in some subpopulations (e.g., approximately 3% of Caucasians and African-Americans and 17% to 23% of Asians are poor metabolizers). Although these subpopulations of pantoprazole poor metabolizers have elimination half-life values of 3.5 to 10 hours in adults, they still have minimal accumulation (23% or less) with once-daily dosing. For adult patients who are CYP2C19 poor metabolizers, no dosage adjustment is needed.

Similar to adults, pediatric patients who have the poor metabolizer genotype of CYP2C19 (CYP2C19 *2/*2) exhibited greater than a 6-fold increase in AUC compared to pediatric extensive (CYP2C19 *1/*1) and intermediate (CYP2C19 *1/*x) metabolizers. Poor metabolizers exhibited approximately 10-fold lower apparent oral clearance compared to extensive metabolizers.

For known pediatric poor metabolizers, a dose reduction should be considered.

In a 24-month carcinogenicity study, Sprague-Dawley rats were treated orally with pantoprazole doses of 0.5 to 200 mg/kg/day, about 0.1 to 40 times the exposure on a body surface area basis of a 50 kg person dosed with 40 mg/day. In the gastric fundus, treatment with 0.5 to 200 mg/kg/day produced enterochromaffin-like (ECL) cell hyperplasia and benign and malignant neuroendocrine cell tumors in a dose-related manner. In the forestomach, treatment with 50 and 200 mg/kg/day (about 10 and 40 times the recommended human dose on a body surface area basis) produced benign squamous cell papillomas and malignant squamous cell carcinomas. Rare gastrointestinal tumors associated with pantoprazole treatment included an adenocarcinoma of the duodenum with 50 mg/kg/day and benign polyps and adenocarcinomas of the gastric fundus with 200 mg/kg/day. In the liver, treatment with 0.5 to 200 mg/kg/day produced dose-related increases in the incidences of hepatocellular adenomas and carcinomas. In the thyroid gland, treatment with 200 mg/kg/day produced increased incidences of follicular cell adenomas and carcinomas for both male and female rats.

In a 24-month carcinogenicity study, Fischer 344 rats were treated orally with doses of 5 to 50 mg/kg/day of pantoprazole, approximately 1 to 10 times the recommended human dose based on body surface area. In the gastric fundus, treatment with 5 to 50 mg/kg/day produced enterochromaffin-like (ECL) cell hyperplasia and benign and malignant neuroendocrine cell tumors. Dose selection for this study may not have been adequate to comprehensively evaluate the carcinogenic potential of pantoprazole.

In a 24-month carcinogenicity study, B6C3F1 mice were treated orally with doses of 5 to 150 mg/kg/day of pantoprazole, 0.5 to 15 times the recommended human dose based on body surface area. In the liver, treatment with 150 mg/kg/day produced increased incidences of hepatocellular adenomas and carcinomas in female mice. Treatment with 5 to 150 mg/kg/day also produced gastric-fundic ECL cell hyperplasia.

A 26-week p53 +/- transgenic mouse carcinogenicity study was not positive.

Pantoprazole was positive in the in vitro human lymphocyte chromosomal aberration assays, in one of two mouse micronucleus tests for clastogenic effects, and in the in vitro Chinese hamster ovarian cell/HGPRT forward mutation assay for mutagenic effects. Equivocal results were observed in the in vivo rat liver DNA covalent binding assay. Pantoprazole was negative in the in vitro Ames mutation assay, the in vitro unscheduled DNA synthesis (UDS) assay with rat hepatocytes, the in vitro AS52/GPT mammalian cell-forward gene mutation assay, the in vitro thymidine kinase mutation test with mouse lymphoma L5178Y cells, and the in vivo rat bone marrow cell chromosomal aberration assay.

There were no effects on fertility or reproductive performance when pantoprazole was given at oral doses up to 500 mg/kg/day in male rats (98 times the recommended human dose based on body surface area) and 450 mg/kg/day in female rats (88 times the recommended human dose based on body surface area).

Adult Patients

A US multicenter, double-blind, placebo-controlled study of PROTONIX Delayed-Release Tablets 10 mg, 20 mg, or 40 mg once daily was conducted in 603 patients with reflux symptoms and endoscopically diagnosed EE of grade 2 or above (Hetzel-Dent scale). In this study, approximately 25% of enrolled patients had severe EE of grade 3, and 10% had grade 4. The percentages of patients healed (per protocol, n = 541) in this study are shown in Table 8.

Table 8: Erosive Esophagitis Healing Rates (Per Protocol)

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <colgroup> <col width="13.86%"/> <col width="22.78%"/> <col width="23.76%"/> <col width="24.76%"/> <col width="14.86%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="4" valign="middle"><span class="Bold">                   –––––––––PROTONIX Delayed-Release Tablets–––––––</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Placebo</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">Week<br/> </td><td align="center" class="Rrule" valign="middle">10 mg daily (n = 153)<span class="Bold"></span> <br/> </td><td align="center" class="Rrule" valign="middle">20 mg daily (n = 158)<span class="Bold"></span> <br/> </td><td align="center" class="Rrule" valign="middle">40 mg daily (n = 162)<span class="Bold"></span> <br/> </td><td align="center" class="Rrule" valign="middle">(n = 68)<span class="Bold"></span> <br/> </td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule" valign="middle">4<span class="Bold"></span> <br/>8<span class="Bold"></span> <br/> </td><td align="center" class="Rrule" valign="middle">45.6%<span class="Sup">+</span><span class="Bold"></span> <br/>66.0%<span class="Sup">+</span><span class="Bold"></span> <br/> </td><td align="center" class="Rrule" valign="middle">58.4%<span class="Sup">+</span>#<span class="Bold"></span> <br/>83.5%<span class="Sup">+</span>#<span class="Bold"></span> <br/> </td><td align="center" class="Rrule" valign="middle">75.0%<span class="Sup">+</span>*<span class="Bold"></span> <br/>92.6%<span class="Sup">+</span>*<span class="Bold"></span> <br/> </td><td align="center" class="Rrule" valign="middle">14.3%<span class="Bold"></span> <br/>39.7%<span class="Bold"></span> <br/> </td> </tr> </tbody> </table></div>

+(p < 0.001) PROTONIX Delayed-Release Tablets versus placebo

*(p < 0.05) versus 10 mg or 20 mg PROTONIX Delayed-Release Tablets

#(p < 0.05) versus 10 mg PROTONIX Delayed-Release Tablets

In this study, all PROTONIX Delayed-Release Tablets treatment groups had significantly greater healing rates than the placebo group. This was true regardless of H. pylori status for the 40 mg and 20 mg PROTONIX Delayed-Release Tablets treatment groups. The 40 mg dose of PROTONIX Delayed-Release Tablets resulted in healing rates significantly greater than those found with either the 20 mg or 10 mg dose.

A significantly greater proportion of patients taking PROTONIX Delayed-Release Tablets 40 mg experienced complete relief of daytime and nighttime heartburn and the absence of regurgitation, starting from the first day of treatment, compared with placebo. Patients taking PROTONIX Delayed-Release Tablets consumed significantly fewer antacid tablets per day than those taking placebo.

PROTONIX Delayed-Release Tablets 40 mg and 20 mg once daily were also compared with nizatidine 150 mg twice daily in a US multicenter, double-blind study of 243 patients with reflux symptoms and endoscopically diagnosed EE of grade 2 or above. The percentages of patients healed (per protocol, n = 212) are shown in Table 9.

Table 9: Erosive Esophagitis Healing Rates (Per Protocol)

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <colgroup> <col width="15.44%"/> <col width="26.14%"/> <col width="27.04%"/> <col width="31.38%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="3" valign="middle"><span class="Bold">                         ––––PROTONIX Delayed-Release Tablets––––</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Nizatidine</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">Week<br/> </td><td align="center" class="Rrule" valign="middle">20 mg daily <br/>(n = 72) <span class="Bold"></span> <br/> </td><td align="center" class="Rrule" valign="middle">40 mg daily<br/> (n = 70) <br/> </td><td align="center" class="Rrule" valign="middle">150 mg twice daily (n = 70) <br/> </td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule" valign="middle">4<span class="Bold"></span> <br/>8<span class="Bold"></span> <br/> </td><td align="center" class="Rrule" valign="middle">61.4%<span class="Sup">+</span> <br/>79.2%<span class="Sup">+</span> <br/> </td><td align="center" class="Rrule" valign="middle">64.0%<span class="Sup">+</span> <br/>82.9%<span class="Sup">+</span> <br/> </td><td align="center" class="Rrule" valign="middle">22.2% <br/>41.4% <br/> </td> </tr> </tbody> </table></div>

+(p < 0.001) PROTONIX Delayed-Release Tablets versus nizatidine

Once-daily treatment with PROTONIX Delayed-Release Tablets 40 mg or 20 mg resulted in significantly superior rates of healing at both 4 and 8 weeks compared with twice-daily treatment with 150 mg of nizatidine. For the 40 mg treatment group, significantly greater healing rates compared to nizatidine were achieved regardless of the H. pylori status.

A significantly greater proportion of the patients in the PROTONIX Delayed-Release Tablets treatment groups experienced complete relief of nighttime heartburn and regurgitation, starting on the first day and of daytime heartburn on the second day, compared with those taking nizatidine 150 mg twice daily. Patients taking PROTONIX Delayed-Release Tablets consumed significantly fewer antacid tablets per day than those taking nizatidine.

Pediatric Patients Ages 5 Years through 16 Years

The efficacy of PROTONIX Delayed-Release Tablets in the treatment of EE associated with GERD in pediatric patients ages 5 years through 16 years is extrapolated from adequate and well-conducted trials in adults, as the pathophysiology is thought to be the same. Four pediatric patients with endoscopically diagnosed EE were studied in multicenter, randomized, double-blind, parallel-treatment trials. Children with endoscopically diagnosed EE (defined as an endoscopic Hetzel-Dent score ≥2) were treated once daily for 8 weeks with one of two dose levels of PROTONIX Delayed-Release Tablets (20 mg or 40 mg). All 4 patients with EE were healed (Hetzel-Dent score of 0 or 1) at 8 weeks.

Two independent, multicenter, randomized, double-blind, comparator-controlled trials of identical design were conducted in adult GERD patients with endoscopically confirmed healed EE to demonstrate efficacy of PROTONIX Delayed-Release Tablets in long-term maintenance of healing. The two US studies enrolled 386 and 404 patients, respectively, to receive either 10 mg, 20 mg, or 40 mg of PROTONIX Delayed-Release Tablets once daily or 150 mg of ranitidine twice daily. As demonstrated in Table 10, PROTONIX Delayed-Release Tablets 40 mg and 20 mg were significantly superior to ranitidine at every timepoint with respect to the maintenance of healing.

In addition, PROTONIX Delayed-Release Tablets 40 mg was superior to all other treatments studied.

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <caption> <span>Table 10: Long-Term Maintenance of Healing of Erosive Gastroesophageal Reflux Disease (GERD Maintenance): Percentage of Patients Who Remained Healed </span> </caption> <colgroup> <col width="17.86%"/> <col width="26.78%"/> <col width="28.78%"/> <col width="26.58%"/> </colgroup> <tfoot> <tr class="First Last"> <td align="justify" colspan="4"><span class="Sup">*</span>(p &lt;0.05 vs. ranitidine) <br/> <span class="Sup">#</span>(p &lt;0.05 vs. PROTONIX Delayed-Release Tablets 20 mg) <br/>Note: PROTONIX Delayed-Release Tablets 10 mg was superior (p &lt;0.05) to ranitidine in Study 2, but not Study 1.<br/> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td class="Lrule Rrule" valign="top"> <br/> </td><td align="center" class="Rrule" valign="middle">PROTONIX Delayed-Release Tablets 20 mg daily<br/> </td><td align="center" class="Rrule" valign="middle">PROTONIX Delayed-Release Tablets <br/>40 mg daily<br/> </td><td align="center" class="Rrule" valign="middle">Ranitidine<br/>150 mg twice daily<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top"><span class="Bold">Study 1</span> <br/> </td><td align="center" class="Rrule" valign="middle">n = 75<br/> </td><td align="center" class="Rrule" valign="middle">n = 74<br/> </td><td align="center" class="Rrule" valign="middle">n = 75<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Month 1<br/> </td><td align="center" class="Rrule" valign="middle">91<span class="Sup">*</span> <br/> </td><td align="center" class="Rrule" valign="middle">99<span class="Sup">*</span> <br/> </td><td align="center" class="Rrule" valign="middle">68<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Month 3<br/> </td><td align="center" class="Rrule" valign="middle">82<span class="Sup">*</span> <br/> </td><td align="center" class="Rrule" valign="middle">93<span class="Sup">*</span><span class="Sup">#</span> <br/> </td><td align="center" class="Rrule" valign="middle">54<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Month 6<br/> </td><td align="center" class="Rrule" valign="middle">76<span class="Sup">*</span> <br/> </td><td align="center" class="Rrule" valign="middle">90<span class="Sup">*</span><span class="Sup">#</span> <br/> </td><td align="center" class="Rrule" valign="middle">44<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Month 12<br/> </td><td align="center" class="Rrule" valign="middle">70<span class="Sup">*</span> <br/> </td><td align="center" class="Rrule" valign="middle">86<span class="Sup">*</span><span class="Sup">#</span> <br/> </td><td align="center" class="Rrule" valign="middle">35<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top"><span class="Bold">Study 2</span> <br/> </td><td align="center" class="Rrule" valign="middle">n = 74<br/> </td><td align="center" class="Rrule" valign="middle">n = 88<br/> </td><td align="center" class="Rrule" valign="middle">n = 84<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Month 1<br/> </td><td align="center" class="Rrule" valign="middle">89<span class="Sup">*</span> <br/> </td><td align="center" class="Rrule" valign="middle">92<span class="Sup">*</span><span class="Sup">#</span> <br/> </td><td align="center" class="Rrule" valign="middle">62<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Month 3<br/> </td><td align="center" class="Rrule" valign="middle">78<span class="Sup">*</span> <br/> </td><td align="center" class="Rrule" valign="middle">91<span class="Sup">*</span><span class="Sup">#</span> <br/> </td><td align="center" class="Rrule" valign="middle">47<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Month 6<br/> </td><td align="center" class="Rrule" valign="middle">72<span class="Sup">*</span> <br/> </td><td align="center" class="Rrule" valign="middle">88<span class="Sup">*</span><span class="Sup">#</span> <br/> </td><td align="center" class="Rrule" valign="middle">39<br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top">Month 12<br/> </td><td align="center" class="Rrule" valign="middle">72<span class="Sup">*</span> <br/> </td><td align="center" class="Rrule" valign="middle">83<span class="Sup">*</span> <br/> </td><td align="center" class="Rrule" valign="middle">37<br/> </td> </tr> </tbody> </table></div>

PROTONIX Delayed-Release Tablets 40 mg was superior to ranitidine in reducing the number of daytime and nighttime heartburn episodes from the first through the twelfth month of treatment. PROTONIX Delayed-Release Tablets 20 mg, administered once daily, was also effective in reducing episodes of daytime and nighttime heartburn in one trial, as presented in Table 11.

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <caption> <span>Table 11: Number of Episodes of Heartburn (mean ± SD)  </span> </caption> <colgroup> <col width="14%"/> <col width="23.32%"/> <col width="27.46%"/> <col width="35.22%"/> </colgroup> <tfoot> <tr class="First Last"> <td colspan="4"><span class="Sup">*</span>(p &lt;0.001 vs. ranitidine, combined data from the two US studies) <br/> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="3" valign="middle">                                                                      PROTONIX <br/>                                                              Delayed-Release Tablets<br/>                                                                     40 mg daily<br/> </td><td align="center" class="Rrule" valign="middle">Ranitidine<br/>150 mg twice daily<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">  Month 1<br/> </td><td class="Rrule" valign="top">  Daytime<br/>  Nighttime<br/> </td><td align="center" class="Rrule" valign="top">5.1 ± 1.6<span class="Sup">*</span> <br/>3.9 ± 1.1<span class="Sup">*</span> <br/> </td><td align="center" class="Rrule" valign="top">18.3 ± 1.6<br/>11.9 ± 1.1<br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top">  Month 12<br/> </td><td class="Rrule" valign="top">  Daytime<br/>  Nighttime<br/> </td><td align="center" class="Rrule" valign="top">2.9 ± 1.5<span class="Sup">*</span> <br/>2.5 ± 1.2<span class="Sup">*</span> <br/> </td><td align="center" class="Rrule" valign="top">17.5 ± 1.5<br/>13.8 ± 1.3<br/> </td> </tr> </tbody> </table></div>

In a multicenter, open-label trial of 35 patients with pathological hypersecretory conditions, such as Zollinger-Ellison Syndrome, with or without multiple endocrine neoplasia-type I, PROTONIX Delayed-Release Tablets successfully controlled gastric acid secretion. Doses ranging from 80 mg daily to 240 mg daily maintained gastric acid output below 10 mEq/h in patients without prior acid-reducing surgery and below 5 mEq/h in patients with prior acid-reducing surgery.

Doses were initially titrated to the individual patient needs, and adjusted in some patients based on the clinical response with time [see Dosage and Administration (2)]. PROTONIX Delayed-Release Tablets was well tolerated at these dose levels for prolonged periods (greater than 2 years in some patients).

How Supplied

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Pantoprazole Sodium For Delayed-Release Oral Suspension is supplied as pale yellowish to yellow, enteric-coated granules containing 40 mg pantoprazole in a unit-dose packet and are available as follows:

{ "type": "p", "children": [], "text": "Pantoprazole Sodium For Delayed-Release Oral Suspension is supplied as pale yellowish to yellow, enteric-coated granules containing 40 mg pantoprazole in a unit-dose packet and are available as follows: " }

{ "type": "ul", "children": [ "NDC 59651-671-30, unit-dose carton of 30 " ], "text": "" }

Storage

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

Store Pantoprazole Sodium For Delayed-Release Oral Suspension at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store Pantoprazole Sodium For Delayed-Release Oral Suspension at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]." }

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

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). " }

Gastric Malignancy

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

Advise patients to return to their healthcare provider if they have a suboptimal response or an early symptomatic relapse [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Advise patients to return to their healthcare provider if they have a suboptimal response or an early symptomatic relapse [see Warnings and Precautions (5.1)]. " }

Acute Tubulointerstitial Nephritis

{ "type": "p", "children": [], "text": "\nAcute Tubulointerstitial Nephritis \n" }

Advise patients to call their healthcare provider immediately if they experience signs and/or symptoms associated with acute tubulointerstitial nephritis [see Contraindications (4), Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Advise patients to call their healthcare provider immediately if they experience signs and/or symptoms associated with acute tubulointerstitial nephritis [see Contraindications (4), Warnings and Precautions (5.2)]. " }

Clostridium difficile-Associated Diarrhea

{ "type": "p", "children": [], "text": "\nClostridium difficile-Associated Diarrhea \n" }

Advise patients to immediately call their healthcare provider if they experience diarrhea that does not improve [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Advise patients to immediately call their healthcare provider if they experience diarrhea that does not improve [see Warnings and Precautions (5.3)]. " }

Bone Fracture

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

Advise patients to report any fractures, especially of the hip, wrist or spine, to their healthcare provider [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "Advise patients to report any fractures, especially of the hip, wrist or spine, to their healthcare provider [see Warnings and Precautions (5.4)]. " }

Severe Cutaneous Adverse Reactions

{ "type": "p", "children": [], "text": "\nSevere Cutaneous Adverse Reactions\n" }

Advise patients to discontinue pantoprazole sodium for delayed-release oral suspension and immediately call their healthcare provider for further evaluation [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "Advise patients to discontinue pantoprazole sodium for delayed-release oral suspension and immediately call their healthcare provider for further evaluation [see Warnings and Precautions (5.5)]." }

Cutaneous and Systemic Lupus Erythematosus

{ "type": "p", "children": [], "text": "\nCutaneous and Systemic Lupus Erythematosus \n" }

Advise patients to immediately call their healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus [see Warnings and Precautions (5.6)].

{ "type": "p", "children": [], "text": "Advise patients to immediately call their healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus [see Warnings and Precautions (5.6)]." }

Cyanocobalamin (Vitamin B-12) Deficiency

{ "type": "p", "children": [], "text": "\nCyanocobalamin (Vitamin B-12) Deficiency \n" }

Advise patients to report any clinical symptoms that may be associated with cyancobalamin deficiency to their healthcare provider if they have been receiving pantoprazole sodium for delayed-release oral suspension for longer than 3 years [see Warnings and Precautions (5.7)].

{ "type": "p", "children": [], "text": "Advise patients to report any clinical symptoms that may be associated with cyancobalamin deficiency to their healthcare provider if they have been receiving pantoprazole sodium for delayed-release oral suspension for longer than 3 years [see Warnings and Precautions (5.7)]. " }

Hypomagnesemia and Mineral Metabolism

{ "type": "p", "children": [], "text": "\nHypomagnesemia and Mineral Metabolism\n" }

Advise patients to report any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia, and/or hypokalemia, to their healthcare provider, if they have been receiving pantoprazole sodium for delayed-release oral suspension for at least 3 months [see Warnings and Precautions (5.8)].

{ "type": "p", "children": [], "text": "Advise patients to report any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia, and/or hypokalemia, to their healthcare provider, if they have been receiving pantoprazole sodium for delayed-release oral suspension for at least 3 months [see Warnings and Precautions (5.8)]. " }

Drug Interactions

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

Instruct patients to inform their healthcare provider of any other medications they are currently taking, including rilpivirine-containing products [see Contraindications (4)], digoxin [see Warnings and Precautions (5.8)]  and high dose methotrexate [see Warnings and Precautions (5.13)].

{ "type": "p", "children": [], "text": "Instruct patients to inform their healthcare provider of any other medications they are currently taking, including rilpivirine-containing products [see Contraindications (4)], digoxin [see Warnings and Precautions (5.8)]  and high dose methotrexate [see Warnings and Precautions (5.13)]. " }

Pregnancy

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

Advise a pregnant woman of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "Advise a pregnant woman of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1)]. " }

Administration

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

{ "type": "ul", "children": [ "Do not split, crush, or chew Pantoprazole Sodium For Delayed-Release Oral Suspension. ", "Pantoprazole sodium for delayed-release oral suspension packet is a fixed dose and cannot be divided to make a smaller dose. ", "Take Pantoprazole Sodium For Delayed-Release Oral Suspension approximately 30 minutes before a meal. ", "Administer Pantoprazole Sodium For Delayed-Release Oral Suspension in apple juice or applesauce, as described in the Instructions for Use. Do not administer in water, other liquids, or foods. ", "For patients with a nasogastric (NG) or gastrostomy tube, Pantoprazole Sodium For Delayed-Release Oral Suspension can be administered with apple juice, as described in the Instructions for Use. ", "Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and take the next dose at the regular scheduled time. Do not take 2 doses at the same time. " ], "text": "" }

The brands listed are trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited.

{ "type": "p", "children": [], "text": "The brands listed are trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited." }

Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides

{ "type": "p", "children": [], "text": "\nDispense with Medication Guide available at: www.aurobindousa.com/medication-guides\n" }

Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Issued: January 2024

{ "type": "p", "children": [], "text": "Distributed by:\nAurobindo Pharma USA, Inc.\n279 Princeton-Hightstown Road East Windsor, NJ 08520\n Manufactured by:\nAurobindo Pharma Limited\nHyderabad-500 032, India\n Issued: January 2024\n" }

Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides

{ "type": "p", "children": [], "text": "\nDispense with Medication Guide available at: www.aurobindousa.com/medication-guides\n" }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="100%"> <colgroup> <col width="100%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" valign="top"><span class="Bold">MEDICATION GUIDE</span> <br/> <span class="Bold">Pantoprazole sodium</span> <br/> <span class="Bold">(pan toe' pra zole soe' dee um)</span> <br/> <span class="Bold">for delayed-release oral suspension</span> <br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">What is the most important information I should know about pantoprazole sodium for delayed-release oral suspension? </span><span class="Bold"></span> <br/> <span class="Bold"></span> <br/> <span class="Bold">You should take pantoprazole sodium for delayed-release oral suspension exactly as prescribed, at the lowest dose possible and for the shortest time needed. </span> <br/> <span class="Bold"> Pantoprazole sodium for delayed-release oral suspension may help your acid-related symptoms, but you could still have serious stomach problems. </span>Talk with your doctor. <br/> <br/> <span class="Bold">Pantoprazole sodium for delayed-release oral suspension can cause serious side effects, including: </span> <br/> <ul class="Disc"> <li> <span class="Bold"> A type of kidney problem (acute tubulointerstitial nephritis). </span>Some people who take proton pump inhibitor (PPI) medicines, including pantoprazole sodium for delayed-release oral suspension, may develop a kidney problem called acute tubulointerstitial nephritis that can happen at any time during treatment with pantoprazole sodium for delayed-release oral suspension. Call your doctor right away if you have a decrease in the amount that you urinate or if you have blood in your urine. </li> <li> <span class="Bold">Diarrhea caused by an infection (<span class="Italics">Clostridium difficile</span>) in your intestines</span>. Call your doctor right away if you have watery stools or stomach pain that does not go away. You may or may not have a fever. </li> <li> <span class="Bold">Bone fractures (hip, wrist, or spine)</span>. Bone fractures in the hip, wrist, or spine may happen in people who take multiple daily doses of PPI medicines and for a long period of time (a year or longer). Tell your doctor if you have a bone fracture, especially in the hip, wrist, or spine. </li> <li> <span class="Bold">Certain types of lupus erythematosus. </span>Lupus erythematosus is an autoimmune disorder (the body’s immune cells attack other cells or organs in the body). Some people who take PPI medicines, including pantoprazole sodium for delayed-release oral suspension, may develop certain types of lupus erythematosus or have worsening of the lupus they already have. Call your doctor right away if you have new or worsening joint pain or a rash on your cheeks or arms that gets worse in the sun.</li> <li> <span class="Bold">Low magnesium and other mineral levels in your body </span>can happen in people who have taken pantoprazole sodium for delayed-release oral suspension for at least 3 months. Tell your doctor if you have symptoms of low magnesium levels, including seizures, dizziness, irregular heartbeat, jitteriness, muscle aches or weakness, and spasms of hands, feet or voice. </li> </ul>Talk to your doctor about your risk of these serious side effects.<br/> <br/>Pantoprazole sodium for delayed-release oral suspension can have other serious side effects. See <span class="Bold">“What are the possible side effects of pantoprazole sodium for delayed-release oral suspension?” </span> <br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">What is Pantoprazole sodium </span><span class="Bold">for delayed-release oral suspension? </span> <br/>A prescription medicine called a proton pump inhibitor (PPI) used to reduce the amount of acid in your stomach. <br/> <span class="Bold"> In adults, </span>pantoprazole sodium for delayed-release oral suspension is used for: <br/> <ul class="Disc"> <li>up to 8 weeks for the healing and symptom relief of acid-related damage to the lining of the esophagus (called erosive esophagitis or EE). Your doctor may prescribe another 8 weeks of pantoprazole sodium for delayed-release oral suspension in patients whose EE does not heal. </li> <li>maintaining healing of EE and to help prevent the return of heartburn symptoms caused by GERD. It is not known if pantoprazole sodium for delayed-release oral suspension is safe and effective when used for longer than 12 months for this purpose. </li> <li>the long-term treatment of conditions where your stomach makes too much acid. This includes a rare condition called Zollinger-Ellison Syndrome. </li> </ul> <span class="Bold">In children 5 years of age and older</span>, pantoprazole sodium for delayed-release oral suspension is used for: <br/> <ul class="Disc"> <li>up to 8 weeks for the healing and symptom relief of EE. </li> </ul>It is not known if pantoprazole sodium for delayed-release oral suspension is safe if used longer than 8 weeks in children. <br/> <br/>Pantoprazole sodium for delayed-release oral suspension is not for use in children under 5 years of age. <br/> <br/>It is not known if pantoprazole sodium for delayed-release oral suspension is safe and effective in children for treatment other than EE. <br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">Do not take pantoprazole sodium for delayed-release oral suspension if you are: </span> <br/> <ul class="Disc"> <li>allergic to pantoprazole sodium, any other PPI medicine, or any of the ingredients in pantoprazole sodium for delayed-release oral suspension. See the end of this Medication Guide for a complete list of ingredients. </li> <li>taking a medicine that contains rilpivirine (EDURANT, COMPLERA, ODEFSEY, JULUCA) used to treat HIV-1 (Human Immunodeficiency Virus). </li> </ul> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">Before taking pantoprazole sodium for delayed-release oral suspension, tell your doctor about all of your medical conditions, including if you: </span> <br/> <ul class="Disc"> <li>have low magnesium levels, low calcium levels and low potassium levels in your blood.</li> <li>are pregnant or plan to become pregnant. Pantoprazole sodium for delayed-release oral suspension may harm your unborn baby. Tell your doctor if you become pregnant or think you may be pregnant during treatment with pantoprazole sodium for delayed-release oral suspension. </li> <li>are breastfeeding or plan to breastfeed. Pantoprazole sodium can pass into your breast milk. Talk with your doctor about the best way to feed your baby if you take pantoprazole sodium for delayed-release oral suspension. </li> </ul> <span class="Bold">Tell your doctor about all the medicines you take, </span>including prescription and over-the-counter medicines, vitamins and herbal supplements. <span class="Bold">Especially tell your doctor if you take </span>methotrexate (Otrexup, Rasuvo, Trexall, XATMEP), digoxin (LANOXIN), or a water pill (diuretic).<br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">How should I take Pantoprazole sodium </span><span class="Bold">for delayed-release oral suspension? </span> <br/> <ul class="Disc"> <li>Take pantoprazole sodium for delayed-release oral suspension exactly as prescribed by your doctor. </li> <li> <span class="Bold">Do not split, chew, or crush pantoprazole sodium for oral suspension. </span> <ul class="Disc"> <li>Take pantoprazole sodium for delayed-release oral suspension about 30 minutes before a meal. </li> <li>Pantoprazole sodium for delayed-release oral suspension should <span class="Bold">only </span>be given by mouth mixed in apple juice or applesauce <span class="Bold">or </span>through a nasogastric (NG) tube or gastrostomy tube mixed in apple juice. Do not mix pantoprazole sodium for delayed-release oral suspension in liquids other than apple juice or foods other than applesauce. </li> <li>Do not divide a packet of pantoprazole sodium for delayed-release oral suspension to make a smaller dose. </li> <li>See the <span class="Bold">“Instructions for Use” </span>at the end of this Medication Guide for instructions on how to mix and take pantoprazole sodium for delayed-release oral suspension by mouth in applesauce or apple juice or how to mix and give the suspension through an NG tube or gastrostomy tube mixed in apple juice. </li> </ul> </li> <li> If you miss a dose of pantoprazole sodium for delayed-release oral suspension, take it as soon as possible. If it is almost time for your next dose, do not take the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time. </li> <li>If you take too much pantoprazole sodium, call your doctor or your poison control center at 1-800-222-1222 right away or go to the nearest emergency room.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">What are the possible side effects of pantoprazole sodium for delayed-release oral suspension?   </span> <br/> <span class="Bold"> Pantoprazole sodium for delayed-release oral suspension can cause serious side effects, including: </span> <br/> <ul class="Disc"> <li> <span class="Bold"> See “What is the most important information I should know about pantoprazole sodium for delayed-release oral suspension?” </span> </li> <li> <span class="Bold">Low vitamin B-12 levels </span>in your body can happen in people who have taken pantoprazole sodium for delayed-release oral suspension for a long time (more than 3 years). Tell your doctor if you have symptoms of low vitamin B-12 levels, including shortness of breath, lightheadedness, irregular heartbeat, muscle weakness, pale skin, feeling tired, mood changes, and tingling or numbness in the arms and legs. </li> <li> <span class="Bold">Stomach growths (fundic gland polyps). </span>People who take PPI medicines for a long time have an increased risk of developing a certain type of stomach growths called fundic gland polyps, especially after taking PPI medicines for more than 1 year.</li> <li> <span class="Bold">Severe skin reactions. </span>Pantoprazole sodium for delayed-release oral suspension can cause rare but severe skin reactions that may affect any part of your body. These serious skin reactions may need to be treated in a hospital and may be life threatening: </li> <li>Skin rash which may have blistering, peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet). </li> <li>You may also have fever, chills, body aches, shortness of breath, or enlarged lymph nodes. </li> </ul>Stop taking pantoprazole sodium for delayed-release oral suspension and call your doctor right away. These symptoms may be the first sign of a severe skin reaction. <br/> <br/> <span class="Bold">The most common side effects of pantoprazole sodium for delayed-release oral suspension in adults include: </span>headache, diarrhea, nausea, stomach-area (abdominal) pain, vomiting, gas, dizziness, and joint pain. <br/> <br/> <span class="Bold">The most common side effects of pantoprazole sodium for delayed-release oral suspension in children include: </span>upper respiratory infection, headache, fever, diarrhea, vomiting, rash, and stomach-area (abdominal) pain. <br/> <br/>These are not all the possible side effects of pantoprazole sodium for delayed-release oral suspension. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. <br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">How should I store pantoprazole sodium for delayed-release oral suspension? </span> <br/>Store pantoprazole sodium for delayed-release oral suspension at room temperature between 68°F to 77°F (20°C to 25°C). <br/> <br/> <span class="Bold"> Keep pantoprazole sodium for delayed-release oral suspension and all medicines out of the reach of children. </span> <br/> </td> </tr> <tr class="Botrule"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold">General information about the safe and effective use of pantoprazole sodium for delayed-release oral suspension. </span> <br/>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use pantoprazole sodium for delayed-release oral suspension for a condition for which it was not prescribed. Do not give pantoprazole sodium for delayed-release oral suspension to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about pantoprazole sodium for delayed-release oral suspension that is written for health professionals. <br/> </td> </tr> <tr class="Last"> <td align="justify" class="Lrule Rrule" valign="top"><span class="Bold"> What are the ingredients in pantoprazole sodium for delayed-release oral suspension? </span> <br/> <span class="Bold"> Active ingredient: </span>pantoprazole sodium <br/> <span class="Bold"> Inactive ingredients in pantoprazole sodium for delayed-release oral suspension: </span>crospovidone, hypromellose, methacrylic acid and ethyl acrylate copolymer dispersion (contains copolymer based on ethyl acrylate and methacrylic acid, polysorbate 80 and sodium lauryl sulfate), microcrystalline cellulose, polysorbate 80, sodium carbonate (anhydrous), sodium lauryl sulfate, talc, titanium dioxide, triethyl citrate, and yellow iron oxide.<br/> <br/>For more information, call Aurobindo Pharma USA, Inc. at 1-866-850-2876.<br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"100%\">\n<colgroup>\n<col width=\"100%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">MEDICATION GUIDE</span>\n<br/>\n<span class=\"Bold\">Pantoprazole sodium</span>\n<br/>\n<span class=\"Bold\">(pan toe' pra zole soe' dee um)</span>\n<br/>\n<span class=\"Bold\">for delayed-release oral suspension</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">What is the most important information I should know about pantoprazole sodium for delayed-release oral suspension? </span><span class=\"Bold\"></span>\n<br/>\n<span class=\"Bold\"></span>\n<br/>\n<span class=\"Bold\">You should take pantoprazole sodium for delayed-release oral suspension exactly as prescribed, at the lowest dose possible and for the shortest time needed. </span>\n<br/>\n<span class=\"Bold\"> Pantoprazole sodium for delayed-release oral suspension may help your acid-related symptoms, but you could still have serious stomach problems. </span>Talk with your doctor. <br/> <br/>\n<span class=\"Bold\">Pantoprazole sodium for delayed-release oral suspension can cause serious side effects, including: </span>\n<br/>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\"> A type of kidney problem (acute tubulointerstitial nephritis). </span>Some people who take proton pump inhibitor (PPI) medicines, including pantoprazole sodium for delayed-release oral suspension, may develop a kidney problem called acute tubulointerstitial nephritis that can happen at any time during treatment with pantoprazole sodium for delayed-release oral suspension. Call your doctor right away if you have a decrease in the amount that you urinate or if you have blood in your urine. </li>\n<li>\n<span class=\"Bold\">Diarrhea caused by an infection (<span class=\"Italics\">Clostridium difficile</span>) in your intestines</span>. Call your doctor right away if you have watery stools or stomach pain that does not go away. You may or may not have a fever. </li>\n<li>\n<span class=\"Bold\">Bone fractures (hip, wrist, or spine)</span>. Bone fractures in the hip, wrist, or spine may happen in people who take multiple daily doses of PPI medicines and for a long period of time (a year or longer). Tell your doctor if you have a bone fracture, especially in the hip, wrist, or spine. </li>\n<li>\n<span class=\"Bold\">Certain types of lupus erythematosus. </span>Lupus erythematosus is an autoimmune disorder (the body’s immune cells attack other cells or organs in the body). Some people who take PPI medicines, including pantoprazole sodium for delayed-release oral suspension, may develop certain types of lupus erythematosus or have worsening of the lupus they already have. Call your doctor right away if you have new or worsening joint pain or a rash on your cheeks or arms that gets worse in the sun.</li>\n<li>\n<span class=\"Bold\">Low magnesium and other mineral levels in your body </span>can happen in people who have taken pantoprazole sodium for delayed-release oral suspension for at least 3 months. Tell your doctor if you have symptoms of low magnesium levels, including seizures, dizziness, irregular heartbeat, jitteriness, muscle aches or weakness, and spasms of hands, feet or voice. </li>\n</ul>Talk to your doctor about your risk of these serious side effects.<br/> <br/>Pantoprazole sodium for delayed-release oral suspension can have other serious side effects. See <span class=\"Bold\">“What are the possible side effects of pantoprazole sodium for delayed-release oral suspension?” </span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">What is Pantoprazole sodium </span><span class=\"Bold\">for delayed-release oral suspension? </span>\n<br/>A prescription medicine called a proton pump inhibitor (PPI) used to reduce the amount of acid in your stomach. <br/>\n<span class=\"Bold\"> In adults, </span>pantoprazole sodium for delayed-release oral suspension is used for: <br/>\n<ul class=\"Disc\">\n<li>up to 8 weeks for the healing and symptom relief of acid-related damage to the lining of the esophagus (called erosive esophagitis or EE). Your doctor may prescribe another 8 weeks of pantoprazole sodium for delayed-release oral suspension in patients whose EE does not heal. </li>\n<li>maintaining healing of EE and to help prevent the return of heartburn symptoms caused by GERD. It is not known if pantoprazole sodium for delayed-release oral suspension is safe and effective when used for longer than 12 months for this purpose. </li>\n<li>the long-term treatment of conditions where your stomach makes too much acid. This includes a rare condition called Zollinger-Ellison Syndrome. </li>\n</ul>\n<span class=\"Bold\">In children 5 years of age and older</span>, pantoprazole sodium for delayed-release oral suspension is used for: <br/>\n<ul class=\"Disc\">\n<li>up to 8 weeks for the healing and symptom relief of EE. </li>\n</ul>It is not known if pantoprazole sodium for delayed-release oral suspension is safe if used longer than 8 weeks in children. <br/> <br/>Pantoprazole sodium for delayed-release oral suspension is not for use in children under 5 years of age. <br/> <br/>It is not known if pantoprazole sodium for delayed-release oral suspension is safe and effective in children for treatment other than EE. <br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">Do not take pantoprazole sodium for delayed-release oral suspension if you are: </span>\n<br/>\n<ul class=\"Disc\">\n<li>allergic to pantoprazole sodium, any other PPI medicine, or any of the ingredients in pantoprazole sodium for delayed-release oral suspension. See the end of this Medication Guide for a complete list of ingredients. </li>\n<li>taking a medicine that contains rilpivirine (EDURANT, COMPLERA, ODEFSEY, JULUCA) used to treat HIV-1 (Human Immunodeficiency Virus). </li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">Before taking pantoprazole sodium for delayed-release oral suspension, tell your doctor about all of your medical conditions, including if you: </span>\n<br/>\n<ul class=\"Disc\">\n<li>have low magnesium levels, low calcium levels and low potassium levels in your blood.</li>\n<li>are pregnant or plan to become pregnant. Pantoprazole sodium for delayed-release oral suspension may harm your unborn baby. Tell your doctor if you become pregnant or think you may be pregnant during treatment with pantoprazole sodium for delayed-release oral suspension. </li>\n<li>are breastfeeding or plan to breastfeed. Pantoprazole sodium can pass into your breast milk. Talk with your doctor about the best way to feed your baby if you take pantoprazole sodium for delayed-release oral suspension. </li>\n</ul>\n<span class=\"Bold\">Tell your doctor about all the medicines you take, </span>including prescription and over-the-counter medicines, vitamins and herbal supplements. <span class=\"Bold\">Especially tell your doctor if you take </span>methotrexate (Otrexup, Rasuvo, Trexall, XATMEP), digoxin (LANOXIN), or a water pill (diuretic).<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">How should I take Pantoprazole sodium </span><span class=\"Bold\">for delayed-release oral suspension? </span>\n<br/>\n<ul class=\"Disc\">\n<li>Take pantoprazole sodium for delayed-release oral suspension exactly as prescribed by your doctor. </li>\n<li>\n<span class=\"Bold\">Do not split, chew, or crush pantoprazole sodium for oral suspension. </span>\n<ul class=\"Disc\">\n<li>Take pantoprazole sodium for delayed-release oral suspension about 30 minutes before a meal. </li>\n<li>Pantoprazole sodium for delayed-release oral suspension should <span class=\"Bold\">only </span>be given by mouth mixed in apple juice or applesauce <span class=\"Bold\">or </span>through a nasogastric (NG) tube or gastrostomy tube mixed in apple juice. Do not mix pantoprazole sodium for delayed-release oral suspension in liquids other than apple juice or foods other than applesauce. </li>\n<li>Do not divide a packet of pantoprazole sodium for delayed-release oral suspension to make a smaller dose. </li>\n<li>See the <span class=\"Bold\">“Instructions for Use” </span>at the end of this Medication Guide for instructions on how to mix and take pantoprazole sodium for delayed-release oral suspension by mouth in applesauce or apple juice or how to mix and give the suspension through an NG tube or gastrostomy tube mixed in apple juice. </li>\n</ul>\n</li>\n<li> If you miss a dose of pantoprazole sodium for delayed-release oral suspension, take it as soon as possible. If it is almost time for your next dose, do not take the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time. </li>\n<li>If you take too much pantoprazole sodium, call your doctor or your poison control center at 1-800-222-1222 right away or go to the nearest emergency room.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">What are the possible side effects of pantoprazole sodium for delayed-release oral suspension?   </span>\n<br/>\n<span class=\"Bold\"> Pantoprazole sodium for delayed-release oral suspension can cause serious side effects, including: </span>\n<br/>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\"> See “What is the most important information I should know about pantoprazole sodium for delayed-release oral suspension?” </span>\n</li>\n<li>\n<span class=\"Bold\">Low vitamin B-12 levels </span>in your body can happen in people who have taken pantoprazole sodium for delayed-release oral suspension for a long time (more than 3 years). Tell your doctor if you have symptoms of low vitamin B-12 levels, including shortness of breath, lightheadedness, irregular heartbeat, muscle weakness, pale skin, feeling tired, mood changes, and tingling or numbness in the arms and legs. </li>\n<li>\n<span class=\"Bold\">Stomach growths (fundic gland polyps). </span>People who take PPI medicines for a long time have an increased risk of developing a certain type of stomach growths called fundic gland polyps, especially after taking PPI medicines for more than 1 year.</li>\n<li>\n<span class=\"Bold\">Severe skin reactions. </span>Pantoprazole sodium for delayed-release oral suspension can cause rare but severe skin reactions that may affect any part of your body. These serious skin reactions may need to be treated in a hospital and may be life threatening: </li>\n<li>Skin rash which may have blistering, peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet). </li>\n<li>You may also have fever, chills, body aches, shortness of breath, or enlarged lymph nodes. </li>\n</ul>Stop taking pantoprazole sodium for delayed-release oral suspension and call your doctor right away. These symptoms may be the first sign of a severe skin reaction. <br/> <br/>\n<span class=\"Bold\">The most common side effects of pantoprazole sodium for delayed-release oral suspension in adults include: </span>headache, diarrhea, nausea, stomach-area (abdominal) pain, vomiting, gas, dizziness, and joint pain. <br/> <br/>\n<span class=\"Bold\">The most common side effects of pantoprazole sodium for delayed-release oral suspension in children include: </span>upper respiratory infection, headache, fever, diarrhea, vomiting, rash, and stomach-area (abdominal) pain. <br/> <br/>These are not all the possible side effects of pantoprazole sodium for delayed-release oral suspension. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. <br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">How should I store pantoprazole sodium for delayed-release oral suspension? </span>\n<br/>Store pantoprazole sodium for delayed-release oral suspension at room temperature between 68°F to 77°F (20°C to 25°C). <br/> <br/>\n<span class=\"Bold\"> Keep pantoprazole sodium for delayed-release oral suspension and all medicines out of the reach of children. </span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\">General information about the safe and effective use of pantoprazole sodium for delayed-release oral suspension. </span>\n<br/>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use pantoprazole sodium for delayed-release oral suspension for a condition for which it was not prescribed. Do not give pantoprazole sodium for delayed-release oral suspension to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about pantoprazole sodium for delayed-release oral suspension that is written for health professionals. <br/>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"justify\" class=\"Lrule Rrule\" valign=\"top\"><span class=\"Bold\"> What are the ingredients in pantoprazole sodium for delayed-release oral suspension? </span>\n<br/>\n<span class=\"Bold\"> Active ingredient: </span>pantoprazole sodium <br/>\n<span class=\"Bold\"> Inactive ingredients in pantoprazole sodium for delayed-release oral suspension: </span>crospovidone, hypromellose, methacrylic acid and ethyl acrylate copolymer dispersion (contains copolymer based on ethyl acrylate and methacrylic acid, polysorbate 80 and sodium lauryl sulfate), microcrystalline cellulose, polysorbate 80, sodium carbonate (anhydrous), sodium lauryl sulfate, talc, titanium dioxide, triethyl citrate, and yellow iron oxide.<br/> <br/>For more information, call Aurobindo Pharma USA, Inc. at 1-866-850-2876.<br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

