ZYMFENTRA is indicated in adults for maintenance treatment of: 

Mixed Dose 

If an injection of ZYMFENTRA is missed, inject the next subcutaneous dose as soon as possible and then every two weeks thereafter.

ZYMFENTRA (infliximab-dyyb) is a clear, colorless to pale brown solution available as follow: 

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ZYMFENTRA is contraindicated in patients with a history of a severe hypersensitivity reaction to infliximab-dyyb, other infliximab products, any of the inactive ingredients in ZYMFENTRA, or any murine proteins. Reactions have included anaphylaxis [see Warnings and Precautions (5.7)]. 

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Patients treated with ZYMFENTRA are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death.

Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, or parasitic organisms including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, salmonellosis and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease.

Treatment with ZYMFENTRA should not be initiated in patients with an active infection, including clinically important localized infections.Patients greater than 65 years of age, patients with comorbid-conditions and/or patients taking concomitant immunosuppressants such as corticosteroids or methotrexate may be at greater risk of infection. The risks and benefits of treatment should be considered prior to initiating therapy in patients: 

Tuberculosis

Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving TNF-blockers, including patients who have previously received treatment for latent or active tuberculosis. Cases of active tuberculosis have also occurred in patients being treated with infliximab products during treatment for latent tuberculosis. Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating ZYMFENTRA and periodically during therapy.

Treatment of latent tuberculosis infection prior to therapy with TNF blockers has been shown to reduce the risk of tuberculosis reactivation during therapy. Induration of 5 mm or greater with tuberculin skin testing should be considered a positive test result when assessing if treatment for latent tuberculosis is needed prior to initiating ZYMFENTRA even for patients previously vaccinated with Bacille Calmette-Guérin (BCG). 

Consider anti-tuberculosis therapy prior to initiation of ZYMFENTRA in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient. 

Tuberculosis should be strongly considered in patients who develop a new infection during treatment with ZYMFENTRA especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis. 

Monitoring

Closely monitor patients for the development of signs and symptoms of infection during and after treatment with ZYMFENTRA including the development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. Tests for latent tuberculosis infection may also be falsely negative while on therapy with ZYMFENTRA. 

Discontinue ZYMFENTRA if a patient develops a serious infection or sepsis. A patient who develops a new infection during treatment with ZYMFENTRA should undergo prompt and complete diagnostic workup appropriate for an immunocompromised patient; and appropriate antimicrobial therapy should be initiated, and the patient should be closely monitored. 

Invasive Fungal Infections

For patients who reside or travel in regions where mycoses are endemic, invasive fungal infection should be suspected if they develop a serious systemic illness. Appropriate empiric antifungal therapy should be considered while a diagnostic workup is being performed. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. When feasible, the decision to administer empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections and should take into account both the risk for severe fungal infection and the risks of antifungal therapy. 

Malignancies, some fatal, have been reported among children, adolescents and young adults who received treatment with TNF blockers (initiation of therapy ≤18 years of age), including infliximab products. AApproximately half of these cases were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months (range 1 to 84 months) after the first dose of TNF blocker therapy. Most of the patients were receiving concomitant immunosuppressants. These cases were reported postmarketing and are derived from a variety of sources, including registries and spontaneous postmarketing reports.

Lymphomas

In the controlled portions of clinical trials of TNF blockers, more cases of lymphoma have been observed among patients receiving a TNF blocker compared with control patients. Cases of acute and chronic leukemia have been reported with postmarketing TNF blocker use, including infliximab products. 

Hepatosplenic T-cell Lymphoma (HSTCL)

Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab products. TThese cases have had a very aggressive disease course and have been fatal. Almost all patients had received treatment with the immunosuppressants azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. The majority of reported cases have occurred in patients with Crohn’s disease or ulcerative colitis and most were in adolescent and young adult males. It is uncertain whether the occurrence of HSTCL is related to TNF blockers or TNF blockers in combination with these other immunosuppressants. When treating patients, consideration of whether to use ZYMFENTRA alone or in combination with other immunosuppressants such as azathioprine or 6-mercaptopurine should take into account a possibility that there is a higher risk of HSTCL with combination therapy versus an observed increased risk of immunogenicity and hypersensitivity reactions with TNF blocker monotherapy from the clinical trial data [see Warnings and Precautions (5.7)]

Skin Cancer

Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy, including infliximab products. Periodic skin examination is recommended for all patients during treatment with ZYMFENTRA, particularly those with risk factors for skin cancer. 

Cervical Cancer

Cases of invasive cervical cancer have been reported postmarketing in women who received infliximab products for other conditions. A causal relationship between infliximab products and cervical cancer cannot be excluded. Routine cervical cancer screening is recommended during treatment with ZYMFENTRA. 

Other Malignancies 

In the controlled pportions of clinical trials of some TNF blockers, including infliximab products, more malignancies (excluding lymphoma and nonmelanoma skin cancer) have been observed in patients receiving those TNF blockers compared with control patients. The most common malignancies were breast, colorectal, and melanoma in these controlled trials of TNF blockers.

In controlled trials of TNF blockers in adult patients at higher risk for malignancies (i.e., patients with COPD with a significant smoking history and cyclophosphamide-treated patients with Wegener’s granulomatosis), a greater proportion of malignancies occurred in the TNF blocker group compared to the control group. Patients had a history of heavy smoking. Avoid ZYMFENTRA in patients with moderate to severe COPD. 

The potential role of TNF blockers in the development of malignancies is not known. Avoid ZYMFENTRA treatment in patients with a history of malignancy or in continuing treatment in patients who develop malignancy while receiving ZYMFENTRA. 

Use of TNF blockers has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus. In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal. The majority of these reports have occurred in patients concomitantly receiving other medications that suppress the immune system, which may also contribute to HBV reactivation. 

Test patients for HBV infection before initiating TNF blocker therapy, including ZYMFENTRA. For patients who test positive for hepatitis B surface antigen, consultation with a physician with expertise in the treatment of hepatitis B is recommended. Adequate data are not available on the safety or efficacy of treating patients who are carriers of HBV with antiviral therapy in conjunction with TNF blocker therapy to prevent HBV reactivation. Patients who are carriers of HBV and require treatment with TNF blockers, including ZYMFENTRA, should be closely monitored for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy. 

In patients who develop HBV reactivation, discontinue ZYMFENTRA and initiate antiviral therapy with appropriate supportive treatment. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known. Therefore, prescribers should exercise caution when considering resumption of ZYMFENTRA in this situation and monitor patients closely. 

Hepatobiliary disorders, including acute liver failure, jaundice abnormal hepatic function, hepatic steatosis, hepatitis, hepatotoxicity, hyperbilirubinemia and non-alcoholic fatty liver, have been reported in postmarketing data in patients receiving infliximab products. Autoimmune hepatitis has been diagnosed in some of these cases. Severe hepatic reactions occurred between two weeks to more than one year after initiation of infliximab products administered intravenously; elevations in hepatic aminotransferase levels were not noted prior to discovery of the liver injury in many of these cases. Some of these cases were fatal or necessitated liver transplantation.

In clinical trials, three subjects treated with ZYMFENTRA had drug induced liver injury based on hepatic transaminase elevations, including one subject with accompanying bilirubin elevation [see Adverse Reactions (6.2)]. 

Monitor hepatic enzymes and liver function tests every 3 to 4 months during treatment with ZYMFENTRA. Prompt investigation of the cause of liver enzyme elevation should be undertaken to identify potential cases of drug-induced liver injury. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfuction. 

Cases of worsening congestive heart failure (CHF) and new onset CHF, with and without identifiable precipitating factors (e.g., pre-existing cardiovascular disease), have been reported with TNF blockers, including infliximab products. Some of these patients have been under 50 years of age, and some cases had a fatal outcome. In several exploratory trials of other TNF blockers in the treatment of CHF, there were greater proportions of TNF-blocker-treated patients who had CHF exacerbations requiring hospitalization or increased mortality. ZYMFENTRA has not been studied in patients with a history of CHF. Avoid ZYMFENTRA in patients with CHF.

If a decision is made to administer ZYMFENTRA to patients with CHF, closely monitor patients during therapy for new or worsening symptoms of heart failure and discontinue ZYMFENTRA if symptoms appear. 

Report of pancytopenia including aplastic anemia have been reported with TNF blocking agents. Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia, some with a fatal outcome, have been reported in patients receiving infliximab products. Clinically significant events of neutropenia were noted in the clinical trials of ZYMFENTRA. The causal relationship to infliximab product therapy remains unclear. Although no high-risk group(s) has been identified, avoid ZYMFENTRA in patients who have ongoing or a history of significant hematologic abnormalities. Advise all patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever) during treatment with ZYMFENTRA. Consider discontinuation of ZYMFENTRA therapy in patients who develop significant hematologic abnormalities. 

In clinical trials of ZYMFENTRA, symptoms compatible with hypersensitivity reactions have been reported including bronchospasm, dyspnea, rash, and edema. In post-marketing experience, serious systemic hypersensitivity reactions (including anaphylaxis, hypotension, and serum sickness) have been reported following administration of infliximab products. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue ZYMFENTRA. There are no data on the risks of using ZYMFENTRA in patients who have experienced a severe hypersensitivity reaction towards another TNF blocker; in these patients, caution is needed. 

Agents that inhibit TNF have been associated with central nervous system (CNS) manifestation of systemic vasculitis, seizure and new onset or exacerbation of clinical symptoms and/or radiographic evidence of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Avoid the use of ZYMFENTRA in patients with these neurologic disorders and consider discontinuation of ZYMFENTRA if these disorders develop.

Serious infections and neutropenia have been reported with concurrent use of TNF-blockers and other immunosuppressive biological products (e.g., anakinra and abatacept). The concurrent use of ZYMFENTRA with other immunosuppressive biological products used to treat ulcerative colitis and Crohn’s disease may increase the risk of infection and is not recommended [see Drug Interactions (7.1)].

Consider the half-life and mode of action of prior biological products to avoid unintended additive immunosuppressive effects when initiating ZYMFENTRA [see Drug Interactions (7.1)].

Treatment with TNF blockers, iincluding ZYMFENTRA may result in the formation of autoantibodies and in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with ZYMFENTRA, discontinue treatment.

Vaccinations

Prior to initiating ZYMFENTRA in adult patients, update vaccinations in accordance with current vaccination guidelines. 

Live Vaccines and Theraeputic Infectious Agents

In patients receiving TNF blockers, limited data are available on the response to vaccination with live vaccines or on the secondary transmission of infection by live vaccines. Use of live vaccines can result in clinical infections, including disseminated infections. The concurrent administration of live vaccines with ZYMFENTRA is not recommended. 

Fatal outcome due to disseminated BCG infection has been reported in an infant who received a BCG vaccine after in utero exposure to infliximab products. Infliximab is known to cross the placenta and has been detected in the serum of infants up to 6 months following birth. A 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to infliximab products. 

Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder instillation for the treatment of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious agents not be given concurrently with ZYMFENTRA. 

The most common adverse reactions reported in ≥3% of subjects and at a higher rate than Placebo in UC Trial I are shown in Table 1.

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="100%"> <thead> <tr class="First"> <td colspan="3" valign="top"> <p class="First First TableCellHeading10pt"> <span class="Bold">Table 1    Adverse Reactions<span class="Sup">a</span> in the Maintenance Phase of a Randomized, Double-Blind</span><span class="Bold">54-Week Study of Subjects with UC (UC Tral I)</span> </p> </td> </tr> <tr class="Last"> <td valign="top"></td><td> <p class="First First TableCellHeading10pt"> <span class="Bold">ZYMFENTRA</span> </p> <p class="First TableCellHeading10pt"> <span class="Bold">120 mg Subcutaneous </span> </p> <p class="First TableCellHeading10pt"> <span class="Bold">Injection<span class="Sup">b</span></span> </p> <p class="First TableCellHeading10pt"> <span class="Bold">N=296</span> </p> <p class="First TableCellHeading10pt"> <span class="Bold">(%)</span> </p> </td><td align="left"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N=140</span> </p> <p> <span class="Bold">(%)</span> </p> </td> </tr> </thead> <tbody> <tr class="First"> <td valign="top"> <p class="First First TableCellText10pt">COVID-19</p> </td><td align="left">10</td><td> <p class="First First TableCellText10pt">6</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableCellText10pt">Anemia<span class="Sup">d</span> </p> </td><td> <p class="First First TableCellText10pt">5</p> </td><td> <p class="First First TableCellText10pt">4</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableCellText10pt">Arthralgia</p> </td><td> <p class="First First TableCellText10pt">4</p> </td><td> <p class="First First TableCellText10pt">1</p> </td> </tr> <tr> <td valign="top">Injection site reaction<span class="Sup">#</span></td><td>3</td><td align="center">2</td> </tr> <tr> <td valign="top"> <p class="First First TableCellText10pt">Increased alanine aminotransferase</p> </td><td> <p class="First First TableCellText10pt">3</p> </td><td> <p class="First First TableCellText10pt">1</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableCellText10ptLeft025">Abominal pain<span class="Sup">f</span> </p> </td><td> <p class="First First TableCellText10pt">3</p> </td><td> <p class="First First TableCellText10pt">1</p> </td> </tr> <tr class="Last"> <td colspan="3" rowspan="2" valign="top"> <p class="First First TableCellText10ptLeft025"> <span class="Sup">a</span>reported in at least 3% of ZYMFENTRA-treated subjects and at a higher than placebo</p> <p class="First TableCellText10ptLeft025"> <span class="Sup">b</span>ZYMFENTRA 120 mg as a subcutaneous injection every two weeks starting Week 10 following 3 intravenous induction doses of inflixiab-dyyb</p> <p class="First TableCellText10ptLeft025"> <span class="Sup">c</span>Includes: COVID-19 and COVID-19 pneumonia</p> <p class="First TableCellText10ptLeft025"> <span class="Sup">d</span>Includes: anemia and iron deficiency anemia</p> <p class="First TableCellText10ptLeft025"> <span class="Sup">#</span>Some subjects had multiple occurences of injection site reactions. In this table, injection site reactions are counted only once per subject. Symptoms in individual subjects included one or more of injection site bruising, edema, erythema, induration, pain, pruritus and swelling. </p> <p class="First TableCellText10ptLeft025"> <span class="Sup">f</span>Includes: abdominal pain, upper abdominal pain, lower abdominal pain, and abdominal discomfort</p> </td> </tr> </tbody> </table></div>

The most common adverse reactions reported in ≥3% of subjects and at a higher rate than placebo in CD Trial I are shown in Table 2.