The brands listed are trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited. This Medication Guide has been approved by the U.S. Food and Drug Administration. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Issued: January 2024

{ "type": "p", "children": [], "text": "The brands listed are trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited.\n This Medication Guide has been approved by the U.S. Food and Drug Administration.\n Distributed by:\nAurobindo Pharma USA, Inc.\n279 Princeton-Hightstown Road East Windsor, NJ 08520\n Manufactured by:\nAurobindo Pharma Limited\nHyderabad-500 032, India\n Issued: January 2024" }

Instructions for Use

{ "type": "p", "children": [], "text": "\nInstructions for Use\n" }

Pantoprazole sodium

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

(pan toe' pra zole soe' dee um)

{ "type": "p", "children": [], "text": "\n(pan toe' pra zole soe' dee um)\n" }

for delayed-release oral suspension

{ "type": "p", "children": [], "text": "\nfor delayed-release oral suspension\n" }

Pantoprazole sodium for delayed-release oral suspension:

{ "type": "p", "children": [], "text": "\nPantoprazole sodium for delayed-release oral suspension: \n" }

Important information:

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

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Taking pantoprazole sodium for delayed-release oral suspension with applesauce:

{ "type": "p", "children": [], "text": "\nTaking pantoprazole sodium for delayed-release oral suspension with applesauce: \n" }

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

Taking pantoprazole sodium for delayed-release oral suspension with apple juice:

{ "type": "p", "children": [], "text": "\nTaking pantoprazole sodium for delayed-release oral suspension with apple juice: \n" }

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

Giving pantoprazole sodium for delayed-release oral suspension through a nasogastric (NG) tube or gastrostomy tube:

{ "type": "p", "children": [], "text": "\nGiving pantoprazole sodium for delayed-release oral suspension through a nasogastric (NG) tube or gastrostomy tube: \n" }

{ "type": "ul", "children": [ " Pantoprazole sodium for delayed-release oral suspension may be given through an NG tube or gastrostomy tube that is size 16 French or larger. Do not give pantoprazole sodium for delayed-release oral suspension through an NG tube or gastrostomy tube smaller than size 16 French. ", " Mix pantoprazole sodium for delayed-release oral suspension only in apple juice when giving through an NG tube or gastrostomy tube. " ], "text": "" }

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

How should I store pantoprazole sodium for delayed-release oral suspension?

{ "type": "p", "children": [], "text": "\nHow should I store pantoprazole sodium for delayed-release oral suspension?\n" }

Store pantoprazole sodium for delayed-release oral suspension at room temperature between 68°F to 77°F (20°C to 25°C).

{ "type": "p", "children": [], "text": "Store pantoprazole sodium for delayed-release oral suspension at room temperature between 68°F to 77°F (20°C to 25°C). " }

Keep pantoprazole sodium for delayed-release oral suspension and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep pantoprazole sodium for delayed-release oral suspension and all medicines out of the reach of children. \n" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Issued: January 2024

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration.\n Distributed by:\nAurobindo Pharma USA, Inc.\n279 Princeton-Hightstown Road East Windsor, NJ 08520\n Manufactured by:\nAurobindo Pharma Limited\nHyderabad-500 032, India\n Issued: January 2024" }

Rx only

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

               NDC 59651-671-22

{ "type": "p", "children": [], "text": "               NDC 59651-671-22" }

Pantoprazole Sodium For Delayed-Release Oral Suspension* 40 mg *suspension in apple juice or applesauce only

{ "type": "p", "children": [], "text": "\nPantoprazole Sodium For Delayed-Release Oral Suspension* 40 mg\n*suspension in apple juice or applesauce only" }

PHARMACIST: Dispense the Medication Guide provided separately to each patient.

{ "type": "p", "children": [], "text": "\nPHARMACIST: Dispense the Medication Guide provided separately to each patient.\n" }

AUROBINDO

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

NDC 59651-671-30 Rx only Pantoprazole Sodium For Delayed-Release Oral Suspension* 40 mg

{ "type": "p", "children": [], "text": "NDC 59651-671-30\n\nRx only\n\n\nPantoprazole Sodium For Delayed-Release Oral Suspension* 40 mg\n" }

*suspension in apple juice or applesauce only

{ "type": "p", "children": [], "text": "*suspension in apple juice or applesauce only" }

PHARMACIST: Dispense the Medication Guide provided separately to each patient.

{ "type": "p", "children": [], "text": "\nPHARMACIST: Dispense the Medication Guide provided separately to each patient.\n" }

AUROBINDO         30 Packets

{ "type": "p", "children": [], "text": "\nAUROBINDO         30 Packets\n\n\n" }

Pantoprazole sodium for delayed-release oral suspension is indicated in adults and pediatric patients five years of age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis (EE). For those adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium for delayed-release oral suspension may be considered. Safety of treatment beyond 8 weeks in pediatric patients has not been established.

Pantoprazole sodium for delayed-release oral suspension is indicated for maintenance of healing of EE and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with GERD. Controlled studies did not extend beyond 12 months. 

Pantoprazole sodium for delayed-release oral suspension is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison (ZE) Syndrome.

Pantoprazole sodium is supplied as delayed-release granules in packets for preparation of oral suspensions. The recommended dosages are outlined in Table 1.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: Recommended Dosing Schedule for Pantoprazole Sodium for Delayed-Release Oral Suspension</span> </caption> <col align="left" valign="middle" width="34%"/> <col align="left" valign="middle" width="33%"/> <col align="left" valign="middle" width="33%"/> <thead> <tr class="First Last"> <th align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Indication</span></th><th align="center" class="Botrule Rrule Toprule"><span class="Bold">Dose</span></th><th align="center" class="Botrule Rrule Toprule"><span class="Bold">Frequency</span></th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Short-Term Treatment of Erosive Esophagitis Associated With GERD</span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">Adults</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">40 mg</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Once daily for up to 8 weeks*</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Children (5 years and older)</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">≥ 40 kg</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">40 mg</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Once daily for up to 8 weeks</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Maintenance of Healing of Erosive Esophagitis</span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">Adults</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">40 mg</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Once Daily***</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome</span> </p> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">Adults</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">40 mg</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Twice Daily**</p> </td> </tr> </tbody> </table></div>

*      For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium for delayed-release oral suspension may be considered.

**   Dosage regimens should be adjusted to individual patient needs and should continue for as long as clinically indicated. Doses up to 240 mg daily have been administered.

*** Controlled studies did not extend beyond 12 months

Directions for method of administration are presented in Table 2.

<div class="scrollingtable"><table class="Noautorules" width="634"> <caption> <span> Table 2: Administration Instructions</span> </caption> <col width="170"/> <col width="113"/> <col width="351"/> <tfoot> <tr> <td align="left" colspan="3"> <p class="First Footnote">* Do not split, chew, or crush pantoprazole sodium for delayed-release oral suspension. </p> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold"> Formulation</span> <br/> </td><td align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> Route</span> <br/> </td><td align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> Instructions*</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold"> For Delayed-Release Oral Suspension</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Oral<br/> </td><td align="left" class="Botrule Rrule" valign="top"> Administered in 1 teaspoonful of applesauce or apple juice approximately 30 minutes prior to a meal<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold"> For Delayed-Release Oral Suspension</span> <br/> </td><td align="left" class="Botrule Rrule" valign="top"> Nasogastric tube<br/> </td><td align="left" class="Botrule Rrule" valign="top"> See instructions below<br/> </td> </tr> </tbody> </table></div>

Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and take the next dose at the regular scheduled time. Do not take 2 doses at the same time.

Pantoprazole Sodium For Delayed-Release Oral Suspension

Administer pantoprazole sodium for delayed-release oral suspension approximately 30 minutes prior to a meal via oral administration in apple juice or applesauce or nasogastric tube in apple juice only. Because proper pH is necessary for stability, do not administer pantoprazole sodium for delayed-release oral suspension in liquids other than apple juice, or foods other than applesauce.

Do not divide the 40 mg pantoprazole sodium for delayed-release oral suspension packet to create a 20 mg dosage for pediatric patients who are unable to take the tablet formulation.

Pantoprazole Sodium For Delayed-Release Oral Suspension - Oral Administration in Applesauce

Pantoprazole Sodium For Delayed-Release Oral Suspension - Oral Administration in Apple Juice

Pantoprazole Sodium For Delayed-Release Oral Suspension - Nasogastric (NG) Tube or Gastrostomy Tube Administration

For patients who have a nasogastric tube or gastrostomy tube in place, pantoprazole sodium for delayed-release oral suspension can be given as follows:

For Delayed-Release Oral Suspension:

{ "type": "p", "children": [], "text": "\nFor Delayed-Release Oral Suspension: " }

{ "type": "ul", "children": [ "40 mg pantoprazole USP, off-white to pale yellowish to greyish brown, enteric-coated granules in a unit dose packets" ], "text": "" }

{ "type": "ul", "children": [ "Pantoprazole sodium for delayed-release oral suspension is contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions (5.2), Adverse Reactions (6)] .", "Proton pump inhibitors (PPIs), including pantoprazole sodium for delayed-release oral suspension, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions (7)] ." ], "text": "" }

In adults, symptomatic response to therapy with pantoprazole sodium for delayed-release oral suspension does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy. 

Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue pantoprazole sodium for delayed-release oral suspension and evaluate patients with suspected acute TIN [see Contraindications (4)].

Published observational studies suggest that PPI therapy like pantoprazole may be associated with an increased risk of Clostridium difficile associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.2)].

Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.

Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2), Adverse Reactions (6.2)].

Severe cutaneous adverse reactions, including erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs [see Adverse Reactions (6.2)]. Discontinue pantoprazole at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including pantoprazole sodium. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematous cases were CLE.

The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement.

Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported.

Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving pantoprazole, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g. ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations.

Generally, daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (Vitamin B-12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, and in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2)].

Consider monitoring magnesium and calcium levels prior to initiation of pantoprazole and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium as necessary. If hypocalcemia is refractory to treatment, consider discontinuing the PPI.

Due to the chronic nature of GERD, there may be a potential for prolonged administration of pantoprazole. In long-term rodent studies, pantoprazole was carcinogenic and caused rare types of gastrointestinal tumors. The relevance of these findings to tumor development in humans is unknown [see Nonclinical Toxicology (13.1)].

PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated.

Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop pantoprazole sodium for delayed-release oral suspension treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary [see Clinical Pharmacology (12.2)].

There have been reports of false-positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including pantoprazole [see Drug Interactions (7)].

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions (7)].

The adverse reaction profiles for pantoprazole sodium for delayed-release oral suspension and pantoprazole sodium delayed-release tablets are similar.

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 clinical practice.

Adults

Safety in nine randomized comparative US clinical trials in patients with GERD included 1,473 patients on oral pantoprazole (20 mg or 40 mg), 299 patients on an H2-receptor antagonist, 46 patients on another PPI, and 82 patients on placebo. The most frequently occurring adverse reactions are listed in Table 3.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 3: Adverse Reactions Reported in Clinical Trials of Adult Patients with GERD at a Frequency of &gt;2%</span> </caption> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <thead> <tr class="First Last"> <td align="left" class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Pantoprazole</span> </p> <p> <span class="Bold">(n=1473)</span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Comparators</span> </p> <p> <span class="Bold">(n=345)</span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">(n=82)</span> </p> <p> <span class="Bold">%</span> </p> </td> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Headache</span> </p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">12.2</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">12.8</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">8.5</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> <p class="First"> <span class="Bold">Diarrhea</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">8.8</p> </td><td align="center" class="Botrule Rrule"> <p class="First">9.6</p> </td><td align="center" class="Botrule Rrule"> <p class="First">4.9</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> <p class="First"> <span class="Bold">Nausea</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">7.0</p> </td><td align="center" class="Botrule Rrule"> <p class="First">5.2</p> </td><td align="center" class="Botrule Rrule"> <p class="First">9.8</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> <p class="First"> <span class="Bold">Abdominal pain</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">6.2</p> </td><td align="center" class="Botrule Rrule"> <p class="First">4.1</p> </td><td align="center" class="Botrule Rrule"> <p class="First">6.1</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> <p class="First"> <span class="Bold">Vomiting</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">4.3</p> </td><td align="center" class="Botrule Rrule"> <p class="First">3.5</p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.4</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> <p class="First"> <span class="Bold">Flatulence</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">3.9</p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.9</p> </td><td align="center" class="Botrule Rrule"> <p class="First">3.7</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> <p class="First"> <span class="Bold">Dizziness</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">3.0</p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.9</p> </td><td align="center" class="Botrule Rrule"> <p class="First">1.2</p> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule"> <p class="First"> <span class="Bold">Arthralgia</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.8</p> </td><td align="center" class="Botrule Rrule"> <p class="First">1.4</p> </td><td align="center" class="Botrule Rrule"> <p class="First">1.2</p> </td> </tr> </tbody> </table></div>

Additional adverse reactions that were reported for pantoprazole in clinical trials with a frequency of ≤2% are listed below by body system:

Body as a Whole: allergic reaction, pyrexia, photosensitivity reaction, facial edema

Gastrointestinal: constipation, dry mouth, hepatitis

Hematologic: leukopenia, thrombocytopenia

Metabolic/Nutritional: elevated CK (creatine kinase), generalized edema, elevated triglycerides, liver enzymes elevated

Musculoskeletal: myalgia

Nervous: depression, vertigo

Skin and Appendages: urticaria, rash, pruritus

Special Senses: blurred vision

Pediatric Patients

Safety of pantoprazole in the treatment of EE associated with GERD was evaluated in pediatric patients ages 1 year through 16 years in three clinical trials. Safety trials involved pediatric patients with EE; however, as EE is uncommon in the pediatric population, 249 pediatric patients with endoscopically-proven or symptomatic GERD were also evaluated. All adult adverse reactions to pantoprazole are considered relevant to pediatric patients. In patients ages 1 year through 16 years, the most commonly reported (>4%) adverse reactions include: URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain. 

For safety information in patients less than 1 year of age see Use in Specific Populations (8.4).

Additional adverse reactions that were reported for pantoprazole in pediatric patients in clinical trials with a frequency of ≤4% are listed below by body system: 

Body as a Whole: allergic reaction, facial edema

Gastrointestinal: constipation, flatulence, nausea

Metabolic/Nutritional: elevated triglycerides, elevated liver enzymes, elevated CK (creatine kinase)

Musculoskeletal: arthralgia, myalgia

Nervous: dizziness, vertigo

Skin and Appendages: urticaria 

The following adverse reactions seen in adults in clinical trials were not reported in pediatric patients in clinical trials, but are considered relevant to pediatric patients: photosensitivity reaction, dry mouth, hepatitis, thrombocytopenia, generalized edema, depression, pruritus, leukopenia, and blurred vision.

Zollinger-Ellison (ZE) Syndrome

In clinical studies of ZE Syndrome, adverse reactions reported in 35 patients taking pantoprazole 80 mg/day to 240 mg/day for up to 2 years were similar to those reported in adult patients with GERD.

The following adverse reactions have been identified during postapproval use of pantoprazole. 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.

These adverse reactions are listed below by body system:

Gastrointestinal Disorders: fundic gland polyps

General Disorders and Administration Conditions: asthenia, fatigue, malaise

Hematologic: pancytopenia, agranulocytosis

Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure

Immune System Disorders: anaphylaxis (including anaphylactic shock), systemic lupus erythematosus

Infections and Infestations: Clostridium difficile associated diarrhea

Investigations: weight changes

Metabolism and Nutritional Disorders: hypomagnesemia, hypocalcemia, hypokalemia, hyponatremia

Musculoskeletal Disorders: rhabdomyolysis, bone fracture 

Nervous: ageusia, dysgeusia

Psychiatric Disorders: hallucination, confusion, insomnia, somnolence

Renal and Genitourinary Disorders: acute tubulointerstitial nephritis, erectile dysfunction

Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions (some fatal), including erythema multiforme, SJS/TEN, DRESS, AGEP, angioedema (Quincke's edema) and cutaneous lupus erythematosus

Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with pantoprazole and instructions for preventing or managing them.

{ "type": "p", "children": [], "text": "Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with pantoprazole and instructions for preventing or managing them. " }

Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.

{ "type": "p", "children": [], "text": "Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. " }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 4: Clinically Relevant Interactions Affecting Drugs Co-Administered with Pantoprazole and Interactions with Diagnostics</span> </caption> <col align="left" valign="middle" width="34%"/> <col align="left" valign="middle" width="33%"/> <col align="left" valign="middle" width="33%"/> <thead align="center"> <tr class="Last"> <th align="left" class="Botrule Lrule Rrule Toprule" colspan="3"><span class="Bold">Antiretrovirals</span></th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Italics">Clinical Impact:</span> </p> </td><td align="left" class="Botrule Rrule Toprule" valign="top"> <p class="First">The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. </p> <p> </p> <ul class="Disc"> <li>Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with pantoprazole may reduce antiviral effect and promote the development of drug resistance. </li> <li>Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with pantoprazole may increase toxicity of the antiretroviral drugs<span class="Italics">. </span> </li> <li>There are other antiretroviral drugs which do not result in clinically relevant interactions with pantoprazole. </li> </ul> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Italics">Intervention: </span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Rilpivirine-containing products: Concomitant use with pantoprazole is contraindicated <span class="Italics">[see Contraindications (</span><span class="Italics Underline"><a href="#ID33">4</a></span><span class="Italics">)]</span> . See prescribing information. <br/>Atazanavir: See prescribing information for atazanavir for dosing information. <br/>Nelfinavir: Avoid concomitant use with pantoprazole. See prescribing information for nelfinavir. <br/>Saquinavir: See the prescribing information for saquinavir and monitor for potential saquinavir toxicities. <br/>Other antiretrovirals: See prescribing information.</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Warfarin</span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Italics">Clinical Impact:</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Increased INR and prothrombin time in patients receiving PPIs, including pantoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Italics">Intervention: </span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin. </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Clopidogrel</span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Italics">Clinical Impact:</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition <span class="Italics">[see Clinical Pharmacology (</span><span class="Italics Underline"><a href="#ID106">12.3</a></span><span class="Italics">)]. </span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Italics">Intervention: </span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">No dose adjustment of clopidogrel is necessary when administered with an approved dose of pantoprazole.</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Methotrexate</span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Italics">Clinical Impact:</span> </p> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top"> <p class="First">Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted <span class="Italics">[see Warnings and Precautions (</span><span class="Italics Underline"><a href="#ID62">5.13</a></span><span class="Italics">)]</span> .</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Italics">Intervention:</span> </p> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top"> <p class="First">A temporary withdrawal of pantoprazole may be considered in some patients receiving high-dose methotrexate. </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole)</span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Italics">Clinical Impact:</span> </p> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top"> <p class="First">Pantoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity.</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Italics">Intervention:</span> </p> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top"> <p class="First">Mycophenolate mofetil (MMF): Co-administration of pantoprazole sodium in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH <span class="Italics">[see Clinical Pharmacology (</span><span class="Italics Underline"><a href="#ID106">12.3</a></span><span class="Italics">)]</span> . The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving pantoprazole and MMF. Use pantoprazole with caution in transplant patients receiving MMF. <br/>See the prescribing information for other drugs dependent on gastric pH for absorption. </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Interactions with Investigations of Neuroendocrine Tumors </span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Italics">Clinical Impact:</span> </p> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top"> <p class="First">CgA levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors <span class="Italics">[see Warnings and Precautions (5.11), Clinical Pharmacology (</span><span class="Italics Underline"><a href="#ID102">12.2</a></span><span class="Italics">)]</span> .</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Italics">Intervention:</span> </p> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top"> <p class="First">Temporarily stop pantoprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary. </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">False Positive Urine Tests for THC</span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Italics">Clinical Impact:</span> </p> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top"> <p class="First">There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs <span class="Italics">[see Warnings and Precautions (</span><span class="Italics Underline"><a href="#ID60">5.12</a></span><span class="Italics">)]</span> .</p> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Italics">Intervention:</span> </p> </td><td align="left" class="Botrule Rrule" colspan="2" valign="top"> <p class="First">An alternative confirmatory method should be considered to verify positive results.</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span>Table 4: Clinically Relevant Interactions Affecting Drugs Co-Administered with Pantoprazole and Interactions with Diagnostics</span>\n</caption>\n<col align=\"left\" valign=\"middle\" width=\"34%\"/>\n<col align=\"left\" valign=\"middle\" width=\"33%\"/>\n<col align=\"left\" valign=\"middle\" width=\"33%\"/>\n<thead align=\"center\">\n<tr class=\"Last\">\n<th align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"3\"><span class=\"Bold\">Antiretrovirals</span></th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Italics\">Clinical Impact:</span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. </p>\n<p> </p>\n<ul class=\"Disc\">\n<li>Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with pantoprazole may reduce antiviral effect and promote the development of drug resistance. </li>\n<li>Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with pantoprazole may increase toxicity of the antiretroviral drugs<span class=\"Italics\">. </span>\n</li>\n<li>There are other antiretroviral drugs which do not result in clinically relevant interactions with pantoprazole. </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Italics\">Intervention: </span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Rilpivirine-containing products: Concomitant use with pantoprazole is contraindicated <span class=\"Italics\">[see Contraindications (</span><span class=\"Italics Underline\"><a href=\"#ID33\">4</a></span><span class=\"Italics\">)]</span> . See prescribing information. <br/>Atazanavir: See prescribing information for atazanavir for dosing information. <br/>Nelfinavir: Avoid concomitant use with pantoprazole. See prescribing information for nelfinavir. <br/>Saquinavir: See the prescribing information for saquinavir and monitor for potential saquinavir toxicities. <br/>Other antiretrovirals: See prescribing information.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Warfarin</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Italics\">Clinical Impact:</span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Increased INR and prothrombin time in patients receiving PPIs, including pantoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. </p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Italics\">Intervention: </span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin. </p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Clopidogrel</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Italics\">Clinical Impact:</span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition <span class=\"Italics\">[see Clinical Pharmacology (</span><span class=\"Italics Underline\"><a href=\"#ID106\">12.3</a></span><span class=\"Italics\">)]. </span> </p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Italics\">Intervention: </span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">No dose adjustment of clopidogrel is necessary when administered with an approved dose of pantoprazole.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Methotrexate</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Italics\">Clinical Impact:</span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted <span class=\"Italics\">[see Warnings and Precautions (</span><span class=\"Italics Underline\"><a href=\"#ID62\">5.13</a></span><span class=\"Italics\">)]</span> .</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Italics\">Intervention:</span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">A temporary withdrawal of pantoprazole may be considered in some patients receiving high-dose methotrexate. </p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole)</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Italics\">Clinical Impact:</span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">Pantoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Italics\">Intervention:</span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">Mycophenolate mofetil (MMF): Co-administration of pantoprazole sodium in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH <span class=\"Italics\">[see Clinical Pharmacology (</span><span class=\"Italics Underline\"><a href=\"#ID106\">12.3</a></span><span class=\"Italics\">)]</span> . The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving pantoprazole and MMF. Use pantoprazole with caution in transplant patients receiving MMF. <br/>See the prescribing information for other drugs dependent on gastric pH for absorption. </p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Interactions with Investigations of Neuroendocrine Tumors </span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Italics\">Clinical Impact:</span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">CgA levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors <span class=\"Italics\">[see Warnings and Precautions (5.11), Clinical Pharmacology (</span><span class=\"Italics Underline\"><a href=\"#ID102\">12.2</a></span><span class=\"Italics\">)]</span> .</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Italics\">Intervention:</span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">Temporarily stop pantoprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary. </p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">False Positive Urine Tests for THC</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Italics\">Clinical Impact:</span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs <span class=\"Italics\">[see Warnings and Precautions (</span><span class=\"Italics Underline\"><a href=\"#ID60\">5.12</a></span><span class=\"Italics\">)]</span> .</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Italics\">Intervention:</span>\n</p>\n</td><td align=\"left\" class=\"Botrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">An alternative confirmatory method should be considered to verify positive results.</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Risk Summary

Available data from published observational studies did not demonstrate an association of major malformations or other adverse pregnancy outcomes with pantoprazole. 

In animal reproduction studies, no evidence of adverse development outcomes was observed with pantoprazole. Reproduction studies have been performed in rats at oral doses up to 450 mg/kg/day (about 88 times the recommended human dose) and rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose) with administration of pantoprazole during organogenesis in pregnant animals and have revealed no evidence of harm to the fetus due to pantoprazole in this study (see Data).

A pre-and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. Oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day) were administered to pregnant females from gestation day (GD) 6 through lactation day (LD) 21. Changes in bone morphology were observed in pups exposed to pantoprazole in utero and through milk during the period of lactation as well as by oral dosing from postnatal day (PND) 4 through PND 21 [see Use in Specific Populations (8.4)]. There were no drug-related findings in maternal animals. Advise pregnant women of the potential risk of fetal harm. 

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

Available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and pantoprazole use. Methodological limitations of these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. In a prospective study by the European Network of Teratology Information Services, outcomes from a group of 53 pregnant women administered median daily doses of 40 mg pantoprazole were compared to a control group of 868 pregnant women who did not take any proton pump inhibitors (PPIs). There was no difference in the rate of major malformations between women exposed to PPIs and the control group, corresponding to a Relative Risk (RR)=0.55, [95% Confidence Interval (CI) 0.08-3.95]. In a population-based retrospective cohort study covering all live births in Denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to pantoprazole in 549 live births. A meta-analysis that compared 1,530 pregnant women exposed to PPIs in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to PPIs (for major malformations OR=1.12 ([95% CI 0.86-1.45] and for spontaneous abortions OR=1.29 [95% CI 0.84-1.97]).

Animal Data

Reproduction studies have been performed in rats at oral pantoprazole doses up to 450 mg/kg/day (about 88 times the recommended human dose based on body surface area) and in rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose based on body surface area) with administration of pantoprazole sodium during organogenesis in pregnant animals. The studies have revealed no evidence of impaired fertility or harm to the fetus due to pantoprazole. 

A pre- and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. Oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day on a body surface area basis) were administered to pregnant females from gestation day (GD) 6 through lactation day (LD) 21. On postnatal day (PND 4) through PND 21, the pups were administered oral doses at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (AUC) in humans at a dose of 40 mg). There were no drug-related findings in maternal animals. During the preweaning dosing phase (PND 4 to 21) of the pups, there were increased mortality and/or moribundity and decreased body weight and body weight gain at 5 mg/kg/day (approximately equal exposures (AUC) in humans receiving the 40 mg dose) and higher doses. On PND 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (AUC) in humans at the 40 mg dose) and higher doses. The femur findings included lower total area, bone mineral content and density, periosteal and endosteal circumference, and cross-sectional moment of inertia. There were no microscopic changes in the distal femur, proximal tibia, or stifle joints. Changes in bone parameters were partially reversible following a recovery period, with findings on PND 70 limited to lower femur metaphysis cortical/subcortical bone mineral density in female pups at 5 mg/kg/day (approximately equal exposures (AUC) in humans at the 40 mg dose) and higher doses.

Risk Summary

Pantoprazole has been detected in breast milk of a nursing mother after a single 40 mg oral dose of pantoprazole. There were no effects on the breastfed infant (see Data). There are no data on pantoprazole effects on milk production.

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

Data

The breast milk of a 42-year-old woman receiving 40 mg of oral pantoprazole, at 10 months postpartum, was studied for 24 hours, to demonstrate low levels of pantoprazole present in the breast milk. Pantoprazole was detectable in milk only 2 and 4 hours after the dose with milk levels of approximately 36 mcg/L and 24 mcg/L, respectively. A milk-to-plasma ratio of 0.022 was observed at 2 hours after drug administration. Pantoprazole was not detectable (<10 mcg/L) in milk at 6, 8 and 24 hours after the dose. The relative dose to the infant was estimated to be 7.3 mcg of pantoprazole, which is equivalent to 0.14% of the weight-adjusted maternal dose. No adverse events in the infant were reported by the mother.

The safety and effectiveness of pantoprazole for short-term treatment (up to eight weeks) of EE associated with GERD have been established in pediatric patients 1 year through 16 years of age. Effectiveness for EE has not been demonstrated in patients less than 1 year of age. In addition, for patients less than 5 years of age, there is no appropriate dosage strength in an age-appropriate formulation available. Therefore, pantoprazole is indicated for the short-term treatment of EE associated with GERD for patients 5 years and older. The safety and effectiveness of pantoprazole for pediatric uses other than EE have not been established.

1 year through 16 years of age

Use of pantoprazole in pediatric patients 1 year through 16 years of age for short-term treatment (up to eight weeks) of EE associated with GERD is supported by: a) extrapolation of results from adequate and well-controlled studies that supported the approval of pantoprazole for treatment of EE associated with GERD in adults, and b) safety, effectiveness, and pharmacokinetic studies performed in pediatric patients [see Clinical Studies (14.1), Clinical Pharmacology (12.3)]. 

Safety of pantoprazole in the treatment of EE associated with GERD in pediatric patients 1 through 16 years of age was evaluated in three multicenter, randomized, double-blind, parallel-treatment studies, involving 249 pediatric patients, including 8 with EE (4 patients ages 1 year to 5 years and 4 patients 5 years to 11 years). The children ages 1 year to 5 years with endoscopically diagnosed EE (defined as an endoscopic Hetzel-Dent score ≥2) were treated once daily for 8 weeks with one of two dose levels of pantoprazole (approximating 0.6 mg/kg or 1.2 mg/kg). All 4 of these patients with EE were healed (Hetzel-Dent score of 0 or 1) at 8 weeks. Because EE is uncommon in the pediatric population, predominantly pediatric patients with endoscopically-proven or symptomatic GERD were also included in these studies. Patients were treated with a range of doses of pantoprazole once daily for 8 weeks. For safety findings see Adverse Reactions (6.1). Because these pediatric trials had no placebo, active comparator, or evidence of a dose response, the trials were inconclusive regarding the clinical benefit of pantoprazole for symptomatic GERD in the pediatric population. The effectiveness of pantoprazole for treating symptomatic GERD in pediatric patients has not been established.

Although the data from the clinical trials support use of pantoprazole for the short-term treatment of EE associated with GERD in pediatric patients 1 year through 5 years, there is no commercially available dosage formulation appropriate for patients less than 5 years of age [see Dosage and Administration (2)].

In a population pharmacokinetic analysis, clearance values in the children 1 to 5 years old with endoscopically proven GERD had a median value of 2.4 L/h. Following a 1.2 mg/kg equivalent dose (15 mg for ≤12.5 kg and 20 mg for >12.5 to <25 kg), the plasma concentrations of pantoprazole were highly variable and the median time to peak plasma concentration was 3 to 6 hours. The estimated AUC for patients 1 to 5 years old was 37% higher than for adults receiving a single 40 mg tablet, with a geometric mean AUC value of 6.8 µg•hr/mL. 

Neonates to less than one year of age

Pantoprazole was not found to be effective in a multicenter, randomized, double-blind, placebo-controlled, treatment-withdrawal study of 129 pediatric patients 1 through 11 months of age. Patients were enrolled if they had symptomatic GERD based on medical history and had not responded to non-pharmacologic interventions for GERD for two weeks. Patients received pantoprazole daily for four weeks in an open-label phase, then patients were randomized in equal proportion to receive pantoprazole treatment or placebo for the subsequent four weeks in a double-blind manner. Efficacy was assessed by observing the time from randomization to study discontinuation due to symptom worsening during the four-week treatment-withdrawal phase. There was no statistically significant difference between pantoprazole and placebo in the rate of discontinuation.

In this trial, the adverse reactions that were reported more commonly (difference of ≥4%) in the treated population compared to the placebo population were elevated CK, otitis media, rhinitis, and laryngitis.

In a population pharmacokinetic analysis, the systemic exposure was higher in patients less than 1 year of age with GERD compared to adults who received a single 40 mg dose (geometric mean AUC was 103% higher in preterm infants and neonates receiving single dose of 2.5 mg of pantoprazole, and 23% higher in infants 1 through 11 months of age receiving a single dose of approximately 1.2 mg/kg). In these patients, the apparent clearance (CL/F) increased with age (median clearance: 0.6 L/hr, range: 0.03 to 3.2 L/hr).

These doses resulted in pharmacodynamic effects on gastric but not esophageal pH. Following once daily dosing of 2.5 mg of pantoprazole in preterm infants and neonates, there was an increase in the mean gastric pH (from 4.3 at baseline to 5.2 at steady-state) and in the mean % time that gastric pH was > 4 (from 60% at baseline to 80% at steady-state). Following once daily dosing of approximately 1.2 mg/kg of pantoprazole in infants 1 through 11 months of age, there was an increase in the mean gastric pH (from 3.1 at baseline to 4.2 at steady-state) and in the mean % time that gastric pH was > 4 (from 32% at baseline to 60% at steady-state). However, no significant changes were observed in mean intraesophageal pH or % time that esophageal pH was <4 in either age group.