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="100%"> <thead> <tr class="First"> <td colspan="3" valign="top"> <p class="First First TableCellHeading10pt"> <span class="Bold">Table 2    Adverse Reactions<span class="Sup">a</span> in the Maintenance Phase of a Randomized, Double-Blind <br/>54-Week Study of Subjects with CD (CD Trial I) </span> </p> </td> </tr> <tr class="Last"> <td valign="top"></td><td> <p class="First First TableCellHeading10pt"> <span class="Bold">ZYMFENTRA</span> </p> <p class="First TableCellHeading10pt"> <span class="Bold">120 mg Subcutaneous </span> </p> <p class="First TableCellHeading10pt"> <span class="Bold">Injection<span class="Sup">b</span></span> </p> <p class="First TableCellHeading10pt"> <span class="Bold">N=222</span> </p> <p class="First TableCellHeading10pt"> <span class="Bold">(%)</span> </p> </td><td align="left"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">N=101</span> </p> <p> <span class="Bold">(%)</span> </p> </td> </tr> </thead> <tbody> <tr class="First"> <td valign="top"> <p class="First First TableCellText10pt">COVID-19</p> </td><td align="left">10</td><td> <p class="First First TableCellText10pt">5</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableCellText10pt">Headache</p> </td><td>8</td><td> <p class="First First TableCellText10pt">4</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableCellText10pt">Upper respiratory track infectionsd<span class="Sup">c</span> </p> </td><td>7</td><td> <p class="First First TableCellText10pt">3</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableCellText10pt">Injection site reaction<span class="Sup">d</span> </p> </td><td>5</td><td> <p class="First First TableCellText10pt">1</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableCellText10pt">Diarrhea</p> </td><td> <p class="First First TableCellText10pt">5</p> </td><td> <p class="First First TableCellText10pt">1</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableCellText10ptLeft025">Increased blood creatine phosphokinase</p> </td><td> <p class="First First TableCellText10pt">4</p> </td><td> <p class="First First TableCellText10pt">2</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableCellText10ptLeft025">Arthralgia</p> </td><td> <p class="First First TableCellText10pt">4</p> </td><td> <p class="First First TableCellText10pt">3</p> </td> </tr> <tr> <td valign="top"> <p class="First First TableCellText10ptLeft025">Increased alaine aninotransferase</p> </td><td> <p class="First First TableCellText10pt">4</p> </td><td> <p class="First First TableCellText10pt">1</p> </td> </tr> <tr> <td valign="top">Hypertensions<span class="Sup">e</span></td><td>3</td><td>2</td> </tr> <tr> <td valign="top">Urinary track infection<span class="Sup">f</span></td><td>3</td><td>2</td> </tr> <tr> <td valign="top">Neutropenia</td><td>3</td><td>0</td> </tr> <tr> <td valign="top">Dizziness</td><td>3</td><td>0</td> </tr> <tr> <td valign="top"> <p class="First First TableCellText10ptLeft025">Leukopenia</p> </td><td> <p class="First First TableCellText10pt">3</p> </td><td> <p class="First First TableCellText10pt">0</p> </td> </tr> <tr class="Last"> <td colspan="3" valign="top"> <p class="First First TableCellText10ptLeft025"> <span class="Sup">a </span>reported in at least 3% of ZYMFENTRA-treated subjects and at a higher rate than placebo</p> <p class="First TableCellText10ptLeft025"> <span class="Sup">b </span>ZYMFENTRA 120 mg administered subcutaneously starting at Week 10 and every 2 weeks thereafter for up to Week 54. </p> <p class="First TableCellText10ptLeft025"> <span class="Sup">c </span>Includes: upper respiratory tract infection, acute sinusitis, chronic sinusitis, influenza like illness, nasopharyngitis, pharyngitis, pharyngitis streptococcal, rhinitis, rhinorrhea, rhinovirus infection, sinusitis, tonsillitis</p> <p class="First TableCellText10ptLeft025"> <span class="Sup">d </span>Some subjects had multiple occurrences of injection site reactions. In this table, injection site reactions are counted only once per subject. Symptoms in individual subjects included one or more of injection site bruising, edema, erythema, induration, pain, pruritus, rash, swelling, warmth. </p> <p class="First TableCellText10ptLeft025"> <span class="Sup">e </span>Includes: hypertension and essential hypertension</p> <p class="First TableCellText10ptLeft025"> <span class="Sup">f </span>Includes: urinary tract infection, pyelonephritis</p> </td> </tr> </tbody> </table></div>

Infections

In UC Trial I, at leaset one serious infection was reported in 3% of ZYMFENTRA-treated subjects compared to 1% in the plaebo group. Serious infections in the ZYMFENTRA-treated subjects were COVID-19, cystitis, pneumonia, salpingitis, and urinary tract injection [seeWarnings and Precautions (5.1)]. 

In CD Trial I, infections were observed in 30% of ZYMFENTRA-treated subjects compare to 187% of placebo-treated subjects. At least one serious infection was reported in 3% of ZYMFENTRA-treated subjects compared to 1% in the placebo group. Serious infections in the ZYMFENTRA-treated subjects were abscess, appendicitis, bacterial arthritis, bartholinitis, bronchiolitis, and urinary tract infection [seeWarnings and Precautions (5.1)].

Malignancies

In UC Trial I, malignancy (prostate cancer) was reported in a ZYMFENTRA-treated subject. No malignancies were reported among placebo-treated subjects [seeWarnings and Precautions (5.2)].

In another clinical trial in patients with CD, one malignancy (non-small cell lung cancer) was reported in a ZYMFENTRA-treated subject [see Warnings and Precautions (5.2)].

Hepatotoxicity

Three cases of drug induced liver injury were noted in ZYMFENTRA-treated subjects that led to study drug discontinuation [see Warnings and Precautions (5.4)]. 

The following adverse reactions have been identified during post-approval use of outside of the U.S with a non-U.S approved infliximab product administered subcutaneously. 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. 

The following additional adverse ractions have been identified during post-approval use of infliximab products administered intravenously. 

The concurrent use of ZYMFENTRA with other immunosuppressive biological products used to treat UC and CD may increase the risk of infection and is not recommended [seeWarnings and Precautions (5.9)].

Consier the half-life and mode of action of prior biologial products to avoid unintended additive immunosuppressive effects when initiating ZYMFENTRA [seeWarnings and Precautions (5.10)].

The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (e.g., TNFα, IL-1, IL-6, IL-10, IFN) during chronic inflammation. Therefore, ZYMFENTRA, an antagonist of TNFα, could normalize the formation of CYP450 enzymes potentially resulting in a decrease in exposure of CYP450 substrates. 

Upon initiation or discontinuation of TNF blockers, including ZYMFENTRA, in patients being treated with CYP450 substrates requiring therapeutic drug monitoring, monitor therpeutic parameters (e.g., INR for warfarin) or drug concentration (e.g., cyclosporine or theophylline). Dosage adjustment may be needed to maintain drug concentrations or parameters within the therapeutic range. See prescribing information for specific drugs. 

It is recommended that live vaccines not be given concurrently with ZYMFENTRA. It is also recommended that live vaccines not be given to infants after in utero exposure to infliximab products for 6 months following birth [see Warnings and Precautions (5.12)]. 

It is recommended that therapeutic infectious agents not be given concurrently with ZYMFENTRA [see Warnings and Precautions (5.12)]. 

Risk Summary

Available data from reports of pregnancy in clinical trials with ZYMFENTRA are insufficient to identify a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with inflammatory bowel diseasein pregnancy (see Clinical Considerations).

Available observational data in pregnant women exposed to infliximab products administered intravenously showed no increased risk of major malformations among live births as compared to those exposed to non-biologics. Most TNF blockers, such as infliximab products, administeredintravenously are transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant. Infants exposed in utero should not be administered live vaccines for at least 6 months after birth (see Clinical Considerations). Because infliximab products do not cross-react with TNFα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with ZYMFENTRA.

The background risk of major birth defects and miscarriage for the indicated populations 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 andmiscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Consideration

Disease-Associated Maternal and/or Embryo/Fetal Risk

Published data suggest that there is an increased risk of adverse pregnancy outcomes in women with inflammatory bowel disease associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2.5kg) and small for gestational age at birth.

Fetal/Neonatal Adverse Reactions

The risk of fetal/neonatal adverse reactions with in utero exposure to infliximab-dyyb administered subcutaneously is unknown. However, most TNF blockers, such as infliximab products, cross the placenta and have been detected in infant serum up to 6 months following birth. Consequently, infants exposed to infliximab products may be at increased risk of infection, including disseminated infection which can become fatal. At least a six-month waiting period following birth is recommended before the administration of live vaccines (e.g., BCG vaccine or other live vaccines, such as the rotavirus vaccine) to infants exposed to intravenous infliximab in utero [see Warnings and Precautions (5.12)].

Cases of agranulocytosis in infants exposed to intravenous infliximab in utero have also been reported. Therefore, ZYMFENTRA, administered during pregnancy may affect immune responses in the in utero-exposed newborn and infant [see Adverse Reactions 6.2].

Data

Animal Data 

Because infliximab products do not cross-react with TNFα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with ZYMFENTRA.

Risk Summary

There are no data on the presence of infliximab-dyyb or its metabolites in either human or animal milk, the effects on the breastfed infant, or the effects on milk production after subcutaneous administration. Published literature show that infliximab is present at low levels in human milk after intravenous administration. Systemic exposure in a breastfed infant is expected to be low because infliximab products are largely degraded in the gastrointestinal tract. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZYMFNETRA and any potential adverse effects on the brestfed child from ZYMFENTRA or from the underlying maternal condition. 

The safety and effectiveness in pediatric patients have not been established. 

Clinical trials of ZYMFENTRA did not include sufficient numbers of sugjects aged 65 and over (8 subjects with UC and 6 subjects with CD) to determined whether they respond differently from younger subjects. 

Infliximab-dyyb, a tumor necrosis factor (TNF) blocker, is a chimeric IgG1κ monoclonal antibody (composed of human constant and murine variable regions). It has a molecular weight of approximately 145.9 kDa. Infliximab-dyyb is produced by a recombinant murine myeloma cell line, SP2/0. 

{ "type": "p", "children": [], "text": "Infliximab-dyyb, a tumor necrosis factor (TNF) blocker, is a chimeric IgG1κ monoclonal antibody (composed of human constant and murine variable regions). It has a molecular weight of approximately 145.9 kDa. Infliximab-dyyb is produced by a recombinant murine myeloma cell line, SP2/0. " }

ZYMFENTRA (inifliximab-dyyb) injection for subcutaneous use is a sterile, preservative-free, clear to opalescent, colorless to pale brown solution. 

{ "type": "p", "children": [], "text": "ZYMFENTRA (inifliximab-dyyb) injection for subcutaneous use is a sterile, preservative-free, clear to opalescent, colorless to pale brown solution. " }

ZYMFENTRA is supplied in a single-dose prefilled syringe with 29 gauge fixed 1/2 inch needle, prefilled syringe with 29 gauge fixed 1/2 inch needle with needle guard, or prefilled pen with 27 gauge fixed 1/2 inch needle. 

{ "type": "p", "children": [], "text": "ZYMFENTRA is supplied in a single-dose prefilled syringe with 29 gauge fixed 1/2 inch needle, prefilled syringe with 29 gauge fixed 1/2 inch needle with needle guard, or prefilled pen with 27 gauge fixed 1/2 inch needle. " }

Each mL of solution contains 120 mg infliximab-dyyb, acetic acid (0.19 mg), polysorbate 80 (0.5 mg), sodium acetate (0.56 mg), sorbitol (45 mg) and Water for Injection, USP. The pH is 5.0. 

{ "type": "p", "children": [], "text": "\nEach mL of solution contains 120 mg infliximab-dyyb, acetic acid (0.19 mg), polysorbate 80 (0.5 mg), sodium acetate (0.56 mg), sorbitol (45 mg) and Water for Injection, USP. The pH is 5.0. \n" }

Infliximab-dyyb neutralize the biological activity of TNFα by binding with high affinity to the soluble and transmembrane forms of TNFα and inhibit binding of TNFα with its receptors. Infliximab-dyyb has shown biological activities, such as TNFα neutralization activity and TNFα binding affinities, complement 1q (C1q) binding affinity and crystallizable fragment (Fc) receptor binding affinities in a wide variety of in vitro bioasays. The relationship of these biological response markers to the mechanism(s) by which infliximab-dyyb exerts its clinical effects is unknown.

No formal pharmacodynamic studies have been conducted. 

Following single and multiple subcutaneous dosing of infliximab-dyyb, exposures to infliximab-dyyb (i.e., AUC) are proportionally increased over the dose range from 120 mg to 240 mg (2 times the recommended dosage). After a single subcutaneous dose of infliximab-dyyb 120 mg in healthy subjects, the median (SD) Cmax and AUCinf were 10.0 (3.2) mcg/mL and 6945.6 (2830.2) mcg·h/mL, respectively. Following recommended subcutaneous maintenance dose of ZYMFENTRA (120 mg every 2 weeks) in adult subjects with UC and CD from Week 10 after intravenous induction treatment with infliximab-dyyb, steady-state was achieved by Week 22, and the mean (SD) trough serum concentrations of infliximab-dyyb at steady-state were 14.6 (7.8) mcg/mL and 14.6 (8.9) mcg/mL in subjects with UC and CD, respectively. Pharmacokinetics are comparable between healthy subjects, and subjects with UC or CD.

Absorption

In healthy subjects, the median time to reach the maximum serum concentration (Tmax) was 7 days after a single subcutaneous dose of infliximab-dyyb 120 mg. In healthy subjects, AUCinf following a single subcutaneous dosed of infliximab-dyyb 120 mg was approximately 23% relative to a single intravenous dose of infliximab-dyyb 5 mg/kg. Following infliximab-dyyb 120 mg subcuaneosly every 2 weeks, steady state AUC for 8-week internal was 25-35% higher compared to infliximab-dyyb 5 mg/kg administered intravenously every 8 weeks in subjects with UC and CD. 

Distribution

Population pharmacokinetic analyses showed that the volume of distribution of infliximab-dyyb was 3.36L. 

Elimination

In healthy subjects, the mean half-life was 332 hours after a single subcutaneous dose of infliximab-dyyb 120 mg.

Populatoin pharmacokinetic analyses showed that the clearance of infliximab-dyyb was 0.013 L/hr and the clearance was increased in the presence of anti-drug antibody. 

The metabolic pathway of infliximab has not been characterized. As a IgG1κ monoclonal antibody, infliximab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. 

Weight

Population pharmacokinetic analysis indicated that exposure to infliximab-dyyb was inversely related to body weight. However, the magnitude of body weight effect on systemic exposure was not clinically meaningful in adult subjects with UC and CD weighing from 39 to 130 kg. 

Age, Sex and Race

Age (≥65 years ofld), sex, or race did not have a clinically meaningful effect on pharmacokinetics of infliximab-dyyb.

Drug Interaction Studies

Population pharmacokinetic analysis showed that co-administered methotrexate did not have clinically meaningful effect on the pharmacokinetics of infliximab-dyyb.

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Difference in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of infliximab-dyyb or of other infliximab products. 

In UC and CD clinical studies (UC Trial I and CD Trial I), approximately 64% subjects developed anti-drug antibodies to infliximab-dyyb following induction treatment with infliximab-dyyb intravenously and maintenance treatment with ZYMFENTRA by Week 54 [183/287 (64%) in subjects with UC, and 151/232 (65%) in subjects with CD] [see Clinical Studies (14)]. Among subjects with anti-drug antibodies, 92% had neutralizing antibodies [161/183 (88%) subjects with UC, and 147/151 (97%) subjects with CD]. Use of concomitant immunosuppressant agents (azathioprine, 6-mercaptopurine and methotrexate) appeared to reduce the frequency of ADA to infliximab-dyyb.

Subjects who were positive for anti-drug antibodies showed lower infliximab-dyyb trough seum concentrations of infliximab-dyyb by approximately 30 to 40% compared to subjects who were negative for anti-drug antibodies. In some subjects with high titers of anti-drug antibodies and positive neutralizing antibodies, trough seum concentrations of infliximab-dyyb were below the lower limit of quantitation (<0.1 mcg/mL). There was no identified clinically significant effect of anti-drug antibodies on the safety and effectiveness of ZYMFENTRA in Study UC I and Study CD I. 

Long-term animal studies of infliximab-dyyb have not been conducted to evaluate the carcinogenic potential or its effect on fertility. 

The safety and efficacy of ZYMFENTRA were assessed in a randomized, double-blind, placebo-controlled clinical trial (UC Trial I; NCT04205643) in adult subjects with moderately to severely active UC (defined as a modified Mayo score [mMS] between 5 to 9 with an endoscopic subscore [ES] of 2 or 3). The mMS is a 3-component Mayo score (0-9), which consists of following subscores (0 to 3 for each subscore): stool frequency (SFS), rectal bleeding (RBS), and findings on centrally read endoscopy score (ES). An ES of 2 was defined by marked erythema, lack of vascular pattern, any friability, and/or erosions, and a score of 3 was defined by spontaneous bleeding and ulceration. 

Subjects had demonstrated an inadequate response or intolerance to treatment with corticosteroids alone or in combination with 6-mercaptopurine or azathioprine. Subjects were permitted to use stable doses of oral aminosalicylates, oral corticosteroids (prednisone ≤20 mg/day or equivalent, budesonide ≤9 mg/day), UC-related antibiotics, and/or immunomodulatory agents (azathioprine, 6-mercaptopurine, or methotrexate). Corticosteroid tapering was permitted after Week 10. 

All subjects received three intravenous induction doses of 5 mg/kg of infliximab-dyyb at Weeks 0, 2 and 6. In order to be randomized to treatment in UC Trial I, subjects had to be in clinical response at Week 10. Clinical response was defined as a decrease from baseline in the mMS of at least 2 points and at least 30%, with an accompanying decrease in the RBS of at least 1 point or an aabsolute RBS of 0 or 1 point. 

A total of 438 subjects were randomized at Week 10 in a double-blind fashion (2:1) to ZYMFENTRA 120 mg as a subcutaneous injection or placebo every two weeks. 

At the time of randomization into the double-blind phase (Week 10), 92% were receiving aminosalicylates, 41% were receiving oral corticosteroids, and 22% were receiving immunomodulators including AZA, 6-MP or MTX. 

A total of 10% of randomized subjects had prior exposure to biological poucts or JAK inhibitors. 

Subjects in the boule-blind phase had a mean age of 39 years (range 18 to 75 years); 44% were female; and 98% identified as White, and 2% as American Indian or Alaska Native. 

The primary endpoint was the proportion of subjects in clinical remission at Week 54. Wecondary endpoints included the proportion of subjects achieving histologic-endoscopic mucosal improvement and corticosteroid-fee remission at Week 54 (see Table 3). 

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <tbody class="Headless"> <tr class="First"> <td colspan="5"> <p class="First"> <span class="Bold">Table 3: Proportion of Subjects with Ulcerative Colitis Meeting Effficacy Endpoints at Week 54 in UC Trial I</span> </p> </td> </tr> <tr> <td> <p class="First First TableCellHeading10pt"> <span class="Bold">Endpoint</span> </p> </td><td></td><td> <p class="First First TableCellHeading10pt"> <span class="Bold">ZYMFENTRA</span> </p> </td><td> <p class="First First TableCellHeading10pt"> <span class="Bold">Placebo</span> </p> </td><td> <p class="First First TableCellHeading10pt"> <span class="Bold">Treatment Difference<span class="Sup">a</span></span> </p> <p class="First TableCellHeading10pt"> <span class="Bold">and 95% CI</span> </p> </td> </tr> <tr> <td> <p class="First First TableCellText10pt"> <span class="Bold">Clinical Remission<span class="Sup">b</span> at Week 54</span> </p> </td><td></td><td></td><td></td><td></td> </tr> <tr> <td>Total population</td><td></td><td> <p class="First"> N=294</p> <p>43%</p> </td><td> <p class="First">N=144</p> <p>21% </p> </td><td> <p class="First"> 21%</p> <p>(12, 29)</p> </td> </tr> <tr> <td>No prior biological product/JAK inhibitor exposure </td><td></td><td> <p class="First"> N=265</p> <p>45%</p> </td><td> <p class="First">N=131</p> <p>21%</p> </td><td></td> </tr> <tr> <td>Prior biological product/JAK inhibitor exposure</td><td></td><td> <p class="First">N=29</p> <p> <span>31% </span> </p> </td><td> <p class="First">N=13</p> <p>15% </p> </td><td></td> </tr> <tr> <td><span class="Bold">Histologic-Endoscopic Mucosal Improvement<span class="Sup">d</span> at Week 54</span></td><td></td><td></td><td></td><td></td> </tr> <tr> <td> <p class="First First TableCellText10pt">Total population</p> </td><td></td><td> <p class="First First TableCellText10pt">N=294</p> <p class="First TableCellText10pt">36%</p> </td><td> <p class="First">N=144</p> <p>17%</p> </td><td> <p class="First">18%</p> <p>(9, 26)</p> </td> </tr> <tr> <td>No prior biological product/JAK inhibitor exposure </td><td></td><td> <p class="First">N=265</p> <p>36% </p> </td><td> <p class="First">N=131</p> <p>18% </p> </td><td></td> </tr> <tr> <td>Prior biological product/JAK inhibitor exposure </td><td></td><td> <p class="First">N=29</p> <p>31% </p> </td><td> <p class="First">N=13</p> <p>8% </p> </td><td></td> </tr> <tr> <td><span class="Bold">Corticosteroid-Fee Remission<span class="Sup">e</span> at Week 54</span></td><td></td><td></td><td></td><td></td> </tr> <tr> <td>Total population</td><td></td><td> <p class="First"> N=120</p> <p>37%</p> </td><td> <p class="First"> N=61</p> <p>18%</p> </td><td> <p class="First"> 17%<span class="Sup">f</span> </p> <p>(3, 29)</p> </td> </tr> <tr> <td> <p class="First First TableCellText10pt">No prior biological product/JAK inhibitor</p> </td><td></td><td> <p class="First">N=107</p> <p>36%</p> </td><td> <p class="First">N=56</p> <p>18%</p> </td><td></td> </tr> <tr> <td>Prior biological product/JAK inhibitor exposure</td><td></td><td> <p class="First First TableCellText10pt">N=13</p> <p class="First TableCellText10pt">39%</p> </td><td> <p class="First">N=5</p> <p>20%</p> </td><td></td> </tr> <tr class="Last"> <td colspan="5"> <p class="First First TableFootnote">CI = confience interval, JAK = Janus kinase </p> <p class="First TableFootnote"> <span class="Sup">a </span>Treatement difference (adjusted for stratification factors of previous exposure to biological product and/or JAK inhibitor, use of treatment with oral corticosteoids Week 0, and clinical remission status at Week 10.)</p> <p class="TableFootnote"> <span class="Sup">b </span>Clinical remissio is defined using the mMS as SFS of 0 or 1 point; RBS of 0 point; and ES of 0 or 1 point (excluding friability).</p> <p class="TableFootnote"> <span class="Sup">c </span>p &lt; 0.0001</p> <p class="TableFootnote"> <span class="Sup">d </span>Histologic-endoscopic mucosal improvement is defined as an absolute ES of 0 or 1 po<span>int (excluding friability) from mMS and an absoluted Robarts Histopathology Index (RHI) score of ≤3 poitns with no lamina propria neutrophils, no neutrophils in epithelium, no erosion or ulceration. </span> </p> <p class="TableFootnote"> <span><span class="Sup">e</span> Corticosteroid-free remission is defined as being in clinical remission by mMS in addition to not requiring any treatment with corticosteroid for at least 8 weeks at Week 54, among the patients who used oral cotricosteroids at baseline. </span> </p> <p class="TableFootnote"> <span><span class="Sup">f</span> p &lt; 0.05</span> </p> </td> </tr> </tbody> </table></div>

The relationship between histologic-endoscopic mucosal improvement at Week 54 and diasease progression and longer-term outcomes after Week 54 was not evaluated in UC Trial I. 

The safety and efficacy of ZYMFENTRA were assessed in a randomized, double-blind, placebo-controlled clinical studies (CD Trial I; NCT03945019) in adult subjects with moderately to severely active CD, defined as Crohn's Disease Activity Index (CDAI) score of 220 to 450 points, and a centrally-reveiwed Simplified Endoscopic Activity Score for Crohn’s Disease (SES-CD) of ≥6 points for ileal-colonic CD (or ≥4 points for isolated ileal disease). 

Subjects had demonstrated an inadequate response or intolerance to treatment with corticosteroids and/or immunosuppressants. Subjects were permitted to use stable doses of oral amisosalicylates, oral corticosteroids (prednisone ≤20 mg/day or equivalent, budesonide ≤9 mg/day), CD-related antibiotics and/or immunomodulatory agents (azathioprine, 6-mercaptopurine, or methotrexate). Corticosteroid dose was tapered after Week 10. 

All subjects received three intravenous induction doses of 5 mg/kg infliximab-dyyb at Week 0, 2 and 6. In order to be ranomized to treatment in CD Trial I, subjects had to be in clinical response at Week 10. Clinical response was defined as a decrease from baseline in CDAI of at least 100 points (i.e., CDAI-100 responders). 

A total of 323 subjects were randomized at Week 10 in a double-blind fashion (2:1) to ZYMFENTRA 120 mg as a subcutaneous injection or placebo every 2 weeks. 

At the time of randomization into thd double-blind phase (Week 10), 61% were receiving aminosalicylates, 40 % were receiving oral corticosteroids, and 32% were receiving immunomodulators including azathioprine, 6-mercaptopurine, or methotrexate. 

A total of 11% of randomized subjects had prior exposure to biological products. 

Subjects in the double-blind phase had a mean age of 35 years (range 18 to 75 years); 40% were female; and 91% identified as White, 4% identified as American Indian or Alaska Native, 4% identified as Asian, 0.3% as Black or African American, and 1% identified as another racial group. 

The co-primary endopoints were clinical remission (based on CDAI) and endoscopic response at Week 54. Secondary endpoints included endoscopic remission, and corticosteroid-free remission at Week 54 (see Table 4). 

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <tbody class="Headless"> <tr class="First"> <td colspan="4"> <p class="First"> <span class="Bold">Table 4:  Proportion of Subjects with Crohn's Disease Meeting Efficacy Endpoints at Week 54 in CD Trial I</span> </p> </td> </tr> <tr> <td> <p class="First First TableCellHeading10pt"> <span class="Bold">Endpoint</span> </p> </td><td> <p class="First First TableCellHeading10pt"> <span class="Bold">ZYMFENTRA</span> </p> </td><td> <p class="First First TableCellHeading10pt"> <span class="Bold">Placebo</span> </p> </td><td> <p class="First First TableCellHeading10pt"> <span class="Bold">Treatment Difference<span class="Sup">a</span></span> </p> <p class="First TableCellHeading10pt"> <span class="Bold">and 95% CI</span> </p> </td> </tr> <tr> <td colspan="4"> <p class="First First TableCellText10pt"> <span class="Bold">Clinical Remission (Based on CDAI)<span class="Sup">b</span></span><span class="Bold">at </span><span class="Bold">Week </span><span class="Bold">54</span> </p> </td> </tr> <tr> <td> <p class="First First TableCellText10pt">Total population</p> </td><td> <p class="First">N=216</p> <p>63%</p> </td><td> <p class="First">N=107</p> <p>30%</p> </td><td> <p class="First">35%<span class="Sup">c</span> </p> <p>(24, 45)  </p> </td> </tr> <tr> <td>No prior biological product expousre</td><td> <p class="First">N=191</p> <p>62% </p> </td><td> <p class="First">N=98</p> <p>31% </p> </td><td></td> </tr> <tr> <td>Prior biological product exposure</td><td> <p class="First">N=25</p> <p>72% </p> </td><td> <p class="First">N=9</p> <p>22% </p> </td><td></td> </tr> <tr> <td> <p class="First First TableCellText10pt"> <span class="Bold">Endoscopic response<span class="Sup">d</span> at Week 54</span> </p> </td><td></td><td></td><td></td> </tr> <tr> <td>Total population</td><td> <p class="First">N=216</p> <p>50%</p> </td><td> <p class="First">N=107</p> <p>87%</p> </td><td> <p class="First"> 34%<span class="Sup">c</span> </p> <p>(23, 43)</p> </td> </tr> <tr> <td>No prior biological product exposure </td><td> <p class="First">N=191</p> <p>51% </p> </td><td> <p class="First">N=98</p> <p>17% </p> </td><td></td> </tr> <tr> <td>Prior biological product exposure  </td><td> <p class="First">N=25</p> <p>48% </p> </td><td> <p class="First">N=9</p> <p>22% </p> </td><td></td> </tr> <tr> <td> <p class="First First TableCellText10pt"> <span class="Bold">Enoscopic Remission<span class="Sup">e</span> at Week 54</span> </p> </td><td></td><td></td><td></td> </tr> <tr> <td> <p class="First First TableCellText10pt">Total population</p> </td><td> <p class="First First TableCellText10pt">N=216</p> <p class="First TableCellText10pt">35%</p> </td><td> <p class="First">N=107</p> <p>10%</p> </td><td> <p class="First First TableCellText10pt">25%<span class="Sup">c</span> </p> <p class="First TableCellText10pt">(16, 33)</p> </td> </tr> <tr> <td> <p class="First First TableCellText10pt">No prior biological product exposure</p> </td><td> <p class="First First TableCellText10pt">N=191</p> <p class="First TableCellText10pt">35%</p> </td><td> <p class="First First TableCellText10pt">N=98</p> <p class="First TableCellText10pt">10%</p> </td><td></td> </tr> <tr> <td> <p class="First First TableCellText10pt">Prior biological product exposure</p> </td><td> <p class="First First TableCellText10pt">N=25</p> <p class="First TableCellText10pt">36%</p> </td><td> <p class="First First TableCellText10pt">N=9</p> <p class="First TableCellText10pt">11%</p> </td><td></td> </tr> <tr> <td> <p class="First First TableCellText10pt"> <span class="Bold">Corticosteroid-free Remission<span class="Sup">f</span> at Week 54</span> </p> </td><td> <p class="First First TableCellText10pt"></p> </td><td> <p class="First First TableCellText10pt"></p> </td><td></td> </tr> <tr> <td>Total population</td><td> <p class="First">N=92</p> <p>40%</p> </td><td> <p class="First">N=43</p> <p>21%</p> </td><td>19%<span class="Sup">g</span></td> </tr> <tr> <td>No prior biological product expousre</td><td> <p class="First">N=81</p> <p>35%</p> </td><td> <p class="First">N=40</p> <p>23%</p> </td><td></td> </tr> <tr> <td>Prior biological product exposure</td><td> <p class="First">N=11</p> <p>82%</p> </td><td> <p class="First">N=3</p> <p>0%</p> </td><td></td> </tr> <tr class="Last"> <td colspan="4"> <p class="First First TableFootnote"> <span>CI=confidence internal, CDAI=Crohn's Disease Activity Index, JAK=Janus kinase</span> </p> <p class="First TableFootnote"> <span class="Sup">a</span> Treatment difference (adjusted for stratification factors of previous exposure to biological product, use of treatment with oral corticosteroids at Week 0, and clinical remission status at Week 10). </p> <p class="TableFootnote"> <span class="Sup">b </span>Clinical remission (based on CDAI) is defined as an absolute CDAI score of &lt;150 points.</p> <p class="TableFootnote"> <span class="Sup">c </span>p &lt; 0.0001.</p> <p class="TableFootnote"> <span class="Sup">d </span>Endoscopic response is defined as a &gt;50% decrease in SES-CD from the baseline value.</p> <p class="TableFootnote"> <span class="Sup">e </span>Endoscopic remission is defined as an absolute SES-CD score of ≤4 with no sub-score of &gt;1.</p> <p class="TableFootnote"> <span class="Sup">f</span> Corticosteroid-free remission is defined as being in clinical remission in additio to not receiving any corticosteroid for at least 8 weeks prior to Week 54, among the subjects who used oral corticosteroids at baseline. </p> <p class="TableFootnote"> <span class="Sup">g</span> p &lt; 0.05</p> </td> </tr> </tbody> </table></div>

How Supplied

ZYMFENTRA (Infliximab-dyyb) injection for subcutaneous use is supplied as a sterile, preservative-free, clear to opalescent, colorless to pale brown solution in a single-use prefilled syringe, prefilled syringe with needle guard or prefilled pen. The syringe is fitted with a needle shield which are not made with natural rubber latex or any derivatives from natural rubber latex in any ingredient. 