Because pantoprazole was not shown to be effective in the randomized, placebo-controlled study in this age group, the use of pantoprazole for treatment of symptomatic GERD in infants less than 1 year of age is not indicated.

Animal Toxicity Data 

In a pre- and post-natal development study in rats, the pups were administered oral doses of pantoprazole at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (AUC) in children aged 6 to 11 years at a dose of 40 mg) on postnatal day (PND 4) through PND 21, in addition to lactational exposure through milk. On PND 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (AUC) in children aged 6 to 11 years at the 40 mg dose) and higher doses. Changes in bone parameters were partially reversible following a recovery period. 

In neonatal/juvenile animals (rats and dogs) toxicities were similar to those observed in adult animals, including gastric alterations, decreases in red cell mass, increases in lipids, enzyme induction and hepatocellular hypertrophy. An increased incidence of eosinophilic chief cells in adult and neonatal/juvenile rats, and atrophy of chief cells in adult rats and in neonatal/juvenile dogs, was observed in the fundic mucosa of stomachs in repeated-dose studies. Full to partial recovery of these effects were noted in animals of both age groups following a recovery period.

In short-term US clinical trials, EE healing rates in the 107 elderly patients (≥65 years old) treated with pantoprazole were similar to those found in patients under the age of 65. The incidence rates of adverse reactions and laboratory abnormalities in patients aged 65 years and older were similar to those associated with patients younger than 65 years of age. 

Experience in patients taking very high doses of pantoprazole (greater than 240 mg) is limited. Spontaneous post-marketing reports of overdose are generally within the known safety profile of pantoprazole.

{ "type": "p", "children": [], "text": "\nExperience in patients taking very high doses of pantoprazole (greater than 240 mg) is limited. Spontaneous post-marketing reports of overdose are generally within the known safety profile of pantoprazole. " }

Pantoprazole is not removed by hemodialysis. In case of overdosage, treatment should be symptomatic and supportive. 

{ "type": "p", "children": [], "text": "Pantoprazole is not removed by hemodialysis. In case of overdosage, treatment should be symptomatic and supportive.  " }

Single oral doses of pantoprazole at 709 mg/kg, 798 mg/kg, and 887 mg/kg were lethal to mice, rats, and dogs, respectively. The symptoms of acute toxicity were hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor.

{ "type": "p", "children": [], "text": "Single oral doses of pantoprazole at 709 mg/kg, 798 mg/kg, and 887 mg/kg were lethal to mice, rats, and dogs, respectively. The symptoms of acute toxicity were hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor. " }

If overexposure to pantoprazole occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage. 

{ "type": "p", "children": [], "text": "If overexposure to pantoprazole occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.  " }

The active ingredient in pantoprazole sodium for delayed-release oral suspension, a PPI, is a substituted benzimidazole, sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl] sulfinyl]-1H-benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its empirical formula is C16H14F2N3NaO4S x 1.5 H2O, with a molecular weight of 432.37. The structural formula is: 

{ "type": "p", "children": [], "text": "\nThe active ingredient in pantoprazole sodium for delayed-release oral suspension, a PPI, is a substituted benzimidazole, sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl] sulfinyl]-1H-benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its empirical formula is C16H14F2N3NaO4S x 1.5 H2O, with a molecular weight of 432.37. The structural formula is:  " }

Pantoprazole sodium sesquihydrate USP is a white to off-white crystalline powder and is racemic. Pantoprazole has weakly basic and acidic properties. Pantoprazole sodium sesquihydrate USP, is freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in n-hexane. 

{ "type": "p", "children": [], "text": "\nPantoprazole sodium sesquihydrate USP is a white to off-white crystalline powder and is racemic. Pantoprazole has weakly basic and acidic properties. Pantoprazole sodium sesquihydrate USP, is freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in n-hexane.  " }

Pantoprazole sodium USP, is supplied as a for delayed-release oral suspension in unit dose packets, available in one strength 40 mg pantoprazole, (equivalent to 45.1 mg of pantoprazole sodium USP). 

{ "type": "p", "children": [], "text": "Pantoprazole sodium USP, is supplied as a for delayed-release oral suspension in unit dose packets, available in one strength 40 mg pantoprazole, (equivalent to 45.1 mg of pantoprazole sodium USP).  " }

Pantoprazole sodium for delayed-release oral suspension, contains the following inactive ingredients: crospovidone, hypromellose, lecithin, macrogol, methacrylic acid and ethyl acrylate copolymer dispersion, microcrystalline cellulose, polysorbate 80, polyvinyl alcohol-part hydrolysed,  sodium carbonate, talc, titanium dioxide, triethyl citrate, and iron oxide yellow. 

{ "type": "p", "children": [], "text": "Pantoprazole sodium for delayed-release oral suspension, contains the following inactive ingredients: crospovidone, hypromellose, lecithin, macrogol, methacrylic acid and ethyl acrylate copolymer dispersion, microcrystalline cellulose, polysorbate 80, polyvinyl alcohol-part hydrolysed,  sodium carbonate, talc, titanium dioxide, triethyl citrate, and iron oxide yellow.  " }

Pantoprazole is a PPI that suppresses the final step in gastric acid production by covalently binding to the (H+, K+)-ATPase enzyme system at the secretory surface of the gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. The binding to the (H+, K+)-ATPase results in a duration of antisecretory effect that persists longer than 24 hours for all doses tested (20 mg to 120 mg). 

Pantoprazole sodium for delayed-release oral suspension, 40 mg has been shown to be comparable to Pantoprazole sodium delayed-release tablets in suppressing pentagastrin-stimulated MAO in patients (n = 49) with GERD and a history of EE. In this multicenter, pharmacodynamic crossover study, a 40 mg oral dose of pantoprazole sodium for delayed-release oral suspension administered in a teaspoonful of applesauce was compared with a 40 mg oral dose of pantoprazole sodium delayed-release tablets after administration of each formulation once daily for 7 days. Both medications were administered thirty minutes before breakfast. Pentagastrin-stimulated (MAO) was assessed from hour 23 to 24 at steady state. 

Antisecretory Activity

Under maximal acid stimulatory conditions using pentagastrin, a dose-dependent decrease in gastric acid output occurs after a single dose of oral (20-80 mg) or a single dose of intravenous (20-120 mg) pantoprazole in healthy subjects. Pantoprazole given once daily results in increasing inhibition of gastric acid secretion. Following the initial oral dose of 40 mg pantoprazole, a 51% mean inhibition was achieved by 2.5 hours. With once-a-day dosing for 7 days, the mean inhibition was increased to 85%. Pantoprazole suppressed acid secretion in excess of 95% in half of the subjects. Acid secretion had returned to normal within a week after the last dose of pantoprazole; there was no evidence of rebound hypersecretion. 

In a series of dose-response studies, pantoprazole, at oral doses ranging from 20 to 120 mg, caused dose-related increases in median basal gastric pH and in the percent of time gastric pH was >3 and >4. Treatment with 40 mg of pantoprazole produced significantly greater increases in gastric pH than the 20 mg dose. Doses higher than 40 mg (60, 80, 120 mg) did not result in further significant increases in median gastric pH. The effects of pantoprazole on median pH from one double-blind crossover study are shown in Table 5. 

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 5: Effect of Single Daily Doses of Oral Pantoprazole on Intragastric pH </span> </caption> <col align="left" valign="middle" width="20%"/> <col align="left" valign="middle" width="20%"/> <col align="left" valign="middle" width="20%"/> <col align="left" valign="middle" width="20%"/> <col align="left" valign="middle" width="20%"/> <thead> <tr class="First Last"> <th align="center" class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">Median pH on day 7</span></th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Time </span> </p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">Placebo</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">20 mg</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">40 mg</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">80 mg</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">8 a.m. -8 a.m.</span> <br/> <span class="Bold">(24 hours)</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">1.3</p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.9*</p> </td><td align="center" class="Botrule Rrule"> <p class="First">3.8*#</p> </td><td align="center" class="Botrule Rrule"> <p class="First">3.9*#</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">8 a.m. -10 p.m. (Daytime)</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">1.6</p> </td><td align="center" class="Botrule Rrule"> <p class="First">3.2*</p> </td><td align="center" class="Botrule Rrule"> <p class="First">4.4*#</p> </td><td align="center" class="Botrule Rrule"> <p class="First">4.8*#</p> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">10 p.m. -8 a.m. (Nighttime)</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">1.2</p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.1*</p> </td><td align="center" class="Botrule Rrule"> <p class="First">3.0*</p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.6*</p> </td> </tr> </tbody> </table></div>

* Significantly different from placebo

# Significantly different from 20 mg

Serum Gastrin Effects

Fasting serum gastrin levels were assessed in two double-blind studies of the acute healing of EE in which 682 patients with gastroesophageal reflux disease (GERD) received 10, 20, or 40 mg of pantoprazole for up to 8 weeks. At 4 weeks of treatment there was an increase in mean gastrin levels of 7%, 35%, and 72% over pretreatment values in the 10, 20, and 40 mg treatment groups, respectively. A similar increase in serum gastrin levels was noted at the 8-week visit with mean increases of 3%, 26%, and 84% for the three pantoprazole dose groups. Median serum gastrin levels remained within normal limits during maintenance therapy with pantoprazole sodium delayed-release tablets. 

In long-term international studies involving over 800 patients, a 2- to 3-fold mean increase from the pretreatment fasting serum gastrin level was observed in the initial months of treatment with pantoprazole at doses of 40 mg per day during GERD maintenance studies and 40 mg or higher per day in patients with refractory GERD. Fasting serum gastrin levels generally remained at approximately 2 to 3 times baseline for up to 4 years of periodic follow-up in clinical trials. 

Following short-term treatment with pantoprazole, elevated gastrin levels return to normal by at least 3 months. 

Enterochromaffin-Like (ECL) Cell Effects

In 39 patients treated with oral pantoprazole 40 mg to 240 mg daily (majority receiving 40 mg to 80 mg) for up to 5 years, there was a moderate increase in ECL-cell density, starting after the first year of use, which appeared to plateau after 4 years. 

In a nonclinical study in Sprague-Dawley rats, lifetime exposure (24 months) to pantoprazole at doses of 0.5 to 200 mg/kg/day resulted in dose-related increases in gastric ECL-cell proliferation and gastric neuroendocrine (NE)-cell tumors. Gastric NE-cell tumors in rats may result from chronic elevation of serum gastrin concentrations. The high density of ECL cells in the rat stomach makes this species highly susceptible to the proliferative effects of elevated gastrin concentrations produced by PPIs. However, there were no observed elevations in serum gastrin following the administration of pantoprazole at a dose of 0.5 mg/kg/day. In a separate study, a gastric NE-cell tumor without concomitant ECL-cell proliferative changes was observed in 1 female rat following 12 months of dosing with pantoprazole at 5 mg/kg/day and a 9 month off-dose recovery [see Nonclinical Toxicology (13.1)]. 

Endocrine Effects

In a clinical pharmacology study, pantoprazole 40 mg given once daily for 2 weeks had no effect on the levels of the following hormones: cortisol, testosterone, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), thyronine-binding protein, parathyroid hormone, insulin, glucagon, renin, aldosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, and growth hormone.

In a 1-year study of GERD patients treated with pantoprazole 40 mg or 20 mg, there were no changes from baseline in overall levels of T3, T4, and TSH.

Pantoprazole sodium delayed-release tablets are prepared as enteric-coated tablets so that absorption of pantoprazole begins only after the tablet leaves the stomach. Peak serum concentration (Cmax) and area under the serum concentration time curve (AUC) increase in a manner proportional to oral and intravenous doses from 10 mg to 80 mg. Pantoprazole does not accumulate, and its pharmacokinetics are unaltered with multiple daily dosing. Following oral or intravenous administration, the serum concentration of pantoprazole declines biexponentially, with a terminal elimination half-life of approximately one hour. 

In extensive metabolizers with normal liver function receiving an oral dose of the enteric-coated 40 mg pantoprazole tablet, the peak concentration (Cmax) is 2.5 mcg/mL; the time to reach the peak concentration (tmax) is 2.5 h, and the mean total area under the plasma concentration versus time curve (AUC) is 4.8 mcg•h/mL (range 1.4 to 13.3 mcg•h/mL). Following intravenous administration of pantoprazole to extensive metabolizers, its total clearance is 7.6-14.0 L/h, and its apparent volume of distribution is 11.0-23.6 L.

A single oral dose of pantoprazole sodium for delayed-release oral suspension, 40 mg, was shown to be bioequivalent when administered to healthy subjects (N = 22) as granules sprinkled over a teaspoonful of applesauce, as granules mixed with apple juice, or mixed with apple juice followed by administration through a nasogastric tube. The plasma pharmacokinetic parameters from a crossover study in healthy subjects are summarized in Table 6. 

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 6: Pharmacokinetics Parameters (mean ± SD) of Pantoprazole Sodium For Delayed-Release Oral Suspension at 40 mg  </span> </caption> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">Pharmacokinetic Parameters</span></th><th align="center" class="Botrule Rrule Toprule"><span class="Bold">Granules in Applesauce</span></th><th align="center" class="Botrule Rrule Toprule"><span class="Bold">Granules in Apple Juice</span></th><th align="center" class="Botrule Rrule Toprule"><span class="Bold">Granules in Nasogastric Tube</span></th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="4" valign="top"> <p class="First"> <span class="Sup">a </span>Median values are reported for T<span class="Sub">max</span>.</p> </td> </tr> </tfoot> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">AUC (mcg•hr/mL)</p> </td><td align="center" class="Botrule Rrule"> <p class="First">4.0 ± 1.5</p> </td><td align="center" class="Botrule Rrule"> <p class="First">4.0 ± 1.5</p> </td><td align="center" class="Botrule Rrule"> <p class="First">4.1 ± 1.7</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">C<span class="Sub">max</span> (mcg/mL)</p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.0 ± 0.7</p> </td><td align="center" class="Botrule Rrule"> <p class="First">1.9 ± 0.5</p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.2 ± 0.7</p> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">T<span class="Sub">max</span> (hr)<span class="Sup">a</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.0</p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.5</p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.0</p> </td> </tr> </tbody> </table></div>

Absorption

After administration of a single or multiple oral 40 mg doses of pantoprazole sodium delayed-release tablets, the peak plasma concentration of pantoprazole was achieved in approximately 2.5 hours, and Cmax was 2.5 mcg/mL. Pantoprazole undergoes little first-pass metabolism, resulting in an absolute bioavailability of approximately 77%. Pantoprazole absorption is not affected by concomitant administration of antacids.

Administration of pantoprazole sodium delayed-release tablets with food may delay its absorption up to 2 hours or longer; however, the Cmax and the extent of pantoprazole absorption (AUC) are not altered. Thus, pantoprazole sodium delayed-release tablets may be taken without regard to timing of meals.

Administration of pantoprazole granules, 40 mg, with a high-fat meal delayed median time to peak plasma concentration by 2 hours. With a concomitant high-fat meal, the Cmax and AUC of pantoprazole granules, 40 mg, sprinkled on applesauce decreased by 51% and 29%, respectively. Thus, pantoprazole sodium for delayed-release oral suspension should be taken approximately 30 minutes before a meal.

Distribution

The apparent volume of distribution of pantoprazole is approximately 11 to 23.6 L, distributing mainly in extracellular fluid. The serum protein binding of pantoprazole is about 98%, primarily to albumin. 

Elimination 

Metabolism

Pantoprazole is extensively metabolized in the liver through the cytochrome P450 (CYP) system. Pantoprazole metabolism is independent of the route of administration (intravenous or oral). The main metabolic pathway is demethylation, by CYP2C19, with subsequent sulfation; other metabolic pathways include oxidation by CYP3A4. There is no evidence that any of the pantoprazole metabolites have significant pharmacologic activity. 

Excretion

After a single oral or intravenous dose of 14C-labeled pantoprazole to healthy, normal metabolizer subjects, approximately 71% of the dose was excreted in the urine, with 18% excreted in the feces through biliary excretion. There was no renal excretion of unchanged pantoprazole. 

Specific Populations

Geriatric Patients

Only slight to moderate increases in the AUC (43%) and Cmax (26%) of pantoprazole were found in elderly subjects (64 to 76 years of age) after repeated oral administration, compared with younger subjects [see Use in Specific Populations (8.5)]. 

Pediatric Patients

The pharmacokinetics of pantoprazole were studied in children less than 16 years of age in four randomized, open-label clinical trials in pediatric patients with presumed/proven GERD. A pediatric granule formulation was studied in children through 5 years of age, and pantoprazole sodium delayed-release tablets were studied in children older than 5 years. 

In a population PK analysis, total clearance increased with increasing bodyweight in a non-linear fashion. The total clearance also increased with increasing age only in children under 3 years of age.

Neonate through 5 Years of Age [see Use in Specific Populations (8.4)]

Children and Adolescents 6 through 16 Years of Age 

The pharmacokinetics of pantoprazole sodium delayed-release tablets were evaluated in children ages 6 through 16 years with a clinical diagnosis of GERD. The PK parameters following a single oral dose of 20 mg or 40 mg of pantoprazole sodium delayed-release tablets in children ages 6 through 16 years were highly variable (%CV ranges 40 to 80%). The geometric mean AUC estimated from population PK analysis after a 40 mg pantoprazole sodium delayed-release tablet in pediatric patients was about 39% and 10% higher respectively in 6 to 11 and 12 to 16 year-old children, compared to that of adults (Table 7). 

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 7: PK Parameters in Children and Adolescents 6 through 16 years with GERD receiving 40 mg Pantoprazole Sodium Delayed-Release Tablets</span> </caption> <col align="left" valign="middle" width="34%"/> <col align="left" valign="middle" width="33%"/> <col align="left" valign="middle" width="33%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule"> </th><th align="center" class="Botrule Rrule Toprule"><span class="Bold">6-11 years (n=12)</span></th><th align="center" class="Botrule Rrule Toprule"><span class="Bold">12-16 years (n=11)</span></th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">C</span><span class="Sub">max</span><span class="Bold"> (µg/mL)</span><span class="Sup">a</span> </p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">1.8</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">1.8</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">t</span><span class="Sub">max</span><span class="Bold"> (h)</span><span class="Sup">b</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.0</p> </td><td align="center" class="Botrule Rrule"> <p class="First">2.0</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">AUC (µg•h/mL)</span><span class="Sup">a </span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">6.9</p> </td><td align="center" class="Botrule Rrule"> <p class="First">5.5</p> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">CL/F (L/h)</span><span class="Sup">b </span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">6.6</p> </td><td align="center" class="Botrule Rrule"> <p class="First">6.8</p> </td> </tr> </tbody> </table></div>

a Geometric mean values

b Median values

Male and Female Patients

There is a modest increase in pantoprazole AUC and Cmax in women compared to men. However, weight-normalized clearance values are similar in women and men. 

In pediatric patients ages 1 through 16 years there were no clinically relevant effects of gender on clearance of pantoprazole, as shown by population pharmacokinetic analysis. 

Patients with Renal Impairment

In patients with severe renal impairment, pharmacokinetic parameters for pantoprazole were similar to those of healthy subjects.

Patients with Hepatic Impairment

In patients with mild to severe hepatic impairment (Child-Pugh A to C cirrhosis), maximum pantoprazole concentrations increased only slightly (1.5-fold) relative to healthy subjects. Although serum half-life values increased to 7-9 hours and AUC values increased by 5- to 7-fold in hepatic-impaired patients, these increases were no greater than those observed in CYP2C19 poor metabolizers, where no dosage adjustment is warranted. These pharmacokinetic changes in hepatic-impaired patients result in minimal drug accumulation following once-daily, multiple-dose administration. Doses higher than 40 mg/day have not been studied in hepatically impaired patients. 

Drug Interaction Studies

Effect of Other Drugs on Pantoprazole

Pantoprazole is metabolized mainly by CYP2C19 and to minor extents by CYPs 3A4, 2D6, and 2C9. In in vivo drug-drug interaction studies with CYP2C19 substrates (diazepam [also a CYP3A4 substrate] and phenytoin [also a CYP3A4 inducer] and clopidogrel), nifedipine, midazolam, and clarithromycin (CYP3A4 substrates), metoprolol (a CYP2D6 substrate), diclofenac, naproxen and piroxicam (CYP2C9 substrates), and theophylline (a CYP1A2 substrate) in healthy subjects, the pharmacokinetics of pantoprazole were not significantly altered.

Effect of Pantoprazole on Other Drugs  

Clopidogrel 

Clopidogrel is metabolized to its active metabolite in part by CYP2C19. In a crossover clinical study, 66 healthy subjects were administered clopidogrel (300 mg loading dose followed by 75 mg per day) alone and with pantoprazole (80 mg at the same time as clopidogrel) for 5 days. On Day 5, the mean AUC of the active metabolite of clopidogrel was reduced by approximately 14% (geometric mean ratio was 86%, with 90% CI of 79 to 93%) when pantoprazole was coadministered with clopidogrel as compared to clopidogrel administered alone. Pharmacodynamic parameters were also measured and demonstrated that the change in inhibition of platelet aggregation (induced by 5 µM ADP) was correlated with the change in the exposure to clopidogrel active metabolite. The clinical significance of this finding is not clear.

Mycophenolate Mofetil (MMF) 

Administration of pantoprazole 40 mg twice daily for 4 days and a single 1000 mg dose of MMF approximately one hour after the last dose of pantoprazole to 12 healthy subjects in a cross-over study resulted in a 57% reduction in the Cmax and 27% reduction in the AUC of MPA. Transplant patients receiving approximately 2000 mg per day of MMF (n=12) were compared to transplant patients receiving approximately the same dose of MMF and pantoprazole 40 mg per day (n=21). There was a 78% reduction in the Cmax and a 45% reduction in the AUC of MPA in patients receiving both pantoprazole and MMF [see Drug Interactions (7)].

Other Drugs 

In vivo studies also suggest that pantoprazole does not significantly affect the kinetics of the following drugs (cisapride, theophylline, diazepam [and its active metabolite, desmethyldiazepam], phenytoin, metoprolol, nifedipine, carbamazepine, midazolam, clarithromycin, diclofenac, naproxen, piroxicam, and oral contraceptives [levonorgestrel/ethinyl estradiol]). In other in vivo studies, digoxin, ethanol, glyburide, antipyrine, caffeine, metronidazole, and amoxicillin had no clinically relevant interactions with pantoprazole. 

Although no significant drug-drug interactions have been observed in clinical studies, the potential for significant drug-drug interactions with more than once-daily dosing with high doses of pantoprazole has not been studied in poor metabolizers or individuals who are hepatically impaired.

Antacids 

There was also no interaction with concomitantly administered antacids.

CYP2C19 displays a known genetic polymorphism due to its deficiency in some subpopulations (e.g., approximately 3% of Caucasians and African-Americans and 17% to 23% of Asians are poor metabolizers). Although these subpopulations of pantoprazole poor metabolizers have elimination half-life values of 3.5 to 10 hours in adults, they still have minimal accumulation (23% or less) with once-daily dosing. For adult patients who are CYP2C19 poor metabolizers, no dosage adjustment is needed. 

Similar to adults, pediatric patients who have the poor metabolizer genotype of CYP2C19 (CYP2C19 *2/*2) exhibited greater than a 6-fold increase in AUC compared to pediatric extensive (CYP2C19 *1/*1) and intermediate (CYP2C19 *1/*x) metabolizers. Poor metabolizers exhibited approximately 10-fold lower apparent oral clearance compared to extensive metabolizers. 

For known pediatric poor metabolizers, a dose reduction should be considered.

In a 24-month carcinogenicity study, Sprague-Dawley rats were treated orally with pantoprazole doses of 0.5 to 200 mg/kg/day, about 0.1 to 40 times the exposure on a body surface area basis of a 50 kg person dosed with 40 mg/day. In the gastric fundus, treatment with 0.5 to 200 mg/kg/day produced enterochromaffin-like (ECL) cell hyperplasia and benign and malignant neuroendocrine cell tumors in a dose-related manner. In the forestomach, treatment with 50 and 200 mg/kg/day (about 10 and 40 times the recommended human dose on a body surface area basis) produced benign squamous cell papillomas and malignant squamous cell carcinomas. Rare gastrointestinal tumors associated with pantoprazole treatment included an adenocarcinoma of the duodenum with 50 mg/kg/day and benign polyps and adenocarcinomas of the gastric fundus with 200 mg/kg/day. In the liver, treatment with 0.5 to 200 mg/kg/day produced dose-related increases in the incidences of hepatocellular adenomas and carcinomas. In the thyroid gland, treatment with 200 mg/kg/day produced increased incidences of follicular cell adenomas and carcinomas for both male and female rats.

In a 24-month carcinogenicity study, Fischer 344 rats were treated orally with doses of 5 to 50 mg/kg/day of pantoprazole, approximately 1 to 10 times the recommended human dose based on body surface area. In the gastric fundus, treatment with 5 to 50 mg/kg/day produced enterochromaffin-like (ECL) cell hyperplasia and benign and malignant neuroendocrine cell tumors. Dose selection for this study may not have been adequate to comprehensively evaluate the carcinogenic potential of pantoprazole.

In a 24-month carcinogenicity study, B6C3F1 mice were treated orally with doses of 5 to 150 mg/kg/day of pantoprazole, 0.5 to 15 times the recommended human dose based on body surface area. In the liver, treatment with 150 mg/kg/day produced increased incidences of hepatocellular adenomas and carcinomas in female mice. Treatment with 5 to 150 mg/kg/day also produced gastric-fundic ECL cell hyperplasia.

A 26-week p53 +/- transgenic mouse carcinogenicity study was not positive.

Pantoprazole was positive in the in vitro human lymphocyte chromosomal aberration assays, in one of two mouse micronucleus tests for clastogenic effects, and in the in vitro Chinese hamster ovarian cell/HGPRT forward mutation assay for mutagenic effects. Equivocal results were observed in the in vivo rat liver DNA covalent binding assay. Pantoprazole was negative in the in vitro Ames mutation assay, the in vitro unscheduled DNA synthesis (UDS) assay with rat hepatocytes, the in vitro AS52/GPT mammalian cell-forward gene mutation assay, the in vitro thymidine kinase mutation test with mouse lymphoma L5178Y cells, and the in vivo rat bone marrow cell chromosomal aberration assay.

There were no effects on fertility or reproductive performance when pantoprazole was given at oral doses up to 500 mg/kg/day in male rats (98 times the recommended human dose based on body surface area) and 450 mg/kg/day in female rats (88 times the recommended human dose based on body surface area).

Adult Patients

A US multicenter, double-blind, placebo-controlled study of pantoprazole sodium delayed-release tablets 10 mg, 20 mg, or 40 mg once daily was conducted in 603 patients with reflux symptoms and endoscopically diagnosed EE of grade 2 or above (Hetzel-Dent scale). In this study, approximately 25% of enrolled patients had severe EE of grade 3, and 10% had grade 4. The percentages of patients healed (per protocol, n = 541) in this study are shown in Table 8. 

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 8: Erosive Esophagitis Healing Rates (Per Protocol)</span> </caption> <col align="left" valign="middle" width="20%"/> <col align="left" valign="middle" width="20%"/> <col align="left" valign="middle" width="20%"/> <col align="left" valign="middle" width="20%"/> <col align="left" valign="middle" width="20%"/> <thead> <tr class="First Last"> <th align="center" class="Botrule Lrule Rrule Toprule"> </th><th align="center" class="Botrule Rrule Toprule" colspan="3"><span class="Bold">Pantoprazole Sodium Delayed-Release Tablets</span></th><th align="center" class="Botrule Rrule Toprule"><span class="Bold">Placebo</span></th> </tr> </thead> <tbody> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">Week</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">10 mg daily</p> <p>(n = 153)</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">20 mg daily</p> <p>(n = 158)</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">40 mg daily</p> <p>(n = 162)</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">(n = 68)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"> <p class="First">4</p> </td><td align="center" class="Botrule Rrule"> <p class="First">45.6%<span class="Sup">+</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">58.4%<span class="Sup">+#</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">75.0%<span class="Sup">+</span>*</p> </td><td align="center" class="Botrule Rrule"> <p class="First">14.3%</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule"> <p class="First">8</p> </td><td align="center" class="Botrule Rrule"> <p class="First">66.0%<span class="Sup">+</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">83.5%<span class="Sup">+#</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">92.6%<span class="Sup">+</span>*</p> </td><td align="center" class="Botrule Rrule"> <p class="First">39.7%</p> </td> </tr> </tbody> </table></div>

+ (p < 0.001) pantoprazole sodium delayed-release tablets versus placebo

* (p < 0.05) versus 10 mg or 20 mg pantoprazole sodium delayed-release tablets

#  (p <  0.05) versus 10 mg pantoprazole sodium delayed-release tablets

In this study, all pantoprazole sodium delayed-release tablets treatment groups had significantly greater healing rates than the placebo group. This was true regardless of H. pylori status for the 40 mg and 20 mg pantoprazole sodium delayed-release tablets treatment groups. The 40 mg dose of pantoprazole sodium delayed-release tablets resulted in healing rates significantly greater than those found with either the 20 mg or 10 mg dose. 

A significantly greater proportion of patients taking pantoprazole sodium delayed-release tablets 40 mg experienced complete relief of daytime and nighttime heartburn and the absence of regurgitation, starting from the first day of treatment, compared with placebo. Patients taking pantoprazole sodium delayed-release tablets consumed significantly fewer antacid tablets per day than those taking placebo. 

Pantoprazole sodium delayed-release tablets 40 mg and 20 mg once daily were also compared with nizatidine 150 mg twice daily in a US multicenter, double-blind study of 243 patients with reflux symptoms and endoscopically diagnosed EE of grade 2 or above. The percentages of patients healed (per protocol, n = 212) are shown in Table 9. 

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 9: Erosive Esophagitis Healing Rates (Per Protocol) </span> </caption> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <thead> <tr class="First Last"> <th align="center" class="Botrule Lrule Rrule Toprule"> </th><th align="center" class="Botrule Rrule Toprule" colspan="2"><span class="Bold">Pantoprazole Sodium Delayed-Release Tablets</span></th><th align="center" class="Botrule Rrule Toprule"><span class="Bold">Nizatidine</span></th> </tr> </thead> <tbody> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">Week</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">20 mg daily</p> <p>(n = 72)</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">40 mg daily</p> <p>(n = 70)</p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First">150 mg twice daily </p> <p>(n = 70)</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"> <p class="First">4</p> </td><td align="center" class="Botrule Rrule"> <p class="First">61.4%<span class="Sup">+</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">64.0%<span class="Sup">+</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">22.2%</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule"> <p class="First">8</p> </td><td align="center" class="Botrule Rrule"> <p class="First">79.2%<span class="Sup">+</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">82.9%<span class="Sup">+</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First">41.4%</p> </td> </tr> </tbody> </table></div>

+ (p < 0.001) pantoprazole sodium delayed-release tablets versus nizatidine

Once-daily treatment with pantoprazole sodium delayed-release tablets 40 mg or 20 mg resulted in significantly superior rates of healing at both 4 and 8 weeks compared with twice-daily treatment with 150 mg of nizatidine. For the 40 mg treatment group, significantly greater healing rates compared to nizatidine were achieved regardless of the H. pylori status. 

A significantly greater proportion of the patients in the pantoprazole sodium delayed-release tablets treatment groups experienced complete relief of nighttime heartburn and regurgitation, starting on the first day and of daytime heartburn on the second day, compared with those taking nizatidine 150 mg twice daily. Patients taking pantoprazole sodium delayed-release tablets consumed significantly fewer antacid tablets per day than those taking nizatidine. 

Pediatric Patients Ages 5 Years through 16 Years

The efficacy of pantoprazole sodium delayed-release tablets in the treatment of EE associated with GERD in pediatric patients ages 5 years through 16 years is extrapolated from adequate and well-conducted trials in adults, as the pathophysiology is thought to be the same. Four pediatric patients with endoscopically diagnosed EE were studied in multicenter, randomized, double-blind, parallel-treatment trials. Children with endoscopically diagnosed EE (defined as an endoscopic Hetzel-Dent score ≥2) were treated once daily for 8 weeks with one of two dose levels of pantoprazole sodium delayed-release tablets (20 mg or 40 mg). All 4 patients with EE were healed (Hetzel-Dent score of 0 or 1) at 8 weeks.

Two independent, multicenter, randomized, double-blind, comparator-controlled trials of identical design were conducted in adult GERD patients with endoscopically confirmed healed EE to demonstrate efficacy of pantoprazole sodium delayed-release tablets in long-term maintenance of healing. The two US studies enrolled 386 and 404 patients, respectively, to receive either 10 mg, 20 mg, or 40 mg of pantoprazole sodium delayed-release tablets once daily or 150 mg of ranitidine twice daily. As demonstrated in Table 10, pantoprazole sodium delayed-release tablets 40 mg and 20 mg were significantly superior to ranitidine at every timepoint with respect to the maintenance of healing. In addition, pantoprazole sodium delayed-release tablets 40 mg was superior to all other treatments studied. 

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 10: Long-Term Maintenance of Healing of Erosive Gastroesophageal Reflux Disease (GERD   Maintenance): Percentage of Patients Who Remained Healed   </span> </caption> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule"> </th><th align="left" class="Botrule Rrule Toprule">Pantoprazole Sodium Delayed-Release Tablets</th><th align="left" class="Botrule Rrule Toprule">Pantoprazole Sodium Delayed-Release Tablets</th><th align="left" class="Botrule Rrule Toprule">Ranitidine </th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> </p> </td><td align="left" class="Botrule Rrule Toprule" valign="top"> <p class="First">20 mg daily</p> </td><td align="left" class="Botrule Rrule Toprule" valign="top"> <p class="First">40 mg daily</p> </td><td align="left" class="Botrule Rrule Toprule" valign="top"> <p class="First">150 mg daily</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Study 1</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">n=75</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">n=74</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">n=75</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">Month 1</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">91*</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">99*</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">68</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">Month 3</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">82*</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">93*#</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">54</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">Month 6</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">76*</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">90*#</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">44</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">Month 12</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">70*</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">86*#</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">35</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Study 2</span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">n=74</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">n=88</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">n=84</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">Month 1</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">89*</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">92*#</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">62</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">Month 3</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">78*</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">91*#</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">47</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">Month 6</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">72*</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">88*#</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">39</p> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">Month 12</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">72*</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">83*</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">37</p> </td> </tr> </tbody> </table></div>

* (p <0.05 vs. ranitidine)  

# (p <0.05 vs. pantoprazole sodium delayed-release tablets 20 mg)

Note: pantoprazole sodium delayed-release tablets 10 mg was superior (p <0.05) to ranitidine in Study 2, but not Study 1.

Pantoprazole sodium delayed-release tablets 40 mg was superior to ranitidine in reducing the number of daytime and nighttime heartburn episodes from the first through the twelfth month of treatment. Pantoprazole sodium delayed-release tablets 20 mg, administered once daily, was also effective in reducing episodes of daytime and nighttime heartburn in one trial, as presented in Table 11. 

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 11: Number of Episodes of Heartburn (mean ± SD) </span> </caption> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="25%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Sup"> </span></th><th align="left" class="Botrule Rrule Toprule">Pantoprazole Sodium Delayed-Release Tablets</th><th align="left" class="Botrule Rrule Toprule">Ranitidine</th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Sup"> </span> </p> </td><td align="left" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Sup"> </span> </p> </td><td align="left" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Sup">40 mg daily</span> </p> </td><td align="left" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Sup">150 mg twice daily</span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">Month 1</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Daytime </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">5.1 ± 1.6*</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">18.3 ± 1.6 </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Nighttime </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">3.9 ± 1.1*</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">11.9 ± 1.1 </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First">Month 12</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Daytime </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">2.9 ± 1.5*</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">17.5 ± 1.5 </p> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Sup"> </span> </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">Nighttime </p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">2.5 ± 1.2*</p> </td><td align="left" class="Botrule Rrule" valign="top"> <p class="First">13.8 ± 1.3 </p> </td> </tr> </tbody> </table></div>

* (p <0.001 vs. ranitidine, combined data from the two US studies)

In a multicenter, open-label trial of 35 patients with pathological hypersecretory conditions, such as Zollinger-Ellison Syndrome, with or without multiple endocrine neoplasia-type I, pantoprazole sodium delayed-release tablets successfully controlled gastric acid secretion. Doses ranging from 80 mg daily to 240 mg daily maintained gastric acid output below 10 mEq/h in patients without prior acid-reducing surgery and below 5 mEq/h in patients with prior acid-reducing surgery. 

Doses were initially titrated to the individual patient needs, and adjusted in some patients based on the clinical response with time [see Dosage and Administration (2)]. Pantoprazole sodium delayed-release tablets was well tolerated at these dose levels for prolonged periods (greater than 2 years in some patients). 

How Supplied

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Pantoprazole sodium for delayed-release oral suspension, is supplied as off-white to pale yellowish to greyish brown, enteric-coated granules containing 40 mg pantoprazole in a unit-dose packet and are available as follows:

{ "type": "p", "children": [], "text": "Pantoprazole sodium for delayed-release oral suspension, is supplied as off-white to pale yellowish to greyish brown, enteric-coated granules containing 40 mg pantoprazole in a unit-dose packet and are available as follows:" }

      NDC 69097-531-53, unit-dose carton of 30

{ "type": "p", "children": [], "text": "      NDC 69097-531-53, unit-dose carton of 30 " }

Storage

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

Store pantoprazole sodium for delayed-release oral suspension, at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store pantoprazole sodium for delayed-release oral suspension, at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. " }

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

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). " }

Gastric Malignancy

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

Advise patients to return to their healthcare provider if they have a suboptimal response or an early symptomatic relapse [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Advise patients to return to their healthcare provider if they have a suboptimal response or an early symptomatic relapse [see Warnings and Precautions (5.1)]. " }

Acute Tubulointerstitial Nephritis

{ "type": "p", "children": [], "text": "\nAcute Tubulointerstitial Nephritis \n" }

Advise patients to call their healthcare provider immediately if they experience signs and/or symptoms associated with acute tubulointerstitial nephritis [see Contraindications (4), Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Advise patients to call their healthcare provider immediately if they experience signs and/or symptoms associated with acute tubulointerstitial nephritis [see Contraindications (4), Warnings and Precautions (5.2)]. " }

Clostridium difficile-Associated Diarrhea 

{ "type": "p", "children": [], "text": "\nClostridium difficile-Associated Diarrhea " }

Advise patients to immediately call their healthcare provider if they experience diarrhea that does not improve [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Advise patients to immediately call their healthcare provider if they experience diarrhea that does not improve [see Warnings and Precautions (5.3)]. " }

Bone Fracture

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

Advise patients to report any fractures, especially of the hip, wrist or spine, to their healthcare provider [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "Advise patients to report any fractures, especially of the hip, wrist or spine, to their healthcare provider [see Warnings and Precautions (5.4)]. " }

Severe Cutaneous Adverse Reactions 

{ "type": "p", "children": [], "text": "\nSevere Cutaneous Adverse Reactions " }

Advise patients to discontinue pantoprazole sodium for delayed-release oral suspension and immediately call their healthcare provider for further evaluation [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "Advise patients to discontinue pantoprazole sodium for delayed-release oral suspension and immediately call their healthcare provider for further evaluation [see Warnings and Precautions (5.5)]. " }

Cutaneous and Systemic Lupus Erythematosus

{ "type": "p", "children": [], "text": "\nCutaneous and Systemic Lupus Erythematosus \n" }

Advise patients to immediately call their healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus [see Warnings and Precautions (5.6)].