Prefilled Syringe

Each prefilled syringe is equipped with a 29 gauge fixed 1/2 inch needle with a rigid needle shield and a plunger stopper. The following configurations are available: 

Prefilled Syringe with Needle Guard

Each prefilled syringe is equipped with a 29 gauge fixed 1/2 inch needle with a rigid needle shield and an automatic needle guard, and a plunger stopper. The following configurations are available: 

Prefilled Pen

Each prefilled pen is equipped with a 27 gauge fixed 1/2 inch needle with a rigid needle shield and a plunger stopper. The following configurations are available:

Storage and Handling

Store in refrigerator at 2°C to 8°C (36°F to 46°F). DO NOT FREEZE. Keep the product in its outer carton until time of administration in order to protect from light. 

If needed, the product may be stored at room temperature at 20°C to 25°C (68°F to 77°F) for up to 14 days with protection from light. Once the product has been stored at room temperature, it should not be placed back into the refrigerator. The product must be discarded if not used within the 14 days.

Infections

Inform patients that ZYMFENTRA increases the risk for developing serious infections. Instruct patients of the importance of contacting their healthcare provider if they develop any symptoms of an infection, including tuberculosis, invasive fungal infections, and reactivation of hepatitis B virus infections [see Warnings and Precautions (5.1, 5.3)]. 

Malignancies

Malignancies have been reported among children, adolescents and young adults who received treatment with TNF blockers. Patients should be counseled about the risk of lymphoma and other malignancies while receiving ZYMFENTRA [see Warnings and Precautions (5.2)].

Hepatotoxicity

Instruct patients to seek medical attention if they develop signs or symptoms of hepatotoxicity (e.g., jaundice) [see Warnings and Precautions (5.4)]. 

Congestive Heart Failure

Instruct patients to seek medical attention and consult their prescriber if they develop signs or symptoms of heart failure [see Warnings and Precautions (5.5)]. 

Hematologic Reactions

Instruct patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever) while on ZYMFENTRA [seeWarnings and Precautions (5.6)]. 

Hypersensitivity

Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.7)]. 

Neurologic Reactions

Advise patients to seek medical attention if they develop signs or symptoms of neurologic reactions [seeWarnings and Precautions (5.8)]. 

Live Vaccines/Therapeutic Infectious Agents

Instruct ZYMFENTRA-treated patients to avoid receiving live vaccines or therapeutic infectious agents [seeWarnings and Precautions (5.12)]

Administration

Instruct patients to follow sharp disposal recommendations, as described in the Instructions for Use.

Manufactured by:  CELLTRION, Inc.  23, Academy-ro, Yeonsu-gu, Incheon 22014, Republic of Korea U.S. License No. 1996

{ "type": "p", "children": [], "text": "Manufactured by:  CELLTRION, Inc.  23, Academy-ro, Yeonsu-gu, Incheon 22014, Republic of Korea U.S. License No. 1996" }

Distributed by:CELLTRION USA, Inc. One Evertrust Plaza Suite 1207, Jersey City, New Jersey, 07302, USA CELLTRION USA, Inc. 

{ "type": "p", "children": [], "text": "Distributed by:CELLTRION USA, Inc. One Evertrust Plaza Suite 1207, Jersey City, New Jersey, 07302, USA CELLTRION USA, Inc. " }

© CELLTRION, Inc.

{ "type": "p", "children": [], "text": "\n© CELLTRION, Inc." }

<div class="scrollingtable"><table width="100%"> <colgroup> <col align="left" valign="top" width="2%"/> <col align="left" valign="top" width="33%"/> <col align="left" valign="top" width="16%"/> <col align="left" valign="top" width="16%"/> <col align="left" valign="top" width="33%"/> </colgroup> <tfoot> <tr class="First First Last Last"> <td align="left" colspan="5">This Medication Guide has been approved by the U.S. Food and Drug Administration                                                         Revised: 02/2024</td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First First"> <td align="center" class="Lrule Rrule" colspan="5"><span class="Bold">MEDICATION GUIDE</span> <br/> <span class="Bold">ZYMFENTRA<span class="Sup">TM </span></span><span class="Bold">(Zim fen' trah)</span> <br/> <span class="Bold">(infliximab-dyyb)</span> <br/> <span class="Bold">injection, for </span><span class="Bold">subcutaneous use</span></td> </tr> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="5">Read the Medication Guide that comes with ZYMFENTRA before you receive the first treatment, and before each time you receive a treatment of ZYMFENTRA. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"> <p class="First"> <span class="Bold">What is the most important information I should know about ZYMFENTRA</span>?</p> <p>ZYMFENTRA may cause serious side effects, including:<br/> <span class="Bold">1. Risk of infection</span> <br/>ZYMFENTRA is a medicine that affects your immune system. ZYMFENTRA can lower the ability of your immune system to fight infections. Serious infections have happened in patients receiving ZYMFENTRA. These infections include tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some patients have died from these infections.</p> <ul class="Disc"> <li>Your doctor should test you for TB before starting ZYMFENTRA.</li> <li>Your doctor should monitor you closely for signs and symptoms of TB during treatment with ZYMFENTRA.</li> </ul> <span class="Bold">Before starting ZYMFENTRA, tell your doctor if you:</span> <ul class="Disc"> <li>think you have an infection. You should not start receiving ZYMFENTRA if you have any kind of infection.</li> <li>are being treated for an infection.</li> <li>have signs of an infection, such as a fever, cough, flu-like symptoms.</li> <li>have any open cuts or sores on your body.</li> <li>get a lot of infections or have infections that keep coming back.</li> <li>have diabetes or an immune system problem as people with these conditions have a higher chance for getting infections.</li> <li>have TB, or have been in close contact with someone with TB.</li> <li>live or have lived in certain parts of the country (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis); these infections may develop or become more severe if you receive ZYMFENTRA. If you do not know if you have lived in an area where histoplasmosis, coccidioidomycosis, or blastomycosis is common, ask your doctor.</li> <li>have or have had hepatitis B.</li> <li>use the medicines KINERET (anakinra), ORENCIA (abatacept), or other medicines called biologics used to treat the same conditions as ZYMFENTRA.</li> </ul> <p> <span class="Bold">After starting ZYMFENTRA,</span> if you have an infection, any sign of an infection including a fever, cough, flu-like symptoms, or have open cuts or sores on your body, call your doctor right away. ZYMFENTRA can make you more likely to get infections or make any infection that you have worse.</p> <p> <br/> <span class="Bold">2. Risk of Cancer</span> </p> <ul class="Disc"> <li>There have been cases of unusual cancers in children and teenage patients using tumor necrosis factor (TNF) blocker medicines, such as ZYMFENTRA.</li> <li>For people receiving TNF blocker medicines, including ZYMFENTRA, the chances of getting lymphoma or other cancers may increase.</li> <li>Some people receiving TNF blockers, including ZYMFENTRA, developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. Most of these people were male teenagers or young men. Also, most people were being treated for Crohn's disease or ulcerative colitis with a TNF blocker and another medicine called azathioprine or 6-mercaptopurine.</li> <li>People who have been treated for Crohn's disease and ulcerative colitis, for a long time may be more likely to develop lymphoma. This is especially true for people with very active disease.</li> <li>Some people treated with infliximab products, such as ZYMFENTRA, have developed certain kinds of skin cancer. If any changes in the appearance of your skin or growths on your skin occur during or after your treatment with ZYMFENTRA, tell your doctor.</li> <li>Patients with Chronic Obstructive Pulmonary Disease (COPD), a specific type of lung disease, may have an increased risk for getting cancer while being treated with ZYMFENTRA.</li> <li>Tell your doctor if you have ever had any type of cancer. Discuss with your doctor any need to adjust medicines you may be taking.</li> </ul>See the section "<span class="Bold">What are the possible side effects of ZYMFENTRA</span>?" below for more information.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">What is ZYMFENTRA?</span> <br/>ZYMFENTRA is a prescription medicine used as an injection uner the skin (subcutaneous injection) by adults for the maintenance treatment of:<ul class="Disc"> <li>moderately to severely active ulcerative colitis following treatment with an infliximab product given by intravenous infusion (IV).</li> <li>moderately to severely active Crohn's disease following treatment with an infliximab product given by intravenous infusion (IV). </li> </ul> <span class="Bold">It is not known if ZYMFENTRA is safe and effective in children under 18 years of age</span>.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Do not take ZYMFNETRA if you: </span> <br/> <ul class="Disc"> <li>have had an allergic reaction to ZYMFENTRA, other infliximab products, any murine proteins or any of the ingredients in ZYMFENTRA. See the end of this Medication Guide for a complete list of ingredients in ZYMFENTRA.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"> <p class="First"> <span class="Bold">Before you receive ZYMFENTRA, tell your doctor all of your medical conditions, including if you: </span> </p> <ul class="Disc"> <li>have an infection (see "<span class="Bold">What is the most important information I should know about ZYMFENTRA</span><span class="Bold">?</span>").</li> <li>have other liver problems including liver failure.</li> <li>have heart failure or other heart conditions. If you have heart failure, it may get worse while you receive ZYMFENTRA.</li> <li>have or have had any type of cancer.</li> <li>have COPD (Chronic Obstructive Pulmonary Disease), a specific type of lung disease. Patients with COPD may have an increased risk of getting cancer while receiving ZYMFENTRA.</li> <li>have or have had a condition that affects your nervous system such as:<br/>- multiple sclerosis, or Guillain-Barré syndrome, or<br/>- if you experience any numbness or tingling, or<br/>- if you have had a seizure.</li> </ul> <ul class="Disc"> <li>have recently received or are scheduled to receive a vaccine. <span class="Bold">Adults receiving ZYMFENTRA should not receive live vaccines (for example, the Bacille Calmette-Guérin [BCG] vaccine) or treatment with a weakened bacteria</span> (such as BCG for bladder cancer). Adults should have all of their vaccines brought up to date before starting treatment with ZYMFENTRA.</li> <li>are pregnant or plan to become pregnant, are breastfeeding or plan to breastfeed. You and your doctor should decide if you should receive ZYMFENTRA while you are pregnant or breastfeeding.</li> </ul> <p>If you have a baby and you were receiving ZYMFENTRA during your pregnancy, it is important to tell your baby's doctor and other healthcare professionals about your ZYMFENTRA use so they can decide when your baby should receive any vaccine. Certain vaccinations can cause infections.</p> <p> <br/>If you received ZYMFENTRA while you were pregnant, your baby may be at higher risk for getting an infection. If your baby receives a live vaccine within 6 months after birth, your baby may develop infections with serious complications that can lead to death. This includes live vaccines such as the BCG, rotavirus, or any other live vaccines. For other types of vaccines, talk with your doctor.</p> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">How should I receive ZYMFENTRA</span>?<br/> <ul> <li>Use ZYMFENTRA exactly as your doctor tells you to.</li> </ul> - ZYMFENTRA is provided as a single-dose prefilled syringe, single-dose prefilled syringe with needle guard or single-dose prefilled pen. Your healthcare provider will prescribe the type that is best for you.<br/> - If your healthcare provider decides that you or your cargiver can give your injections of ZYMFENTRA at home, you or your caregiver should be shown the right way to prepare and inject ZYMFENTRA.<br/> - Do not try to inject ZYMFENTRA yourself until you or your caregiver have been shown how to inject ZYMFENTRA by your healthcare provider.<br/> - ZYMFENTRA is injected under your skin (subcutaneously) 1 time every two weeks. <br/> - Inject ZYMFENTRA under the skin (subcutaneous injection), in your upper arms, stomach area (abdomen), or upper legs (thighs).<br/> - Do no give an injection in an area of the skin that is tender, bruised, red or hard.  <br/> - Use a different injection site each time you use ZYMFENTRA. <br/> - If you are not able to inject ZYMFENTRA at your regular scheduled time or you miss a dose of ZYMFENTRA, inject the dose as soon as possible. Then, inject your next dose every two weeks thereafter. If you are not sure when to inject ZYMFENTRA, call your healthcare provider. <br/> - If you inject more than prescribed, call your doctor right away. <br/> - Be sure to keep all of your scheduled follow-up appointments.<br/> <p class="First"></p> <p> <span class="Bold">Read the detailed Instructions for Use at the end of this Medication Guide for insructions about how to prepare and inject a dose of ZYMFENTRA, and how to properly throw away (dispose of) used needles and syringes. The syringe and needle must never be re-used. After the rubber stopper is puntured, ZYMFENTRA can become contaiminated by harmful bacteria which could cause an infection if re-used. Therefore, throw away any unused portion of ZYMFENTRA</span>.</p> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"> <p class="First"> <span class="Bold">What should I avoid while taking ZYMFENTRA?</span> <br/>Do not take ZYMFENTRA together with other medicines medicines called biologics that are used to treat the same conditions as ZYMFENTRA.</p> <p> <br/> <span class="Bold">Tell your doctor about all the medicines you take</span>, including prescription and over-the-counter medicines, vitamins, and herbal supplements. These include any other medicines to treat Crohn's disease, or ulcerative colitis.</p> <p> <br/>Know the medicines you take. Keep a list of your medicines and show them to your doctor and pharmacist when you get a new medicine.</p> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">What are the possible side effects of ZYMFENTRA</span>?<br/>ZYMFENTRA can cause serious side effects, including (see "<span class="Bold">What is the most important information I should know about ZYMFENTRA</span><span class="Bold">?</span>"):<br/> <span class="Bold">Serious Infections</span> <ul class="Disc"> <li>Some patients, especially those 65 years and older have had serious infections while receiving infliximab products, such as ZYMFENTRA. These serious infections include TB and infections caused by viruses, fungi, or bacteria that have spread throughout the body or cause infections in certain areas (such as skin). Some patients die from these infections. If you get an infection while receiving treatment with ZYMFENTRA your doctor will treat your infection and may need to stop your ZYMFENTRA treatment.</li> <li>Tell your doctor right away if you have any of the following signs of an infection while receiving or after receiving ZYMFENTRA:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul> <li>a fever</li> <li>feel very tired</li> <li>have a cough</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul> <li>have flu-like symptoms</li> <li>warm, red, or painful skin</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"> <ul class="Disc"> <li>Your doctor will examine you for TB and perform a test to see if you have TB. If your doctor feels that you are at risk for TB, you may be treated with medicine for TB before you begin treatment with ZYMFENTRA and during treatment with ZYMFENTRA.</li> <li>Even if your TB test is negative, your doctor should carefully monitor you for TB infections while you are receiving ZYMFENTRA. Patients who had a<span class="Bold"> negative </span>TB skin test before receiving infliximab products may develop active TB after receiving infliximab products.</li> <li>If you are a chronic carrier of the hepatitis B virus, the virus can become active while you are being treated with ZYMFENTRA. In some cases, patients have died as a result of hepatitis B virus being reactivated. Your doctor should do a blood test for hepatitis B virus before you start treatment with ZYMFENTRA, while you are being treated and for several months after you finish treatment. Tell your doctor if you have any of the following symptoms:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul> <li>feel unwell</li> <li>poor appetite</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul> <li>tiredness (fatigue)</li> <li>fever, skin rash, or joint pain</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule" colspan="5"> <p class="First"></p> <p> <span class="Bold">Liver Injury</span> </p> <p>Some patients receiving infliximab products have developed serious liver problems. Tell your doctor if you have: </p> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul> <li>jaundice (skin and eyes turning yellow) </li> <li>dark, brwon-colored urine</li> <li>pain on the right side of your stomach area (right-sided abdominal pain)</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul> <li>fever </li> <li>extreme tiredness (sevre fatigue)</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"> <p class="First"></p> <p> <span class="Bold">Heart Failure</span> </p> <p>If you have a heart problem called congestive heart failure, your doctor should check you closely while you are receiving ZYMFENTRA. Your congestive heart failure may get worse while you are receiving ZYMFENTRA. Be sure to tell your doctor of any new or worse symptoms including:</p> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>shortness of breath</li> <li>swelling of ankles or feet</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>sudden weight gain</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"> <p class="First">Treatment with ZYMFENTRA may need to be stopped if you get new or worse congestive heart failure.</p> <p></p> <p> <span class="Bold">Blood Probelms</span> </p> <p>In some patiens receiving infliximab products, the body may not make enough of the blood cells tha help fight infections or help stop bleeding. Tell your doctor if you:</p> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>have a fever that does not go away</li> <li>bruise or bleed very easily</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>look very pale</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"> <p class="First"></p> <p> <span class="Bold">Allergic Reactions</span> <br/>Some patients have had allergic reactions to infliximab products. Some of these reactions were severe. These reactions can happen while you are getting your ZYMFENTRA treatment or shortly afterward. Your doctor may need to stop or pause your treatment with ZYMFENTRA and may give you medicines to treat the allergic reaction. Signs of an allergic reactio can include: </p> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>hives (red, raised, itchy patches of skin)</li> <li>difficulty breathing </li> <li>chest pain</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>high or low blood pressure</li> <li>fever</li> <li>chills</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"> <p class="First">Some patients treated with infliximab products have had delayed allergic reactions. Tell your doctor right away if you have any of these signs of delayed reaction to ZYMFENTRA:</p> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>fever</li> <li>rash</li> <li>headache</li> <li>sore throat</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>muscle or joint pain</li> <li>swelling of the face and hands</li> <li>difficulty swallowing</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"> <p class="First"></p> <p> <span class="Bold">Nervous System Disorders</span> </p> <p>Some patients receiving infliximab products have developed problems with their nervous system. Tell your doctor if you have: </p> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>changes in your vision</li> <li>numbness or tingling in any part of your body</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>seizures</li> <li>weakness in your arms or legs</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"> <p class="First"></p> <p>Some patients have experienced a stroke within approximately 24 hours of their infusion with infliximab products. Tell your doctor right away if you have symptoms of a stroke which may include: numbness or weakness of the face, arm, or leg, especially on one side of the body; sudden confusion, trouble speaking or understanding; sudden trouble seeing in one or both eyes, sudden trouble walking, dizziness, loss of balance or coordination or a sudden, severe headache. </p> <p></p> <p> <span class="Bold">Lupus-like Syndrome</span> </p> <p>Some patient have developed symptoms that are like the symptoms of Lupus. If you develop any of the following symptoms, your doctor may decide to stop your treatment with ZYMFENTRA:</p> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>chest disomfort or painthat does not go away</li> <li>shortness of breath</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>joint pain</li> <li>rash on the cheeks or arms that gets worse in the sun</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"> <p class="First"></p> <p> <span class="Bold">The most common side effects of ZYMFENTRA include:</span> </p> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>COVID-19</li> <li>respiratory infections, such as sinus infections and sore throat</li> <li>injection site reactions</li> <li>headache</li> <li>abdominal pain</li> <li>abnormal liver enzymes</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul> <li>joint pain</li> <li>diarrhea</li> <li>high blood pressure</li> <li>urinary tract infections</li> <li>dizziness</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"> <p class="First">Tell your doctor about any side effect that bothers you or does not go away.</p> <p> <br/>These are not all of the side effects with ZYMFENTRA. Ask your doctor or pharmacist for more information.<br/> <span class="Bold">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</span> </p> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"> <p class="First"> <span class="Bold">How should I store ZYMFENTRA? </span> </p> <ul> <li>Store ZYMFENTRA prefilled syringes and prefilled pens in a refrigerator between 36°F to 46°F (2°C to 8°C).</li> <li>If needed, ZYMFENTRA prefilled syringes and prefilled pens may be stored at room temperature between 68°F to 77°F (20°C to 25°C) for up to 14 days with protection from light.</li> <li>When ZYMFENTRA prefilled syringes and prefilled pens have reached room temperature, <span class="Bold">do not</span> put ZYMFENTRA back in the refrigerator. ZYMFENTRA must be thrown away (discarded) if not used within the 14 days.</li> <li>Do not freeze ZYMFENTRA. </li> <li>Do not shake ZYMFENTRA.</li> <li>Keep ZYMFENTRA in the original carton until ready to use to protect it from light. </li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"> <p class="First"> <span class="Bold">General information about ZYMFENTRA</span> <br/>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.</p> <p> <br/>You can ask your doctor or pharmacist for information about ZYMFENTRA that is written for health professionals.</p> <p> <br/>Do not use ZYMFENTRA for a condition for which it was not prescribed. Do not give ZYMFENTRA to other people, even if they have the same symptoms that you have. </p> <p> <br/>For more information call 1-888-804-3433.</p> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"> <p class="First"> <span class="Bold">What are the ingredients in ZYMFENTRA?</span> <br/>The active ingredient is infliximab-dyyb.</p> <p> <br/>The inactive ingredients in ZYMFENTRA include: acetic acid, polysorbate 80, sodium acetate, and sorbitol in water for injections. No preservatives are present.</p> </td> </tr> <tr class="Last"> <td align="left" colspan="5">Manufactured by: CELLTRION, Inc. 23, Academy-ro, Yeonsu-gu, Incheon, 22014, Republic of Korea<br/>U.S. License No. 1996 <span class="Sup">©</span>CELLTRION, Inc.<br/>Distributed by CELLTRION USA, Inc. One Evertrust Plaza Suite 1207, Jersey City, New Jersey, 07302, USA<br/> <br/>For more information call 1-888-804-3433 </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<colgroup>\n<col align=\"left\" valign=\"top\" width=\"2%\"/>\n<col align=\"left\" valign=\"top\" width=\"33%\"/>\n<col align=\"left\" valign=\"top\" width=\"16%\"/>\n<col align=\"left\" valign=\"top\" width=\"16%\"/>\n<col align=\"left\" valign=\"top\" width=\"33%\"/>\n</colgroup>\n<tfoot>\n<tr class=\"First First Last Last\">\n<td align=\"left\" colspan=\"5\">This Medication Guide has been approved by the U.S. Food and Drug Administration                                                         Revised: 02/2024</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">MEDICATION GUIDE</span>\n<br/>\n<span class=\"Bold\">ZYMFENTRA<span class=\"Sup\">TM </span></span><span class=\"Bold\">(Zim fen' trah)</span>\n<br/>\n<span class=\"Bold\">(infliximab-dyyb)</span>\n<br/>\n<span class=\"Bold\">injection, for </span><span class=\"Bold\">subcutaneous use</span></td>\n</tr>\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">Read the Medication Guide that comes with ZYMFENTRA before you receive the first treatment, and before each time you receive a treatment of ZYMFENTRA. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about ZYMFENTRA</span>?</p>\n<p>ZYMFENTRA may cause serious side effects, including:<br/>\n<span class=\"Bold\">1. Risk of infection</span>\n<br/>ZYMFENTRA is a medicine that affects your immune system. ZYMFENTRA can lower the ability of your immune system to fight infections. Serious infections have happened in patients receiving ZYMFENTRA. These infections include tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some patients have died from these infections.</p>\n<ul class=\"Disc\">\n<li>Your doctor should test you for TB before starting ZYMFENTRA.</li>\n<li>Your doctor should monitor you closely for signs and symptoms of TB during treatment with ZYMFENTRA.</li>\n</ul>\n<span class=\"Bold\">Before starting ZYMFENTRA, tell your doctor if you:</span>\n<ul class=\"Disc\">\n<li>think you have an infection. You should not start receiving ZYMFENTRA if you have any kind of infection.</li>\n<li>are being treated for an infection.</li>\n<li>have signs of an infection, such as a fever, cough, flu-like symptoms.</li>\n<li>have any open cuts or sores on your body.</li>\n<li>get a lot of infections or have infections that keep coming back.</li>\n<li>have diabetes or an immune system problem as people with these conditions have a higher chance for getting infections.</li>\n<li>have TB, or have been in close contact with someone with TB.</li>\n<li>live or have lived in certain parts of the country (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis); these infections may develop or become more severe if you receive ZYMFENTRA. If you do not know if you have lived in an area where histoplasmosis, coccidioidomycosis, or blastomycosis is common, ask your doctor.</li>\n<li>have or have had hepatitis B.</li>\n<li>use the medicines KINERET (anakinra), ORENCIA (abatacept), or other medicines called biologics used to treat the same conditions as ZYMFENTRA.</li>\n</ul>\n<p>\n<span class=\"Bold\">After starting ZYMFENTRA,</span> if you have an infection, any sign of an infection including a fever, cough, flu-like symptoms, or have open cuts or sores on your body, call your doctor right away. ZYMFENTRA can make you more likely to get infections or make any infection that you have worse.</p>\n<p>\n<br/>\n<span class=\"Bold\">2. Risk of Cancer</span>\n</p>\n<ul class=\"Disc\">\n<li>There have been cases of unusual cancers in children and teenage patients using tumor necrosis factor (TNF) blocker medicines, such as ZYMFENTRA.</li>\n<li>For people receiving TNF blocker medicines, including ZYMFENTRA, the chances of getting lymphoma or other cancers may increase.</li>\n<li>Some people receiving TNF blockers, including ZYMFENTRA, developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. Most of these people were male teenagers or young men. Also, most people were being treated for Crohn's disease or ulcerative colitis with a TNF blocker and another medicine called azathioprine or 6-mercaptopurine.</li>\n<li>People who have been treated for Crohn's disease and ulcerative colitis, for a long time may be more likely to develop lymphoma. This is especially true for people with very active disease.</li>\n<li>Some people treated with infliximab products, such as ZYMFENTRA, have developed certain kinds of skin cancer. If any changes in the appearance of your skin or growths on your skin occur during or after your treatment with ZYMFENTRA, tell your doctor.</li>\n<li>Patients with Chronic Obstructive Pulmonary Disease (COPD), a specific type of lung disease, may have an increased risk for getting cancer while being treated with ZYMFENTRA.</li>\n<li>Tell your doctor if you have ever had any type of cancer. Discuss with your doctor any need to adjust medicines you may be taking.</li>\n</ul>See the section \"<span class=\"Bold\">What are the possible side effects of ZYMFENTRA</span>?\" below for more information.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">What is ZYMFENTRA?</span>\n<br/>ZYMFENTRA is a prescription medicine used as an injection uner the skin (subcutaneous injection) by adults for the maintenance treatment of:<ul class=\"Disc\">\n<li>moderately to severely active ulcerative colitis following treatment with an infliximab product given by intravenous infusion (IV).</li>\n<li>moderately to severely active Crohn's disease following treatment with an infliximab product given by intravenous infusion (IV). </li>\n</ul>\n<span class=\"Bold\">It is not known if ZYMFENTRA is safe and effective in children under 18 years of age</span>.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">Do not take ZYMFNETRA if you: </span>\n<br/>\n<ul class=\"Disc\">\n<li>have had an allergic reaction to ZYMFENTRA, other infliximab products, any murine proteins or any of the ingredients in ZYMFENTRA. See the end of this Medication Guide for a complete list of ingredients in ZYMFENTRA.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">Before you receive ZYMFENTRA, tell your doctor all of your medical conditions, including if you: </span>\n</p>\n<ul class=\"Disc\">\n<li>have an infection (see \"<span class=\"Bold\">What is the most important information I should know about ZYMFENTRA</span><span class=\"Bold\">?</span>\").</li>\n<li>have other liver problems including liver failure.</li>\n<li>have heart failure or other heart conditions. If you have heart failure, it may get worse while you receive ZYMFENTRA.</li>\n<li>have or have had any type of cancer.</li>\n<li>have COPD (Chronic Obstructive Pulmonary Disease), a specific type of lung disease. Patients with COPD may have an increased risk of getting cancer while receiving ZYMFENTRA.</li>\n<li>have or have had a condition that affects your nervous system such as:<br/>- multiple sclerosis, or Guillain-Barré syndrome, or<br/>- if you experience any numbness or tingling, or<br/>- if you have had a seizure.</li>\n</ul>\n<ul class=\"Disc\">\n<li>have recently received or are scheduled to receive a vaccine. <span class=\"Bold\">Adults receiving ZYMFENTRA should not receive live vaccines (for example, the Bacille Calmette-Guérin [BCG] vaccine) or treatment with a weakened bacteria</span> (such as BCG for bladder cancer). Adults should have all of their vaccines brought up to date before starting treatment with ZYMFENTRA.</li>\n<li>are pregnant or plan to become pregnant, are breastfeeding or plan to breastfeed. You and your doctor should decide if you should receive ZYMFENTRA while you are pregnant or breastfeeding.</li>\n</ul>\n<p>If you have a baby and you were receiving ZYMFENTRA during your pregnancy, it is important to tell your baby's doctor and other healthcare professionals about your ZYMFENTRA use so they can decide when your baby should receive any vaccine. Certain vaccinations can cause infections.</p>\n<p>\n<br/>If you received ZYMFENTRA while you were pregnant, your baby may be at higher risk for getting an infection. If your baby receives a live vaccine within 6 months after birth, your baby may develop infections with serious complications that can lead to death. This includes live vaccines such as the BCG, rotavirus, or any other live vaccines. For other types of vaccines, talk with your doctor.</p>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">How should I receive ZYMFENTRA</span>?<br/>\n<ul>\n<li>Use ZYMFENTRA exactly as your doctor tells you to.</li>\n</ul> - ZYMFENTRA is provided as a single-dose prefilled syringe, single-dose prefilled syringe with needle guard or single-dose prefilled pen. Your healthcare provider will prescribe the type that is best for you.<br/> - If your healthcare provider decides that you or your cargiver can give your injections of ZYMFENTRA at home, you or your caregiver should be shown the right way to prepare and inject ZYMFENTRA.<br/> - Do not try to inject ZYMFENTRA yourself until you or your caregiver have been shown how to inject ZYMFENTRA by your healthcare provider.<br/> - ZYMFENTRA is injected under your skin (subcutaneously) 1 time every two weeks. <br/> - Inject ZYMFENTRA under the skin (subcutaneous injection), in your upper arms, stomach area (abdomen), or upper legs (thighs).<br/> - Do no give an injection in an area of the skin that is tender, bruised, red or hard.  <br/> - Use a different injection site each time you use ZYMFENTRA. <br/> - If you are not able to inject ZYMFENTRA at your regular scheduled time or you miss a dose of ZYMFENTRA, inject the dose as soon as possible. Then, inject your next dose every two weeks thereafter. If you are not sure when to inject ZYMFENTRA, call your healthcare provider. <br/> - If you inject more than prescribed, call your doctor right away. <br/> - Be sure to keep all of your scheduled follow-up appointments.<br/>\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\">Read the detailed Instructions for Use at the end of this Medication Guide for insructions about how to prepare and inject a dose of ZYMFENTRA, and how to properly throw away (dispose of) used needles and syringes. The syringe and needle must never be re-used. After the rubber stopper is puntured, ZYMFENTRA can become contaiminated by harmful bacteria which could cause an infection if re-used. Therefore, throw away any unused portion of ZYMFENTRA</span>.</p>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">What should I avoid while taking ZYMFENTRA?</span>\n<br/>Do not take ZYMFENTRA together with other medicines medicines called biologics that are used to treat the same conditions as ZYMFENTRA.</p>\n<p>\n<br/>\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. These include any other medicines to treat Crohn's disease, or ulcerative colitis.</p>\n<p>\n<br/>Know the medicines you take. Keep a list of your medicines and show them to your doctor and pharmacist when you get a new medicine.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">What are the possible side effects of ZYMFENTRA</span>?<br/>ZYMFENTRA can cause serious side effects, including (see \"<span class=\"Bold\">What is the most important information I should know about ZYMFENTRA</span><span class=\"Bold\">?</span>\"):<br/>\n<span class=\"Bold\">Serious Infections</span>\n<ul class=\"Disc\">\n<li>Some patients, especially those 65 years and older have had serious infections while receiving infliximab products, such as ZYMFENTRA. These serious infections include TB and infections caused by viruses, fungi, or bacteria that have spread throughout the body or cause infections in certain areas (such as skin). Some patients die from these infections. If you get an infection while receiving treatment with ZYMFENTRA your doctor will treat your infection and may need to stop your ZYMFENTRA treatment.</li>\n<li>Tell your doctor right away if you have any of the following signs of an infection while receiving or after receiving ZYMFENTRA:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul>\n<li>a fever</li>\n<li>feel very tired</li>\n<li>have a cough</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul>\n<li>have flu-like symptoms</li>\n<li>warm, red, or painful skin</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<ul class=\"Disc\">\n<li>Your doctor will examine you for TB and perform a test to see if you have TB. If your doctor feels that you are at risk for TB, you may be treated with medicine for TB before you begin treatment with ZYMFENTRA and during treatment with ZYMFENTRA.</li>\n<li>Even if your TB test is negative, your doctor should carefully monitor you for TB infections while you are receiving ZYMFENTRA. Patients who had a<span class=\"Bold\"> negative </span>TB skin test before receiving infliximab products may develop active TB after receiving infliximab products.</li>\n<li>If you are a chronic carrier of the hepatitis B virus, the virus can become active while you are being treated with ZYMFENTRA. In some cases, patients have died as a result of hepatitis B virus being reactivated. Your doctor should do a blood test for hepatitis B virus before you start treatment with ZYMFENTRA, while you are being treated and for several months after you finish treatment. Tell your doctor if you have any of the following symptoms:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul>\n<li>feel unwell</li>\n<li>poor appetite</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul>\n<li>tiredness (fatigue)</li>\n<li>fever, skin rash, or joint pain</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" colspan=\"5\">\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\">Liver Injury</span>\n</p>\n<p>Some patients receiving infliximab products have developed serious liver problems. Tell your doctor if you have: </p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul>\n<li>jaundice (skin and eyes turning yellow) </li>\n<li>dark, brwon-colored urine</li>\n<li>pain on the right side of your stomach area (right-sided abdominal pain)</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul>\n<li>fever </li>\n<li>extreme tiredness (sevre fatigue)</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\">Heart Failure</span>\n</p>\n<p>If you have a heart problem called congestive heart failure, your doctor should check you closely while you are receiving ZYMFENTRA. Your congestive heart failure may get worse while you are receiving ZYMFENTRA. Be sure to tell your doctor of any new or worse symptoms including:</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>shortness of breath</li>\n<li>swelling of ankles or feet</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>sudden weight gain</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<p class=\"First\">Treatment with ZYMFENTRA may need to be stopped if you get new or worse congestive heart failure.</p>\n<p></p>\n<p>\n<span class=\"Bold\">Blood Probelms</span>\n</p>\n<p>In some patiens receiving infliximab products, the body may not make enough of the blood cells tha help fight infections or help stop bleeding. Tell your doctor if you:</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>have a fever that does not go away</li>\n<li>bruise or bleed very easily</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>look very pale</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\">Allergic Reactions</span>\n<br/>Some patients have had allergic reactions to infliximab products. Some of these reactions were severe. These reactions can happen while you are getting your ZYMFENTRA treatment or shortly afterward. Your doctor may need to stop or pause your treatment with ZYMFENTRA and may give you medicines to treat the allergic reaction. Signs of an allergic reactio can include: </p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>hives (red, raised, itchy patches of skin)</li>\n<li>difficulty breathing </li>\n<li>chest pain</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>high or low blood pressure</li>\n<li>fever</li>\n<li>chills</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<p class=\"First\">Some patients treated with infliximab products have had delayed allergic reactions. Tell your doctor right away if you have any of these signs of delayed reaction to ZYMFENTRA:</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>fever</li>\n<li>rash</li>\n<li>headache</li>\n<li>sore throat</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>muscle or joint pain</li>\n<li>swelling of the face and hands</li>\n<li>difficulty swallowing</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\">Nervous System Disorders</span>\n</p>\n<p>Some patients receiving infliximab products have developed problems with their nervous system. Tell your doctor if you have: </p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>changes in your vision</li>\n<li>numbness or tingling in any part of your body</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>seizures</li>\n<li>weakness in your arms or legs</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<p class=\"First\"></p>\n<p>Some patients have experienced a stroke within approximately 24 hours of their infusion with infliximab products. Tell your doctor right away if you have symptoms of a stroke which may include: numbness or weakness of the face, arm, or leg, especially on one side of the body; sudden confusion, trouble speaking or understanding; sudden trouble seeing in one or both eyes, sudden trouble walking, dizziness, loss of balance or coordination or a sudden, severe headache. </p>\n<p></p>\n<p>\n<span class=\"Bold\">Lupus-like Syndrome</span>\n</p>\n<p>Some patient have developed symptoms that are like the symptoms of Lupus. If you develop any of the following symptoms, your doctor may decide to stop your treatment with ZYMFENTRA:</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>chest disomfort or painthat does not go away</li>\n<li>shortness of breath</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>joint pain</li>\n<li>rash on the cheeks or arms that gets worse in the sun</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\">The most common side effects of ZYMFENTRA include:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>COVID-19</li>\n<li>respiratory infections, such as sinus infections and sore throat</li>\n<li>injection site reactions</li>\n<li>headache</li>\n<li>abdominal pain</li>\n<li>abnormal liver enzymes</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul>\n<li>joint pain</li>\n<li>diarrhea</li>\n<li>high blood pressure</li>\n<li>urinary tract infections</li>\n<li>dizziness</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<p class=\"First\">Tell your doctor about any side effect that bothers you or does not go away.</p>\n<p>\n<br/>These are not all of the side effects with ZYMFENTRA. Ask your doctor or pharmacist for more information.<br/>\n<span class=\"Bold\">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</span>\n</p>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store ZYMFENTRA? </span>\n</p>\n<ul>\n<li>Store ZYMFENTRA prefilled syringes and prefilled pens in a refrigerator between 36°F to 46°F (2°C to 8°C).</li>\n<li>If needed, ZYMFENTRA prefilled syringes and prefilled pens may be stored at room temperature between 68°F to 77°F (20°C to 25°C) for up to 14 days with protection from light.</li>\n<li>When ZYMFENTRA prefilled syringes and prefilled pens have reached room temperature, <span class=\"Bold\">do not</span> put ZYMFENTRA back in the refrigerator. ZYMFENTRA must be thrown away (discarded) if not used within the 14 days.</li>\n<li>Do not freeze ZYMFENTRA. </li>\n<li>Do not shake ZYMFENTRA.</li>\n<li>Keep ZYMFENTRA in the original carton until ready to use to protect it from light. </li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">General information about ZYMFENTRA</span>\n<br/>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.</p>\n<p>\n<br/>You can ask your doctor or pharmacist for information about ZYMFENTRA that is written for health professionals.</p>\n<p>\n<br/>Do not use ZYMFENTRA for a condition for which it was not prescribed. Do not give ZYMFENTRA to other people, even if they have the same symptoms that you have. </p>\n<p>\n<br/>For more information call 1-888-804-3433.</p>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in ZYMFENTRA?</span>\n<br/>The active ingredient is infliximab-dyyb.</p>\n<p>\n<br/>The inactive ingredients in ZYMFENTRA include: acetic acid, polysorbate 80, sodium acetate, and sorbitol in water for injections. No preservatives are present.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" colspan=\"5\">Manufactured by: CELLTRION, Inc. 23, Academy-ro, Yeonsu-gu, Incheon, 22014, Republic of Korea<br/>U.S. License No. 1996 <span class=\"Sup\">©</span>CELLTRION, Inc.<br/>Distributed by CELLTRION USA, Inc. One Evertrust Plaza Suite 1207, Jersey City, New Jersey, 07302, USA<br/>\n<br/>For more information call 1-888-804-3433 </td>\n</tr>\n</tbody>\n</table></div>" }