{ "type": "p", "children": [], "text": "Advise patients to immediately call their healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus [see Warnings and Precautions (5.6)]. " }

Cyanocobalamin (Vitamin B-12) Deficiency

{ "type": "p", "children": [], "text": "\nCyanocobalamin (Vitamin B-12) Deficiency \n" }

Advise patients to report any clinical symptoms that may be associated with cyancobalamin deficiency to their healthcare provider if they have been receiving pantoprazole sodium for delayed-release oral suspension for longer than 3 years [see Warnings and Precautions (5.7)].

{ "type": "p", "children": [], "text": "Advise patients to report any clinical symptoms that may be associated with cyancobalamin deficiency to their healthcare provider if they have been receiving pantoprazole sodium for delayed-release oral suspension for longer than 3 years [see Warnings and Precautions (5.7)]. " }

Hypomagnesemia and Mineral Metabolism  

{ "type": "p", "children": [], "text": "\nHypomagnesemia and Mineral Metabolism  \n" }

Advise patients to report any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia, and/or hypokalemia, to their healthcare provider, if they have been receiving pantoprazole sodium for delayed-release oral suspension for at least 3 months [see Warnings and Precautions (5.8)].

{ "type": "p", "children": [], "text": "Advise patients to report any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia, and/or hypokalemia, to their healthcare provider, if they have been receiving pantoprazole sodium for delayed-release oral suspension for at least 3 months [see Warnings and Precautions (5.8)]. " }

Drug Interactions  

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

Instruct patients to inform their healthcare provider of any other medications they are currently taking, including rilpivirine-containing products [see Contraindications (4)], digoxin [see Warnings and Precautions (5.8)] and high dose methotrexate [see Warnings and Precautions (5.13)].  

{ "type": "p", "children": [], "text": "Instruct patients to inform their healthcare provider of any other medications they are currently taking, including rilpivirine-containing products [see Contraindications (4)], digoxin [see Warnings and Precautions (5.8)] and high dose methotrexate [see Warnings and Precautions (5.13)].  " }

Pregnancy 

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

Advise a pregnant woman of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "Advise a pregnant woman of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1)]. " }

Administration

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

{ "type": "ul", "children": [ "Do not split, crush, or chew pantoprazole sodium for delayed-release oral suspension. ", "Pantoprazole sodium for delayed-release oral suspension packet is a fixed dose and cannot be divided to make a smaller dose.", "Take pantoprazole sodium for delayed-release oral suspension approximately 30 minutes before a meal. ", "Administer pantoprazole sodium for delayed-release oral suspension in apple juice or applesauce, as described in the Instructions for Use. Do not administer in water, other liquids, or foods.", "For patients with a nasogastric (NG) or gastrostomy tube, pantoprazole sodium for delayed-release oral suspension can be administered with apple juice, as described in the Instructions for Use.", "Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and take the next dose at the regular scheduled time. Do not take 2 doses at the same time." ], "text": "" }

For Medical Information about pantoprazole sodium for delayed-release oral suspension, call 1-866-604-3268.

{ "type": "p", "children": [], "text": "For Medical Information about pantoprazole sodium for delayed-release oral suspension, call 1-866-604-3268." }

Manufactured by:

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

Cipla Limited, (Kurkumbh)

{ "type": "p", "children": [], "text": "\nCipla Limited, (Kurkumbh)\n" }

Plot D-7, D-22, D-27,

{ "type": "p", "children": [], "text": "Plot D-7, D-22, D-27, " }

MIDC Industrial Area, Pune,

{ "type": "p", "children": [], "text": "MIDC Industrial Area, Pune, " }

India -413802

{ "type": "p", "children": [], "text": "India -413802" }

Manufactured for: 

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

Cipla USA, Inc.

{ "type": "p", "children": [], "text": "Cipla USA, Inc. " }

10 Independence Boulevard,

{ "type": "p", "children": [], "text": "10 Independence Boulevard, " }

Suite 300 Warren, NJ 07059  

{ "type": "p", "children": [], "text": "Suite 300 Warren, NJ 07059  " }

Issued: 8/2023

{ "type": "p", "children": [], "text": "\nIssued: 8/2023\n" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="middle" width="100%"/> <thead align="center"> <tr class="Last"> <th align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">MEDICATION GUIDE </span> <br/> <span class="Bold">Pantoprazole Sodium (pan toe′ pra zole soe′ dee um) </span> <br/> <span class="Bold">for delayed-release oral suspension </span></th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">What is the most important information I should know about Pantoprazole Sodium For Delayed-Release Oral Suspension? </span> </p> <p> <span class="Bold">You should take Pantoprazole Sodium For Delayed-Release Oral Suspension exactly as prescribed, at the lowest dose possible and for the shortest time needed. </span> </p> <p> <span class="Bold">Pantoprazole Sodium For Delayed-Release Oral Suspension may help your acid-related symptoms, but you could still have serious stomach problems. </span>Talk with your doctor. </p> <p> <span class="Bold">Pantoprazole Sodium For Delayed-Release Oral Suspension can cause serious side effects, including: </span> </p> <p> </p> <ul class="Disc"> <li> <span class="Bold">A type of kidney problem (acute tubulointerstitial nephritis). </span>Some people who take proton pump inhibitor (PPI) medicines, including Pantoprazole Sodium For Delayed-Release Oral Suspension, may develop a kidney problem called acute tubulointerstitial nephritis that can happen at any time during treatment with Pantoprazole Sodium For Delayed-Release Oral Suspension. Call your doctor right away if you have a decrease in the amount that you urinate or if you have blood in your urine. </li> <li> <span class="Bold">Diarrhea caused by an infection (</span><span class="Bold Italics">Clostridium difficile</span><span class="Bold">) in your intestines</span>. Call your doctor right away if you have watery stools or stomach pain that does not go away. You may or may not have a fever. </li> <li> <span class="Bold">Bone fractures (hip, wrist, or spine)</span>. Bone fractures in the hip, wrist, or spine may happen in people who take multiple daily doses of PPI medicines and for a long period of time (a year or longer). Tell your doctor if you have a bone fracture, especially in the hip, wrist, or spine. </li> <li> <span class="Bold">Certain types of lupus erythematosus. </span>Lupus erythematosus is an autoimmune disorder (the body’s immune cells attack other cells or organs in the body). Some people who take PPI medicines, including Pantoprazole Sodium For Delayed-Release Oral Suspension, may develop certain types of lupus erythematosus or have worsening of the lupus they already have. Call your doctor right away if you have new or worsening joint pain or a rash on your cheeks or arms that gets worse in the sun. </li> <li> <span class="Bold">Low magnesium and other mineral levels in your body</span> can happen in people who have taken Pantoprazole Sodium For Delayed-Release Oral Suspension for at least 3 months. Tell your doctor if you have symptoms of low magnesium levels, including seizures, dizziness, irregular heartbeat, jitteriness, muscle aches or weakness, and spasms of hands, feet or voice.</li> </ul> <p> </p> <p>Talk to your doctor about your risk of these serious side effects. </p> <p> </p> <p>Pantoprazole Sodium For Delayed-Release Oral Suspension can have other serious side effects. See <span class="Bold">“What are the possible side effects of </span><span class="Bold">Pantoprazole Sodium For Delayed-Release Oral Suspension</span><span class="Bold">?”  </span> </p> <p> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">What is </span><span class="Bold">Pantoprazole Sodium For Delayed-Release Oral Suspension</span><span class="Bold">? </span> </p> <p> </p> <p>A prescription medicine called a proton pump inhibitor (PPI) used to reduce the amount of acid in your stomach. </p> <p> <span class="Bold">In adults, </span>Pantoprazole Sodium For Delayed-Release Oral Suspension is used for: </p> <ul class="Disc"> <li>up to 8 weeks for the healing and symptom relief of acid-related damage to the lining of the esophagus (called erosive esophagitis or EE). Your doctor may prescribe another 8 weeks of Pantoprazole Sodium For Delayed-Release Oral Suspension in patients whose EE does not heal. </li> <li>maintaining healing of EE and to help prevent the return of heartburn symptoms caused by GERD. It is not known if Pantoprazole Sodium For Delayed-Release Oral Suspension is safe and effective when used for longer than 12 months for this purpose. </li> <li>the long-term treatment of conditions where your stomach makes too much acid. This includes a rare condition called Zollinger-Ellison Syndrome. </li> </ul> <p> <span class="Bold">In children 5 years of age and older</span>, Pantoprazole Sodium For Delayed-Release Oral Suspension is used for: </p> <ul class="Disc"> <li>up to 8 weeks for the healing and symptom relief of EE. </li> </ul> <p> </p> <p>It is not known if Pantoprazole Sodium For Delayed-Release Oral Suspension is safe if used longer than 8 weeks in children. </p> <p> </p> <p>Pantoprazole Sodium For Delayed-Release Oral Suspension is not for use in children under 5 years of age. </p> <p> </p> <p>It is not known if Pantoprazole Sodium For Delayed-Release Oral Suspension is safe and effective in children for treatment other than EE. </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Do not take </span><span class="Bold">Pantoprazole Sodium For Delayed-Release Oral Suspension</span><span class="Bold"> if you are: </span> </p> <ul class="Disc"> <li>allergic to pantoprazole sodium, any other PPI medicine, or any of the ingredients in Pantoprazole Sodium For Delayed-Release Oral Suspension. See the end of this Medication Guide for a complete list of ingredients. </li> <li>taking a medicine that contains rilpivirine (EDURANT, COMPLERA, ODEFSEY, JULUCA) used to treat HIV-1 (Human Immunodeficiency Virus).  </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Before taking </span><span class="Bold">Pantoprazole Sodium For Delayed-Release Oral Suspension</span><span class="Bold">, tell your doctor about all of your medical conditions, including if you: </span> </p> <ul class="Disc"> <li>have low magnesium levels, low calcium levels and low potassium levels in your blood. </li> <li>are pregnant or plan to become pregnant. Pantoprazole may harm your unborn baby. Tell your doctor if you become pregnant or think you may be pregnant during treatment with Pantoprazole Sodium For Delayed-Release Oral Suspension. </li> <li>are breastfeeding or plan to breastfeed. Pantoprazole can pass into your breast milk. Talk with your doctor about the best way to feed your baby if you take Pantoprazole Sodium For Delayed-Release Oral Suspension. </li> </ul> <p> <span class="Bold">Tell your doctor about all the medicines you take, </span>including prescription and over-the-counter medicines, vitamins and herbal supplements. <span class="Bold">Especially tell your doctor if you take </span>methotrexate (Otrexup, Rasuvo, Trexall, XATMEP), digoxin (LANOXIN), or a water pill (diuretic). </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">How should I take Pantoprazole Sodium For Delayed-Release Oral Suspension? </span> </p> <p> </p> <ul class="Disc"> <li>Take Pantoprazole Sodium For Delayed-Release Oral Suspension exactly as prescribed by your doctor. </li> </ul> <ul class="Circle"> <li> <span class="Bold">Do not split, chew, or crush Pantoprazole Sodium For Delayed-Release Oral Suspension. </span> </li> <li>Take Pantoprazole Sodium For Delayed-Release Oral Suspension about 30 minutes before a meal. </li> <li>Pantoprazole Sodium For Delayed-Release Oral Suspension should <span class="Bold">only </span>be given by mouth mixed in apple juice or applesauce <span class="Bold">or </span>through a nasogastric (NG) tube or gastrostomy tube mixed in apple juice. Do not mix Pantoprazole Sodium For Delayed-Release Oral Suspension in liquids other than apple juice or foods other than applesauce. </li> <li>Do not divide a packet of Pantoprazole Sodium For Delayed-Release Oral Suspension to make a smaller dose. </li> <li>See the <span class="Bold">“Instructions for Use” </span>at the end of this Medication Guide for instructions on how to mix and take Pantoprazole Sodium For Delayed-Release Oral Suspension by mouth in applesauce or apple juice or how to mix and give the suspension through an NG tube or gastrostomy tube mixed in apple juice. </li> </ul> <ul class="Disc"> <li>If you miss a dose of Pantoprazole Sodium For Delayed-Release Oral Suspension, take it as soon as possible. If it is almost time for your next dose, do not take the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time. </li> </ul> <p>If you take too much Pantoprazole Sodium For Delayed-Release Oral Suspension, call your doctor or your poison control center at 1-800-222-1222 right away or go to the nearest emergency room.</p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of Pantoprazole Sodium For Delayed-Release Oral Suspension? </span> </p> <p> <span class="Bold">Pantoprazole Sodium For Delayed-Release Oral Suspension can cause serious side effects, including:  </span> </p> <ul class="Disc"> <li> <span class="Bold">See “What is the most important information I should know about Pantoprazole Sodium For Delayed-Release Oral Suspension?”  </span> </li> <li> <span class="Bold">Low vitamin B-12 levels </span>in your body can happen in people who have taken Pantoprazole Sodium For Delayed-Release Oral Suspension for a long time (more than 3 years). Tell your doctor if you have symptoms of low vitamin B-12 levels, including shortness of breath, lightheadedness, irregular heartbeat, muscle weakness, pale skin, feeling tired, mood changes, and tingling or numbness in the arms and legs. </li> <li> <span class="Bold">Stomach growths (fundic gland polyps). </span>People who take PPI medicines for a long time have an increased risk of developing a certain type of stomach growths called fundic gland polyps, especially after taking PPI medicines for more than 1 year. </li> <li> <span class="Bold">Severe skin reactions. </span>Pantoprazole Sodium For Delayed-Release Oral Suspension can cause rare but severe skin reactions that may affect any part of your body. These serious skin reactions may need to be treated in a hospital and may be life threatening:</li> <li>Skin rash which may have blistering, peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet).</li> <li>You may also have fever, chills, body aches, shortness of breath, or enlarged lymph nodes. Stop taking Pantoprazole Sodium For Delayed-Release Oral Suspension and call your doctor right away. These symptoms may be the first sign of a severe skin reaction.</li> </ul> <p> <span class="Bold">The most common side effects of Pantoprazole Sodium For Delayed-Release Oral Suspension in adults include: </span>headache, diarrhea, nausea, stomach-area (abdominal) pain, vomiting, gas, dizziness, and joint pain. </p> <p> <span class="Bold">The most common side effects of Pantoprazole Sodium For Delayed-Release Oral Suspension in children include: </span>upper respiratory infection, headache, fever, diarrhea, vomiting, rash, and stomach-area (abdominal) pain. </p> <p> </p> <p>These are not all the possible side effects of Pantoprazole Sodium For Delayed-Release Oral Suspension. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">How should I store Pantoprazole Sodium For Delayed-Release Oral Suspension? </span> <br/>Store Pantoprazole Sodium For Delayed-Release Oral Suspension at room temperature between 68°F to 77°F (20°C to 25°C). <br/> <br/> <span class="Bold">Keep Pantoprazole Sodium For Delayed-Release Oral Suspension and all medicines out of the reach of children. </span> </p> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">General information about the safe and effective use of Pantoprazole Sodium For Delayed-Release Oral Suspension. </span> <br/> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Pantoprazole Sodium For Delayed-Release Oral Suspension for a condition for which it was not prescribed. Do not give Pantoprazole Sodium For Delayed-Release Oral Suspension to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about Pantoprazole Sodium For Delayed-Release Oral Suspension that is written for health professionals.<br/> </p> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">What are the ingredients in Pantoprazole Sodium For Delayed-Release Oral Suspension? </span> <br/> <br/> <span class="Bold">Active ingredient: </span>pantoprazole sodium sesquihydrate <br/> <br/> <span class="Bold">Inactive ingredients in Pantoprazole Sodium For Delayed-Release Oral Suspension: </span>crospovidone, hypromellose, lecithin, macrogol, methacrylic acid and ethyl acrylate copolymer dispersion, microcrystalline cellulose, polysorbate 80, polyvinyl alcohol-part hydrolyzed, sodium carbonate, talc, titanium dioxide, triethyl citrate, and iron oxide yellow.  <br/>This Medication Guide has been approved by the U.S. Food and Drug Administration.<br/>For more information call 1-866-604-3268.<br/> <br/>Disclaimer: Other brands listed are the registered trademarks of their respective owners and are not trademarks of Cipla Limited.<br/> <br/>Manufactured by:<br/> <span class="Bold">Cipla Limited, (Kurkumbh)</span> <br/>Plot D-7, D-22, D-27,<br/>MIDC Industrial Area, Pune,<br/>India -413802<br/>Manufactured for:<br/> <span class="Bold">Cipla USA, Inc.</span> <br/>10 Independence Boulevard,<br/>Suite 300 Warren, NJ 07059<br/> <br/> <span class="Bold">Issued: 8/2023</span> <br/> </p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"middle\" width=\"100%\"/>\n<thead align=\"center\">\n<tr class=\"Last\">\n<th align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">MEDICATION GUIDE </span>\n<br/>\n<span class=\"Bold\">Pantoprazole Sodium (pan toe′ pra zole soe′ dee um) </span>\n<br/>\n<span class=\"Bold\">for delayed-release oral suspension </span></th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about Pantoprazole Sodium For Delayed-Release Oral Suspension? </span>\n</p>\n<p>\n<span class=\"Bold\">You should take Pantoprazole Sodium For Delayed-Release Oral Suspension exactly as prescribed, at the lowest dose possible and for the shortest time needed. </span>\n</p>\n<p>\n<span class=\"Bold\">Pantoprazole Sodium For Delayed-Release Oral Suspension may help your acid-related symptoms, but you could still have serious stomach problems. </span>Talk with your doctor. </p>\n<p>\n<span class=\"Bold\">Pantoprazole Sodium For Delayed-Release Oral Suspension can cause serious side effects, including: </span>\n</p>\n<p> </p>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">A type of kidney problem (acute tubulointerstitial nephritis). </span>Some people who take proton pump inhibitor (PPI) medicines, including Pantoprazole Sodium For Delayed-Release Oral Suspension, may develop a kidney problem called acute tubulointerstitial nephritis that can happen at any time during treatment with Pantoprazole Sodium For Delayed-Release Oral Suspension. Call your doctor right away if you have a decrease in the amount that you urinate or if you have blood in your urine. </li>\n<li>\n<span class=\"Bold\">Diarrhea caused by an infection (</span><span class=\"Bold Italics\">Clostridium difficile</span><span class=\"Bold\">) in your intestines</span>. Call your doctor right away if you have watery stools or stomach pain that does not go away. You may or may not have a fever. </li>\n<li>\n<span class=\"Bold\">Bone fractures (hip, wrist, or spine)</span>. Bone fractures in the hip, wrist, or spine may happen in people who take multiple daily doses of PPI medicines and for a long period of time (a year or longer). Tell your doctor if you have a bone fracture, especially in the hip, wrist, or spine. </li>\n<li>\n<span class=\"Bold\">Certain types of lupus erythematosus. </span>Lupus erythematosus is an autoimmune disorder (the body’s immune cells attack other cells or organs in the body). Some people who take PPI medicines, including Pantoprazole Sodium For Delayed-Release Oral Suspension, may develop certain types of lupus erythematosus or have worsening of the lupus they already have. Call your doctor right away if you have new or worsening joint pain or a rash on your cheeks or arms that gets worse in the sun. </li>\n<li>\n<span class=\"Bold\">Low magnesium and other mineral levels in your body</span> can happen in people who have taken Pantoprazole Sodium For Delayed-Release Oral Suspension for at least 3 months. Tell your doctor if you have symptoms of low magnesium levels, including seizures, dizziness, irregular heartbeat, jitteriness, muscle aches or weakness, and spasms of hands, feet or voice.</li>\n</ul>\n<p> </p>\n<p>Talk to your doctor about your risk of these serious side effects. </p>\n<p> </p>\n<p>Pantoprazole Sodium For Delayed-Release Oral Suspension can have other serious side effects. See <span class=\"Bold\">“What are the possible side effects of </span><span class=\"Bold\">Pantoprazole Sodium For Delayed-Release Oral Suspension</span><span class=\"Bold\">?”  </span>\n</p>\n<p> </p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is </span><span class=\"Bold\">Pantoprazole Sodium For Delayed-Release Oral Suspension</span><span class=\"Bold\">? </span>\n</p>\n<p> </p>\n<p>A prescription medicine called a proton pump inhibitor (PPI) used to reduce the amount of acid in your stomach. </p>\n<p>\n<span class=\"Bold\">In adults, </span>Pantoprazole Sodium For Delayed-Release Oral Suspension is used for: </p>\n<ul class=\"Disc\">\n<li>up to 8 weeks for the healing and symptom relief of acid-related damage to the lining of the esophagus (called erosive esophagitis or EE). Your doctor may prescribe another 8 weeks of Pantoprazole Sodium For Delayed-Release Oral Suspension in patients whose EE does not heal. </li>\n<li>maintaining healing of EE and to help prevent the return of heartburn symptoms caused by GERD. It is not known if Pantoprazole Sodium For Delayed-Release Oral Suspension is safe and effective when used for longer than 12 months for this purpose. </li>\n<li>the long-term treatment of conditions where your stomach makes too much acid. This includes a rare condition called Zollinger-Ellison Syndrome. </li>\n</ul>\n<p>\n<span class=\"Bold\">In children 5 years of age and older</span>, Pantoprazole Sodium For Delayed-Release Oral Suspension is used for: </p>\n<ul class=\"Disc\">\n<li>up to 8 weeks for the healing and symptom relief of EE. </li>\n</ul>\n<p> </p>\n<p>It is not known if Pantoprazole Sodium For Delayed-Release Oral Suspension is safe if used longer than 8 weeks in children. </p>\n<p> </p>\n<p>Pantoprazole Sodium For Delayed-Release Oral Suspension is not for use in children under 5 years of age. </p>\n<p> </p>\n<p>It is not known if Pantoprazole Sodium For Delayed-Release Oral Suspension is safe and effective in children for treatment other than EE. </p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Do not take </span><span class=\"Bold\">Pantoprazole Sodium For Delayed-Release Oral Suspension</span><span class=\"Bold\"> if you are: </span>\n</p>\n<ul class=\"Disc\">\n<li>allergic to pantoprazole sodium, any other PPI medicine, or any of the ingredients in Pantoprazole Sodium For Delayed-Release Oral Suspension. See the end of this Medication Guide for a complete list of ingredients. </li>\n<li>taking a medicine that contains rilpivirine (EDURANT, COMPLERA, ODEFSEY, JULUCA) used to treat HIV-1 (Human Immunodeficiency Virus).  </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Before taking </span><span class=\"Bold\">Pantoprazole Sodium For Delayed-Release Oral Suspension</span><span class=\"Bold\">, tell your doctor about all of your medical conditions, including if you: </span>\n</p>\n<ul class=\"Disc\">\n<li>have low magnesium levels, low calcium levels and low potassium levels in your blood. </li>\n<li>are pregnant or plan to become pregnant. Pantoprazole may harm your unborn baby. Tell your doctor if you become pregnant or think you may be pregnant during treatment with Pantoprazole Sodium For Delayed-Release Oral Suspension. </li>\n<li>are breastfeeding or plan to breastfeed. Pantoprazole can pass into your breast milk. Talk with your doctor about the best way to feed your baby if you take Pantoprazole Sodium For Delayed-Release Oral Suspension. </li>\n</ul>\n<p>\n<span class=\"Bold\">Tell your doctor about all the medicines you take, </span>including prescription and over-the-counter medicines, vitamins and herbal supplements. <span class=\"Bold\">Especially tell your doctor if you take </span>methotrexate (Otrexup, Rasuvo, Trexall, XATMEP), digoxin (LANOXIN), or a water pill (diuretic). </p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I take Pantoprazole Sodium For Delayed-Release Oral Suspension? </span>\n</p>\n<p> </p>\n<ul class=\"Disc\">\n<li>Take Pantoprazole Sodium For Delayed-Release Oral Suspension exactly as prescribed by your doctor. </li>\n</ul>\n<ul class=\"Circle\">\n<li>\n<span class=\"Bold\">Do not split, chew, or crush Pantoprazole Sodium For Delayed-Release Oral Suspension. </span>\n</li>\n<li>Take Pantoprazole Sodium For Delayed-Release Oral Suspension about 30 minutes before a meal. </li>\n<li>Pantoprazole Sodium For Delayed-Release Oral Suspension should <span class=\"Bold\">only </span>be given by mouth mixed in apple juice or applesauce <span class=\"Bold\">or </span>through a nasogastric (NG) tube or gastrostomy tube mixed in apple juice. Do not mix Pantoprazole Sodium For Delayed-Release Oral Suspension in liquids other than apple juice or foods other than applesauce. </li>\n<li>Do not divide a packet of Pantoprazole Sodium For Delayed-Release Oral Suspension to make a smaller dose. </li>\n<li>See the <span class=\"Bold\">“Instructions for Use” </span>at the end of this Medication Guide for instructions on how to mix and take Pantoprazole Sodium For Delayed-Release Oral Suspension by mouth in applesauce or apple juice or how to mix and give the suspension through an NG tube or gastrostomy tube mixed in apple juice. </li>\n</ul>\n<ul class=\"Disc\">\n<li>If you miss a dose of Pantoprazole Sodium For Delayed-Release Oral Suspension, take it as soon as possible. If it is almost time for your next dose, do not take the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time. </li>\n</ul>\n<p>If you take too much Pantoprazole Sodium For Delayed-Release Oral Suspension, call your doctor or your poison control center at 1-800-222-1222 right away or go to the nearest emergency room.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of Pantoprazole Sodium For Delayed-Release Oral Suspension? </span>\n</p>\n<p>\n<span class=\"Bold\">Pantoprazole Sodium For Delayed-Release Oral Suspension can cause serious side effects, including:  </span>\n</p>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">See “What is the most important information I should know about Pantoprazole Sodium For Delayed-Release Oral Suspension?”  </span>\n</li>\n<li>\n<span class=\"Bold\">Low vitamin B-12 levels </span>in your body can happen in people who have taken Pantoprazole Sodium For Delayed-Release Oral Suspension for a long time (more than 3 years). Tell your doctor if you have symptoms of low vitamin B-12 levels, including shortness of breath, lightheadedness, irregular heartbeat, muscle weakness, pale skin, feeling tired, mood changes, and tingling or numbness in the arms and legs. </li>\n<li>\n<span class=\"Bold\">Stomach growths (fundic gland polyps). </span>People who take PPI medicines for a long time have an increased risk of developing a certain type of stomach growths called fundic gland polyps, especially after taking PPI medicines for more than 1 year. </li>\n<li>\n<span class=\"Bold\">Severe skin reactions. </span>Pantoprazole Sodium For Delayed-Release Oral Suspension can cause rare but severe skin reactions that may affect any part of your body. These serious skin reactions may need to be treated in a hospital and may be life threatening:</li>\n<li>Skin rash which may have blistering, peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet).</li>\n<li>You may also have fever, chills, body aches, shortness of breath, or enlarged lymph nodes. Stop taking Pantoprazole Sodium For Delayed-Release Oral Suspension and call your doctor right away. These symptoms may be the first sign of a severe skin reaction.</li>\n</ul>\n<p>\n<span class=\"Bold\">The most common side effects of Pantoprazole Sodium For Delayed-Release Oral Suspension in adults include: </span>headache, diarrhea, nausea, stomach-area (abdominal) pain, vomiting, gas, dizziness, and joint pain. </p>\n<p>\n<span class=\"Bold\">The most common side effects of Pantoprazole Sodium For Delayed-Release Oral Suspension in children include: </span>upper respiratory infection, headache, fever, diarrhea, vomiting, rash, and stomach-area (abdominal) pain. </p>\n<p> </p>\n<p>These are not all the possible side effects of Pantoprazole Sodium For Delayed-Release Oral Suspension. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. </p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store Pantoprazole Sodium For Delayed-Release Oral Suspension? </span>\n<br/>Store Pantoprazole Sodium For Delayed-Release Oral Suspension at room temperature between 68°F to 77°F (20°C to 25°C). <br/>\n<br/>\n<span class=\"Bold\">Keep Pantoprazole Sodium For Delayed-Release Oral Suspension and all medicines out of the reach of children. </span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of Pantoprazole Sodium For Delayed-Release Oral Suspension. </span>\n<br/> </p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Pantoprazole Sodium For Delayed-Release Oral Suspension for a condition for which it was not prescribed. Do not give Pantoprazole Sodium For Delayed-Release Oral Suspension to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about Pantoprazole Sodium For Delayed-Release Oral Suspension that is written for health professionals.<br/> </p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in Pantoprazole Sodium For Delayed-Release Oral Suspension? </span>\n<br/>\n<br/>\n<span class=\"Bold\">Active ingredient: </span>pantoprazole sodium sesquihydrate <br/>\n<br/>\n<span class=\"Bold\">Inactive ingredients in Pantoprazole Sodium For Delayed-Release Oral Suspension: </span>crospovidone, hypromellose, lecithin, macrogol, methacrylic acid and ethyl acrylate copolymer dispersion, microcrystalline cellulose, polysorbate 80, polyvinyl alcohol-part hydrolyzed, sodium carbonate, talc, titanium dioxide, triethyl citrate, and iron oxide yellow.  <br/>This Medication Guide has been approved by the U.S. Food and Drug Administration.<br/>For more information call 1-866-604-3268.<br/>\n<br/>Disclaimer: Other brands listed are the registered trademarks of their respective owners and are not trademarks of Cipla Limited.<br/>\n<br/>Manufactured by:<br/>\n<span class=\"Bold\">Cipla Limited, (Kurkumbh)</span>\n<br/>Plot D-7, D-22, D-27,<br/>MIDC Industrial Area, Pune,<br/>India -413802<br/>Manufactured for:<br/>\n<span class=\"Bold\">Cipla USA, Inc.</span>\n<br/>10 Independence Boulevard,<br/>Suite 300 Warren, NJ 07059<br/>\n<br/>\n<span class=\"Bold\">Issued: 8/2023</span>\n<br/> </p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="middle" width="100%"/> <thead align="center"> <tr class="Last"> <th align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Instructions for Use</span>  <br/> <span class="Bold">Pantoprazole Sodium ((pan toe′ pra zole soe′ dee um)</span> <br/> <span class="Bold">for delayed-release oral suspension</span></th> </tr> </thead> <tbody> <tr class="First Last"> <td align="left" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Pantoprazole Sodium For Delayed-Release Oral Suspension (Pantoprazole Sodium For Oral Suspension): </span> </p> <p> <span class="Bold">Important information: </span> </p> <p> </p> <ul class="Disc"> <li> <span class="Bold">Do not split, chew, or crush Pantoprazole Sodium For Delayed-Release Oral Suspension. </span> </li> <li>Take Pantoprazole Sodium For Delayed-Release Oral Suspension about 30 minutes before a meal. </li> <li> <span class="Bold">Pantoprazole Sodium For Delayed-Release Oral Suspension: </span> <ul class="Circle"> <li>should <span class="Bold">only be taken with applesauce or apple juice. </span> </li> <li>should <span class="Bold">not be mixed in water or other liquids, or other foods. </span> </li> <li>packet should <span class="Bold">not </span>be divided to make a smaller dose. </li> </ul> </li> </ul> <p> <span class="Bold">Taking Pantoprazole Sodium For Delayed-Release Oral Suspension with applesauce: </span> </p> <ol class="Arabic"> <li>Open the packet of Pantoprazole Sodium For Delayed-Release Oral Suspension. </li> <li>Sprinkle all of the granules in the packet on 1 teaspoon of applesauce. </li> <li>Swallow the granules and applesauce <span class="Bold">within 10 minutes </span>of putting the granules on the teaspoon of applesauce. </li> <li>Take sips of water to make sure the granules are washed down into the stomach. Take more sips of water as needed. </li> </ol> <p> <span class="Bold">Taking Pantoprazole Sodium For Delayed-Release Oral Suspension with apple juice: </span> </p> <ol class="Arabic"> <li>Open the packet of Pantoprazole Sodium For Delayed-Release Oral Suspension. </li> <li>Empty all of the granules in the packet into a small cup that contains 1 teaspoon of apple juice. </li> <li>Stir the granules-apple juice mixture for 5 seconds. The granules will not break up. </li> <li>Swallow the mixture right away. </li> <li>To make sure that the entire dose is taken, add more apple juice to the cup, stir and swallow the apple juice right away. </li> <li>Repeat step 5 if there are granules left in the cup. </li> </ol> <p> <span class="Bold">Giving Pantoprazole Sodium For Delayed-Release Oral Suspension through a nasogastric (NG) tube or gastrostomy tube: </span> </p> <ul class="Disc"> <li>Pantoprazole Sodium For Delayed-Release Oral Suspension may be given through an NG tube or gastrostomy tube that is <span class="Bold">size 16 French or larger. </span>Do not give Pantoprazole Sodium For Delayed-Release Oral Suspension through an NG tube or gastrostomy tube smaller than size 16 French. </li> <li>Mix Pantoprazole Sodium For Delayed-Release Oral Suspension <span class="Bold">only in apple juice </span>when giving through an NG tube or gastrostomy tube. <ol class="Arabic"> <li>Remove the plunger from a 60 mL (2 ounce) catheter-tip syringe. Throw away the plunger. </li> <li>Connect the tip of the catheter-tip syringe to the NG tube or gastrostomy tube. </li> <li>Hold the syringe attached to the NG tube or gastrostomy tube as high as possible while giving Pantoprazole Sodium For Delayed-Release Oral Suspension to prevent the tubing from bending. </li> <li>Open the packet of Pantoprazole Sodium For Delayed-Release Oral Suspension. </li> <li>Empty all the granules in the packet into the catheter-tip syringe. </li> <li>Add 10 mL (2 teaspoons) of apple juice into the catheter-tip syringe and gently tap or shake the syringe to help empty the syringe. </li> <li>Repeat step 6 at least 2 more times until there are no granules left in the catheter-tip syringe. </li> </ol> </li> </ul> <p> <span class="Bold">How should I store Pantoprazole Sodium For Delayed-Release Oral Suspension? </span> </p> <p> </p> <p>Store Pantoprazole Sodium For Delayed-Release Oral Suspension at room temperature between 68°F to 77°F (20°C to 25°C). </p> <p> <span class="Bold">Keep Pantoprazole Sodium For Delayed-Release Oral Suspension and all medicines out of the reach of children. </span> </p> <p> </p> <p>This Instructions for Use has been approved by the U.S. Food and Drug Administration. </p> <p> </p> <p> </p> <p>Manufactured by:<br/> <span class="Bold">Cipla Limited, (Kurkumbh)</span> <br/>Plot D-7, D-22, D-27,<br/>MIDC Industrial Area, Pune,<br/>India -413802<br/>Manufactured for:<br/> <span class="Bold">Cipla USA, Inc</span> .<br/>10 Independence Boulevard,<br/>Suite 300 Warren, NJ 07059<br/> <span class="Bold">Issued: 8/2023</span> </p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"middle\" width=\"100%\"/>\n<thead align=\"center\">\n<tr class=\"Last\">\n<th align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Instructions for Use</span>  <br/>\n<span class=\"Bold\">Pantoprazole Sodium ((pan toe′ pra zole soe′ dee um)</span>\n<br/>\n<span class=\"Bold\">for delayed-release oral suspension</span></th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First Last\">\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Pantoprazole Sodium For Delayed-Release Oral Suspension (Pantoprazole Sodium For Oral Suspension): </span>\n</p>\n<p>\n<span class=\"Bold\">Important information: </span>\n</p>\n<p> </p>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Do not split, chew, or crush Pantoprazole Sodium For Delayed-Release Oral Suspension. </span>\n</li>\n<li>Take Pantoprazole Sodium For Delayed-Release Oral Suspension about 30 minutes before a meal. </li>\n<li>\n<span class=\"Bold\">Pantoprazole Sodium For Delayed-Release Oral Suspension: </span>\n<ul class=\"Circle\">\n<li>should <span class=\"Bold\">only be taken with applesauce or apple juice. </span>\n</li>\n<li>should <span class=\"Bold\">not be mixed in water or other liquids, or other foods. </span>\n</li>\n<li>packet should <span class=\"Bold\">not </span>be divided to make a smaller dose. </li>\n</ul>\n</li>\n</ul>\n<p>\n<span class=\"Bold\">Taking Pantoprazole Sodium For Delayed-Release Oral Suspension with applesauce: </span>\n</p>\n<ol class=\"Arabic\">\n<li>Open the packet of Pantoprazole Sodium For Delayed-Release Oral Suspension. </li>\n<li>Sprinkle all of the granules in the packet on 1 teaspoon of applesauce. </li>\n<li>Swallow the granules and applesauce <span class=\"Bold\">within 10 minutes </span>of putting the granules on the teaspoon of applesauce. </li>\n<li>Take sips of water to make sure the granules are washed down into the stomach. Take more sips of water as needed. </li>\n</ol>\n<p>\n<span class=\"Bold\">Taking Pantoprazole Sodium For Delayed-Release Oral Suspension with apple juice: </span>\n</p>\n<ol class=\"Arabic\">\n<li>Open the packet of Pantoprazole Sodium For Delayed-Release Oral Suspension. </li>\n<li>Empty all of the granules in the packet into a small cup that contains 1 teaspoon of apple juice. </li>\n<li>Stir the granules-apple juice mixture for 5 seconds. The granules will not break up. </li>\n<li>Swallow the mixture right away. </li>\n<li>To make sure that the entire dose is taken, add more apple juice to the cup, stir and swallow the apple juice right away. </li>\n<li>Repeat step 5 if there are granules left in the cup. </li>\n</ol>\n<p>\n<span class=\"Bold\">Giving Pantoprazole Sodium For Delayed-Release Oral Suspension through a nasogastric (NG) tube or gastrostomy tube: </span>\n</p>\n<ul class=\"Disc\">\n<li>Pantoprazole Sodium For Delayed-Release Oral Suspension may be given through an NG tube or gastrostomy tube that is <span class=\"Bold\">size 16 French or larger. </span>Do not give Pantoprazole Sodium For Delayed-Release Oral Suspension through an NG tube or gastrostomy tube smaller than size 16 French. </li>\n<li>Mix Pantoprazole Sodium For Delayed-Release Oral Suspension <span class=\"Bold\">only in apple juice </span>when giving through an NG tube or gastrostomy tube. <ol class=\"Arabic\">\n<li>Remove the plunger from a 60 mL (2 ounce) catheter-tip syringe. Throw away the plunger. </li>\n<li>Connect the tip of the catheter-tip syringe to the NG tube or gastrostomy tube. </li>\n<li>Hold the syringe attached to the NG tube or gastrostomy tube as high as possible while giving Pantoprazole Sodium For Delayed-Release Oral Suspension to prevent the tubing from bending. </li>\n<li>Open the packet of Pantoprazole Sodium For Delayed-Release Oral Suspension. </li>\n<li>Empty all the granules in the packet into the catheter-tip syringe. </li>\n<li>Add 10 mL (2 teaspoons) of apple juice into the catheter-tip syringe and gently tap or shake the syringe to help empty the syringe. </li>\n<li>Repeat step 6 at least 2 more times until there are no granules left in the catheter-tip syringe. </li>\n</ol>\n</li>\n</ul>\n<p>\n<span class=\"Bold\">How should I store Pantoprazole Sodium For Delayed-Release Oral Suspension? </span>\n</p>\n<p> </p>\n<p>Store Pantoprazole Sodium For Delayed-Release Oral Suspension at room temperature between 68°F to 77°F (20°C to 25°C). </p>\n<p>\n<span class=\"Bold\">Keep Pantoprazole Sodium For Delayed-Release Oral Suspension and all medicines out of the reach of children. </span>\n</p>\n<p> </p>\n<p>This Instructions for Use has been approved by the U.S. Food and Drug Administration. </p>\n<p> </p>\n<p> </p>\n<p>Manufactured by:<br/>\n<span class=\"Bold\">Cipla Limited, (Kurkumbh)</span>\n<br/>Plot D-7, D-22, D-27,<br/>MIDC Industrial Area, Pune,<br/>India -413802<br/>Manufactured for:<br/>\n<span class=\"Bold\">Cipla USA, Inc</span> .<br/>10 Independence Boulevard,<br/>Suite 300 Warren, NJ 07059<br/>\n<span class=\"Bold\">Issued: 8/2023</span>\n</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

NDC 69097-531-31     Rx Only

{ "type": "p", "children": [], "text": "\nNDC 69097-531-31     Rx Only" }

Pantoprazole Sodium 40 mg

{ "type": "p", "children": [], "text": "Pantoprazole Sodium 40 mg " }

For Delayed-Release Oral Suspension* *suspension in apple juice or applesauce only

{ "type": "p", "children": [], "text": "For Delayed-Release Oral Suspension* *suspension in apple juice or applesauce only" }

Each packet contains: Pantoprazole………40 mg (equivalent to 45.1 mg of pantoprazole sodium)

{ "type": "p", "children": [], "text": "Each packet contains: Pantoprazole………40 mg (equivalent to 45.1 mg of pantoprazole sodium)" }

TO OPEN: Fold back on dotted line and tear at

{ "type": "p", "children": [], "text": "TO OPEN: Fold back on dotted line and tear at" }

notch or use scissors. Do not use if opened.

{ "type": "p", "children": [], "text": "notch or use scissors. Do not use if opened." }

Cipla

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

NDC 69097-531-53                                Rx Only

{ "type": "p", "children": [], "text": "\nNDC 69097-531-53                                Rx Only" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "ALWAYS DISPENSE WITH MEDICATION GUIDE" }

Pantoprazole Sodium 40 mg

{ "type": "p", "children": [], "text": "Pantoprazole Sodium 40 mg " }

For Delayed-Release Oral Suspension*

{ "type": "p", "children": [], "text": "For Delayed-Release Oral Suspension*" }

*suspension in apple juice or applesauce only

{ "type": "p", "children": [], "text": " *suspension in apple juice or applesauce only" }

30 Packets

{ "type": "p", "children": [], "text": " 30 Packets" }

Cipla

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

Pantoprazole Sodium for Injection is indicated for short-term treatment (7 to 10 days) of adult patients with gastroesophageal reflux disease (GERD) and a history of erosive esophagitis (EE).

Safety and efficacy of Pantoprazole Sodium for Injection as a treatment of patients with GERD and a history of EE for more than 10 days have not been demonstrated.

Pantoprazole Sodium for Injection is indicated for the treatment of pathological hypersecretory conditions including Zollinger-Ellison (ZE) Syndrome in adults.

The recommended adult dosage of Pantoprazole Sodium for Injection is 40 mg given once daily by intravenous infusion for 7 to 10 days.

Discontinue treatment with Pantoprazole Sodium for Injection as soon as the patient is able to receive treatment with pantoprazole sodium delayed-release tablets or oral suspension.

Data on the safe and effective dosing for conditions other than those described [see Indications and Usage (1)] such as life-threatening upper gastrointestinal bleeds, are not available. Pantoprazole Sodium for Injection 40 mg once daily does not raise gastric pH to levels sufficient to contribute to the treatment of such life-threatening conditions.

For intravenous infusion only.

Fifteen Minute Infusion

1.   Reconstitute Pantoprazole Sodium for Injection with 10 mL of 0.9% Sodium Chloride Injection, USP

2.   Further dilute with 100 mL of 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer's Injection, USP, to a final concentration of approximately 0.4 mg/mL.

3.   Inspect the diluted Pantoprazole Sodium for Injection solution visually for particulate matter and discoloration prior to and during administration.

4.   Administer intravenously over a period of approximately 15 minutes at a rate of approximately 7 mL/minute.

Storage

The reconstituted solution may be stored for up to 6 hours at room temperature prior to further dilution. The diluted solution may be stored at room temperature and must be used within 24 hours from the time of initial reconstitution. Both the reconstituted solution and the diluted solution do not need to be protected from light.

Do not freeze either the reconstituted or diluted solutions.

Two Minute Infusion

1.   Reconstitute Pantoprazole Sodium for Injection with 10 mL of 0.9% Sodium Chloride Injection, USP, to a final concentration of approximately 4 mg/mL.

2.   Inspect the diluted Pantoprazole Sodium for Injection solution visually for particulate matter and discoloration prior to and during administration.

3.   Administer intravenously over a period of at least 2 minutes.

Storage

The reconstituted solution may be stored for up to 24 hours at room temperature prior to intravenous infusion and does not need to be protected from light.

Do not freeze either the reconstituted or diluted solutions.

The recommended adult dosage of Pantoprazole Sodium for Injection is 80 mg intravenously every 12 hours. The frequency of dosing can be adjusted to individual patient needs based on acid output measurements. In those patients who need a higher dosage, 80 mg intravenously every 8 hours is expected to maintain acid output below 10 mEq/h. Daily doses higher than 240 mg or administered for more than 6 days have not been studied [see Clinical Studies (14.2)]. Transition from oral to intravenous and from intravenous to oral formulations of gastric acid inhibitors should be performed in such a manner to ensure continuity of effect of suppression of acid secretion. Patients with ZE Syndrome may be vulnerable to serious clinical complications of increased acid production even after a short period of loss of effective inhibition.

For intravenous infusion only.

Fifteen Minute Infusion

1.         Reconstitute each vial of Pantoprazole Sodium for Injection with 10 mL of 0.9% Sodium Chloride Injection, USP.

2.         Combine the contents of the two vials and further dilute with 80 mL of 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer's Injection, USP, to a total volume of 100 mL with a final concentration of approximately 0.8 mg/mL.

3.         Inspect the diluted Pantoprazole Sodium for Injection solution visually for particulate matter and discoloration prior to and during administration.

4.         Administer intravenously over a period of approximately 15 minutes at a rate of approximately 7 mL/minute.

Storage

The reconstituted solution may be stored for up to 6 hours at room temperature prior to further dilution. The diluted solution may be stored at room temperature and must be used within 24 hours from the time of initial reconstitution. Both the reconstituted solution and the diluted solution do not need to be protected from light.

Do not freeze either the reconstituted or diluted solutions.

Two Minute Infusion

1.   Reconstitute Pantoprazole Sodium for Injection with 10 mL of 0.9% Sodium Chloride Injection, USP, per vial to a final concentration of approximately 4 mg/mL.

2.   Inspect the reconstituted Pantoprazole Sodium for Injection solution visually for particulate matter and discoloration prior to and during administration.

3.   Administer the total volume from both vials intravenously over a period of at least 2 minutes.

Storage

The reconstituted solution may be stored for up to 24 hours at room temperature prior to intravenous infusion and does not need to be protected from light.

Do not freeze the reconstituted solution.

•      Administer Pantoprazole Sodium for Injection intravenously through a dedicated line or through a Y-site.

•      Flush the intravenous line before and after administration of Pantoprazole Sodium for Injection with either 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer's Injection, USP.

•      When administered through a Y-site, Pantoprazole Sodium for Injection is compatible with the following solutions: 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer's Injection, USP.

•      Midazolam HCl has been shown to be incompatible with Y-site administration of Pantoprazole Sodium for Injection.

•      Pantoprazole Sodium for Injection may not be compatible with products containing zinc.

•      When administered through a Y-site, immediately discontinue the infusion if precipitation or discoloration occurs.

For Injection: 40 mg pantoprazole white to off-white lyophilized powder in a single-dose vial for reconstitution.

{ "type": "p", "children": [], "text": "For Injection: 40 mg pantoprazole white to off-white lyophilized powder in a single-dose vial for reconstitution." }

•     Pantoprazole Sodium for Injection is contraindicated in patients with known hypersensitivity reactions including anaphylaxis to the formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions (5.3), Adverse Reactions (6)].

{ "type": "p", "children": [], "text": "•     Pantoprazole Sodium for Injection is contraindicated in patients with known hypersensitivity reactions including anaphylaxis to the formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions (5.3), Adverse Reactions (6)]." }

•     Proton pump inhibitors (PPIs), including Pantoprazole Sodium for Injection, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions (7)].

{ "type": "p", "children": [], "text": "•     Proton pump inhibitors (PPIs), including Pantoprazole Sodium for Injection, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions (7)]." }

In adults, symptomatic response to therapy with Pantoprazole Sodium for Injection does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy.

Thrombophlebitis was associated with the administration of another intravenous pantoprazole sodium product.

Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue Pantoprazole Sodium for Injection and evaluate patients with suspected acute TIN [see Contraindications (4)].

Published observational studies suggest that PPI therapy like Pantoprazole Sodium for Injection may be associated with an increased risk of Clostridium difficile-associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.2)].

Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.

Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2.2, 2.4) and Adverse Reactions (6)].

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs [see Adverse Reactions (6.2)]. Discontinue Pantoprazole Sodium for Injection at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including pantoprazole sodium. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematous cases were CLE.

The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement.

Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported.

Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving Pantoprazole Sodium for Injection, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g. ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations.

Mild, transient transaminase elevations have been observed in clinical studies. The clinical significance of this finding in a large population of subjects administered intravenous pantoprazole sodium is unknown [see Adverse Reactions (6.1)].

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, and in most cases after a year of therapy. Serious adverse reactions include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. 

For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), healthcare professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2)].

Consider monitoring magnesium and calcium levels prior to initiation of Pantoprazole Sodium for Injection and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium as necessary. If hypocalcemia is refractory to treatment, consider discontinuing the PPI.

PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated.

Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop Pantoprazole Sodium for Injection treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary [see Clinical Pharmacology (12.2)].

Pantoprazole sodium may produce a false-positive urine screen for THC (tetrahydrocannabinol) [see Drug Interactions (7)].

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions (7)].

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 clinical practice.

The safety of Pantoprazole Sodium for Injection has been established from adequate and well-controlled studies of another intravenous pantoprazole sodium product [see Clinical Studies (14)]. Below is a display of the adverse reactions of pantoprazole sodium in these adequate and well-controlled studies.

Gastroesophageal Reflux Disease (GERD)

Safety in nine randomized comparative US clinical trials in patients with GERD included 1,473 patients on oral pantoprazole (20 mg or 40 mg), 299 patients on an H2-receptor antagonist, 46 patients on another PPI, and 82 patients on placebo. The most frequently occurring adverse reactions are listed in Table 1.

The number of patients treated in comparative studies with intravenous pantoprazole sodium is limited; however, the adverse reactions seen were similar to those seen in the oral studies. Thrombophlebitis was the only new adverse reaction identified with intravenous pantoprazole sodium.

Table 1: Adverse Reactions Reported in Clinical Trials of Adult Patients with GERD at a Frequency of >2%

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <br/> </td><td> <p class="First"> <span class="Bold">O</span><span class="Bold">ral Pantoprazole Sodium<br/> </span><span class="Bold">(</span><span class="Bold">n=1473)<br/> </span><span class="Bold">%</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">C</span><span class="Bold">o</span><span class="Bold">m</span><span class="Bold">parators<br/> </span><span class="Bold">(</span><span class="Bold">n=345)<br/> </span><span class="Bold">%</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">P</span><span class="Bold">lacebo<br/> </span><span class="Bold">(</span><span class="Bold">n=82)<br/> </span><span class="Bold">%</span> </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">12.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">12.8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">8.5</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">8.8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">9.6</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">4.9</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">7</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">5.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">9.8</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">6.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">4.1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">6.1</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">4.3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">3.5</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">2.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Flatulence</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">3.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">2.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">3.7</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">3</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">2.9</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.2</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Arthralgia</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">2.8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.2</p> </td> </tr> </tbody> </table></div>

Additional adverse reactions that were reported for oral pantoprazole sodium in US clinical trials with a frequency of 2% or less are listed below by body system:

Body as a Whole: allergic reaction, fever, photosensitivity reaction, facial edema, thrombophlebitis (intravenous only)

Gastrointestinal: constipation, dry mouth, hepatitis Hematologic: leukopenia (reported in ex-US clinical trials only), thrombocytopenia

Metabolic/Nutritional: elevated CPK (creatine phosphokinase), generalized edema, elevated triglycerides, liver function tests abnormal

Musculoskeletal: myalgia

Nervous: depression, vertigo

Skin and Appendages: urticaria, rash, pruritus

Special Senses: blurred vision

Zollinger-Ellison Syndrome

In clinical studies of Zollinger-Ellison Syndrome, adverse reactions reported in 35 patients administered oral pantoprazole doses of 80 mg to 240 mg per day for up to 2 years were similar to those reported in adult patients with GERD.

The following adverse reactions have been identified during postapproval use of other pantoprazole sodium products. 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.

These adverse reactions are listed below by body system:

General Disorders and Administration Conditions: asthenia, fatigue, malaise

Immune System Disorders: anaphylaxis (including anaphylactic shock), systemic lupus erythematosus

Investigations: weight changes

Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions (some fatal), including erythema multiforme, SJS/TEN, DRESS, AGEP [see Warnings and Precautions (5.6)], and angioedema (Quincke's edema) and cutaneous lupus erythematosus

Musculoskeletal Disorders: rhabdomyolysis, bone fracture

Renal and Genitourinary Disorders: interstitial nephritis, erectile dysfunction

Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure

Psychiatric Disorder: hallucinations, confusion, insomnia, somnolence

Metabolism and Nutritional Disorders: hypomagnesemia, hypocalcemia, hypokalemia [see Warnings and Precautions (5.9)], hyponatremia 

Infections and Infestations: Clostridium difficile-associated diarrhea

Hematologic: pancytopenia, agranulocytosis

Nervous: ageusia, dysgeusia

Gastrointestinal Disorders: fundic gland polyps

Table 2 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with Pantoprazole Sodium for Injection and instructions for preventing or managing them.

{ "type": "p", "children": [], "text": "Table 2 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with Pantoprazole Sodium for Injection and instructions for preventing or managing them." }

Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.

{ "type": "p", "children": [], "text": "Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs." }

Table 2: Clinically Relevant Interactions Affecting Drugs Co-Administered with Pantoprazole Sodium for Injection and Interaction with Diagnostics

{ "type": "p", "children": [], "text": "\nTable 2: Clinically Relevant Interactions Affecting Drugs Co-Administered with Pantoprazole Sodium for Injection and Interaction with Diagnostics\n" }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Antiretrovirals</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">C</span><span class="Italics">linical Impact:</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known.</p> <p>• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with pantoprazole may reduce antiviral effect and promote the development of drug resistance<span class="Italics">.</span> </p> <p>• Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with pantoprazole may increase toxicity <span class="Italics">[see <a href="#www.splportal.comLINK_a0e3b629-b55b-404c-9c1a-02bf5af9d7ec">Clinical Pharmacology (12.3</a>)]</span>. </p> <p>• There are other antiretroviral drugs which do not result in clinically relevant interactions with pantoprazole.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Underline">R</span><span class="Underline">ilpivirine-containing products:</span> Concomitant use with Pantoprazole Sodium for Injection is contraindicated <span class="Italics">[see <a href="#www.splportal.comLINK_ee48c310-f899-46d5-8513-3f5b635aa4f4">Contraindications (4)</a>]</span>. See prescribing information. </p> <p> <span class="Underline">Atazanavir:</span> See prescribing information for atazanavir for dosing information.</p> <p> <span class="Underline">Nelfinavir:</span> Avoid concomitant use with Pantoprazole Sodium for Injection. See prescribing information for nelfinavir.</p> <p> <span class="Underline">S</span><span class="Underline">a</span><span class="Underline">quinavir:</span> See the prescribing information for saquinavir and for monitoring of potential saquinavir-related toxicities.</p> <p> <span class="Underline">Other antiretrovirals:</span> See prescribing information for specific antiretroviral drugs. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Warfarin</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">C</span><span class="Italics">linical Impact:</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Increased INR and prothrombin time in patients receiving PPIs, including pantoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Monitor INR and prothrombin time and adjust the dose of warfarin, if needed, to maintain the target INR range. See prescribing information for warfarin. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Clopidogrel</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">C</span><span class="Italics">linical Impact:</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel-induced platelet inhibition <span class="Italics">[see <a href="#www.splportal.comLINK_a0e3b629-b55b-404c-9c1a-02bf5af9d7ec">Clinical Pharmacology (12.3)</a>]. </span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">No dose adjustment of clopidogrel is necessary when administered with an approved dose of Pantoprazole Sodium for Injection. </p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Antiretrovirals</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Italics\">C</span><span class=\"Italics\">linical Impact:</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known.</p>\n<p>• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with pantoprazole may reduce antiviral effect and promote the development of drug resistance<span class=\"Italics\">.</span>\n</p>\n<p>• Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with pantoprazole may increase toxicity <span class=\"Italics\">[see <a href=\"#www.splportal.comLINK_a0e3b629-b55b-404c-9c1a-02bf5af9d7ec\">Clinical Pharmacology (12.3</a>)]</span>. </p>\n<p>• There are other antiretroviral drugs which do not result in clinically relevant interactions with pantoprazole.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Italics\">I</span><span class=\"Italics\">ntervention:</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Underline\">R</span><span class=\"Underline\">ilpivirine-containing products:</span> Concomitant use with Pantoprazole Sodium for Injection is contraindicated <span class=\"Italics\">[see <a href=\"#www.splportal.comLINK_ee48c310-f899-46d5-8513-3f5b635aa4f4\">Contraindications (4)</a>]</span>. See prescribing information. </p>\n<p>\n<span class=\"Underline\">Atazanavir:</span> See prescribing information for atazanavir for dosing information.</p>\n<p>\n<span class=\"Underline\">Nelfinavir:</span> Avoid concomitant use with Pantoprazole Sodium for Injection. See prescribing information for nelfinavir.</p>\n<p>\n<span class=\"Underline\">S</span><span class=\"Underline\">a</span><span class=\"Underline\">quinavir:</span> See the prescribing information for saquinavir and for monitoring of potential saquinavir-related toxicities.</p>\n<p>\n<span class=\"Underline\">Other antiretrovirals:</span> See prescribing information for specific antiretroviral drugs. </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Warfarin</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Italics\">C</span><span class=\"Italics\">linical Impact:</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Increased INR and prothrombin time in patients receiving PPIs, including pantoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Italics\">I</span><span class=\"Italics\">ntervention:</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Monitor INR and prothrombin time and adjust the dose of warfarin, if needed, to maintain the target INR range. See prescribing information for warfarin. </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Clopidogrel</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Italics\">C</span><span class=\"Italics\">linical Impact:</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel-induced platelet inhibition <span class=\"Italics\">[see <a href=\"#www.splportal.comLINK_a0e3b629-b55b-404c-9c1a-02bf5af9d7ec\">Clinical Pharmacology (12.3)</a>]. </span>\n</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Italics\">I</span><span class=\"Italics\">ntervention:</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">No dose adjustment of clopidogrel is necessary when administered with an approved dose of Pantoprazole Sodium for Injection. </p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Met</span><span class="Bold">h</span><span class="Bold">otrexate</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">C</span><span class="Italics">linical Impact:</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted <span class="Italics">[see <a href="#www.splportal.comLINK_edad2b28-8198-472c-947f-bc044440cc2b">Warnings and Precautions (5.13)</a>].</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">A temporary withdrawal of Pantoprazole Sodium for Injection may be considered in some patients receiving high-dose methotrexate.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, </span><span class="Bold">n</span><span class="Bold">ilotinib, mycophenoloate mofetil, ketoconazole/itraconazole)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">C</span><span class="Italics">linical Impact:</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Pantoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Mycophenolate mofetil (MMF): Co-administration of pantoprazole sodium in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH <span class="Italics">[see <a href="#www.splportal.comLINK_a0e3b629-b55b-404c-9c1a-02bf5af9d7ec">Clinical Pharmacology (12.3</a>)]</span>. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving Pantoprazole Sodium for Injection and MMF. Use Pantoprazole Sodium for Injection with caution in transplant patients receiving MMF <span class="Italics">[see <a href="#www.splportal.comLINK_a0e3b629-b55b-404c-9c1a-02bf5af9d7ec">Clinical Pharmacology (12.3)</a>]</span>.</p> <p>See the prescribing information for other drugs dependent on gastric pH for absorption.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Interactions with Investigations of Neuroendocrine Tumors </span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">C</span><span class="Italics">linical Impact:</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">CgA levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors <span class="Italics">[see <a href="#www.splportal.comLINK_399b8431-8bd0-4b26-9074-c5472022155b">Warnings and Precautions (5.11)</a>, <a href="#www.splportal.comLINK_1a08c30c-33d2-4898-b57c-8dd379621245">Clinical Pharmacology (12.2)</a>]</span>. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Temporarily stop Pantoprazole Sodium for Injection treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">F</span><span class="Bold">alse Positive Urine Tests for THC</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">C</span><span class="Italics">linical Impact:</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including pantoprazole sodium <span class="Italics">[see <a href="#www.splportal.comLINK_02346b5a-d93d-43b0-a49d-ec2d8273bdd9">Warnings and Precautions (5.12</a>)]</span>.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">I</span><span class="Italics">ntervention:</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">An alternative confirmatory method should be considered to verify positive results.</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Met</span><span class=\"Bold\">h</span><span class=\"Bold\">otrexate</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Italics\">C</span><span class=\"Italics\">linical Impact:</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted <span class=\"Italics\">[see <a href=\"#www.splportal.comLINK_edad2b28-8198-472c-947f-bc044440cc2b\">Warnings and Precautions (5.13)</a>].</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Italics\">I</span><span class=\"Italics\">ntervention:</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">A temporary withdrawal of Pantoprazole Sodium for Injection may be considered in some patients receiving high-dose methotrexate.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, </span><span class=\"Bold\">n</span><span class=\"Bold\">ilotinib, mycophenoloate mofetil, ketoconazole/itraconazole)</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Italics\">C</span><span class=\"Italics\">linical Impact:</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Pantoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Italics\">I</span><span class=\"Italics\">ntervention:</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Mycophenolate mofetil (MMF): Co-administration of pantoprazole sodium in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH <span class=\"Italics\">[see <a href=\"#www.splportal.comLINK_a0e3b629-b55b-404c-9c1a-02bf5af9d7ec\">Clinical Pharmacology (12.3</a>)]</span>. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving Pantoprazole Sodium for Injection and MMF. Use Pantoprazole Sodium for Injection with caution in transplant patients receiving MMF <span class=\"Italics\">[see <a href=\"#www.splportal.comLINK_a0e3b629-b55b-404c-9c1a-02bf5af9d7ec\">Clinical Pharmacology (12.3)</a>]</span>.</p>\n<p>See the prescribing information for other drugs dependent on gastric pH for absorption.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Interactions with Investigations of Neuroendocrine Tumors </span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Italics\">C</span><span class=\"Italics\">linical Impact:</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">CgA levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors <span class=\"Italics\">[see <a href=\"#www.splportal.comLINK_399b8431-8bd0-4b26-9074-c5472022155b\">Warnings and Precautions (5.11)</a>, <a href=\"#www.splportal.comLINK_1a08c30c-33d2-4898-b57c-8dd379621245\">Clinical Pharmacology (12.2)</a>]</span>. </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Italics\">I</span><span class=\"Italics\">ntervention:</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Temporarily stop Pantoprazole Sodium for Injection treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary. </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">F</span><span class=\"Bold\">alse Positive Urine Tests for THC</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Italics\">C</span><span class=\"Italics\">linical Impact:</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including pantoprazole sodium <span class=\"Italics\">[see <a href=\"#www.splportal.comLINK_02346b5a-d93d-43b0-a49d-ec2d8273bdd9\">Warnings and Precautions (5.12</a>)]</span>.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Italics\">I</span><span class=\"Italics\">ntervention:</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">An alternative confirmatory method should be considered to verify positive results.</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Risk Summary

Available data from published observational studies did not demonstrate an association of major malformations or other adverse pregnancy outcomes with pantoprazole (see Data).

In animal reproduction studies, no evidence of adverse development outcomes was observed with pantoprazole. Reproduction studies have been performed in rats at intravenous doses up to 20 mg/kg/day (4 times the recommended human dose) and rabbits at intravenous doses up to 15 mg/kg/day (6 times the recommended human dose) with administration of pantoprazole during organogenesis in pregnant animals and have revealed no evidence of harm to the fetus due to pantoprazole in this study (see Data).

A pre- and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. Oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day) were administered to pregnant females from gestation day (GD) 6 through lactation day (LD) 21. Changes in bone morphology were observed in pups exposed to pantoprazole in utero and through milk during the period of lactation as well as by oral dosing from postnatal day (PND) 4 through PND 21 [see Use in Specific Populations (8.4)]. There were no drug-related findings in maternal animals.  Advise pregnant women of the potential risk of fetal harm.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

Available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and pantoprazole use. Methodological limitations of these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. In a prospective study by the European Network of Teratology Information Services, outcomes from a group of 53 pregnant women administered median daily doses of 40 mg pantoprazole were compared to a control group of 868 pregnant women who did not take any proton pump inhibitors (PPIs). There was no difference in the rate of major malformations between women exposed to PPIs and the control group, corresponding to a Relative Risk (RR)= 0.55, [95% Confidence Interval (CI) 0.08-3.95]. In a population-based retrospective cohort study covering all live births in Denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to pantoprazole in 549 live births. A meta-analysis that compared 1,530 pregnant women exposed to PPIs in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to PPIs (for major malformations OR=1.12 [95% CI 0.86-1.45] and for spontaneous abortions OR=1.29 [95% CI 0.84-1.97]).

Animal Data

Reproduction studies have been performed in rats at intravenous pantoprazole doses up to 20 mg/kg/day (4 times the recommended human dose based on body surface area) and rabbits at intravenous doses up to 15 mg/kg/day (6 times the recommended human dose based on body surface area) with administration of pantoprazole sodium during organogenesis in pregnant animals and have revealed no evidence of impaired fertility or harm to the fetus due to pantoprazole.

A pre- and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. Oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day on a body surface area basis) were administered to pregnant females from gestation day (GD) 6 through lactation day (LD) 21. On postnatal day (PND) 4 through PND 21, the pups were administered oral doses at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (AUC) in humans at a dose of 40 mg). There were no drug-related findings in maternal animals. During the preweaning dosing phase (PND 4 to 21) of the pups, there were increased mortality and/or moribundity and decreased body weight and body weight gain at 5 mg/kg/day (approximately equal exposures (AUC) in humans receiving the 40 mg dose) and higher doses. On PND 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (AUC) in humans at the 40 mg dose) and higher doses. The femur findings included lower total area, bone mineral content and density, periosteal and endosteal circumference, and cross-sectional moment of inertia. There were no microscopic changes in the distal femur, proximal tibia, or stifle joints.

Changes in bone parameters were partially reversible following a recovery period, with findings on PND 70 limited to lower femur metaphysis cortical/subcortical bone mineral density in female pups at 5 mg/kg/day (approximately equal exposures (AUC) in humans at the 40 mg dose) and higher doses.

Risk Summary

The limited data from a single case reports the presence of pantoprazole in human breast milk. There were no effects on the breastfed infant (see Data). There are no data on pantoprazole effects on milk production.

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

Data

The breast milk of a 42-year-old woman receiving 40 mg of oral pantoprazole, at 10 months postpartum, was studied for 24 hours, to demonstrate low levels of pantoprazole present in the breast milk. Pantoprazole was detectable in milk only 2 and 4 hours after the dose with milk levels of approximately 36 mcg/L and 24 mcg/L, respectively. A milk-to-plasma ratio of 0.022 was observed at 2 hours after drug administration. Pantoprazole was not detectable (less than 10 mcg/L) in milk at 6, 8 and 24 hours after the dose. The relative dose to the infant was estimated to be 7.3 mcg of pantoprazole, which is equivalent to 0.14% of the weight-adjusted maternal dose. No adverse events in the infant were reported by the mother.

The safety and effectiveness of Pantoprazole Sodium for Injection have not been established in pediatric patients.

Animal Toxicity Data

In a pre- and post-natal development study in rats, the pups were administered oral doses of pantoprazole at 5, 15, and 30 mg/kg/day on postnatal day (PND 4) through PND 21, in addition to lactational exposure through milk.  On PND 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day and higher doses. Changes in bone parameters were partially reversible following a recovery period [see Use in Specific Populations (8.1)].

In neonatal/juvenile animals (rats and dogs) toxicities were similar to those observed in adult animals including gastric alterations, decreases in red cell mass, increases in lipids, enzyme induction and hepatocellular hypertrophy. An increased incidence of eosinophilic chief cells in adult and neonatal/juvenile rats, and atrophy of chief cells in adult rats and in neonatal/juvenile dogs, was observed in the fundic mucosa of stomachs in repeated-dose studies. Full to partial recovery of these effects were noted in animals of both age groups following a recovery period.

Of 286 patients in clinical studies of intravenous pantoprazole sodium in patients with GERD and a history of EE, 86 (43%) were 65 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience with oral pantoprazole sodium has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Experience in patients taking very high doses of pantoprazole (greater than 240 mg) is limited. Adverse reactions seen in spontaneous reports of overdose generally reflect the known safety profile of pantoprazole.

{ "type": "p", "children": [], "text": "Experience in patients taking very high doses of pantoprazole (greater than 240 mg) is limited. Adverse reactions seen in spontaneous reports of overdose generally reflect the known safety profile of pantoprazole." }

Pantoprazole is not removed by hemodialysis. In case of overdose, treatment should be symptomatic and supportive.

{ "type": "p", "children": [], "text": "Pantoprazole is not removed by hemodialysis. In case of overdose, treatment should be symptomatic and supportive." }

Single intravenous doses of pantoprazole at 378, 230, and 266 mg/kg (38, 46, and 177 times the recommended human dose based on body surface area) were lethal to mice, rats and dogs, respectively. The symptoms of acute toxicity were hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor.

{ "type": "p", "children": [], "text": "Single intravenous doses of pantoprazole at 378, 230, and 266 mg/kg (38, 46, and 177 times the recommended human dose based on body surface area) were lethal to mice, rats and dogs, respectively. The symptoms of acute toxicity were hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor." }

The active ingredient in Pantoprazole Sodium for Injection, a PPI, is a substituted benzimidazole, sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its empirical formula is C16H14F2N3NaO4S•1.5 H2O, with a molecular weight of 432.37. The structural formula is:

{ "type": "p", "children": [], "text": "The active ingredient in Pantoprazole Sodium for Injection, a PPI, is a substituted benzimidazole, sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its empirical formula is C16H14F2N3NaO4S•1.5 H2O, with a molecular weight of 432.37. The structural formula is: " }

Pantoprazole sodium is a white to off-white crystalline powder and is racemic. Pantoprazole sodium is freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in n-hexane. The stability of the compound in aqueous solution is pH-dependent. The rate of degradation increases with decreasing pH. The reconstituted solution of Pantoprazole Sodium for Injection is in the pH range 9.5 to 11.5.

{ "type": "p", "children": [], "text": "Pantoprazole sodium is a white to off-white crystalline powder and is racemic. Pantoprazole sodium is freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in n-hexane. The stability of the compound in aqueous solution is pH-dependent. The rate of degradation increases with decreasing pH. The reconstituted solution of Pantoprazole Sodium for Injection is in the pH range 9.5 to 11.5." }

Pantoprazole Sodium for Injection is supplied for intravenous administration as a sterile lyophilized powder in a single-dose clear glass vial fitted with a rubber stopper and crimp seal. Each vial contains 40 mg pantoprazole (equivalent to 45.1 mg of pantoprazole sodium), and sodium hydroxide to adjust pH.

{ "type": "p", "children": [], "text": "Pantoprazole Sodium for Injection is supplied for intravenous administration as a sterile lyophilized powder in a single-dose clear glass vial fitted with a rubber stopper and crimp seal. Each vial contains 40 mg pantoprazole (equivalent to 45.1 mg of pantoprazole sodium), and sodium hydroxide to adjust pH." }

Pantoprazole is a PPI that suppresses the final step in gastric acid production by covalently binding to the (H+, K+)-ATPase enzyme system at the secretory surface of the gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion irrespective of the stimulus. The binding to the (H+, K+)-ATPase results in a duration of antisecretory effect that persists longer than 24 hours for all doses tested (20 mg to 120 mg).

Antisecretory Activity

The magnitude and time course for inhibition of pentagastrin-stimulated acid output (PSAO) by single intravenous doses (20 to 120 mg) of pantoprazole were assessed in a single-dose, open-label, placebo-controlled, dose-response study. The results of this study are shown in Table 3. Healthy subjects received a continuous infusion for 25 hours of pentagastrin (PG) at 1 mcg/kg/hour, a dose known to produce submaximal gastric acid secretion. The placebo group showed a sustained, continuous acid output for 25 hours, validating the reliability of the testing model. Intravenous administration of pantoprazole sodium had an onset of antisecretory activity within 15 to 30 minutes of administration.

Intravenous doses of 20 to 80 mg of pantoprazole substantially reduced the 24-hour cumulative PSAO in a dose-dependent manner, despite a short plasma elimination half-life. Complete suppression of PSAO was achieved with 80 mg within approximately 2 hours and no further significant suppression was seen with 120 mg. The duration of action of intravenous pantoprazole sodium was 24 hours.

Table 3: Gastric Acid Output (mEq/hr, Mean ± SD) and Percent Inhibition* (Mean ± SD) of Pentagastrin-Stimulated Acid Output Over 24 Hours Following a Single Dose of Another Intravenous Pantoprazole Sodium† Product in Healthy Subjects

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0"> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <br/> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">2 hours</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">4 hours</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">1</span><span class="Bold">2 hours</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">2</span><span class="Bold">4 hours</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Treatment Dose</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Acid</span> </p> <p> <span class="Bold">O</span><span class="Bold">utput</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">% Inhibition</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Acid</span> </p> <p> <span class="Bold">O</span><span class="Bold">utput</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">% Inhibition</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Acid</span> </p> <p> <span class="Bold">O</span><span class="Bold">utput</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">% Inhibition</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Acid</span> </p> <p> <span class="Bold">O</span><span class="Bold">utput</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">% Inhibition</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">0 mg</p> <p>(Placebo, n=4)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">39 ± 21</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">NA</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">26 ± 14</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">NA</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">32 ± 20</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">NA</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">38 ± 24</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">NA</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">20 mg</p> <p>(n=4-6)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">13 ± 18</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">47 ± 27</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">6 ± 8</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">83 ± 21</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">20 ± 20</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">54 ± 44</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">30 ± 23</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">45 ± 43</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">40 mg</p> <p>(n=8)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">5 ± 5</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">82 ± 11</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">4 ± 4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">90 ± 11</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">11 ± 10</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">81 ± 13</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">16 ± 12</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">52 ± 36</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">80 mg</p> <p>(n=8)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.1 ± 0.2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">96 ± 6</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.3 ± 0.4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">99 ± 1</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">2 ± 2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">90 ± 7</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">7 ± 4</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">63 ± 18</p> </td> </tr> </tbody> </table></div>

NA = not applicable.* Compared to individual subject baseline prior to treatment with intravenous pantoprazole sodium.† Inhibition of gastric acid output and the percent inhibition of stimulated acid output in response to intravenous pantoprazole sodium may be higher after repeated doses.

In one study of gastric pH in healthy subjects, pantoprazole was administered orally (40 mg enteric coated tablets) or intravenously (40 mg) once daily for 5 days and pH was measured for 24 hours following the fifth dose. The outcome measure was median percent of time that pH was ≥ 4 and the results were similar for intravenous and oral medications; however, the clinical significance of this parameter is unknown.

Serum Gastrin Effects

Serum gastrin concentrations were assessed in two placebo-controlled studies.

In a 5-day study of oral pantoprazole with 40 and 60 mg doses in healthy subjects, following the last dose on day 5, median 24-hour serum gastrin concentrations were elevated by 3 to 4 fold compared to placebo in both 40 and 60 mg dose groups. However, by 24 hours following the last dose, median serum gastrin concentrations for both groups returned to normal levels.

In another placebo-controlled, 7-day study of 40 mg intravenous or oral pantoprazole in patients with GERD and a history of EE, the mean serum gastrin concentration increased approximately 50% from baseline and as compared with placebo, but remained within the normal range.

During 6 days of repeated administration of intravenous pantoprazole sodium in patients with ZE Syndrome, consistent changes of serum gastrin concentrations from baseline were not observed.

Enterochromaffin-Like (ECL) Cell Effects

There are no data available on the effects of intravenous pantoprazole sodium on ECL cells.

In a nonclinical study in Sprague-Dawley rats, lifetime exposure (24 months) to oral pantoprazole at doses of 0.5 to 200 mg/kg/day resulted in dose-related increases in gastric ECL-cell proliferation and gastric neuroendocrine (NE)-cell tumors. Gastric NE-cell tumors in rats may result from chronic elevation of serum gastrin concentrations. The high density of ECL cells in the rat stomach makes this species highly susceptible to the proliferative effects of elevated gastrin concentrations produced by PPIs. However, there were no observed elevations in serum gastrin following the administration of oral pantoprazole at a dose of 0.5 mg/kg/day. In a separate study, a gastric NE-cell tumor without concomitant ECL-cell proliferative changes was observed in 1 female rat following 12 months of dosing with oral pantoprazole at 5 mg/kg/day and a 9 month off-dose recovery [see Nonclinical Toxicology (13.1)].

Endocrine Effects

In a clinical pharmacology study, pantoprazole 40 mg given orally once daily for 2 weeks had no effect on the levels of the following hormones: cortisol, testosterone, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone, thyronine-binding protein, parathyroid hormone, insulin, glucagon, renin, aldosterone, follicle-stimulating hormone, luteinizing hormone, prolactin and growth hormone.

Pantoprazole peak serum concentration (Cmax) and area under the serum concentration-time curve (AUC) increase in a manner proportional to intravenous doses of pantoprazole from 10 mg to 80 mg. Pantoprazole does not accumulate and its pharmacokinetics are unaltered with multiple daily dosing. Following the administration of intravenous pantoprazole sodium, the serum concentration of pantoprazole declines biexponentially with a terminal elimination half-life of approximately one hour. In CYP2C19 extensive metabolizers [see Clinical Pharmacology (12.5)] with normal liver function receiving a 40 mg intravenous dose of pantoprazole by constant rate over 15 minutes, the peak concentration (Cmax) is 5.52 ± 1.42 mcg/mL and the total area under the plasma concentration versus time curve (AUC) is 5.4 ± 1.5 mcg•hr/mL. The total clearance is 7.6 to 14 L/h.

Distribution

The apparent volume of distribution of pantoprazole is approximately 11 to 23.6 L, distributing mainly in extracellular fluid. The serum protein binding of pantoprazole is about 98%, primarily to albumin.