Read and follow the Instruction for Use that come with your ZYMFENTRA Prefilled Pen before you start using it and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. 

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Figure A: Parts of ZYMFENTRA Prefilled Pen

{ "type": "p", "children": [], "text": "\nFigure A: Parts of ZYMFENTRA Prefilled Pen\n" }

Important Information

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

{ "type": "ul", "children": [ "Use the Prefilled Pen only if your healthcare provider has trained you on the right way to prepare for and to give an injection.", "Ask your healthcare provider how often you will need to give an injection.", "Rotate the injection site each time you give an injection. Each new injection site should be at least 1.2 inches away from the previous injection site.", "\nDo not shake the Prefilled Pen at any time.", "\nDo not remove the Cap until you are ready to inject.", "\nDo not share the Prefilled Pen with anyone." ], "text": "" }

How to store the Prefilled Pen

{ "type": "p", "children": [], "text": "\nHow to store the Prefilled Pen\n" }

{ "type": "ul", "children": [ "\nStore the Prefilled Pen in a refrigerator between 36°F to 46°F (2°C to 8°C).\n", "Keep the Prefilled Pen in the original carton until use to protect it from light.", "\nDo not use the Prefilled Pen that has been left in direct sunlight.", "\nDo not freeze the Prefilled Pen. If the Prefilled Pen has been frozen, do not use the Prefilled Pen even if it is thawed.", "\nDo not warm the Prefilled Pen using heat sources such as hot water or a microwave. Let the Prefilled Pen naturally warm at room temperature between 68°F to 77°F (20°C to 25°C) for 30 minutes before giving an injection.", "When the Prefilled Pen has reached room temperature, do not put it back in the refrigerator. The Prefilled Pen must be thrown away (discarded) if not used within the 14 days. ", "\nKeep the Prefilled Pen and all medicines out of the reach of children.\n" ], "text": "" }

Prepare for the Injection

{ "type": "p", "children": [], "text": "\nPrepare for the Injection\n" }

1. Gather the supplies for the injection.

{ "type": "p", "children": [], "text": "\n1. Gather the supplies for the injection.\n" }

1a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.1b. Remove 1 Prefilled Pen from the carton stored in your refrigerator.      Note: Return the carton with any unused Prefilled Pens to refrigerator immediately after taking out one Prefilled Pen.1c. Make sure you have the following supplies:     - Prefilled Pen               - 1 Alcohol swab      Not included in the carton:      - 1 Cotton ball or gauze     - 1 Adhesive bandage     - FDA-cleared sharps disposal container