Elimination

Metabolism

Pantoprazole is extensively metabolized in the liver through the cytochrome P450 (CYP) system. Pantoprazole metabolism is independent of the route of administration (intravenous or oral). The main metabolic pathway is demethylation, by CYP2C19, with subsequent sulfation; other metabolic pathways include oxidation by CYP3A4. There is no evidence that any of the pantoprazole metabolites have significant pharmacologic activity. CYP2C19 displays a known genetic polymorphism due to its deficiency in some sub-populations (e.g., 3% of Caucasians and African-Americans and 17 to 23% of Asians). Although these sub-populations of slow pantoprazole metabolizers have elimination half-life values from 3.5 to 10 hours, they still have minimal accumulation (23% or less) with once daily dosing.

Excretion

After administration of a single intravenous dose of 14C-labeled pantoprazole sodium to healthy, extensive CYP2C19 metabolizers, approximately 71% of the dose was excreted in the urine with 18% excreted in the feces through biliary excretion. There was no renal excretion of unchanged pantoprazole.

Specific Populations

Geriatric Patients

After repeated intravenous administration in elderly subjects (65 to 76 years of age), the AUC and elimination half-life values of pantoprazole were similar to those observed in younger subjects.

Male and Female Patients

After oral administration there was a modest increase in the AUC and Cmax of pantoprazole in women compared to men. However, weight-normalized clearance values are similar in women and men.

Patients with Renal Impairment

In patients with severe renal impairment, pharmacokinetic parameters for pantoprazole were similar to those of healthy subjects.

Patients with Hepatic Impairment

In patients with mild to severe hepatic impairment (Child-Pugh Class A to C), maximum pantoprazole concentrations increased only slightly (1.5-fold) relative to healthy subjects when pantoprazole sodium was administered orally. Although serum half-life values increased to 7 to 9 hours and AUC values increased by 5- to 7-fold in hepatic-impaired patients, these increases were no greater than those observed in CYP2C19 poor metabolizers, where no dosage adjustment is warranted. These pharmacokinetic changes in hepatic-impaired patients result in minimal drug accumulation following once-daily, multiple-dose administration. Oral pantoprazole doses higher than 40 mg per day have not been studied in hepatically impaired patients.

Drug Interaction Studies

Effect of Other Drugs on Pantoprazole

Pantoprazole is metabolized mainly by CYP2C19 and to minor extents by CYPs 3A4, 2D6 and 2C9.

In in vivo drug-drug interaction studies with CYP2C19 substrates (diazepam [also a CYP3A4 substrate] and phenytoin [also a CYP3A4 inducer]), nifedipine, midazolam, and clarithromycin (CYP3A4 substrates), metoprolol (a CYP2D6 substrate), diclofenac, naproxen and piroxicam (CYP2C9 substrates) and theophylline (a CYP1A2 substrate) in healthy subjects, the pharmacokinetics of pantoprazole were not significantly altered.

Effect of Pantoprazole on Other Drugs

Clopidogrel

Clopidogrel is metabolized to its active metabolite in part by CYP2C19. In a crossover clinical study, 66 healthy subjects were administered clopidogrel (300 mg loading dose followed by 75 mg per day) alone and with oral pantoprazole (80 mg at the same time as clopidogrel) for 5 days. On Day 5, the mean AUC of the active metabolite of clopidogrel was reduced by approximately 14% (geometric mean ratio was 86%, with 90% CI of 79 to 93%) when pantoprazole sodium was coadministered with clopidogrel as compared to clopidogrel administered alone. Pharmacodynamic parameters were also measured and demonstrated that the change in inhibition of platelet aggregation (induced by 5 micromolar ADP) was correlated with the change in the exposure to clopidogrel active metabolite. The clinical significance of this finding is not clear.

Mycophenolate Mofetil (MMF)

Administration of oral pantoprazole 40 mg twice daily for 4 days and a single 1000 mg dose of MMF approximately one hour after the last dose of pantoprazole to 12 healthy subjects in a cross-over study resulted in a 57% reduction in the Cmax and 27% reduction in the AUC of MPA. Transplant patients receiving approximately 2000 mg per day of MMF (n=12) were compared to transplant patients receiving approximately the same dose of MMF and oral pantoprazole 40 mg per day (n=21). There was a 78% reduction in the Cmax and a 45% reduction in the AUC of MPA in patients receiving both pantoprazole sodium and MMF [see Drug Interactions (7)].

Other Drugs

In vivo studies also suggest that pantoprazole does not significantly affect the kinetics of other drugs (theophylline, diazepam [and its active metabolite, desmethyldiazepam], phenytoin, metoprolol, nifedipine, carbamazepine, midazolam, clarithromycin, diclofenac, naproxen, piroxicam and oral contraceptives [levonorgestrel/ethinyl estradiol]). In other in vivo studies, digoxin, ethanol, glyburide, antipyrine, caffeine, metronidazole, and amoxicillin had no clinically relevant interactions with pantoprazole.

Although no significant drug-drug interactions have been observed in clinical studies, the potential for significant drug-drug interactions with more than once daily dosing with high doses of pantoprazole has not been studied in poor metabolizers or individuals who are hepatically impaired.

Antacids

There was also no interaction with concomitantly administered antacids.

CYP2C19 displays a known genetic polymorphism due to its deficiency in some subpopulations (e.g., approximately 3% of Caucasians and African-Americans and 17% to 23% of Asians are poor metabolizers). Although these subpopulations of pantoprazole poor metabolizers have elimination half-life values of 3.5 to 10 hours in adults, they still have minimal accumulation (less than or equal to 23%) with once-daily dosing. For adult patients who are CYP2C19 poor metabolizers, no dosage adjustment is needed.

Similar to adults, pediatric patients who have the poor metabolizer genotype of CYP2C19 (CYP2C19*2/*2) exhibited greater than a 6-fold increase in AUC compared to pediatric extensive (CYP2C19*1/*1) and intermediate (CYP2C19 *1/*x) metabolizers. Poor metabolizers exhibited approximately 10-fold lower apparent oral clearance compared to extensive metabolizers.

In a 24-month carcinogenicity study, Sprague-Dawley rats were treated orally with pantoprazole doses of 0.5 to 200 mg/kg/day, about 0.1 to 40 times the exposure on a body surface area basis of a 50-kg person dosed at 40 mg/day. In the gastric fundus, treatment with 0.5 to 200 mg/kg/day produced enterochromaffin-like (ECL) cell hyperplasia and benign and malignant neuroendocrine cell tumors in a dose-related manner. In the forestomach, treatment with 50 and 200 mg/kg/day (about 10 and 40 times the recommended human dose on a body surface area basis) produced benign squamous cell papillomas and malignant squamous cell carcinomas. Rare gastrointestinal tumors associated with pantoprazole treatment included an adenocarcinoma of the duodenum with 50 mg/kg/day and benign polyps and adenocarcinomas of the gastric fundus with 200 mg/kg/day. In the liver, treatment with 0.5 to 200 mg/kg/day produced dose-related increases in the incidences of hepatocellular adenomas and carcinomas. In the thyroid gland, treatment with 200 mg/kg/day produced increased incidences of follicular cell adenomas and carcinomas for both male and female rats.

In a 24-month carcinogenicity study, Fischer 344 rats were treated orally with pantoprazole doses of 5 to 50 mg/kg/day, approximately 1 to 10 times the recommended human dose based on body surface area. In the gastric fundus, treatment at 5 to 50 mg/kg/day produced enterochromaffin-like (ECL) cell hyperplasia and benign and malignant neuroendocrine cell tumors. Dose selection for this study may not have been adequate to comprehensively evaluate the carcinogenic potential of pantoprazole.

In a 24-month carcinogenicity study, B6C3F1 mice were treated orally with pantoprazole doses of 5 to 150 mg/kg/day, 0.5 to 15 times the recommended human dose based on body surface area. In the liver, treatment at 150 mg/kg/day produced increased incidences of hepatocellular adenomas and carcinomas in female mice. Treatment at 5 to 150 mg/kg/day also produced gastric fundic ECL cell hyperplasia.

A 26-week p53 +/- transgenic mouse carcinogenicity study was not positive.

Pantoprazole was positive in the in vitro human lymphocyte chromosomal aberration assays, in one of two mouse micronucleus tests for clastogenic effects, and in the in vitro Chinese hamster ovarian cell/HGPRT forward mutation assay for mutagenic effects. Equivocal results were observed in the in vivo rat liver DNA covalent binding assay. Pantoprazole was negative in the in vitro Ames mutation assay, the in vitro unscheduled DNA synthesis (UDS) assay with rat hepatocytes, the in vitro AS52/GPT mammalian cell-forward gene mutation assay, the in vitro thymidine kinase mutation test with mouse lymphoma L5178Y cells, and the in vivo rat bone marrow cell chromosomal aberration assay.

There were no effects on fertility or reproductive performance when pantoprazole was given at oral doses up to 500 mg/kg/day in male rats (98 times the recommended human dose based on body surface area) and 450 mg/kg/day in female rats (88 times the recommended human dose based on body surface area).

A multicenter, double-blind, two-period placebo-controlled study was conducted to assess the ability of pantoprazole sodium to maintain gastric acid suppression in patients switched from the oral dosage form to the intravenous dosage form. GERD patients (n=65, 26 to 64 years; 35 female; 9 Black, 11 Hispanic, 44 White, 1 other) with a history of EE were randomized to receive either 20 or 40 mg of oral pantoprazole once per day for 10 days (period 1), and then were switched in period 2 to either daily intravenous pantoprazole sodium or placebo for 7 days, matching their respective dose level from period 1. Patients were administered all test medication with a light meal. Maximum acid output (MAO) and basal acid output (BAO) were determined 24 hours following the last day of oral medication (day 10), the first day (day 1) of intravenous administration and the last day of intravenous administration (day 7). MAO was estimated from a 1 hour continuous collection of gastric contents following subcutaneous injection of 6 mcg/kg of pentagastrin.

This study demonstrated that, after 10 days of repeated oral administration followed by 7 days of intravenous administration, the oral and intravenous dosage forms of pantoprazole 40 mg are similar in their ability to suppress MAO and BAO in patients with GERD and a history of erosive esophagitis (see Table 4). Also, patients on oral pantoprazole sodium who were switched to intravenous placebo experienced a significant increase in acid output within 48 hours of their last oral dose (see Table 4). However, at 48 hours after their last oral dose, patients treated with intravenous pantoprazole sodium had a significantly lower mean basal acid output (see Table 4) than those treated with placebo.

Table 4: Antisecretory Effects (mEq/h) of 40 mg Intravenous Pantoprazole Sodium and 40 mg Oral Pantoprazole in GERD Patients with a History of Erosive Esophagitis

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="440.8pt"> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Pa</span><span class="Bold">rameter</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Pa</span><span class="Bold">ntoprazole Sodium<br/> </span><span class="Bold">Delayed-Release Tablets<br/> </span><span class="Bold">DAY 10</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">I</span><span class="Bold">ntravenous<br/> </span><span class="Bold">Pantoprazole Sodium*<br/> </span><span class="Bold">DAY 7</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Intravenous <br/> </span><span class="Bold">P</span><span class="Bold">lacebo<br/> </span><span class="Bold">DAY 7</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Mean maximum acid output</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">6.49<br/> n=30</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">6.62<br/> n=23</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">29.19**<br/> n=7</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Mean basal acid output</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.80<br/> n=30</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.53<br/> n=23</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">4.14**<br/> n=7</p> </td> </tr> </tbody> </table></div>

* another intravenous pantoprazole sodium product **p<0.0001 Significantly different from intravenous pantoprazole sodium.

To evaluate the effectiveness of intravenous pantoprazole sodium as an initial treatment to suppress gastric acid secretion, two studies were conducted.

Study 1 was a multicenter, double-blind, placebo-controlled, study of the pharmacodynamic effects of intravenous and oral pantoprazole sodium. Patients with GERD and a history of EE (n=78, 20 to 67 years; 39 females; 7 Black, 19 Hispanic, 52 White) were randomized to receive either 40 mg pantoprazole intravenously, 40 mg pantoprazole orally, or placebo once daily for 7 days. Following an overnight fast, test medication was administered and patients were given a light meal within 15 minutes. MAO and BAO were determined 24 hours following the last day of study medication. MAO was estimated from a 1 hour continuous collection of gastric contents following subcutaneous injection of 6 mcg/kg of pentagastrin to stimulate acid secretion. This study demonstrated that, after treatment for 7 days, patients treated with intravenous pantoprazole sodium had a significantly lower MAO and BAO than those treated with placebo (p<0.001), and results were comparable to those of patients treated with oral pantoprazole sodium (see Table 5). 

Table 5: Antisecretory Effects (mEq/h) of Initial Treatment with 40 mg Intravenous Pantoprazole Sodium* and 40 mg Oral Pantoprazole in GERD Patients with a History of Erosive Esophagitis

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0"> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Pa</span><span class="Bold">rameter</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">I</span><span class="Bold">ntravenous<br/> </span><span class="Bold">Pantoprazole Sodium*<br/> </span><span class="Bold">DAY 7</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Pa</span><span class="Bold">ntoprazole Sodium <br/> </span><span class="Bold">Delayed-Release Tablets<br/> </span><span class="Bold">DAY 7</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">P</span><span class="Bold">lacebo<br/> </span><span class="Bold">DAY 7<br/> </span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Maximum acid output (mean ±SD)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">8.4 ± 5.9</p> <p>n=25</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">6.3 ± 6.6</p> <p>n=22</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">20.9 ± 14.5**</p> <p>n=24</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Basal acid output (mean±SD)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.4 ± 0.5</p> <p>n=25</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.6 ± 0.8</p> <p>n=22</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">2.8 ± 3**</p> <p>n=23</p> </td> </tr> </tbody> </table></div>

* another intravenous pantoprazole sodium product** p<0.0001 Significantly different from intravenous pantoprazole sodium

Study 2 was a single-center, double-blind, parallel-group study to compare the clinical effects of intravenous and oral pantoprazole sodium. Patients (n=45, median age 56 years, 21 males and 24 females) with acute endoscopically proven reflux esophagitis (Savary/Miller Stage II or III) with at least 1 of 3 symptoms typical for reflux esophagitis (acid eructation, heartburn, or pain on swallowing) were randomized to receive either 40 mg intravenous pantoprazole or 40 mg oral pantoprazole once daily for 5 days. After the initial 5 days, all patients were treated with 40 mg oral pantoprazole daily to complete a total of 8 weeks of treatment. Symptom relief was assessed by calculating the daily mean of the sums of the average scores for these 3 symptoms and the daily mean of the average score for each of the symptoms separately. There was no significant difference in symptom relief between intravenous and oral pantoprazole sodium therapy within the first 5 days. A repeat endoscopy after 8 weeks of treatment revealed that 20 out of 23 (87%) of the intravenous plus oral pantoprazole sodium patients and 19 out of 22 (86%) of the oral pantoprazole sodium patients had endoscopically proven healing of their esophageal lesions.

Data comparing intravenous pantoprazole sodium to other PPIs (oral or intravenous) or H2-receptor antagonists (oral or intravenous) are limited, and therefore, are inadequate to support any conclusions regarding comparative efficacy.

Two studies measured the pharmacodynamic effects of 6 day treatment with intravenous pantoprazole sodium in patients with ZE Syndrome (with and without multiple endocrine neoplasia type I). In one of these studies, an initial treatment with intravenous pantoprazole sodium in 21 patients (29 to 75 years; 8 female; 4 Black, 1 Hispanic, 16 White) reduced acid output to the target level (less than or equal to 10 mEq/h) and significantly reduced H+ concentration and the volume of gastric secretions; target levels were achieved within 45 minutes of drug administration.

In the other study of 14 patients (38 to 67 years; 5 female; 2 Black, 12 White) with ZE Syndrome, treatment was switched from an oral PPI to intravenous pantoprazole sodium. Intravenous pantoprazole sodium maintained or improved control of gastric acid secretion.

In both studies, total doses of 160 or 240 mg intravenous pantoprazole, administered in divided doses, maintained basal acid secretion below target levels in all patients. Target levels were 10 mEq/hour in patients without prior gastric surgery, and 5 mEq/h in all patients with prior gastric acid-reducing surgery. Once gastric acid secretion was controlled, there was no evidence of tolerance during this 7 day study. Basal acid secretion was maintained below target levels for at least 24 hours in all patients and through the end of treatment in these studies (3 to 7 days) in all but 1 patient who required a dose adjustment guided by acid output measurements until acid control was achieved. In both studies, doses were adjusted to the individual patient need, but gastric acid secretion was controlled in greater than 80% of patients by a starting regimen of 80 mg every 12 hours.

How Supplied

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Pantoprazole Sodium for Injection is supplied in a single-dose vial as a white to off-white sterile lyophilized powder for reconstitution containing 40 mg of pantoprazole.

{ "type": "p", "children": [], "text": "Pantoprazole Sodium for Injection is supplied in a single-dose vial as a white to off-white sterile lyophilized powder for reconstitution containing 40 mg of pantoprazole." }

Pantoprazole Sodium for Injection is available as follows:

{ "type": "p", "children": [], "text": "Pantoprazole Sodium for Injection is available as follows:" }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <col width="107.95pt"/> <col width="157.7pt"/> <col width="1.25in"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Underline">NDC Number</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Underline">S</span><span class="Underline">trength</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Underline">P</span><span class="Underline">ac</span><span class="Underline">kage Size</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">72572-553-10</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">40 mg pantoprazole</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">10 vials</p> </td> </tr> </tbody> </table></div>

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Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

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Protect from light.

{ "type": "p", "children": [], "text": "Protect from light." }

Adverse Reactions

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Advise patients to report to their healthcare provider if they experience any signs or symptoms consistent with:

{ "type": "p", "children": [], "text": "Advise patients to report to their healthcare provider if they experience any signs or symptoms consistent with:" }

•         Injection Site Reactions [see Warnings and Precautions (5.2)]

{ "type": "p", "children": [], "text": "•         Injection Site Reactions [see Warnings and Precautions (5.2)]\n" }

•         Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.3)]

{ "type": "p", "children": [], "text": "•         Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.3)]\n" }

•         Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.4)]

{ "type": "p", "children": [], "text": "•         Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.4)]\n" }

•         Bone Fracture [see Warnings and Precautions (5.5)]

{ "type": "p", "children": [], "text": "•         Bone Fracture [see Warnings and Precautions (5.5)]\n" }

•         Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.6)]

{ "type": "p", "children": [], "text": "\n•         Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.6)]\n" }

•         Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.7)]

{ "type": "p", "children": [], "text": "•         Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.7)]\n" }

•         Hepatic Effects [see Warnings and Precautions (5.8)]

{ "type": "p", "children": [], "text": "•         Hepatic Effects [see Warnings and Precautions (5.8)]\n" }

•         Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.9)]

{ "type": "p", "children": [], "text": "•         Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.9)]\n" }

Drug Interactions

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

Advise patients to report to their healthcare provider before they start treatment with any of the following:

{ "type": "p", "children": [], "text": "Advise patients to report to their healthcare provider before they start treatment with any of the following:" }

•     Rilpivirine-containing products [see Contraindications (4)]

{ "type": "p", "children": [], "text": "•     Rilpivirine-containing products [see Contraindications (4)]\n" }

•     High-dose methotrexate [see Warnings and Precautions (5.13)]

{ "type": "p", "children": [], "text": "•     High-dose methotrexate [see Warnings and Precautions (5.13)]\n" }

Pregnancy

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

Advise a pregnant woman of the potential risk to a fetus. Advise females of reproductive potential to inform their prescriber of a known or suspected pregnancy [see Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "Advise a pregnant woman of the potential risk to a fetus. Advise females of reproductive potential to inform their prescriber of a known or suspected pregnancy [see Use in Specific Populations (8.1)].\n" }

Distributed by Civica, Inc. Lehi, Utah 84043

{ "type": "p", "children": [], "text": "\nDistributed by\n\nCivica, Inc.\nLehi, Utah 84043" }

Manufactured by HIKMA FARMACÊUTICA (PORTUGAL), S.A. Estrada do Rio da Mó, 8, 8A e 8B – Fervença – 2705-906 Terrugem SNT, PORTUGAL

{ "type": "p", "children": [], "text": "\nManufactured by\n\nHIKMA FARMACÊUTICA (PORTUGAL), S.A.\nEstrada do Rio da Mó, 8, 8A e 8B – Fervença – 2705-906 Terrugem SNT, PORTUGAL" }

PIN676-CIV/1

{ "type": "p", "children": [], "text": "PIN676-CIV/1" }

 Revised: October 2024

{ "type": "p", "children": [], "text": " Revised: October 2024" }

NDC 72572-553-01     Rx only Pantoprazole Sodium for Injection Equivalent to pantoprazole 40 mg per vial Sterile For Intravenous Infusion ONLY Single Dose Vial Discard unused portion

{ "type": "p", "children": [], "text": "NDC 72572-553-01     Rx only\nPantoprazole\nSodium for Injection\nEquivalent to pantoprazole\n40 mg per vial\n\nSterile\nFor Intravenous Infusion ONLY\nSingle Dose Vial\nDiscard unused portion\n" }

NDC 72572-553-10    Rx only Pantoprazole Sodium for Injection Equivalent to pantoprazole 40 mg per vial Sterile For Intravenous Infusion ONLY Single Dose Vial Discard unused portion No filter required      Contains 10 Vials

{ "type": "p", "children": [], "text": "NDC 72572-553-10    Rx only\nPantoprazole\nSodium for Injection\nEquivalent to pantoprazole\n40 mg per vial\n\nSterile\nFor Intravenous Infusion ONLY\nSingle Dose Vial\nDiscard unused portion\nNo filter required      Contains 10 Vials\n" }

Pantoprazole is indicated in adults and pediatric patients five years of age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis (EE). For those adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of Pantoprazole may be considered. Safety of treatment beyond 8 weeks in pediatric patients has not been established.

Pantoprazole is indicated for maintenance of healing of EE and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with GERD. Controlled studies did not extend beyond 12 months.

Pantoprazole is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

Pantoprazole is supplied as delayed-release tablets. The recommended dosages are outlined in Table 1.

<div class="scrollingtable"><table> <caption> <span>Table 1: Recommended Dosing Schedule for Pantoprazole</span> </caption> <col/> <col/> <col/> <thead> <tr class="First Last"> <th valign="top"> Indication</th><th align="center" valign="top"> Dose</th><th valign="top"> Frequency</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of Pantoprazole may be considered.</dd> <dt> <a href="#footnote-reference-3" name="footnote-3">†</a> </dt> <dd>Controlled studies did not extend beyond 12 months</dd> <dt> <a href="#footnote-reference-4" name="footnote-4">‡</a> </dt> <dd>Dosage regimens should be adjusted to individual patient needs and should continue for as long as clinically indicated. Doses up to 240 mg daily have been administered.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td colspan="3" valign="top"> <span class="Bold">Short-Term Treatment of Erosive Esophagitis Associated With GERD</span></td> </tr> <tr> <td valign="top">   Adults</td><td align="center" class="Botrule" valign="top"> 40 mg</td><td class="Botrule" valign="top"> Once daily for up to 8 weeks<a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a></td> </tr> <tr> <td valign="top">   Children (5 years and older)</td><td align="center" valign="top"> </td><td valign="top"> </td> </tr> <tr> <td valign="top">   ≥ 15 kg to &lt; 40 kg</td><td align="center" valign="top"> 20 mg</td><td valign="top"> Once daily for up to 8 weeks</td> </tr> <tr> <td class="Botrule" valign="top">   ≥ 40 kg</td><td align="center" class="Botrule" valign="top"> 40 mg</td><td class="Botrule" valign="top"> </td> </tr> <tr> <td colspan="3" valign="top"> <span class="Bold">Maintenance of Healing of Erosive Esophagitis</span></td> </tr> <tr> <td class="Botrule" valign="top">   Adults</td><td align="center" class="Botrule" valign="top"> 40 mg</td><td class="Botrule" valign="top"> Once daily<a class="Sup" href="#footnote-3" name="footnote-reference-3">†</a> </td> </tr> <tr> <td colspan="3" valign="top"> <span class="Bold">Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome</span></td> </tr> <tr class="Last"> <td valign="top">   Adults</td><td align="center" valign="top"> 40 mg</td><td valign="top"> Twice daily<a class="Sup" href="#footnote-4" name="footnote-reference-4">‡</a> </td> </tr> </tbody> </table></div>

Directions for method of administration for each dosage form are presented in Table 2.

<div class="scrollingtable"><table> <caption> <span>Table 2: Administration Instructions</span> </caption> <col/> <col/> <col/> <thead> <tr class="First Last"> <th valign="top"> Formulation</th><th align="center" valign="top"> Route</th><th valign="top"> Instructions<a class="Sup" href="#footnote-5" name="footnote-reference-5">*</a></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-5" name="footnote-5">*</a> </dt> <dd>Patients should be cautioned that Pantoprazole Sodium Delayed-Release Tablets should not be split, chewed, or crushed.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First Last"> <td valign="top"> <span class="Bold">Delayed-Release Tablets</span></td><td align="center" valign="top"> Oral</td><td valign="top"> Swallowed whole, with or without food</td> </tr> </tbody> </table></div>

Pantoprazole Sodium Delayed-Release Tablets

Pantoprazole Sodium Delayed-Release Tablets should be swallowed whole, with or without food in the stomach. If patients are unable to swallow a 40 mg tablet, two 20 mg tablets may be taken. Concomitant administration of antacids does not affect the absorption of Pantoprazole Sodium Delayed-Release Tablets.

Delayed-Release Tablets:

{ "type": "p", "children": [], "text": "Delayed-Release Tablets:" }

{ "type": "ul", "children": [ "40 mg, white oval biconvex tablets debossed with \"17\" on one side", "20 mg, white oval biconvex tablets imprinted in black ink with \"KU\" on one side and \"180\" on the other side" ], "text": "" }

{ "type": "ul", "children": [ "\nPantoprazole is contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria [see Adverse Reactions (6)].\n", "\nProton pump inhibitors (PPIs), including Pantoprazole, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions (7)].\n" ], "text": "" }

In adults, symptomatic response to therapy with Pantoprazole does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy.

Acute interstitial nephritis has been observed in patients taking PPIs including Pantoprazole. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue Pantoprazole if acute interstitial nephritis develops [see Contraindications (4)].

Published observational studies suggest that PPI therapy like Pantoprazole may be associated with an increased risk of Clostridium difficile associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.2)].

Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.

Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2) and Adverse Reactions (6.2)].

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including pantoprazole sodium. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematous cases were CLE.

The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement.

Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported.

Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving Pantoprazole, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g. ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations.

Generally, daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (Vitamin B-12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2)].

Due to the chronic nature of GERD, there may be a potential for prolonged administration of Pantoprazole. In long-term rodent studies, pantoprazole was carcinogenic and caused rare types of gastrointestinal tumors. The relevance of these findings to tumor development in humans is unknown [see Nonclinical Toxicology (13.1)].

There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including Pantoprazole [see Drug Interactions (7)].

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions (7)].

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 clinical practice.

Adults

Safety in nine randomized comparative US clinical trials in patients with GERD included 1,473 patients on oral Pantoprazole (20 mg or 40 mg), 299 patients on an H2-receptor antagonist, 46 patients on another PPI, and 82 patients on placebo. The most frequently occurring adverse reactions are listed in Table 3.

<div class="scrollingtable"><table> <caption> <span>Table 3: Adverse Reactions Reported in Clinical Trials of Adult Patients with GERD at a Frequency of &gt; 2%</span> </caption> <col/> <col/> <col/> <col/> <thead> <tr class="First Last"> <th valign="top"></th><th>Pantoprazole<br/>(n=1473)<br/>%</th><th align="center" valign="top">Comparators<br/>(n=345)<br/>%</th><th align="center" valign="top">Placebo<br/>(n=82)<br/>%</th> </tr> </thead> <tbody> <tr class="First"> <td valign="top"> Headache</td><td align="center" valign="top"> 12.2</td><td align="center" valign="top"> 12.8</td><td align="center" valign="top"> 8.5</td> </tr> <tr> <td valign="top"> Diarrhea</td><td align="center" valign="top"> 8.8</td><td align="center" valign="top"> 9.6</td><td align="center" valign="top"> 4.9</td> </tr> <tr> <td valign="top"> Nausea</td><td align="center" valign="top"> 7.0</td><td align="center" valign="top"> 5.2</td><td align="center" valign="top"> 9.8</td> </tr> <tr> <td valign="top"> Abdominal pain</td><td align="center" valign="top"> 6.2</td><td align="center" valign="top"> 4.1</td><td align="center" valign="top"> 6.1</td> </tr> <tr> <td valign="top"> Vomiting</td><td align="center" valign="top"> 4.3</td><td align="center" valign="top"> 3.5</td><td align="center" valign="top"> 2.4</td> </tr> <tr> <td valign="top"> Flatulence</td><td align="center" valign="top"> 3.9</td><td align="center" valign="top"> 2.9</td><td align="center" valign="top"> 3.7</td> </tr> <tr> <td valign="top"> Dizziness</td><td align="center" valign="top"> 3.0</td><td align="center" valign="top"> 2.9</td><td align="center" valign="top"> 1.2</td> </tr> <tr class="Last"> <td valign="top"> Arthralgia</td><td align="center" valign="top"> 2.8</td><td align="center" valign="top"> 1.4</td><td align="center" valign="top"> 1.2</td> </tr> </tbody> </table></div>

Additional adverse reactions that were reported for Pantoprazole in clinical trials with a frequency of ≤ 2% are listed below by body system:

Body as a Whole: allergic reaction, pyrexia, photosensitivity reaction, facial edema

Gastrointestinal: constipation, dry mouth, hepatitis

Hematologic: leukopenia, thrombocytopenia

Metabolic/Nutritional: elevated CK (creatine kinase), generalized edema, elevated triglycerides, liver enzymes elevated

Musculoskeletal: myalgia

Nervous: depression, vertigo

Skin and Appendages: urticaria, rash, pruritus

Special Senses: blurred vision

Pediatric Patients

Safety of Pantoprazole in the treatment of Erosive Esophagitis (EE) associated with GERD was evaluated in pediatric patients ages 1 year through 16 years in three clinical trials. Safety trials involved pediatric patients with EE; however, as EE is uncommon in the pediatric population, 249 pediatric patients with endoscopically-proven or symptomatic GERD were also evaluated. All adult adverse reactions to Pantoprazole are considered relevant to pediatric patients. In patients ages 1 year through 16 years, the most commonly reported (> 4%) adverse reactions include: URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain.

For safety information in patients less than 1 year of age see Use in Specific Populations (8.4).

Additional adverse reactions that were reported for Pantoprazole in pediatric patients in clinical trials with a frequency of ≤ 4% are listed below by body system:

Body as a Whole: allergic reaction, facial edema

Gastrointestinal: constipation, flatulence, nausea

Metabolic/Nutritional: elevated triglycerides, elevated liver enzymes, elevated CK (creatine kinase)

Musculoskeletal: arthralgia, myalgia

Nervous: dizziness, vertigo

Skin and Appendages: urticaria

The following adverse reactions seen in adults in clinical trials were not reported in pediatric patients in clinical trials, but are considered relevant to pediatric patients: photosensitivity reaction, dry mouth, hepatitis, thrombocytopenia, generalized edema, depression, pruritus, leukopenia, and blurred vision.

Zollinger-Ellison Syndrome

In clinical studies of Zollinger-Ellison Syndrome, adverse reactions reported in 35 patients taking Pantoprazole 80 mg/day to 240 mg/day for up to 2 years were similar to those reported in adult patients with GERD.

The following adverse reactions have been identified during postapproval use of Pantoprazole. 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.

These adverse reactions are listed below by body system:

General Disorders and Administration Conditions: asthenia, fatigue, malaise

Hematologic: pancytopenia, agranulocytosis

Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure

Immune System Disorders: anaphylaxis (including anaphylactic shock), systemic lupus erythematosus

Infections and Infestations:Clostridium difficile associated diarrhea

Investigations: weight changes

Metabolism and Nutritional Disorders: hyponatremia, hypomagnesemia

Musculoskeletal Disorders: rhabdomyolysis, bone fracture

Nervous: ageusia, dysgeusia

Psychiatric Disorders: hallucination, confusion, insomnia, somnolence

Renal and Urinary Disorders: interstitial nephritis

Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions (some fatal), including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN, some fatal), angioedema (Quincke’s edema) and cutaneous lupus erythematosus

Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with Pantoprazole and instructions for preventing or managing them.

{ "type": "p", "children": [], "text": "Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with Pantoprazole and instructions for preventing or managing them." }

Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.

{ "type": "p", "children": [], "text": "Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs." }

Table 4: Clinically relevant Interactions Affecting Drugs Co-Administered with Pantoprazole and Interaction with Diagnostics

{ "type": "p", "children": [], "text": "\nTable 4: Clinically relevant Interactions Affecting Drugs Co-Administered with Pantoprazole and Interaction with Diagnostics\n" }

<div class="scrollingtable"><table> <col width="1px"/> <col width="1px"/> <tbody class="Headless"> <tr class="First"> <td class="Lrule Toprule"><span class="Bold">Antiretrovirals</span> </td><td class="Rrule Toprule"> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <span class="Italics">Clinical Impact:</span></td><td class="Botrule Lrule Rrule Toprule">The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. <ul class="Disc"> <li> <p class="First">Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with Pantoprazole may reduce antiviral effect and promote the development of drug resistance.</p> </li> <li> <p class="First">Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with Pantoprazole may increase toxicity<span class="Italics">.</span> </p> </li> <li> <p class="First">There are other antiretroviral drugs which do not result in clinically relevant interactions with pantoprazole sodium.</p> </li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <span class="Italics">Intervention:</span></td><td class="Botrule Lrule Rrule Toprule">Rilpivirine-containing products: Concomitant use with Pantoprazole is contraindicated [<span class="Italics">see Contraindications (<span class="Underline"><a href="#LINK_f6181774-93a7-4dcb-adb6-55b8f727d968">4</a></span>)</span>]. <p class="First">Atazanavir: See prescribing information for atazanavir for dosing information.</p> <p>Nelfinavir: Avoid concomitant use with Pantoprazole. See prescribing information for nelfinavir.</p> <p>Saquinavir: See the prescribing information for saquinavir for monitoring of potential saquinavir-related toxicities.</p> <p>Other antiretrovirals: See prescribing information for specific antiretroviral drugs.</p> </td> </tr> <tr> <td class="Botrule Lrule Toprule"> <span class="Bold">Warfarin</span></td><td class="Botrule Rrule Toprule"> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <span class="Italics">Clinical Impact:</span></td><td class="Botrule Lrule Rrule Toprule">Increased INR and prothrombin time in patients receiving PPIs, including pantoprazole sodium, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <span class="Italics">Intervention:</span></td><td class="Botrule Lrule Rrule Toprule">Monitor INR and prothrombin time and adjust the dose of warfarin, if needed, to maintain the target INR range.</td> </tr> <tr> <td class="Botrule Lrule Toprule"> <span class="Bold">Methotrexate</span></td><td class="Botrule Rrule Toprule"> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <span class="Italics">Clinical Impact:</span></td><td class="Botrule Lrule Rrule Toprule">Concomitant use of pantoprazole sodium with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [<span class="Italics">see Warnings and Precautions (<span class="Underline"><a href="#LINK_baa72df1-24d9-4647-bcff-15e1b7ba6691">5.10</a></span>)</span>].</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <span class="Italics">Intervention:</span></td><td class="Botrule Lrule Rrule Toprule">A temporary withdrawal of Pantoprazole may be considered in some patients receiving high-dose methotrexate.</td> </tr> <tr> <td class="Botrule Lrule Toprule"><span class="Bold">Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole)</span></td><td class="Botrule Rrule Toprule"> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <span class="Italics">Clinical Impact:</span></td><td class="Botrule Lrule Rrule Toprule">Pantoprazole sodium can reduce the absorption of other drugs due to its effect on reducing intragastric acidity</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <span class="Italics">Intervention:</span></td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Mycophenolate mofetil (MMF): Co-administration of pantoprazole sodium in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving Pantoprazole Sodium for Injection and MMF. Use Pantoprazole with caution in transplant patients receiving MMF [<span class="Italics">see Clinical Pharmacology (<span class="Underline"><a href="#LINK_b4cec4f5-ec53-4091-be7e-381f5064aabd">12.3</a></span>)</span>].</p> <p>See the prescribing information for other drugs dependent on gastric pH for absorption.</p> </td> </tr> <tr> <td class="Botrule Lrule Toprule"><span class="Bold">False Positive Urine Tests for THC</span></td><td class="Botrule Rrule Toprule">  </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <span class="Italics">Clinical Impact:</span></td><td class="Botrule Lrule Rrule Toprule">There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including Pantoprazole [<span class="Italics">see Warnings and Precautions (</span><span class="Italics"><span class="Underline"><a href="#LINK_509504d6-5f4e-4104-91c6-7a98542b6d26">5.9</a></span></span><span class="Italics">)</span>]. </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <span class="Italics">Intervention:</span></td><td class="Botrule Lrule Rrule Toprule"> An alternative confirmatory method should be considered to verify positive results.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col width=\"1px\"/>\n<col width=\"1px\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Lrule Toprule\"><span class=\"Bold\">Antiretrovirals</span> </td><td class=\"Rrule Toprule\"> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> <span class=\"Italics\">Clinical Impact:</span></td><td class=\"Botrule Lrule Rrule Toprule\">The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. <ul class=\"Disc\">\n<li>\n<p class=\"First\">Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with Pantoprazole may reduce antiviral effect and promote the development of drug resistance.</p>\n</li>\n<li>\n<p class=\"First\">Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with Pantoprazole may increase toxicity<span class=\"Italics\">.</span>\n</p>\n</li>\n<li>\n<p class=\"First\">There are other antiretroviral drugs which do not result in clinically relevant interactions with pantoprazole sodium.</p>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> <span class=\"Italics\">Intervention:</span></td><td class=\"Botrule Lrule Rrule Toprule\">Rilpivirine-containing products: Concomitant use with Pantoprazole is contraindicated [<span class=\"Italics\">see Contraindications (<span class=\"Underline\"><a href=\"#LINK_f6181774-93a7-4dcb-adb6-55b8f727d968\">4</a></span>)</span>]. <p class=\"First\">Atazanavir: See prescribing information for atazanavir for dosing information.</p>\n<p>Nelfinavir: Avoid concomitant use with Pantoprazole. See prescribing information for nelfinavir.</p>\n<p>Saquinavir: See the prescribing information for saquinavir for monitoring of potential saquinavir-related toxicities.</p>\n<p>Other antiretrovirals: See prescribing information for specific antiretroviral drugs.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Toprule\"> <span class=\"Bold\">Warfarin</span></td><td class=\"Botrule Rrule Toprule\"> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> <span class=\"Italics\">Clinical Impact:</span></td><td class=\"Botrule Lrule Rrule Toprule\">Increased INR and prothrombin time in patients receiving PPIs, including pantoprazole sodium, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death.</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> <span class=\"Italics\">Intervention:</span></td><td class=\"Botrule Lrule Rrule Toprule\">Monitor INR and prothrombin time and adjust the dose of warfarin, if needed, to maintain the target INR range.</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Toprule\"> <span class=\"Bold\">Methotrexate</span></td><td class=\"Botrule Rrule Toprule\"> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> <span class=\"Italics\">Clinical Impact:</span></td><td class=\"Botrule Lrule Rrule Toprule\">Concomitant use of pantoprazole sodium with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [<span class=\"Italics\">see Warnings and Precautions (<span class=\"Underline\"><a href=\"#LINK_baa72df1-24d9-4647-bcff-15e1b7ba6691\">5.10</a></span>)</span>].</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> <span class=\"Italics\">Intervention:</span></td><td class=\"Botrule Lrule Rrule Toprule\">A temporary withdrawal of Pantoprazole may be considered in some patients receiving high-dose methotrexate.</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Toprule\"><span class=\"Bold\">Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole)</span></td><td class=\"Botrule Rrule Toprule\"> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> <span class=\"Italics\">Clinical Impact:</span></td><td class=\"Botrule Lrule Rrule Toprule\">Pantoprazole sodium can reduce the absorption of other drugs due to its effect on reducing intragastric acidity</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> <span class=\"Italics\">Intervention:</span></td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Mycophenolate mofetil (MMF): Co-administration of pantoprazole sodium in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving Pantoprazole Sodium for Injection and MMF. Use Pantoprazole with caution in transplant patients receiving MMF [<span class=\"Italics\">see Clinical Pharmacology (<span class=\"Underline\"><a href=\"#LINK_b4cec4f5-ec53-4091-be7e-381f5064aabd\">12.3</a></span>)</span>].</p>\n<p>See the prescribing information for other drugs dependent on gastric pH for absorption.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Toprule\"><span class=\"Bold\">False Positive Urine Tests for THC</span></td><td class=\"Botrule Rrule Toprule\">  </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> <span class=\"Italics\">Clinical Impact:</span></td><td class=\"Botrule Lrule Rrule Toprule\">There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including Pantoprazole [<span class=\"Italics\">see Warnings and Precautions (</span><span class=\"Italics\"><span class=\"Underline\"><a href=\"#LINK_509504d6-5f4e-4104-91c6-7a98542b6d26\">5.9</a></span></span><span class=\"Italics\">)</span>]. </td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\"> <span class=\"Italics\">Intervention:</span></td><td class=\"Botrule Lrule Rrule Toprule\"> An alternative confirmatory method should be considered to verify positive results.</td>\n</tr>\n</tbody>\n</table></div>" }

Pregnancy Category C

Reproduction studies have been performed in rats at oral pantoprazole doses up to 450 mg/kg/day (about 88 times the recommended human dose based on body surface area) and in rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose based on body surface area) with administration of pantoprazole sodium during organogenesis in pregnant animals. The studies have revealed no evidence of impaired fertility or harm to the fetus due to pantoprazole.