{ "type": "p", "children": [], "text": "1a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.1b. Remove 1 Prefilled Pen from the carton stored in your refrigerator.      Note: Return the carton with any unused Prefilled Pens to refrigerator immediately after taking out one Prefilled Pen.1c. Make sure you have the following supplies:     - Prefilled Pen               - 1 Alcohol swab\n     Not included in the carton:\n     - 1 Cotton ball or gauze     - 1 Adhesive bandage     - FDA-cleared sharps disposal container" }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="99%"> <tbody class="Headless"> <tr class="First"> <td> <p class="First"> <span class="Bold">2. Inspect the Prefilled Pen.</span> </p> <p>2a. Make sure you have the correct medicine (ZYMFENTRA).</p> <p>2b. Check the expiration (EXP) date on the label of the Prefilled Pen (See Figure B).</p> <p>2c. Look at the Prefilled Pen and make sure it is not cracked or damaged.</p> <ul> <li> <span class="Bold">Do not </span>use the Prefilled Pen if:<br/> - it is cracked or damaged.<br/> - the expiration (EXP) date has passed.</li> </ul> </td><td> <p class="First"></p> <p> <span class="Bold"><img alt="Figure B" src="/dailymed/image.cfm?name=zymfentra-2.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/>Figure B</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">3. Inspect the Medicine.</span> </p> <p>3a. Look through the Window and make sure that the liquid is clear, colorless to pale brown, and free of particles (see Figure C).</p> <ul> <li> <span class="Bold">Do not</span> use the Prefilled Pen if the liquid is the discolored (yellow or dark brown), cloudy, or contains particles in it.</li> <li>You may see air bubbles in the liquid. This is normal.</li> </ul> </td><td> <p class="First"> <img alt="Figure C" src="/dailymed/image.cfm?name=zymfentra-3.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/><span class="Bold">Figure C</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">4. Wait 30 minutes.</span> </p> <p>4a. Leave the Prefilled Pen at room temperature 68°F to 77°F (20°C to 25°C) for 30 minutes to allow it to warm up (see Figure D).</p> <ul> <li> <span class="Bold">Do not</span> warm the Prefilled Pen using heat sources such as hot water or a microwave.</li> </ul> </td><td> <p class="First"> <span class="Bold"><img alt="Figure D" src="/dailymed/image.cfm?name=zymfentra-4.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span> </p> <p> <span class="Bold">Figure D</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">5. Choose an injection site (see Figure E).</span> </p> <p>5a. You may inject into:</p> <p>   - the front of your thighs.</p> <p>   - the stomach area (abdomen) except for the 2 inches around the belly button (navel).</p> <p>   - the outer area of the upper arm if you are a caregiver.</p> <ul> <li> <span class="Bold">Do not</span> inject into skin that is within 2 inches of your belly button (navel), or is red, hard, tender, damaged, bruised, or scarred.</li> <li> <span class="Bold">Do not</span> inject through your clothes.</li> </ul> <p>5b. <span class="Bold">Rotate the injection site</span> each time you give an injection. </p> <ul> <li> <span class="Bold">Do not</span> inject the same injection site each time you give an injection.</li> <li>Each new injection site should be at least 1.2 inches away from the injection site you used before.</li> </ul> </td><td> <p class="First"> <img alt="Figure E" src="/dailymed/image.cfm?name=zymfentra-5.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></p> <p> <span class="Bold">Figure E</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">6. Wash your han</span> </p> <p> <span>6a. Wash your hands with soap and water and dry them thoroughly (see Figure F).</span> </p> </td><td> <p class="First"></p> <p> <span class="Bold"><span><img alt="Figure F" src="/dailymed/image.cfm?name=zymfentra-6.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span></span> </p> <p> <span class="Bold"><span><span>Figure F</span></span></span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">7. Clean the injection site.</span> </p> <p>7a. Clean the injection site with an alcohol swab using a circular motion (see Figure G).<br/> 7b. Let the skin dry before injecting.</p> <ul> <li> <span class="Bold">Do not</span> blow on or touch the injection site again before giving the injection.</li> </ul> </td><td> <p class="First"> <img alt="Figure G" src="/dailymed/image.cfm?name=zymfentra-7.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></p> <p> <span class="Bold">Figure G</span> </p> </td> </tr> <tr> <td colspan="2"> <p class="First"> <span class="Bold">Give the injection</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">8. Remove the Cap.</span> </p> <p>8a. Hold the Prefilled Pen by the injector body with the Cap on top using one hand. Gently pull the Cap straight off with the other hand.</p> <ul> <li> <span class="Bold">Do not</span> recap the Prefilled Pen.</li> <li> <span class="Bold">Do not</span> remove the Cap until you are ready to inject.</li> <li> <span class="Bold">Do not</span> touch the Needle or Needle Cover. Doing so may result in a needle stick injury.</li> </ul> <p>8b. Dispose of the Cap in an FDA cleared sharps container (see Step 12 and Figure H).</p> </td><td> <p class="First"> <img alt="Figure H" src="/dailymed/image.cfm?name=zymfentra-8.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></p> <p> <span class="Bold">Figure H</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">9. Place the Prefilled Pen on the injection site.</span> </p> <p>9a. Hold the Prefilled Pen so that you can see the Window.</p> <p>9b. Without pinching or stretching the skin, place the Prefilled Pen over the injection site at a 90-degree angle (see Figure I).</p> </td><td> <p class="First"></p> <p> <span class="Bold"><img alt="Figure I" src="/dailymed/image.cfm?name=zymfentra-9.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span> </p> <p> <span class="Bold"><span>Figure I</span></span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">10.</span><span class="Bold">Give the injection (see Figure J).</span> </p> <p>10a. Press the Prefilled Pen <span class="Bold">firmly </span>against the skin.</p> <ul> <li>When the injection starts you will hear the first loud "click" and the purple Plunger Rod will begin to fill the Window.</li> </ul> <p>10b. Keep holding the Prefilled Pen <span class="Bold">firmly </span>against the skin and listen for the second loud "click." This can take up to 10 seconds.</p> <ul> <li> <span class="Bold">Do not</span> change the position of the Prefilled Pen after the injection has started.</li> </ul> <p>10c. After you hear the second loud "click" continue to keep holding the Prefilled Pen <span class="Bold">firmly</span> against the skin and <span class="Bold">count slowly to 5</span> to make sure you inject the full dose.</p> <p>10d. Look at the Prefilled Pen and make sure that the purple Plunger Rod is filling the Window completely.</p> </td><td> <p class="First"></p> <p> <span class="Bold"><img alt="Figure J" src="/dailymed/image.cfm?name=zymfentra-10.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span> </p> <p> <span class="Bold"><span>Figure J</span></span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">11. Remove the Prefilled Pen from your skin.</span> </p> <p>11a. Remove the Prefilled Pen from your skin (see Figure K).</p> <ul> <li>After you remove the Prefilled Pen from the injection site, the needle will be automatically covered (see Figure L).</li> <li>If the Window has not turned completely purple or if the medicine is still injecting, this means you have not received a full dose. Call your healthcare provider immediately.</li> <li>You may see grey stopper in the Window. This is normal.</li> <li>Some bleeding may occur.</li> <li> <span class="Bold">Do not</span> reuse the Prefilled Pen.</li> <li> <span class="Bold">Do not</span> rub the injection site</li> </ul> </td><td> <p class="First"> <span class="Bold"><img alt="Figure K" src="/dailymed/image.cfm?name=zymfentra-11.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span> </p> <p> <span class="Bold"><span>Figure K</span></span> </p> <p></p> <p> <span class="Bold"><img alt="Figure L" src="/dailymed/image.cfm?name=zymfentra-12.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span> </p> <p> <span class="Bold"><span>Figure L</span></span> </p> <p></p> </td> </tr> <tr> <td colspan="2"> <p class="First"> <span class="Bold">After the injection</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">12. Throw away (dispose of) the Prefilled Pen.</span> </p> <p>12a. Put the used Prefilled Pen in an FDA-cleared sharps disposal container right away after use (see Figure M).</p> <ul> <li> <span class="Bold">Do not</span> throw away (dispose of) the Prefilled Pen in your household trash.<ul> <li>If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:<br/> - made of a heavy-duty plastic,<br/> - can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,<br/> - upright and stable during use,<br/> - leak-resistant, and<br/> - properly labeled to warn of hazardous waste inside the container.</li> <li>When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of it. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.</li> <li> <span class="Bold">Do not</span> dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. <span class="Bold">Do not</span> recycle your used sharps disposal container.</li> </ul> </li> </ul> </td><td> <p class="First"> <img alt="Figure M" src="/dailymed/image.cfm?name=zymfentra-13.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></p> <p> <span class="Bold">Figure M</span> </p> </td> </tr> <tr> <td colspan="2"> <p class="First"> <span class="Bold">13. Care for the injection site.</span> </p> <p>13a. Treat the injection site by gently pressing, not rubbing, a cotton ball or gauze to the site and apply an adhesive bandage, if necessary.</p> </td> </tr> <tr class="Last"> <td colspan="2"> <p class="First">Manufactured by: CELLTRION, Inc., 23, Academy-ro, Yeonsu-gu, Incheon, 22014, Republic of Korea<br/> US License Number 1996</p> <p>Distributed by: CELLTRION USA, Inc., 1 Evertrust Plaza Suite 1207, Jersey City, NJ 07302</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"99%\">\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<p class=\"First\">\n<span class=\"Bold\">2. Inspect the Prefilled Pen.</span>\n</p>\n<p>2a. Make sure you have the correct medicine (ZYMFENTRA).</p>\n<p>2b. Check the expiration (EXP) date on the label of the Prefilled Pen (See Figure B).</p>\n<p>2c. Look at the Prefilled Pen and make sure it is not cracked or damaged.</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not </span>use the Prefilled Pen if:<br/> - it is cracked or damaged.<br/> - the expiration (EXP) date has passed.</li>\n</ul>\n</td><td>\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\"><img alt=\"Figure B\" src=\"/dailymed/image.cfm?name=zymfentra-2.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/>Figure B</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">3. Inspect the Medicine.</span>\n</p>\n<p>3a. Look through the Window and make sure that the liquid is clear, colorless to pale brown, and free of particles (see Figure C).</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> use the Prefilled Pen if the liquid is the discolored (yellow or dark brown), cloudy, or contains particles in it.</li>\n<li>You may see air bubbles in the liquid. This is normal.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<img alt=\"Figure C\" src=\"/dailymed/image.cfm?name=zymfentra-3.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/><span class=\"Bold\">Figure C</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">4. Wait 30 minutes.</span>\n</p>\n<p>4a. Leave the Prefilled Pen at room temperature 68°F to 77°F (20°C to 25°C) for 30 minutes to allow it to warm up (see Figure D).</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> warm the Prefilled Pen using heat sources such as hot water or a microwave.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"Figure D\" src=\"/dailymed/image.cfm?name=zymfentra-4.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span>\n</p>\n<p>\n<span class=\"Bold\">Figure D</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">5. Choose an injection site (see Figure E).</span>\n</p>\n<p>5a. You may inject into:</p>\n<p>   - the front of your thighs.</p>\n<p>   - the stomach area (abdomen) except for the 2 inches around the belly button (navel).</p>\n<p>   - the outer area of the upper arm if you are a caregiver.</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> inject into skin that is within 2 inches of your belly button (navel), or is red, hard, tender, damaged, bruised, or scarred.</li>\n<li>\n<span class=\"Bold\">Do not</span> inject through your clothes.</li>\n</ul>\n<p>5b. <span class=\"Bold\">Rotate the injection site</span> each time you give an injection. </p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> inject the same injection site each time you give an injection.</li>\n<li>Each new injection site should be at least 1.2 inches away from the injection site you used before.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<img alt=\"Figure E\" src=\"/dailymed/image.cfm?name=zymfentra-5.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></p>\n<p>\n<span class=\"Bold\">Figure E</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">6. Wash your han</span>\n</p>\n<p>\n<span>6a. Wash your hands with soap and water and dry them thoroughly (see Figure F).</span>\n</p>\n</td><td>\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\"><span><img alt=\"Figure F\" src=\"/dailymed/image.cfm?name=zymfentra-6.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span></span>\n</p>\n<p>\n<span class=\"Bold\"><span><span>Figure F</span></span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">7. Clean the injection site.</span>\n</p>\n<p>7a. Clean the injection site with an alcohol swab using a circular motion (see Figure G).<br/> 7b. Let the skin dry before injecting.</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> blow on or touch the injection site again before giving the injection.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<img alt=\"Figure G\" src=\"/dailymed/image.cfm?name=zymfentra-7.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></p>\n<p>\n<span class=\"Bold\">Figure G</span>\n</p>\n</td>\n</tr>\n<tr>\n<td colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Give the injection</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">8. Remove the Cap.</span>\n</p>\n<p>8a. Hold the Prefilled Pen by the injector body with the Cap on top using one hand. Gently pull the Cap straight off with the other hand.</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> recap the Prefilled Pen.</li>\n<li>\n<span class=\"Bold\">Do not</span> remove the Cap until you are ready to inject.</li>\n<li>\n<span class=\"Bold\">Do not</span> touch the Needle or Needle Cover. Doing so may result in a needle stick injury.</li>\n</ul>\n<p>8b. Dispose of the Cap in an FDA cleared sharps container (see Step 12 and Figure H).</p>\n</td><td>\n<p class=\"First\">\n<img alt=\"Figure H\" src=\"/dailymed/image.cfm?name=zymfentra-8.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></p>\n<p>\n<span class=\"Bold\">Figure H</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">9. Place the Prefilled Pen on the injection site.</span>\n</p>\n<p>9a. Hold the Prefilled Pen so that you can see the Window.</p>\n<p>9b. Without pinching or stretching the skin, place the Prefilled Pen over the injection site at a 90-degree angle (see Figure I).</p>\n</td><td>\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\"><img alt=\"Figure I\" src=\"/dailymed/image.cfm?name=zymfentra-9.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span>\n</p>\n<p>\n<span class=\"Bold\"><span>Figure I</span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">10.</span><span class=\"Bold\">Give the injection (see Figure J).</span>\n</p>\n<p>10a. Press the Prefilled Pen <span class=\"Bold\">firmly </span>against the skin.</p>\n<ul>\n<li>When the injection starts you will hear the first loud \"click\" and the purple Plunger Rod will begin to fill the Window.</li>\n</ul>\n<p>10b. Keep holding the Prefilled Pen <span class=\"Bold\">firmly </span>against the skin and listen for the second loud \"click.\" This can take up to 10 seconds.</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> change the position of the Prefilled Pen after the injection has started.</li>\n</ul>\n<p>10c. After you hear the second loud \"click\" continue to keep holding the Prefilled Pen <span class=\"Bold\">firmly</span> against the skin and <span class=\"Bold\">count slowly to 5</span> to make sure you inject the full dose.</p>\n<p>10d. Look at the Prefilled Pen and make sure that the purple Plunger Rod is filling the Window completely.</p>\n</td><td>\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\"><img alt=\"Figure J\" src=\"/dailymed/image.cfm?name=zymfentra-10.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span>\n</p>\n<p>\n<span class=\"Bold\"><span>Figure J</span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">11. Remove the Prefilled Pen from your skin.</span>\n</p>\n<p>11a. Remove the Prefilled Pen from your skin (see Figure K).</p>\n<ul>\n<li>After you remove the Prefilled Pen from the injection site, the needle will be automatically covered (see Figure L).</li>\n<li>If the Window has not turned completely purple or if the medicine is still injecting, this means you have not received a full dose. Call your healthcare provider immediately.</li>\n<li>You may see grey stopper in the Window. This is normal.</li>\n<li>Some bleeding may occur.</li>\n<li>\n<span class=\"Bold\">Do not</span> reuse the Prefilled Pen.</li>\n<li>\n<span class=\"Bold\">Do not</span> rub the injection site</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"Figure K\" src=\"/dailymed/image.cfm?name=zymfentra-11.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span>\n</p>\n<p>\n<span class=\"Bold\"><span>Figure K</span></span>\n</p>\n<p></p>\n<p>\n<span class=\"Bold\"><img alt=\"Figure L\" src=\"/dailymed/image.cfm?name=zymfentra-12.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span>\n</p>\n<p>\n<span class=\"Bold\"><span>Figure L</span></span>\n</p>\n<p></p>\n</td>\n</tr>\n<tr>\n<td colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">After the injection</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">12. Throw away (dispose of) the Prefilled Pen.</span>\n</p>\n<p>12a. Put the used Prefilled Pen in an FDA-cleared sharps disposal container right away after use (see Figure M).</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> throw away (dispose of) the Prefilled Pen in your household trash.<ul>\n<li>If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:<br/> - made of a heavy-duty plastic,<br/> - can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,<br/> - upright and stable during use,<br/> - leak-resistant, and<br/> - properly labeled to warn of hazardous waste inside the container.</li>\n<li>When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of it. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.</li>\n<li>\n<span class=\"Bold\">Do not</span> dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. <span class=\"Bold\">Do not</span> recycle your used sharps disposal container.</li>\n</ul>\n</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<img alt=\"Figure M\" src=\"/dailymed/image.cfm?name=zymfentra-13.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></p>\n<p>\n<span class=\"Bold\">Figure M</span>\n</p>\n</td>\n</tr>\n<tr>\n<td colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">13. Care for the injection site.</span>\n</p>\n<p>13a. Treat the injection site by gently pressing, not rubbing, a cotton ball or gauze to the site and apply an adhesive bandage, if necessary.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td colspan=\"2\">\n<p class=\"First\">Manufactured by: CELLTRION, Inc., 23, Academy-ro, Yeonsu-gu, Incheon, 22014, Republic of Korea<br/> US License Number 1996</p>\n<p>Distributed by: CELLTRION USA, Inc., 1 Evertrust Plaza Suite 1207, Jersey City, NJ 07302</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

For subcutaneous use only

{ "type": "p", "children": [], "text": "\nFor subcutaneous use only\n" }

Read and follow Instructions for Use that come with your ZYMFENTRA Prefilled Syringe before using it and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

{ "type": "p", "children": [], "text": "Read and follow Instructions for Use that come with your ZYMFENTRA Prefilled Syringe before using it and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment." }

Figure A: Parts of ZYMFENTRA Prefilled Syringe

{ "type": "p", "children": [], "text": "\nFigure A: Parts of ZYMFENTRA Prefilled Syringe\n" }

Caution! Do not remove the Cap until you are ready to inject.  When you remove the Cap, do not recap the Prefilled Syringe.