A pre- and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. Oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day on a body surface area basis) were administered to pregnant females from gestation day (GD) 6 through lactation day (LD) 21. On postnatal day (PND 4) through PND 21, the pups were administered oral doses at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (AUC) in humans at a dose of 40 mg). There were no drug-related findings in maternal animals. During the preweaning dosing phase (PND 4 to 21) of the pups, there were increased mortality and/or moribundity and decreased body weight and body weight gain at 5 mg/kg/day (approximately equal exposures (AUC) in humans receiving the 40 mg dose) and higher doses. On PND 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (AUC) in humans at the 40 mg dose) and higher doses. The femur findings included lower total area, bone mineral content and density, periosteal and endosteal circumference, and cross-sectional moment of inertia. There were no microscopic changes in the distal femur, proximal tibia, or stifle joints. Changes in bone parameters were partially reversible following a recovery period, with findings on PND 70 limited to lower femur metaphysis cortical/subcortical bone mineral density in female pups at 5 mg/kg/day (approximately equal exposures (AUC) in humans at the 40 mg dose) and higher doses.

There are no adequate and well-controlled studies in pregnant women. Advise pregnant women of the potential risk of fetal harm. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pantoprazole and its metabolites are excreted in the milk of rats. Pantoprazole excretion in human milk has been detected in a study of a single nursing mother after a single 40 mg oral dose of pantoprazole sodium. The clinical relevance of this finding is not known. Many drugs which are excreted in human milk have a potential for serious adverse reactions in nursing infants. Based on the potential for tumorigenicity shown for pantoprazole sodium in rodent carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the benefit of the drug to the mother.

The safety and effectiveness of Pantoprazole for short-term treatment (up to eight weeks) of erosive esophagitis (EE) associated with GERD have been established in pediatric patients 1 year through 16 years of age. Effectiveness for EE has not been demonstrated in patients less than 1 year of age. In addition, for patients less than 5 years of age, there is no appropriate dosage strength in an age-appropriate formulation available. Therefore, Pantoprazole is indicated for the short-term treatment of EE associated with GERD for patients 5 years and older. The safety and effectiveness of Pantoprazole for pediatric uses other than EE have not been established.

1 year through 16 years of age

Use of Pantoprazole in pediatric patients 1 year through 16 years of age for short-term treatment (up to eight weeks) of EE associated with GERD is supported by: a) extrapolation of results from adequate and well-controlled studies that supported the approval of Pantoprazole for treatment of EE associated with GERD in adults, and b) safety, effectiveness, and pharmacokinetic studies performed in pediatric patients [see Clinical Studies (14.1), and Clinical Pharmacology (12.3)].

Safety of Pantoprazole in the treatment of EE associated with GERD in pediatric patients 1 through 16 years of age was evaluated in three multicenter, randomized, double-blind, parallel-treatment studies, involving 249 pediatric patients, including 8 with EE (4 patients ages 1 year to 5 years and 4 patients 5 years to 11 years). The children ages 1 year to 5 years with endoscopically diagnosed EE (defined as an endoscopic Hetzel-Dent score ≥ 2) were treated once daily for 8 weeks with one of two dose levels of Pantoprazole (approximating 0.6 mg/kg or 1.2 mg/kg). All 4 of these patients with EE were healed (Hetzel-Dent score of 0 or 1) at 8 weeks. Because EE is uncommon in the pediatric population, predominantly pediatric patients with endoscopically-proven or symptomatic GERD were also included in these studies. Patients were treated with a range of doses of Pantoprazole once daily for 8 weeks. For safety findings see Adverse Reactions (6.1). Because these pediatric trials had no placebo, active comparator, or evidence of a dose response, the trials were inconclusive regarding the clinical benefit of Pantoprazole for symptomatic GERD in the pediatric population. The effectiveness of Pantoprazole for treating symptomatic GERD in pediatric patients has not been established.

Although the data from the clinical trials support use of Pantoprazole for the short-term treatment of EE associated with GERD in pediatric patients 1 year through 5 years, there is no commercially available dosage formulation appropriate for patients less than 5 years of age [see Dosage and Administration (2)].

In a population pharmacokinetic analysis, clearance values in the children 1 to 5 years old with endoscopically proven GERD had a median value of 2.4 L/h. Following a 1.2 mg/kg equivalent dose (15 mg for ≤ 12.5 kg and 20 mg for > 12.5 to < 25 kg), the plasma concentrations of pantoprazole were highly variable and the median time to peak plasma concentration was 3 to 6 hours. The estimated AUC for patients 1 to 5 years old was 37% higher than for adults receiving a single 40 mg tablet, with a geometric mean AUC value of 6.8 mcg•hr/mL.

Neonates to less than one year of age

Pantoprazole was not found to be effective in a multicenter, randomized, double-blind, placebo-controlled, treatment-withdrawal study of 129 pediatric patients 1 through 11 months of age. Patients were enrolled if they had symptomatic GERD based on medical history and had not responded to non-pharmacologic interventions for GERD for two weeks. Patients received Pantoprazole daily for four weeks in an open-label phase, then patients were randomized in equal proportion to receive Pantoprazole treatment or placebo for the subsequent four weeks in a double-blind manner. Efficacy was assessed by observing the time from randomization to study discontinuation due to symptom worsening during the four-week treatment-withdrawal phase. There was no statistically significant difference between Pantoprazole and placebo in the rate of discontinuation.

In this trial, the adverse reactions that were reported more commonly (difference of ≥ 4%) in the treated population compared to the placebo population were elevated CK, otitis media, rhinitis, and laryngitis.

In a population pharmacokinetic analysis, the systemic exposure was higher in patients less than 1 year of age with GERD compared to adults who received a single 40 mg dose (geometric mean AUC was 103% higher in preterm infants and neonates receiving single dose of 2.5 mg of Pantoprazole, and 23% higher in infants 1 through 11 months of age receiving a single dose of approximately 1.2 mg/kg). In these patients, the apparent clearance (CL/F) increased with age (median clearance: 0.6 L/hr, range: 0.03 to 3.2 L/hr).

These doses resulted in pharmacodynamic effects on gastric but not esophageal pH. Following once daily dosing of 2.5 mg of Pantoprazole in preterm infants and neonates, there was an increase in the mean gastric pH (from 4.3 at baseline to 5.2 at steady-state) and in the mean % time that gastric pH was > 4 (from 60% at baseline to 80% at steady-state). Following once daily dosing of approximately 1.2 mg/kg of Pantoprazole in infants 1 through 11 months of age, there was an increase in the mean gastric pH (from 3.1 at baseline to 4.2 at steady-state) and in the mean % time that gastric pH was > 4 (from 32% at baseline to 60% at steady-state). However, no significant changes were observed in mean intraesophageal pH or % time that esophageal pH was < 4 in either age group.

Because Pantoprazole was not shown to be effective in the randomized, placebo-controlled study in this age group, the use of Pantoprazole for treatment of symptomatic GERD in infants less than 1 year of age is not indicated.

Animal Toxicity Data

In a pre- and post-natal development study in rats, the pups were administered oral doses of pantoprazole at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (AUC) in children aged 6 to 11 years at a dose of 40 mg) on postnatal day (PND 4) through PND 21, in addition to lactational exposure through milk. On PND 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (AUC) in children aged 6 to 11 years at the 40 mg dose) and higher doses. Changes in bone parameters were partially reversible following a recovery period.

In neonatal/juvenile animals (rats and dogs) toxicities were similar to those observed in adult animals, including gastric alterations, decreases in red cell mass, increases in lipids, enzyme induction and hepatocellular hypertrophy. An increased incidence of eosinophilic chief cells in adult and neonatal/juvenile rats, and atrophy of chief cells in adult rats and in neonatal/juvenile dogs, was observed in the fundic mucosa of stomachs in repeated-dose studies. Full to partial recovery of these effects were noted in animals of both age groups following a recovery period.

In short-term US clinical trials, erosive esophagitis healing rates in the 107 elderly patients (≥ 65 years old) treated with Pantoprazole were similar to those found in patients under the age of 65. The incidence rates of adverse reactions and laboratory abnormalities in patients aged 65 years and older were similar to those associated with patients younger than 65 years of age.

Experience in patients taking very high doses of Pantoprazole (greater than 240 mg) is limited. Spontaneous post-marketing reports of overdose are generally within the known safety profile of Pantoprazole.

{ "type": "p", "children": [], "text": "Experience in patients taking very high doses of Pantoprazole (greater than 240 mg) is limited. Spontaneous post-marketing reports of overdose are generally within the known safety profile of Pantoprazole." }

Pantoprazole is not removed by hemodialysis. In case of overdosage, treatment should be symptomatic and supportive.

{ "type": "p", "children": [], "text": "Pantoprazole is not removed by hemodialysis. In case of overdosage, treatment should be symptomatic and supportive. " }

Single oral doses of pantoprazole at 709 mg/kg, 798 mg/kg, and 887 mg/kg were lethal to mice, rats, and dogs, respectively. The symptoms of acute toxicity were hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor.

{ "type": "p", "children": [], "text": "Single oral doses of pantoprazole at 709 mg/kg, 798 mg/kg, and 887 mg/kg were lethal to mice, rats, and dogs, respectively. The symptoms of acute toxicity were hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor. " }

The active ingredient in Pantoprazole Sodium Delayed-Release Tablets, USP is a substituted benzimidazole, sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl] sulfinyl]-1H-benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its empirical formula is C16H14F2N3NaO4S × 1.5 H2O, with a molecular weight of 432.4. The structural formula is:

{ "type": "p", "children": [], "text": "The active ingredient in Pantoprazole Sodium Delayed-Release Tablets, USP is a substituted benzimidazole, sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl] sulfinyl]-1H-benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its empirical formula is C16H14F2N3NaO4S × 1.5 H2O, with a molecular weight of 432.4. The structural formula is: " }

Pantoprazole sodium sesquihydrate is a white to off-white crystalline powder and is racemic. Pantoprazole has weakly basic and acidic properties. Pantoprazole sodium sesquihydrate is freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in n-hexane.

{ "type": "p", "children": [], "text": "Pantoprazole sodium sesquihydrate is a white to off-white crystalline powder and is racemic. Pantoprazole has weakly basic and acidic properties. Pantoprazole sodium sesquihydrate is freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in n-hexane. " }

The stability of the compound in aqueous solution is pH-dependent. The rate of degradation increases with decreasing pH. At ambient temperature, the degradation half-life is approximately 2.8 hours at pH 5 and approximately 220 hours at pH 7.8.

{ "type": "p", "children": [], "text": "The stability of the compound in aqueous solution is pH-dependent. The rate of degradation increases with decreasing pH. At ambient temperature, the degradation half-life is approximately 2.8 hours at pH 5 and approximately 220 hours at pH 7.8. " }

Pantoprazole is supplied as a delayed-release tablet, available in two strengths (20 mg and 40 mg).

{ "type": "p", "children": [], "text": "Pantoprazole is supplied as a delayed-release tablet, available in two strengths (20 mg and 40 mg). " }

Each Pantoprazole Sodium Delayed-Release Tablet contains 45.1 mg or 22.55 mg of pantoprazole sodium sesquihydrate (equivalent to 40 mg or 20 mg pantoprazole, respectively) with the following inactive ingredients: crospovidone, glyceryl dibehenate, hypromellose, lactose monohydrate, methacrylic acid copolymer dispersion, talc, titanium dioxide, and triethyl citrate. The 20 mg tablet also contains black iron oxide, isopropyl alcohol, and propylene glycol. Pantoprazole Sodium Delayed-Release Tablets (40 mg and 20 mg) complies with USP dissolution test 4.

{ "type": "p", "children": [], "text": "Each Pantoprazole Sodium Delayed-Release Tablet contains 45.1 mg or 22.55 mg of pantoprazole sodium sesquihydrate (equivalent to 40 mg or 20 mg pantoprazole, respectively) with the following inactive ingredients: crospovidone, glyceryl dibehenate, hypromellose, lactose monohydrate, methacrylic acid copolymer dispersion, talc, titanium dioxide, and triethyl citrate. The 20 mg tablet also contains black iron oxide, isopropyl alcohol, and propylene glycol. Pantoprazole Sodium Delayed-Release Tablets (40 mg and 20 mg) complies with USP dissolution test 4.\n\n" }

Pantoprazole is a PPI that suppresses the final step in gastric acid production by covalently binding to the (H+, K+)-ATPase enzyme system at the secretory surface of the gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. The binding to the (H+, K+)-ATPase results in a duration of antisecretory effect that persists longer than 24 hours for all doses tested (20 mg to 120 mg).

Antisecretory Activity

Under maximal acid stimulatory conditions using pentagastrin, a dose-dependent decrease in gastric acid output occurs after a single dose of oral (20-80 mg) pantoprazole in healthy subjects. Pantoprazole given once daily results in increasing inhibition of gastric acid secretion. Following the initial oral dose of 40 mg pantoprazole, a 51% mean inhibition was achieved by 2.5 hours. With once-a-day dosing for 7 days, the mean inhibition was increased to 85%. Pantoprazole suppressed acid secretion in excess of 95% in half of the subjects. Acid secretion had returned to normal within a week after the last dose of pantoprazole; there was no evidence of rebound hypersecretion.

In a series of dose-response studies, pantoprazole, at oral doses ranging from 20 to 120 mg, caused dose-related increases in median basal gastric pH and in the percent of time gastric pH was > 3 and > 4. Treatment with 40 mg of pantoprazole produced significantly greater increases in gastric pH than the 20 mg dose. Doses higher than 40 mg (60, 80, 120 mg) did not result in further significant increases in median gastric pH. The effects of pantoprazole on median pH from one double-blind crossover study are shown in Table 5.

<div class="scrollingtable"><table> <caption> <span>Table 5: Effect of Single Daily Doses of Oral Pantoprazole on Intragastric pH </span> </caption> <col/> <col/> <col/> <col/> <col/> <thead> <tr class="First"> <th valign="top"></th><th>Median pH on day 7</th> </tr> <tr class="Last"> <th valign="top">Time</th><th align="center" valign="bottom">Placebo</th><th align="center" valign="bottom">20 mg</th><th align="center" valign="bottom">40 mg</th><th align="center" valign="bottom">80 mg</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-6" name="footnote-6">*</a> </dt> <dd>Significantly different from placebo</dd> <dt> <a href="#footnote-reference-7" name="footnote-7">†</a> </dt> <dd>Significantly different from 20 mg</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td valign="top"> 8 a.m. -  8 a.m.<br/>(24 hours)</td><td align="center" valign="bottom"> 1.3</td><td align="center" valign="bottom"> 2.9<a class="Sup" href="#footnote-6" name="footnote-reference-6">*</a></td><td align="center" valign="bottom"> 3.8<a class="Sup" href="#footnote-6">*</a><a class="Sup" href="#footnote-7" name="footnote-reference-7">†</a></td><td align="center" valign="bottom"> 3.9<a class="Sup" href="#footnote-6">*</a><a class="Sup" href="#footnote-7">†</a></td> </tr> <tr> <td valign="top"> 8 a.m. -  10 p.m.<br/>(Daytime)<br/> </td><td align="center" valign="bottom"> 1.6</td><td align="center" valign="bottom"> 3.2<a class="Sup" href="#footnote-6">*</a></td><td align="center" valign="bottom"> 4.4<a class="Sup" href="#footnote-6">*</a><a class="Sup" href="#footnote-7">†</a></td><td align="center" valign="bottom"> 4.8<a class="Sup" href="#footnote-6">*</a><a class="Sup" href="#footnote-7">†</a></td> </tr> <tr class="Last"> <td valign="top"> 10 p.m. -  8 a.m.<br/>(Nighttime)<br/> </td><td align="center" valign="bottom"> 1.2</td><td align="center" valign="bottom"> 2.1<a class="Sup" href="#footnote-6">*</a></td><td align="center" valign="bottom"> 3.0<a class="Sup" href="#footnote-6">*</a></td><td align="center" valign="bottom"> 2.6<a class="Sup" href="#footnote-6">*</a></td> </tr> </tbody> </table></div>

Serum Gastrin Effects

Fasting serum gastrin levels were assessed in two double-blind studies of the acute healing of erosive esophagitis (EE) in which 682 patients with gastroesophageal reflux disease (GERD) received 10, 20, or 40 mg of Pantoprazole for up to 8 weeks. At 4 weeks of treatment there was an increase in mean gastrin levels of 7%, 35%, and 72% over pretreatment values in the 10, 20, and 40 mg treatment groups, respectively. A similar increase in serum gastrin levels was noted at the 8-week visit with mean increases of 3%, 26%, and 84% for the three pantoprazole dose groups. Median serum gastrin levels remained within normal limits during maintenance therapy with Pantoprazole Sodium Delayed-Release Tablets.

In long-term international studies involving over 800 patients, a 2- to 3-fold mean increase from the pretreatment fasting serum gastrin level was observed in the initial months of treatment with pantoprazole at doses of 40 mg per day during GERD maintenance studies and 40 mg or higher per day in patients with refractory GERD. Fasting serum gastrin levels generally remained at approximately 2 to 3 times baseline for up to 4 years of periodic follow-up in clinical trials.

Following short-term treatment with Pantoprazole, elevated gastrin levels return to normal by at least 3 months.

Enterochromaffin-Like (ECL) Cell Effects

In 39 patients treated with oral pantoprazole 40 mg to 240 mg daily (majority receiving 40 mg to 80 mg) for up to 5 years, there was a moderate increase in ECL-cell density, starting after the first year of use, which appeared to plateau after 4 years.

In a nonclinical study in Sprague-Dawley rats, lifetime exposure (24 months) to pantoprazole at doses of 0.5 to 200 mg/kg/day resulted in dose-related increases in gastric ECL cell proliferation and gastric neuroendocrine (NE)-cell tumors. Gastric NE-cell tumors in rats may result from chronic elevation of serum gastrin concentrations. The high density of ECL cells in the rat stomach makes this species highly susceptible to the proliferative effects of elevated gastrin concentrations produced by PPIs. However, there were no observed elevations in serum gastrin following the administration of pantoprazole at a dose of 0.5 mg/kg/day. In a separate study, a gastric NE-cell tumor without concomitant ECL-cell proliferative changes was observed in 1 female rat following 12 months of dosing with pantoprazole at 5 mg/kg/day and a 9 month off-dose recovery [see Nonclinical Toxicology (13.1)].

Endocrine Effects

In a clinical pharmacology study, Pantoprazole 40 mg given once daily for 2 weeks had no effect on the levels of the following hormones: cortisol, testosterone, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone, thyronine-binding protein, parathyroid hormone, insulin, glucagon, renin, aldosterone, follicle-stimulating hormone, luteinizing hormone, prolactin and growth hormone.

In a 1-year study of GERD patients treated with Pantoprazole 40 mg or 20 mg, there were no changes from baseline in overall levels of T3, T4, and TSH.

Pantoprazole Sodium Delayed-Release Tablets are prepared as enteric-coated tablets so that absorption of pantoprazole begins only after the tablet leaves the stomach. Peak serum concentration (Cmax) and area under the serum concentration time curve (AUC) increase in a manner proportional to oral doses from 10 mg to 80 mg. Pantoprazole does not accumulate, and its pharmacokinetics are unaltered with multiple daily dosing. Following oral administration, the serum concentration of pantoprazole declines biexponentially, with a terminal elimination half-life of approximately one hour.

In extensive metabolizers with normal liver function receiving an oral dose of the enteric-coated 40 mg pantoprazole tablet, the peak concentration (Cmax) is 2.5 mcg/mL; the time to reach the peak concentration (tmax) is 2.5 h, and the mean total area under the plasma concentration versus time curve (AUC) is 4.8 mcg∙h/mL (range 1.4 to 13.3 mcg∙h/mL).

Absorption

After administration of a single or multiple oral 40 mg doses of Pantoprazole Sodium Delayed-Release Tablets, the peak plasma concentration of pantoprazole was achieved in approximately 2.5 hours, and Cmax was 2.5 mcg/mL. Pantoprazole undergoes little first-pass metabolism, resulting in an absolute bioavailability of approximately 77%. Pantoprazole absorption is not affected by concomitant administration of antacids.

Administration of Pantoprazole Sodium Delayed-Release Tablets with food may delay its absorption up to 2 hours or longer; however, the Cmax and the extent of pantoprazole absorption (AUC) are not altered. Thus, Pantoprazole Sodium Delayed-Release Tablets may be taken without regard to timing of meals.

Distribution

The apparent volume of distribution of pantoprazole is approximately 11.0-23.6 L, distributing mainly in extracellular fluid. The serum protein binding of pantoprazole is about 98%, primarily to albumin.

Elimination

Metabolism

Pantoprazole is extensively metabolized in the liver through the cytochrome P450 (CYP) system. Pantoprazole metabolism is independent of the route of administration (oral). The main metabolic pathway is demethylation, by CYP2C19, with subsequent sulfation; other metabolic pathways include oxidation by CYP3A4. There is no evidence that any of the pantoprazole metabolites have significant pharmacologic activity.

Excretion

After a single oral dose of 14C-labeled pantoprazole to healthy, normal metabolizer subjects, approximately 71% of the dose was excreted in the urine, with 18% excreted in the feces through biliary excretion. There was no renal excretion of unchanged pantoprazole.

Specific populations

Age: Geriatric Population

Only slight to moderate increases in the AUC (43%) and Cmax (26%) of pantoprazole were found in elderly subjects (64 to 76 years of age) after repeated oral administration, compared with younger subjects [see Use in Specific Populations (8.5)].

Age: Pediatric Population

The pharmacokinetics of pantoprazole were studied in children less than 16 years of age in four randomized, open-label clinical trials in pediatric patients with presumed/proven GERD. A pediatric granule formulation was studied in children through 5 years of age, and Pantoprazole Delayed-Release Tablets were studied in children older than 5 years.

In a population PK analysis, total clearance increased with increasing bodyweight in a non-linear fashion. The total clearance also increased with increasing age only in children under 3 years of age.

Neonate through 5 years of age

See Use in Specific Populations (8.4).

Children and Adolescents 6 through 16 Years of Age

The pharmacokinetics of Pantoprazole Sodium Delayed-Release Tablets were evaluated in children ages 6 through 16 years with a clinical diagnosis of GERD. The PK parameters following a single oral dose of 20 mg or 40 mg of Pantoprazole tablets in children ages 6 through 16 years were highly variable (%CV ranges 40 to 80%). The geometric mean AUC estimated from population PK analysis after a 40 mg Pantoprazole tablet in pediatric patients was about 39% and 10% higher respectively in 6 to 11 and 12 to 16 year-old children, compared to that of adults (Table 6).

<div class="scrollingtable"><table> <caption> <span>Table 6: PK Parameters in Children and Adolescents 6 through 16 years with GERD receiving 40 mg Pantoprazole Sodium Delayed-Release Tablets</span> </caption> <col/> <col/> <col/> <thead> <tr class="First Last"> <th align="center" valign="top"></th><th>6-11 years (n=12)</th><th align="center" valign="top">12-16 years (n=11)</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-8" name="footnote-8">*</a> </dt> <dd>Geometric mean values</dd> <dt> <a href="#footnote-reference-9" name="footnote-9">†</a> </dt> <dd>Median values</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td valign="top"> C<span class="Sub">max</span> (mcg/mL)<a class="Sup" href="#footnote-8" name="footnote-reference-8">*</a></td><td align="center" valign="top"> 1.8</td><td align="center" valign="top"> 1.8</td> </tr> <tr> <td valign="top"> T<span class="Sub">max</span> (h)<a class="Sup" href="#footnote-9" name="footnote-reference-9">†</a></td><td align="center" valign="top"> 2.0</td><td align="center" valign="top"> 2.0</td> </tr> <tr> <td valign="top"> AUC (mcg∙h/mL)<a class="Sup" href="#footnote-8">*</a></td><td align="center" valign="top"> 6.9</td><td align="center" valign="top"> 5.5</td> </tr> <tr class="Last"> <td valign="top"> CL/F (L/h)<a class="Sup" href="#footnote-9">†</a></td><td align="center" valign="top"> 6.6</td><td align="center" valign="top"> 6.8</td> </tr> </tbody> </table></div>

Sex

There is a modest increase in pantoprazole AUC and Cmax in women compared to men. However, weight-normalized clearance values are similar in women and men. In pediatric patients ages 1 through 16 years there were no clinically relevant effects of gender on clearance of pantoprazole, as shown by population pharmacokinetic analysis.

Renal Impairment

In patients with severe renal impairment, pharmacokinetic parameters for pantoprazole were similar to those of healthy subjects.

Hepatic Impairment

In patients with mild to severe hepatic impairment (Child-Pugh A to C cirrhosis), maximum pantoprazole concentrations increased only slightly (1.5-fold) relative to healthy subjects. Although serum half-life values increased to 7-9 hours and AUC values increased by 5- to 7‑fold in hepatic-impaired patients, these increases were no greater than those observed in CYP2C19 poor metabolizers, where no dosage adjustment is warranted. These pharmacokinetic changes in hepatic-impaired patients result in minimal drug accumulation following once-daily, multiple-dose administration. Doses higher than 40 mg per day of Pantoprazole have not been studied in hepatically impaired patients.

Drug Interaction Studies

Effect of Other Drugs on Pantoprazole

Pantoprazole is metabolized mainly by CYP2C19 and to minor extents by CYPs 3A4, 2D6, and 2C9. In in vivo drug-drug interaction studies with CYP2C19 substrates (diazepam [also a CYP3A4 substrate] and phenytoin [also a CYP3A4 inducer] and clopidogrel), nifedipine, midazolam, and clarithromycin (CYP3A4 substrates), metoprolol (a CYP2D6 substrate), diclofenac, naproxen and piroxicam (CYP2C9 substrates), and theophylline (a CYP1A2 substrate) in healthy subjects, the pharmacokinetics of pantoprazole were not significantly altered.

Effect of Pantoprazole on Other Drugs

Clopidogrel

Clopidogrel is metabolized to its active metabolite in part by CYP2C19. In a crossover clinical study, 66 healthy subjects were administered clopidogrel (300 mg loading dose followed by 75 mg per day) alone and with pantoprazole (80 mg at the same time as clopidogrel) for 5 days. On Day 5, the mean AUC of the active metabolite of clopidogrel was reduced by approximately 14% (geometric mean ratio was 86%, with 90% CI of 79 to 93%) when pantoprazole was coadministered with clopidogrel as compared to clopidogrel administered alone. Pharmacodynamic parameters were also measured and demonstrated that the change in inhibition of platelet aggregation (induced by 5 μM ADP) was correlated with the change in the exposure to clopidogrel active metabolite. The clinical significance of this finding is not clear.

Mycophenolate Mofetil (MMF)

Administration of pantoprazole 40 mg twice daily for 4 days and a single 1000 mg dose of MMF approximately one hour after the last dose of pantoprazole to 12 healthy subjects in a cross-over study resulted in a 57% reduction in the Cmaxand 27% reduction in the AUC of MPA. Transplant patients receiving approximately 2000 mg per day of MMF (n=12) were compared to transplant patients receiving approximately the same dose of MMF and pantoprazole 40 mg per day (n=21). There was a 78% reduction in the Cmax and a 45% reduction in the AUC of MPA in patients receiving both pantoprazole and MMF [see Drug Interactions (7)].

Other Drugs

In vivo studies also suggest that pantoprazole does not significantly affect the kinetics of the following drugs (cisapride, theophylline, diazepam [and its active metabolite, desmethyldiazepam], phenytoin, metoprolol, nifedipine, carbamazepine, midazolam, clarithromycin, naproxen, piroxicam, and oral contraceptives [levonorgestrel/ethinyl estradiol]). In other in vivo studies, digoxin, ethanol, glyburide, antipyrine, caffeine, metronidazole, and amoxicillin had no clinically relevant interactions with pantoprazole.

Although no significant drug-drug interactions have been observed in clinical studies, the potential for significant drug-drug interactions with more than once-daily dosing with high doses of pantoprazole has not been studied in poor metabolizers or individuals who are hepatically impaired.

Antacids

There was also no interaction with concomitantly administered antacids.

CYP2C19 displays a known genetic polymorphism due to its deficiency in some subpopulations (e.g., approximately 3% of Caucasians and African-Americans and 17% to 23% of Asians are poor metabolizers). Although these subpopulations of pantoprazole poor metabolizers have elimination half-life values of 3.5 to 10 hours in adults, they still have minimal accumulation (≤ 23%) with once-daily dosing. For adult patients who are CYP2C19 poor metabolizers, no dosage adjustment is needed.

Similar to adults, pediatric patients who have the poor metabolizer genotype of CYP2C19 (CYP2C19 *2/*2) exhibited greater than a 6-fold increase in AUC compared to pediatric extensive (CYP2C19 *1/*1) and intermediate (CYP2C19 *1/*x) metabolizers. Poor metabolizers exhibited approximately 10‑fold lower apparent oral clearance compared to extensive metabolizers.

For known pediatric poor metabolizers, a dose reduction should be considered.

In a 24-month carcinogenicity study, Sprague-Dawley rats were treated orally with doses of 0.5 to 200 mg/kg/day, about 0.1 to 40 times the exposure on a body surface area basis of a 50 kg person dosed with 40 mg/day. In the gastric fundus, treatment at 0.5 to 200 mg/kg/day produced enterochromaffin-like (ECL) cell hyperplasia and benign and malignant neuroendocrine cell tumors in a dose-related manner. In the forestomach, treatment with 50 and 200 mg/kg/day (about 10 and 40 times the recommended human dose on a body surface area basis) produced benign squamous cell papillomas and malignant squamous cell carcinomas. Rare gastrointestinal tumors associated with pantoprazole treatment included an adenocarcinoma of the duodenum with 50 mg/kg/day and benign polyps and adenocarcinomas of the gastric fundus with 200 mg/kg/day. In the liver, treatment at 0.5 to 200 mg/kg/day produced dose-related increases in the incidences of hepatocellular adenomas and carcinomas. In the thyroid gland, treatment with 200 mg/kg/day produced increased incidences of follicular cell adenomas and carcinomas for both male and female rats.

In a 24-month carcinogenicity study, Fischer 344 rats were treated orally with doses of 5 to 50 mg/kg/day of pantoprazole, approximately 1 to 10 times the recommended human dose based on body surface area. In the gastric fundus, treatment with 5 to 50 mg/kg/day produced enterochromaffin-like (ECL) cell hyperplasia and benign and malignant neuroendocrine cell tumors. Dose selection for this study may not have been adequate to comprehensively evaluate the carcinogenic potential of pantoprazole.

In a 24-month carcinogenicity study, B6C3F1 mice were treated orally with doses of 5 to 150 mg/kg/day of pantoprazole, 0.5 to 15 times the recommended human dose based on body surface area. In the liver, treatment with 150 mg/kg/day produced increased incidences of hepatocellular adenomas and carcinomas in female mice. Treatment with 5 to 150 mg/kg/day also produced gastric-fundic ECL cell hyperplasia.

A 26-week p53 +/- transgenic mouse carcinogenicity study was not positive.

Pantoprazole was positive in the in vitro human lymphocyte chromosomal aberration assays, in one of two mouse micronucleus tests for clastogenic effects, and in the in vitro Chinese hamster ovarian cell/HGPRT forward mutation assay for mutagenic effects. Equivocal results were observed in the in vivo rat liver DNA covalent binding assay. Pantoprazole was negative in the in vitro Ames mutation assay, the in vitro unscheduled DNA synthesis (UDS) assay with rat hepatocytes, the in vitro AS52/GPT mammalian cell-forward gene mutation assay, the in vitro thymidine kinase mutation test with mouse lymphoma L5178Y cells, and the in vivo rat bone marrow cell chromosomal aberration assay.

There were no effects on fertility or reproductive performance when pantoprazole was given at oral doses up to 500 mg/kg/day in male rats (98 times the recommended human dose based on body surface area) and 450 mg/kg/day in female rats (88 times the recommended human dose based on body surface area).

Adult Patients

A US multicenter, double-blind, placebo-controlled study of Pantoprazole 10 mg, 20 mg, or 40 mg once daily was conducted in 603 patients with reflux symptoms and endoscopically diagnosed EE of grade 2 or above (Hetzel-Dent scale). In this study, approximately 25% of enrolled patients had severe EE of grade 3, and 10% had grade 4. The percentages of patients healed (per protocol, n = 541) in this study are shown in Table 7.

<div class="scrollingtable"><table> <caption> <span>Table 7: Erosive Esophagitis Healing Rates (Per Protocol)</span> </caption> <col/> <col/> <col/> <col/> <col/> <thead> <tr class="First"> <th align="center" valign="top"></th><th> Pantoprazole</th><th align="center" valign="top"> Placebo</th> </tr> <tr class="Last"> <th align="center" valign="bottom"> Week</th><th align="center" valign="top"> 10 mg daily<br/> (n = 153)</th><th align="center" valign="top"> 20 mg daily<br/> (n = 158)</th><th align="center" valign="top"> 40 mg daily<br/> (n = 162)</th><th align="center" valign="bottom"> (n = 68)</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-10" name="footnote-10">*</a> </dt> <dd>(p &lt; 0.001) Pantoprazole versus placebo</dd> <dt> <a href="#footnote-reference-11" name="footnote-11">†</a> </dt> <dd>(p &lt; 0.05) versus 10 mg Pantoprazole</dd> <dt> <a href="#footnote-reference-12" name="footnote-12">‡</a> </dt> <dd>(p &lt; 0.05) versus 10 mg or 20 mg Pantoprazole</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td align="center" valign="top"> 4</td><td align="center" valign="top"> 45.6%<a class="Sup" href="#footnote-10" name="footnote-reference-10">*</a></td><td align="center" valign="top"> 58.4%<a class="Sup" href="#footnote-10">*</a><a class="Sup" href="#footnote-11" name="footnote-reference-11">†</a></td><td align="center" valign="top"> 75.0%<a class="Sup" href="#footnote-10">*</a><a class="Sup" href="#footnote-12" name="footnote-reference-12">‡</a></td><td align="center" valign="top"> 14.3%</td> </tr> <tr class="Last"> <td align="center" valign="top"> 8</td><td align="center" valign="top"> 66.0%<a class="Sup" href="#footnote-10">*</a></td><td align="center" valign="top"> 83.5%<a class="Sup" href="#footnote-10">*</a><a class="Sup" href="#footnote-11">†</a></td><td align="center" valign="top"> 92.6%<a class="Sup" href="#footnote-10">*</a><a class="Sup" href="#footnote-12">‡</a></td><td align="center" valign="top"> 39.7%</td> </tr> </tbody> </table></div>

In this study, all Pantoprazole treatment groups had significantly greater healing rates than the placebo group. This was true regardless of H. pylori status for the 40 mg and 20 mg Pantoprazole treatment groups. The 40 mg dose of Pantoprazole resulted in healing rates significantly greater than those found with either the 20 mg or 10 mg dose.

A significantly greater proportion of patients taking Pantoprazole 40 mg experienced complete relief of daytime and nighttime heartburn and the absence of regurgitation, starting from the first day of treatment, compared with placebo. Patients taking Pantoprazole consumed significantly fewer antacid tablets per day than those taking placebo.

Pantoprazole 40 mg and 20 mg once daily were also compared with nizatidine 150 mg twice daily in a US multicenter, double-blind study of 243 patients with reflux symptoms and endoscopically diagnosed EE of grade 2 or above. The percentages of patients healed (per protocol, n = 212) are shown in Table 8.

<div class="scrollingtable"><table> <caption> <span>Table 8: Erosive Esophagitis Healing Rates (Per Protocol) </span> </caption> <col/> <col/> <col/> <col/> <thead> <tr class="First"> <th align="center" valign="top"></th><th> Pantoprazole</th><th align="center" valign="top"> Nizatidine</th> </tr> <tr class="Last"> <th align="center" valign="bottom"> Week </th><th align="center" valign="top"> 20 mg daily<br/> (n = 72)</th><th align="center" valign="top"> 40 mg daily<br/> (n = 70) </th><th align="center" valign="top"> 150 mg twice daily<br/> (n = 70)</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-13" name="footnote-13">*</a> </dt> <dd>(p &lt; 0.001) Pantoprazole versus nizatidine</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td align="center" valign="top"> 4</td><td align="center" valign="top"> 61.4%<a class="Sup" href="#footnote-13" name="footnote-reference-13">*</a></td><td align="center" valign="top"> 64.0%<a class="Sup" href="#footnote-13">*</a></td><td align="center" valign="top"> 22.2%</td> </tr> <tr class="Last"> <td align="center" valign="top"> 8</td><td align="center" valign="top"> 79.2%<a class="Sup" href="#footnote-13">*</a></td><td align="center" valign="top"> 82.9%<a class="Sup" href="#footnote-13">*</a></td><td align="center" valign="top"> 41.4%</td> </tr> </tbody> </table></div>

Once-daily treatment with Pantoprazole 40 mg or 20 mg resulted in significantly superior rates of healing at both 4 and 8 weeks compared with twice-daily treatment with 150 mg of nizatidine. For the 40 mg treatment group, significantly greater healing rates compared to nizatidine were achieved regardless of the H. pylori status.

A significantly greater proportion of the patients in the Pantoprazole treatment groups experienced complete relief of nighttime heartburn and regurgitation, starting on the first day and of daytime heartburn on the second day, compared with those taking nizatidine 150 mg twice daily. Patients taking Pantoprazole consumed significantly fewer antacid tablets per day than those taking nizatidine.

Pediatric Patients Ages 5 Years through 16 Years

The efficacy of Pantoprazole in the treatment of EE associated with GERD in pediatric patients ages 5 years through 16 years is extrapolated from adequate and well-conducted trials in adults, as the pathophysiology is thought to be the same. Four pediatric patients with endoscopically diagnosed EE were studied in multicenter, randomized, double-blind, parallel-treatment trials. Children with endoscopically diagnosed EE (defined as an endoscopic Hetzel-Dent score ≥ 2) were treated once daily for 8 weeks with one of two dose levels of Pantoprazole (20 mg or 40 mg). All 4 patients with EE were healed (Hetzel-Dent score of 0 or 1) at 8 weeks.

Two independent, multicenter, randomized, double-blind, comparator-controlled trials of identical design were conducted in adult GERD patients with endoscopically confirmed healed erosive esophagitis to demonstrate efficacy of Pantoprazole in long-term maintenance of healing. The two US studies enrolled 386 and 404 patients, respectively, to receive either 10 mg, 20 mg, or 40 mg of Pantoprazole Sodium Delayed-Release Tablets once daily or 150 mg of ranitidine twice daily. As demonstrated in Table 9, Pantoprazole 40 mg and 20 mg were significantly superior to ranitidine at every timepoint with respect to the maintenance of healing. In addition, Pantoprazole 40 mg was superior to all other treatments studied.

<div class="scrollingtable"><table> <caption> <span>Table 9: Long-Term Maintenance of Healing of Erosive Gastroesophageal Reflux Disease (GERD Maintenance): Percentage of Patients Who Remained Healed</span> </caption> <col/> <col/> <col/> <col/> <thead> <tr class="First Last"> <th valign="top"></th><th> Pantoprazole<br/> 20 mg daily</th><th align="center" valign="top"> Pantoprazole<br/> 40 mg daily</th><th align="center" valign="top"> Ranitidine<br/> 150 mg twice daily</th> </tr> </thead> <tfoot> <tr class="First Last"> <td colspan="4" valign="top"> Note: Pantoprazole 10 mg was superior (p &lt; 0.05) to ranitidine in Study 2, but not Study 1. </td> </tr> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-14" name="footnote-14">*</a> </dt> <dd>(p &lt; 0.05 vs. ranitidine)</dd> <dt> <a href="#footnote-reference-15" name="footnote-15">†</a> </dt> <dd>(p &lt; 0.05 vs. Pantoprazole 20 mg)</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td valign="top"> <span class="Bold">Study 1</span></td><td align="center" valign="top"> n = 75</td><td align="center" valign="top"> n = 74</td><td align="center" valign="top"> n = 75</td> </tr> <tr> <td valign="top"> Month 1</td><td align="center" valign="top"> 91<a class="Sup" href="#footnote-14" name="footnote-reference-14">*</a></td><td align="center" valign="top"> 99<a class="Sup" href="#footnote-14">*</a></td><td align="center" valign="top"> 68</td> </tr> <tr> <td valign="top"> Month 3</td><td align="center" valign="top"> 82<a class="Sup" href="#footnote-14">*</a></td><td align="center" valign="top"> 93<a class="Sup" href="#footnote-14">*</a><a class="Sup" href="#footnote-15" name="footnote-reference-15">†</a></td><td align="center" valign="top"> 54</td> </tr> <tr> <td valign="top"> Month 6</td><td align="center" valign="top"> 76<a class="Sup" href="#footnote-14">*</a></td><td align="center" valign="top"> 90<a class="Sup" href="#footnote-14">*</a><a class="Sup" href="#footnote-15">†</a></td><td align="center" valign="top"> 44</td> </tr> <tr> <td valign="top"> Month 12 </td><td align="center" valign="top"> 70<a class="Sup" href="#footnote-14">*</a></td><td align="center" valign="top"> 86<a class="Sup" href="#footnote-14">*</a><a class="Sup" href="#footnote-15">†</a></td><td align="center" valign="top"> 35</td> </tr> <tr> <td valign="top">  </td><td align="center" valign="top">  </td><td align="center" valign="top">  </td><td align="center" valign="top">  </td> </tr> <tr> <td valign="top"> <span class="Bold">Study 2</span></td><td align="center" valign="top"> n = 74</td><td align="center" valign="top"> n = 88</td><td align="center" valign="top"> n = 84</td> </tr> <tr> <td valign="top"> Month 1</td><td align="center" valign="top"> 89<a class="Sup" href="#footnote-14">*</a></td><td align="center" valign="top"> 92<a class="Sup" href="#footnote-14">*</a></td><td align="center" valign="top"> 62</td> </tr> <tr> <td valign="top"> Month 3 </td><td align="center" valign="top"> 78<a class="Sup" href="#footnote-14">*</a></td><td align="center" valign="top"> 91<a class="Sup" href="#footnote-14">*</a><a class="Sup" href="#footnote-15">†</a></td><td align="center" valign="top"> 47 </td> </tr> <tr> <td valign="top"> Month 6 </td><td align="center" valign="top"> 72<a class="Sup" href="#footnote-14">*</a></td><td align="center" valign="top"> 88<a class="Sup" href="#footnote-14">*</a><a class="Sup" href="#footnote-15">†</a></td><td align="center" valign="top"> 39 </td> </tr> <tr class="Last"> <td valign="top"> Month 12 </td><td align="center" valign="top"> 72<a class="Sup" href="#footnote-14">*</a></td><td align="center" valign="top"> 83<a class="Sup" href="#footnote-14">*</a></td><td align="center" valign="top"> 37 </td> </tr> </tbody> </table></div>

Pantoprazole 40 mg was superior to ranitidine in reducing the number of daytime and nighttime heartburn episodes from the first through the twelfth month of treatment. Pantoprazole 20 mg, administered once daily, was also effective in reducing episodes of daytime and nighttime heartburn in one trial, as presented in Table 10.

<div class="scrollingtable"><table> <caption> <span>Table 10: Number of Episodes of Heartburn (mean ± SD)</span> </caption> <col/> <col/> <col/> <col/> <thead> <tr class="First Last"> <th valign="top"></th><th></th><th> Pantoprazole<br/>40 mg daily</th><th align="center" valign="top"> Ranitidine<br/>150 mg twice daily</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-16" name="footnote-16">*</a> </dt> <dd>(p &lt; 0.001 vs. ranitidine, combined data from the two US studies)</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td valign="top"> Month 1</td><td valign="top"> Daytime </td><td align="center" valign="top"> 5.1 ± 1.6<a class="Sup" href="#footnote-16" name="footnote-reference-16">*</a></td><td align="center" valign="top"> 18.3 ± 1.6</td> </tr> <tr> <td valign="top"> </td><td valign="top"> Nighttime</td><td align="center" valign="top"> 3.9 ± 1.1<a class="Sup" href="#footnote-16">*</a></td><td align="center" valign="top"> 11.9 ± 1.1</td> </tr> <tr> <td valign="top"> Month 12</td><td valign="top"> Daytime</td><td align="center" valign="top"> 2.9 ± 1.5<a class="Sup" href="#footnote-16">*</a></td><td align="center" valign="top"> 17.5 ± 1.5</td> </tr> <tr class="Last"> <td valign="top"> </td><td valign="top"> Nighttime</td><td align="center" valign="top"> 2.5 ± 1.2<a class="Sup" href="#footnote-16">*</a></td><td align="center" valign="top"> 13.8 ± 1.3</td> </tr> </tbody> </table></div>

In a multicenter, open-label trial of 35 patients with pathological hypersecretory conditions, such as Zollinger-Ellison syndrome, with or without multiple endocrine neoplasia-type I, Pantoprazole successfully controlled gastric acid secretion. Doses ranging from 80 mg daily to 240 mg daily maintained gastric acid output below 10 mEq/h in patients without prior acid-reducing surgery and below 5 mEq/h in patients with prior acid-reducing surgery.

Doses were initially titrated to the individual patient needs, and adjusted in some patients based on the clinical response with time [see Dosage and Administration (2)]. Pantoprazole was well tolerated at these dose levels for prolonged periods (greater than 2 years in some patients).

How Supplied

Pantoprazole Sodium Delayed-Release Tablets, USP are supplied as 40 mg white, oval biconvex delayed-release tablets debossed with "17" on one side and are available as follows:

Pantoprazole Sodium Delayed-Release Tablets, USP are supplied as 20 mg white, oval biconvex delayed-release tablets imprinted in black ink with "KU" on one side and "180" on the other side and are available as follows:

Storage

Store Pantoprazole Sodium Delayed-Release Tablets, USP at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

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Adverse Reactions

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{ "type": "ul", "children": [ "\nHypersensitivity Reactions [see Contraindications (4)]\n", "\nAcute Interstitial Nephritis [see Warnings and Precautions (5.2)]\n", "\n\nClostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.3)]\n", "\nBone Fracture [see Warnings and Precautions (5.4)]\n", "\nCutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.5)]\n", "\nCyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.6)]\n", "\nHypomagnesemia [see Warnings and Precautions (5.7)]\n" ], "text": "" }

Drug Interactions

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Instruct patients to inform their healthcare provider of any other medications they are currently taking, including rilpivirine-containing products [Contraindications (4)], high dose methotrexate [Warnings and Precautions (5.10)] and over-the-counter medications.

{ "type": "p", "children": [], "text": "Instruct patients to inform their healthcare provider of any other medications they are currently taking, including rilpivirine-containing products [Contraindications (4)], high dose methotrexate [Warnings and Precautions (5.10)] and over-the-counter medications." }

Pregnancy

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

Inform female patients of reproductive potential that Pantoprazole may cause fetal harm and to inform their prescriber of a known or suspected pregnancy [see Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "Inform female patients of reproductive potential that Pantoprazole may cause fetal harm and to inform their prescriber of a known or suspected pregnancy [see Use in Specific Populations (8.1)]." }

Administration

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

{ "type": "ul", "children": [ "\nCaution patients that Pantoprazole Sodium Delayed-Release Tablets should not be split, crushed, or chewed.\n", "\nTell patients that Pantoprazole Sodium Delayed-Release Tablets should be swallowed whole, with or without food in the stomach.\n", "\nLet patients know that concomitant administration of antacids does not affect the absorption of Pantoprazole Sodium Delayed-Release Tablets. \n" ], "text": "" }

This product’s label may have been updated.  For more information, call 1-844-834-0530.

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Distributed by:

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Lannett Company, Inc.

{ "type": "p", "children": [], "text": "Lannett Company, Inc." }

Philadelphia, PA 19154

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CIA72949N

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Rev. 07/2017

{ "type": "p", "children": [], "text": " Rev. 07/2017" }

<div class="scrollingtable"><table> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">                                     <span class="Bold">Pantoprazole (pan-TOE-pruh-zole) Sodium Delayed-Release Tablets, USP</span>       </p> <p>                                     CIA77568J                                                 Rev. 07/2017</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Read this Medication Guide before you start taking Pantoprazole and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">What is the most important information I should know about </span><span class="Bold">Pantoprazole? </span> <p class="First"> <span class="Bold">Pantoprazole may help your acid-related symptoms, but you could still have serious stomach problems. Talk with your doctor. </span> </p> <p> <span class="Bold">Pantoprazole can cause serious side effects, including: </span> </p> <ul class="Disc"> <li> <p class="First"> <span class="Bold">A type of kidney problem (acute interstitial nephritis)</span>. Some people who take proton pump inhibitor (PPI) medicines, including Pantoprazole, may develop a kidney problem called acute interstitial nephritis that can happen at any time during treatment with Pantoprazole. Call your doctor if you have a decrease in the amount that you urinate or if you have blood in your urine.</p> </li> <li> <p class="First"> <span class="Bold">Diarrhea</span>. Pantoprazole may increase your risk of getting severe diarrhea. This diarrhea may be caused by an infection (<span class="Italics">Clostridium difficile</span>) in your intestines. Call your doctor right away if you have watery stool, stomach pain, and fever that does not go away. </p> </li> <li> <p class="First"> <span class="Bold">Bone fractures</span>. People who take multiple daily doses of PPI medicines for a long period of time (a year or longer) may have an increased risk of fractures of the hip, wrist or spine. You should take Pantoprazole exactly as prescribed, at the lowest dose possible for your treatment and for the shortest time needed. Talk to your doctor about your risk of bone fracture if you take Pantoprazole. </p> </li> <li> <p class="First"> <span class="Bold">Certain types of lupus erythematosus.</span> Lupus erythematosus is an autoimmune disorder (the body’s immune cells attack other cells or organs in the body). Some people who take PPI medicines, including Pantoprazole, may develop certain types of lupus erythematosus or have worsening of the lupus they already have. Call your doctor right away if you have new or worsening joint pain or a rash on your cheeks or arms that gets worse in the sun. </p> </li> </ul> Pantoprazole can have other serious side effects. See <span class="Bold">“</span><span class="Bold"><a href="#final.docx#what_are_the_possible_side_effects">What are the possible side effects of Pantoprazole</a></span><span class="Bold">?"</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">What is </span><span class="Bold">Pantoprazole?</span> <p class="First">Pantoprazole is a prescription medicine called a proton pump inhibitor (PPI).</p> <p>Pantoprazole reduces the amount of acid in your stomach.</p> <p>Pantoprazole is used in adults:</p> <ul class="Disc"> <li> <p class="First">for up to 8 weeks to heal acid-related damage to the lining of the esophagus (erosive esophagitis or EE) and to relieve symptoms caused by gastroesophageal reflux disease (GERD). If needed, your doctor may decide to prescribe another 8 weeks of Pantoprazole. </p> </li> <li> <p class="First">to maintain the healing of acid-related damage to the lining of the esophagus and help prevent return of heartburn symptoms caused by GERD. It is not known if Pantoprazole is safe and effective if used longer than 12 months (1 year).</p> <p>GERD happens when acid in your stomach backs up into the tube (esophagus) that connects your mouth to your stomach.  This may cause a burning feeling in your chest or throat, sour taste, or burping.</p> </li> <li> <p class="First">for the long-term treatment of conditions where your stomach makes too much acid.  This includes a rare condition called Zollinger-Ellison syndrome.</p> </li> </ul> <p>Pantoprazole is used in children 5 years of age and older for up to 8 weeks to heal acid-related damage to the lining of the esophagus (erosive esophagitis or EE) caused by GERD. </p> It is not known if Pantoprazole is safe if used longer than 8 weeks in children. Pantoprazole is not for use in children under 5 years of age.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Who should not take </span><span class="Bold">Pantoprazole?</span> <p class="First">Do not take Pantoprazole if you are:</p> <ul class="Disc"> <li> <p class="First">allergic to pantoprazole sodium or any of the other ingredients in Pantoprazole. See the end of this Medication Guide for a complete list of ingredients in Pantoprazole.</p> </li> <li> <p class="First">allergic to any proton pump inhibitor (PPI) medicine. </p> </li> <li> <p class="First">are taking a medicine that contains rilpivirine (EDURANT, COMPLERA, ODEFSEY) used to treat HIV-1 (Human Immunodeficiency Virus).</p> </li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">What should I tell my doctor before taking </span><span class="Bold">Pantoprazole?</span> <p class="First"> <span class="Bold">Before taking </span><span class="Bold">Pantoprazole, tell your doctor if you:</span> </p> <ul class="Disc"> <li> <p class="First">have been told that you have low magnesium levels in your blood</p> </li> <li> <p class="First">have any other medical conditions</p> </li> <li> <p class="First">are pregnant or plan to become pregnant. Pantoprazole may harm your unborn baby.</p> </li> <li> <p class="First">are breastfeeding or plan to breastfeed. Pantoprazole may pass into your milk. You and your doctor should decide if you will take Pantoprazole or breastfeed. You should not do both. Talk with your doctor about the best way to feed your baby if you take Pantoprazole.</p> </li> </ul> <p> <span class="Bold">Tell your doctor about all of the medicines you take,</span> including prescription and non-prescription drugs, vitamins and herbal supplements. Pantoprazole may affect how other medicines work, and other medicines may affect how Pantoprazole works. </p> <p>Especially tell your doctor if you take:</p> <ul class="Disc"> <li> <p class="First">atazanavir (Reyataz)</p> </li> <li> <p class="First">nelfinavir (Viracept)</p> </li> <li> <p class="First">warfarin (Coumadin, Jantoven)</p> </li> <li> <p class="First">ketoconazole (Nizoral)</p> </li> <li> <p class="First">a product that contains iron</p> </li> <li> <p class="First">methotrexate</p> </li> <li> <p class="First">mycophenolate mofetil (Cellcept)  </p> </li> </ul> <p>Ask your doctor or pharmacist for a list of these medicines, if you are not sure.</p> Know the medicines that you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">How should I take </span><span class="Bold">Pantoprazole?</span> <ul class="Disc"> <li> <p class="First">Take Pantoprazole exactly as prescribed by your doctor.</p> </li> <li> <p class="First">Do not change your dose or stop Pantoprazole without talking to your doctor.</p> </li> <li> <p class="First">If you forget to take a dose of Pantoprazole, take it as soon as you remember. If it is almost time for your next dose, do not take the missed dose. Take the next dose at your regular time. Do not take two doses to try to make up for a missed dose.</p> </li> <li> <p class="First">If you take too much Pantoprazole, call your doctor right away or go to the nearest hospital emergency room.</p> </li> <li> <p class="First">See the Instructions for Use at the end of this Medication Guide for detailed instructions about:  </p> </li> </ul> <p class="First">         ◦  how to take Pantoprazole Tablets</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">What are the possible side effects of </span><span class="Bold">Pantoprazole?</span> <p class="First"> <span class="Bold">Pantoprazole may cause serious side effects, including:</span> </p> <p> <span class="Bold">See “</span><a href="#final.docx#what_is_most_important_information">What is the most important information I should know about Pantoprazole</a><span class="Bold">?”</span> </p> <ul class="Disc"> <li> <p class="First"> <span class="Bold">Vitamin B-12 deficiency.</span>  Pantoprazole reduces the amount of acid in your stomach.  Stomach acid is needed to absorb vitamin B-12 properly.  Talk with your doctor about the possibility of vitamin B-12 deficiency if you have been on Pantoprazole for a long time (more than 3 years).</p> </li> </ul> <ul class="Disc"> <li> <p class="First"> <span class="Bold">Low magnesium levels in your body</span>. This problem can be serious. Low magnesium can happen in some people who take a PPI medicine for at least 3 months. If low magnesium levels happen, it is usually after a year of treatment. You may or may not have symptoms of low magnesium. Tell your doctor right away if you have any of these symptoms:</p> <p> <span class="Bold">   ◦  </span>seizures                                                       ◦  muscle weakness</p> <p>   ◦  dizziness                                                     ◦  spasms of the hands and feet</p> <p>   ◦  abnormal or fast heartbeat                          ◦  cramps or muscle aches</p> <p>   ◦  jitteriness                                                    ◦  spasm of the voice box</p> <p>   ◦  jerking movements or shaking (tremors)</p> </li> </ul> <p>Your doctor may check the level of magnesium in your body before you start taking Pantoprazole or during treatment, if you will be taking Pantoprazole for a long period of time.</p> <p>The most common side effects with Pantoprazole in adults include:</p> <p>                ●   Headache                                                    ●  Vomiting</p> <p>                ●   Diarrhea                                                      ●  Gas         </p> <p>                ●    Nausea                                                       ●  Dizziness</p> <p>                ●    Stomach pain                                             ●  Pain in your joints                </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">The most common side effects with Pantoprazole in children include: <p class="First">                ●   Upper respiratory infection                      ●  Vomiting</p> <p>                ●   Headache                                                  ●  Rash     </p> <p>                ●    Fever                                                        ●  Stomach pain</p> <p>                ●    Diarrhea </p> <p>Other side effects:</p> <ul class="Disc"> <li> <p class="First"> <span class="Bold">Serious allergic reactions.</span>  Tell your doctor if you get any of the following symptoms with Pantoprazole:</p> <p>●   rash                                                           ●  throat tightness                                 </p> <p>●   face swelling                                             ● difficult breathing</p> </li> </ul> <p>Your doctor may stop Pantoprazole if these symptoms happen. </p> <p>Tell your doctor about any side effects that bother you or that do not go away.</p> <p>These are not all the possible side effects with Pantoprazole. For more information, ask your doctor or pharmacist.</p> Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">How should I store </span><span class="Bold">Pantoprazole?</span> <ul class="Disc"> <li> <p class="First">­Store Pantoprazole at room temperature between 59° to 86°F (15° to 30°C).</p> </li> </ul> <span class="Bold">Keep Pantoprazole and all medicines out of the reach of children.</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">General information about Pantoprazole</span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Pantoprazole for a condition for which it was not prescribed. Do not give Pantoprazole to other people, even if they have the same symptoms you have. It may harm them. </p> This Medication Guide summarizes the most important information about Pantoprazole. For more information, ask your doctor. You can ask your doctor or pharmacist for information that is written for healthcare professionals. </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">What are the ingredients in </span><span class="Bold">Pantoprazole?</span> <p class="First"> <span class="Bold">Active ingredient:</span> pantoprazole sodium sesquihydrate</p> <p> <span class="Bold">Inactive ingredients in </span><span class="Bold">Pantoprazole Sodium Delayed-Release Tablets:</span> crospovidone, glyceryl dibehenate, hypromellose, lactose monohydrate, methacrylic acid copolymer dispersion, talc, titanium dioxide, and triethyl citrate. The 20 mg tablets also contains black iron oxide, isopropyl alcohol, and propylene glycol. </p> For more information, call 1-844-834-0530.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">                                     <span class=\"Bold\">Pantoprazole (pan-TOE-pruh-zole) Sodium Delayed-Release Tablets, USP</span>       </p>\n<p>                                     CIA77568J                                                 Rev. 07/2017</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">Read this Medication Guide before you start taking Pantoprazole and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">What is the most important information I should know about </span><span class=\"Bold\">Pantoprazole? </span>\n<p class=\"First\">\n<span class=\"Bold\">Pantoprazole may help your acid-related symptoms, but you could still have serious stomach problems. Talk with your doctor. </span>\n</p>\n<p>\n<span class=\"Bold\">Pantoprazole can cause serious side effects, including: </span>\n</p>\n<ul class=\"Disc\">\n<li>\n<p class=\"First\">\n<span class=\"Bold\">A type of kidney problem (acute interstitial nephritis)</span>. Some people who take proton pump inhibitor (PPI) medicines, including Pantoprazole, may develop a kidney problem called acute interstitial nephritis that can happen at any time during treatment with Pantoprazole. Call your doctor if you have a decrease in the amount that you urinate or if you have blood in your urine.</p>\n</li>\n<li>\n<p class=\"First\">\n<span class=\"Bold\">Diarrhea</span>. Pantoprazole may increase your risk of getting severe diarrhea. This diarrhea may be caused by an infection (<span class=\"Italics\">Clostridium difficile</span>) in your intestines. Call your doctor right away if you have watery stool, stomach pain, and fever that does not go away. </p>\n</li>\n<li>\n<p class=\"First\">\n<span class=\"Bold\">Bone fractures</span>. People who take multiple daily doses of PPI medicines for a long period of time (a year or longer) may have an increased risk of fractures of the hip, wrist or spine. You should take Pantoprazole exactly as prescribed, at the lowest dose possible for your treatment and for the shortest time needed. Talk to your doctor about your risk of bone fracture if you take Pantoprazole. </p>\n</li>\n<li>\n<p class=\"First\">\n<span class=\"Bold\">Certain types of lupus erythematosus.</span> Lupus erythematosus is an autoimmune disorder (the body’s immune cells attack other cells or organs in the body). Some people who take PPI medicines, including Pantoprazole, may develop certain types of lupus erythematosus or have worsening of the lupus they already have. Call your doctor right away if you have new or worsening joint pain or a rash on your cheeks or arms that gets worse in the sun. </p>\n</li>\n</ul> Pantoprazole can have other serious side effects. See <span class=\"Bold\">“</span><span class=\"Bold\"><a href=\"#final.docx#what_are_the_possible_side_effects\">What are the possible side effects of Pantoprazole</a></span><span class=\"Bold\">?\"</span></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">What is </span><span class=\"Bold\">Pantoprazole?</span>\n<p class=\"First\">Pantoprazole is a prescription medicine called a proton pump inhibitor (PPI).</p>\n<p>Pantoprazole reduces the amount of acid in your stomach.</p>\n<p>Pantoprazole is used in adults:</p>\n<ul class=\"Disc\">\n<li>\n<p class=\"First\">for up to 8 weeks to heal acid-related damage to the lining of the esophagus (erosive esophagitis or EE) and to relieve symptoms caused by gastroesophageal reflux disease (GERD). If needed, your doctor may decide to prescribe another 8 weeks of Pantoprazole. </p>\n</li>\n<li>\n<p class=\"First\">to maintain the healing of acid-related damage to the lining of the esophagus and help prevent return of heartburn symptoms caused by GERD. It is not known if Pantoprazole is safe and effective if used longer than 12 months (1 year).</p>\n<p>GERD happens when acid in your stomach backs up into the tube (esophagus) that connects your mouth to your stomach.  This may cause a burning feeling in your chest or throat, sour taste, or burping.</p>\n</li>\n<li>\n<p class=\"First\">for the long-term treatment of conditions where your stomach makes too much acid.  This includes a rare condition called Zollinger-Ellison syndrome.</p>\n</li>\n</ul>\n<p>Pantoprazole is used in children 5 years of age and older for up to 8 weeks to heal acid-related damage to the lining of the esophagus (erosive esophagitis or EE) caused by GERD. </p> It is not known if Pantoprazole is safe if used longer than 8 weeks in children. Pantoprazole is not for use in children under 5 years of age.</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Who should not take </span><span class=\"Bold\">Pantoprazole?</span>\n<p class=\"First\">Do not take Pantoprazole if you are:</p>\n<ul class=\"Disc\">\n<li>\n<p class=\"First\">allergic to pantoprazole sodium or any of the other ingredients in Pantoprazole. See the end of this Medication Guide for a complete list of ingredients in Pantoprazole.</p>\n</li>\n<li>\n<p class=\"First\">allergic to any proton pump inhibitor (PPI) medicine. </p>\n</li>\n<li>\n<p class=\"First\">are taking a medicine that contains rilpivirine (EDURANT, COMPLERA, ODEFSEY) used to treat HIV-1 (Human Immunodeficiency Virus).</p>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">What should I tell my doctor before taking </span><span class=\"Bold\">Pantoprazole?</span>\n<p class=\"First\">\n<span class=\"Bold\">Before taking </span><span class=\"Bold\">Pantoprazole, tell your doctor if you:</span>\n</p>\n<ul class=\"Disc\">\n<li>\n<p class=\"First\">have been told that you have low magnesium levels in your blood</p>\n</li>\n<li>\n<p class=\"First\">have any other medical conditions</p>\n</li>\n<li>\n<p class=\"First\">are pregnant or plan to become pregnant. Pantoprazole may harm your unborn baby.</p>\n</li>\n<li>\n<p class=\"First\">are breastfeeding or plan to breastfeed. Pantoprazole may pass into your milk. You and your doctor should decide if you will take Pantoprazole or breastfeed. You should not do both. Talk with your doctor about the best way to feed your baby if you take Pantoprazole.</p>\n</li>\n</ul>\n<p>\n<span class=\"Bold\">Tell your doctor about all of the medicines you take,</span> including prescription and non-prescription drugs, vitamins and herbal supplements. Pantoprazole may affect how other medicines work, and other medicines may affect how Pantoprazole works. </p>\n<p>Especially tell your doctor if you take:</p>\n<ul class=\"Disc\">\n<li>\n<p class=\"First\">atazanavir (Reyataz)</p>\n</li>\n<li>\n<p class=\"First\">nelfinavir (Viracept)</p>\n</li>\n<li>\n<p class=\"First\">warfarin (Coumadin, Jantoven)</p>\n</li>\n<li>\n<p class=\"First\">ketoconazole (Nizoral)</p>\n</li>\n<li>\n<p class=\"First\">a product that contains iron</p>\n</li>\n<li>\n<p class=\"First\">methotrexate</p>\n</li>\n<li>\n<p class=\"First\">mycophenolate mofetil (Cellcept)  </p>\n</li>\n</ul>\n<p>Ask your doctor or pharmacist for a list of these medicines, if you are not sure.</p> Know the medicines that you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">How should I take </span><span class=\"Bold\">Pantoprazole?</span>\n<ul class=\"Disc\">\n<li>\n<p class=\"First\">Take Pantoprazole exactly as prescribed by your doctor.</p>\n</li>\n<li>\n<p class=\"First\">Do not change your dose or stop Pantoprazole without talking to your doctor.</p>\n</li>\n<li>\n<p class=\"First\">If you forget to take a dose of Pantoprazole, take it as soon as you remember. If it is almost time for your next dose, do not take the missed dose. Take the next dose at your regular time. Do not take two doses to try to make up for a missed dose.</p>\n</li>\n<li>\n<p class=\"First\">If you take too much Pantoprazole, call your doctor right away or go to the nearest hospital emergency room.</p>\n</li>\n<li>\n<p class=\"First\">See the Instructions for Use at the end of this Medication Guide for detailed instructions about:  </p>\n</li>\n</ul>\n<p class=\"First\">         ◦  how to take Pantoprazole Tablets</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">What are the possible side effects of </span><span class=\"Bold\">Pantoprazole?</span>\n<p class=\"First\">\n<span class=\"Bold\">Pantoprazole may cause serious side effects, including:</span>\n</p>\n<p>\n<span class=\"Bold\">See “</span><a href=\"#final.docx#what_is_most_important_information\">What is the most important information I should know about Pantoprazole</a><span class=\"Bold\">?”</span>\n</p>\n<ul class=\"Disc\">\n<li>\n<p class=\"First\">\n<span class=\"Bold\">Vitamin B-12 deficiency.</span>  Pantoprazole reduces the amount of acid in your stomach.  Stomach acid is needed to absorb vitamin B-12 properly.  Talk with your doctor about the possibility of vitamin B-12 deficiency if you have been on Pantoprazole for a long time (more than 3 years).</p>\n</li>\n</ul>\n<ul class=\"Disc\">\n<li>\n<p class=\"First\">\n<span class=\"Bold\">Low magnesium levels in your body</span>. This problem can be serious. Low magnesium can happen in some people who take a PPI medicine for at least 3 months. If low magnesium levels happen, it is usually after a year of treatment. You may or may not have symptoms of low magnesium. Tell your doctor right away if you have any of these symptoms:</p>\n<p>\n<span class=\"Bold\">   ◦  </span>seizures                                                       ◦  muscle weakness</p>\n<p>   ◦  dizziness                                                     ◦  spasms of the hands and feet</p>\n<p>   ◦  abnormal or fast heartbeat                          ◦  cramps or muscle aches</p>\n<p>   ◦  jitteriness                                                    ◦  spasm of the voice box</p>\n<p>   ◦  jerking movements or shaking (tremors)</p>\n</li>\n</ul>\n<p>Your doctor may check the level of magnesium in your body before you start taking Pantoprazole or during treatment, if you will be taking Pantoprazole for a long period of time.</p>\n<p>The most common side effects with Pantoprazole in adults include:</p>\n<p>                ●   Headache                                                    ●  Vomiting</p>\n<p>                ●   Diarrhea                                                      ●  Gas         </p>\n<p>                ●    Nausea                                                       ●  Dizziness</p>\n<p>                ●    Stomach pain                                             ●  Pain in your joints                </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">The most common side effects with Pantoprazole in children include: <p class=\"First\">                ●   Upper respiratory infection                      ●  Vomiting</p>\n<p>                ●   Headache                                                  ●  Rash     </p>\n<p>                ●    Fever                                                        ●  Stomach pain</p>\n<p>                ●    Diarrhea </p>\n<p>Other side effects:</p>\n<ul class=\"Disc\">\n<li>\n<p class=\"First\">\n<span class=\"Bold\">Serious allergic reactions.</span>  Tell your doctor if you get any of the following symptoms with Pantoprazole:</p>\n<p>●   rash                                                           ●  throat tightness                                 </p>\n<p>●   face swelling                                             ● difficult breathing</p>\n</li>\n</ul>\n<p>Your doctor may stop Pantoprazole if these symptoms happen. </p>\n<p>Tell your doctor about any side effects that bother you or that do not go away.</p>\n<p>These are not all the possible side effects with Pantoprazole. For more information, ask your doctor or pharmacist.</p> Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">How should I store </span><span class=\"Bold\">Pantoprazole?</span>\n<ul class=\"Disc\">\n<li>\n<p class=\"First\">­Store Pantoprazole at room temperature between 59° to 86°F (15° to 30°C).</p>\n</li>\n</ul>\n<span class=\"Bold\">Keep Pantoprazole and all medicines out of the reach of children.</span></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">General information about Pantoprazole</span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Pantoprazole for a condition for which it was not prescribed. Do not give Pantoprazole to other people, even if they have the same symptoms you have. It may harm them. </p> This Medication Guide summarizes the most important information about Pantoprazole. For more information, ask your doctor. You can ask your doctor or pharmacist for information that is written for healthcare professionals. </td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">What are the ingredients in </span><span class=\"Bold\">Pantoprazole?</span>\n<p class=\"First\">\n<span class=\"Bold\">Active ingredient:</span> pantoprazole sodium sesquihydrate</p>\n<p>\n<span class=\"Bold\">Inactive ingredients in </span><span class=\"Bold\">Pantoprazole Sodium Delayed-Release Tablets:</span> crospovidone, glyceryl dibehenate, hypromellose, lactose monohydrate, methacrylic acid copolymer dispersion, talc, titanium dioxide, and triethyl citrate. The 20 mg tablets also contains black iron oxide, isopropyl alcohol, and propylene glycol. </p> For more information, call 1-844-834-0530.</td>\n</tr>\n</tbody>\n</table></div>" }

Instructions for Use

{ "type": "p", "children": [], "text": "\nInstructions for Use\n" }

Pantoprazole Sodium Delayed-Release Tablets:

{ "type": "p", "children": [], "text": "\nPantoprazole Sodium Delayed-Release Tablets:\n" }

{ "type": "ul", "children": [ "You can take Pantoprazole sodium delayed-release tablets with food or on an empty stomach.\n", "Swallow Pantoprazole sodium delayed-release tablets whole.\n", "If you have trouble swallowing a Pantoprazole sodium delayed-release 40 mg tablet, you can take two 20 mg tablets instead.\n", "Do not split, chew, or crush Pantoprazole sodium delayed-release tablets." ], "text": "" }

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

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This product's label may have been updated. For more information, call 1-844-834-0530.

{ "type": "p", "children": [], "text": "This product's label may have been updated. For more information, call 1-844-834-0530." }

Distributed by:

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Lannett Company, Inc.

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Philadelphia, PA 19154

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CIA77568JRev. 07/2017

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All brand names are the trademarks of their respective owners.

{ "type": "p", "children": [], "text": "All brand names are the trademarks of their respective owners." }

Please reference the How Supplied section listed above for a description of individual tablets. This drug product has been received by Aphena Pharma - TN in a manufacturer or distributor packaged configuration and repackaged in full compliance with all applicable cGMP regulations. The package configurations available from Aphena are listed below:

{ "type": "p", "children": [], "text": "Please reference the How Supplied section listed above for a description of individual tablets. This drug product has been received by Aphena Pharma - TN in a manufacturer or distributor packaged configuration and repackaged in full compliance with all applicable cGMP regulations. The package configurations available from Aphena are listed below:" }

<div class="scrollingtable"><table border="0" cellpadding="1" cellspacing="1" width="28%"> <colgroup> <col width="10%"/> <col/> </colgroup> <tbody class="Headless"> <tr class="First Toprule"> <td align="center" class="Bold" valign="bottom">Count</td><td align="center" valign="bottom"><span class="Bold">20mg</span></td> </tr> <tr> <td align="center" valign="bottom">30</td><td align="center">43353-027-30</td> </tr> <tr> <td align="center" valign="bottom">60</td><td align="center">43353-027-53</td> </tr> <tr> <td align="center" valign="bottom">90</td><td align="center">43353-027-60</td> </tr> <tr> <td align="center" valign="bottom">180</td><td align="center">43353-027-80</td> </tr> <tr class="Toprule"> <td align="center" class="Bold" valign="bottom">Count</td><td align="center" valign="bottom"><span class="Bold">40mg</span></td> </tr> <tr class="Last"> <td align="center" valign="bottom">9000</td><td align="center">43353-916-09</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"1\" cellspacing=\"1\" width=\"28%\">\n<colgroup>\n<col width=\"10%\"/>\n<col/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"First Toprule\">\n<td align=\"center\" class=\"Bold\" valign=\"bottom\">Count</td><td align=\"center\" valign=\"bottom\"><span class=\"Bold\">20mg</span></td>\n</tr>\n<tr>\n<td align=\"center\" valign=\"bottom\">30</td><td align=\"center\">43353-027-30</td>\n</tr>\n<tr>\n<td align=\"center\" valign=\"bottom\">60</td><td align=\"center\">43353-027-53</td>\n</tr>\n<tr>\n<td align=\"center\" valign=\"bottom\">90</td><td align=\"center\">43353-027-60</td>\n</tr>\n<tr>\n<td align=\"center\" valign=\"bottom\">180</td><td align=\"center\">43353-027-80</td>\n</tr>\n<tr class=\"Toprule\">\n<td align=\"center\" class=\"Bold\" valign=\"bottom\">Count</td><td align=\"center\" valign=\"bottom\"><span class=\"Bold\">40mg</span></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" valign=\"bottom\">9000</td><td align=\"center\">43353-916-09</td>\n</tr>\n</tbody>\n</table></div>" }

Store between 20°-25°C (68°-77°F). See USP Controlled Room Temperature. Dispense in a tight light-resistant container as defined by USP. Keep this and all drugs out of the reach of children.

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Repackaged by: Cookeville, TN 38506 20170818JH

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PRINCIPAL DISPLAY PANEL - 20 mg Tablet Bottle Label

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NDC 43353--916-09

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Pantoprazole Sodium

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Delayed-ReleaseTablets, USP

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20 mg*

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Rx Only

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9000 Tablets

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PRINCIPAL DISPLAY PANEL - 40 mg Tablet Bottle Label

{ "type": "p", "children": [], "text": "\nPRINCIPAL DISPLAY PANEL - 40 mg Tablet Bottle Label\n" }

NDC 43353-027-60

{ "type": "p", "children": [], "text": "NDC 43353-027-60" }

Pantoprazole Sodium

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

Delayed-ReleaseTablets, USP

{ "type": "p", "children": [], "text": "\nDelayed-ReleaseTablets, USP\n" }

40 mg*

{ "type": "p", "children": [], "text": "\n40 mg*\n" }

Rx Only

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

90 Tablets

{ "type": "p", "children": [], "text": "90 Tablets" }