{ "type": "p", "children": [], "text": "\nCaution! Do not remove the Cap until you are ready to inject.  When you remove the Cap, do not recap the Prefilled Syringe.\n" }

Important Information

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

{ "type": "ul", "children": [ "Use the Prefilled Syringe only if your healthcare provider has trained you on the right way to prepare for and to give an injection.", "Ask your healthcare provider how often you will need to give an injection.", "Rotate the injection site each time you give an injection. Each new injection site should be at least 1.2 inches away from the previous injection site.", "\nDo not use Prefilled Syringe if it has been dropped or is visibly damaged.", "\nDo not reuse the Prefilled Syringe.", "\nDo not shake the Prefilled Syringe at any time.", "\nDo not share the Prefilled Syringe with anyone.", "\nDo not pull back on the plunger rod at any time.", "Only use each Prefilled Syringe for one injection." ], "text": "" }

How to store the Prefilled Syringe

{ "type": "p", "children": [], "text": "\nHow to store the Prefilled Syringe\n" }

{ "type": "ul", "children": [ "Store the Prefilled Syringe in a refrigerator between 36°F to 46°F (2°C to 8°C).", "Keep the Prefilled Syringe in the original carton to protect it from light.", "\nDo not use the Prefilled Syringe that has been left in direct sunlight.", "\nDo not freeze the Prefilled Syringe. If the Prefilled Pen has been frozen, do not use the Prefilled Syringe even if it is thawed.", "\nDo not warm the Prefilled Syringe using heat sources such as hot water or a microwave. Let the Prefilled Syringe naturally warm at room temperature between 68°F to 77°F (20°C to 25°C) for 30 minutes before giving an injection. ", "When the Prefilled Syringe has reached room temperature, do not put it back in the refrigerator. The Prefilled Syringe must be thrown away (discarded) if not used within the 14 days. ", "\nKeep the Prefilled Syringe and all medicines out of the reach of children.\n" ], "text": "" }

Prepare for the Injection

{ "type": "p", "children": [], "text": "\nPrepare for the Injection\n" }

1. Gather the supplies for the injection.

{ "type": "p", "children": [], "text": "\n1. Gather the supplies for the injection.\n" }

1a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area. 1b. Remove 1 Prefilled Syringe from the carton by holding the middle of the Prefilled Syringe Body.

{ "type": "p", "children": [], "text": "1a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area. 1b. Remove 1 Prefilled Syringe from the carton by holding the middle of the Prefilled Syringe Body." }

{ "type": "ul", "children": [ "\nDo not touch the plunger rod." ], "text": "" }

Note: Return the carton with any unused Prefilled Syringe to the refrigerator immediately after taking out one Prefilled Syringe.

{ "type": "p", "children": [], "text": "Note: Return the carton with any unused Prefilled Syringe to the refrigerator immediately after taking out one Prefilled Syringe." }

1c. Make sure you have the following supplies:

{ "type": "p", "children": [], "text": "1c. Make sure you have the following supplies:" }

- Prefilled Syringe - Alcohol swab Not included in the carton: - Cotton ball or gauze - Adhesive bandage - FDA-cleared sharps disposal container

{ "type": "p", "children": [], "text": "- Prefilled Syringe - Alcohol swab\nNot included in the carton:\n - Cotton ball or gauze - Adhesive bandage - FDA-cleared sharps disposal container" }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="99%"> <tbody class="Headless"> <tr class="First"> <td> <p class="First"> <span class="Bold">2. Inspect the Prefilled Syringe.</span> </p> <p>2a. Make sure you have the correct medicine (ZYMFENTRA).</p> <p>2b. Check the expiration (EXP) date on label of the Prefilled Syringe (See Figure B).</p> <p>2c. Look at the Prefilled Syringe and make sure it is not cracked or damaged.</p> <ul> <li> <span class="Bold">Do not </span>use the Prefilled Syringe if:<br/> - it is cracked or damaged.<br/> - the expiration (EXP) date has passed.</li> </ul> </td><td> <p class="First"> <span class="Bold"><img alt="Figure B" src="/dailymed/image.cfm?name=zymfentra-15.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span> </p> <p> <span class="Bold">Figure B</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">3. Inspect the Medicine.</span> </p> <p>3a. Look at the Prefilled Syringe Body and check the liquid is clear and colorless to pale brown (see Figure C).</p> <ul> <li> <span class="Bold">Do not</span> use the Prefilled Syringe if the liquid is wrong color, cloudy, or contains particles in it.</li> <li>You may see air bubbles in the liquid. This is normal.</li> </ul> </td><td> <p class="First"> <img alt="Figure C" src="/dailymed/image.cfm?name=zymfentra-16.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/><span class="Bold">Figure C</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">4. Wait 30 minutes.</span> </p> <p>4a. Leave the Prefilled Syringe at room temperature 68°F to 77°F (20°C to 25°C) for 30 minutes to allow it to warm up (see Figure D).</p> <ul> <li> <span class="Bold">Do not</span> warm the Prefilled Syringe using heat sources such as hot water or a microwave.</li> </ul> </td><td> <p class="First"> <img alt="Figure D" src="/dailymed/image.cfm?name=zymfentra-17.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></p> <p> <span class="Bold">Figure D</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">5. Choose an injection site (see Figure E).</span> </p> <p>5a. You may inject into:</p> <p>- the front of your thighs.</p> <p>- the stomach area (abdomen) except for the 2 inches around the belly button (navel).</p> <p>- the outer area of the upper arm (<span class="Bold">caregiver only</span>).</p> <ul> <li> <span class="Bold">Do not</span> inject into skin that is within 2 inches of your belly button (navel), or is red, hard, tender, damaged, bruised, or scarred.</li> <li> <span class="Bold">Do not</span> inject through your clothes.</li> </ul> <p>5b. <span class="Bold">Rotate the injection site</span> each time you give an injection.</p> <ul> <li> <span class="Bold">Do not</span> inject the same injection site each time you give an injection.</li> <li>Each new injection site should be at least 1.2 inches away from the previous injection site.</li> </ul> </td><td> <p class="First"> <span class="Bold"><img alt="Figure E" src="/dailymed/image.cfm?name=zymfentra-18.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span> </p> <p> <span class="Bold"><span>Figure E</span></span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">6. Wash your hands.</span> </p> <p>6a. Wash your hands with soap and water and dry them thoroughly (see Figure F).</p> </td><td> <p class="First"> <span class="Bold"><img alt="Figure F" src="/dailymed/image.cfm?name=zymfentra-19.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span> </p> <p> <span class="Bold"><span>Figure F</span></span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">7. Clean the injection site.</span> </p> <p>7a. Clean the injection site with an alcohol swab using a circular motion (see Figure G).<br/> 7b. Let the skin dry before injecting.</p> <ul> <li> <span class="Bold">Do not</span> blow on or touch the injection site again before giving the injection.</li> </ul> </td><td> <p class="First"> <span class="Bold"><img alt="Figure G" src="/dailymed/image.cfm?name=zymfentra-20.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span> </p> <p> <span class="Bold"><span>Figure G</span></span> </p> </td> </tr> <tr> <td colspan="2"> <p class="First"> <span class="Bold">Give the injection</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">8. Remove the Cap.</span> </p> <p>8a. Hold the Prefilled Syringe by the injector body with the Cap on top using one hand. Gently pull the Cap straight off with the other hand.</p> <ul> <li> <span class="Bold">Do not</span> pull back on plunger rod at any time.</li> <li> <span class="Bold">Do not</span> remove the Cap until you are ready to inject.</li> <li> <span class="Bold">Do not </span>try to put the Cap back onto the Prefilled Syringe.</li> <li> <span class="Bold">Do not</span> touch the Needle.</li> </ul> <p>8b. Throw away (dispose of) the Cap in an FDA cleared sharps container (see Step 12 and Figure H).</p> </td><td> <p class="First"> <img alt="Figure H" src="/dailymed/image.cfm?name=zymfentra-21.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></p> <p> <span class="Bold">Figure H</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">9. Insert the Prefilled Syringe into the injection site.</span> </p> <p>9a. Hold the Prefilled Syringe by its body in one hand between your thumb and index finger.</p> <p>9b. Gently pinch a fold of skin at the injection site with one hand.</p> <p>9c. With a quick and “dart-like” motion, insert the Needle completely into the fold of the skin at a 45-defree angle (see Figure I).</p> <ul> <li> <span class="Bold">Do not </span>change the position of the Prefilled Syringe after the injection has started.</li> </ul> </td><td> <p class="First"> <span class="Bold"><img alt="Figure I" src="/dailymed/image.cfm?name=zymfentra-22.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span> </p> <p> <span class="Bold"><span>Figure I</span></span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">10.</span><span class="Bold">Give the injection.</span> </p> <p>10a. After the Needle is inserted, release the pinched skin.</p> <p>10b. Push the Plunger down slowly and as far as it will go until the Prefilled Syringe is empty (See Figure J).</p> </td><td> <p class="First"> <span class="Bold"><img alt="Figure J" src="/dailymed/image.cfm?name=zymfentra-23.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span> </p> <p> <span class="Bold"><span>Figure J</span></span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">11. Remove the Prefilled Syringe from the injection site.</span> </p> <p>11a. Remove the Needle from your skin at the same angle it was inserted (see Figure K).</p> <ul> <li> <span class="Bold">Do not</span> reuse the Prefilled Syringe.</li> <li> <span class="Bold">Do not </span>try to put the needle cover back on the Prefilled Syringe.</li> <li> <span class="Bold">Do not </span>touch the Needle.</li> <li>Some bleeding may occur.</li> <li> <span class="Bold">Do not</span> rub the injection site.</li> </ul> </td><td> <p class="First"> <span class="Bold"><img alt="Figure K" src="/dailymed/image.cfm?name=zymfentra-24.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span> </p> <p> <span class="Bold"><span>Figure K</span></span> </p> </td> </tr> <tr> <td colspan="2"> <p class="First"> <span class="Bold">After the injection</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">12. Throw away (dispose of) the Prefilled Syringe.</span> </p> <p>12a. Put the used Prefilled Syringe in an FDA-cleared sharps disposal container right away after use (see Figure L).</p> <ul> <li> <span class="Bold">Do not </span>try to put the Cap back onto the Prefilled Syringe.</li> <li> <span class="Bold">Do not</span> throw away (dispose of) the Prefilled Syringe in your household trash.</li> <li>If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:<br/> - made of a heavy-duty plastic,<br/> - able to close with a tight-fitting, puncture-resistant lid, without sharps being able to come out,<br/> - upright and stable during use,<br/> - leak-resistant, and<br/> - properly labeled to warn of hazardous waste inside the container.</li> <li>When your sharps disposal container is almost full, you will need to follow your community guidelines for right way to disposal of it. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: <a href="http://www.fda.gov/safesharpsdisposal">http://www.fda.gov/safesharpsdisposal</a>.</li> <li> <span class="Bold">Do not</span> dispose of your sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.</li> </ul> </td><td> <p class="First"> <span class="Bold"><img alt="Figure L" src="/dailymed/image.cfm?name=zymfentra-25.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span> </p> <p> <span class="Bold"><span>Figure L</span></span> </p> </td> </tr> <tr> <td colspan="2"> <p class="First"> <span class="Bold">13. Care for the injection site.</span> </p> <p>13a. Treat the injection site by gently pressing a cotton ball or gauze to the site and apply an adhesive bandage, if necessary.</p> </td> </tr> <tr class="Last"> <td colspan="2"> <p class="First">Manufactured by: CELLTRION, Inc., 23, Academy-ro, Yeonsu-gu, Incheon, 22014, Republic of Korea<br/> US License Number 1996</p> <p>Distributed by: CELLTRION USA, Inc., 1 Evertrust Plaza Suite 1207, Jersey City, NJ 07302</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"99%\">\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<p class=\"First\">\n<span class=\"Bold\">2. Inspect the Prefilled Syringe.</span>\n</p>\n<p>2a. Make sure you have the correct medicine (ZYMFENTRA).</p>\n<p>2b. Check the expiration (EXP) date on label of the Prefilled Syringe (See Figure B).</p>\n<p>2c. Look at the Prefilled Syringe and make sure it is not cracked or damaged.</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not </span>use the Prefilled Syringe if:<br/> - it is cracked or damaged.<br/> - the expiration (EXP) date has passed.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"Figure B\" src=\"/dailymed/image.cfm?name=zymfentra-15.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span>\n</p>\n<p>\n<span class=\"Bold\">Figure B</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">3. Inspect the Medicine.</span>\n</p>\n<p>3a. Look at the Prefilled Syringe Body and check the liquid is clear and colorless to pale brown (see Figure C).</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> use the Prefilled Syringe if the liquid is wrong color, cloudy, or contains particles in it.</li>\n<li>You may see air bubbles in the liquid. This is normal.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<img alt=\"Figure C\" src=\"/dailymed/image.cfm?name=zymfentra-16.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/><span class=\"Bold\">Figure C</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">4. Wait 30 minutes.</span>\n</p>\n<p>4a. Leave the Prefilled Syringe at room temperature 68°F to 77°F (20°C to 25°C) for 30 minutes to allow it to warm up (see Figure D).</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> warm the Prefilled Syringe using heat sources such as hot water or a microwave.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<img alt=\"Figure D\" src=\"/dailymed/image.cfm?name=zymfentra-17.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></p>\n<p>\n<span class=\"Bold\">Figure D</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">5. Choose an injection site (see Figure E).</span>\n</p>\n<p>5a. You may inject into:</p>\n<p>- the front of your thighs.</p>\n<p>- the stomach area (abdomen) except for the 2 inches around the belly button (navel).</p>\n<p>- the outer area of the upper arm (<span class=\"Bold\">caregiver only</span>).</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> inject into skin that is within 2 inches of your belly button (navel), or is red, hard, tender, damaged, bruised, or scarred.</li>\n<li>\n<span class=\"Bold\">Do not</span> inject through your clothes.</li>\n</ul>\n<p>5b. <span class=\"Bold\">Rotate the injection site</span> each time you give an injection.</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> inject the same injection site each time you give an injection.</li>\n<li>Each new injection site should be at least 1.2 inches away from the previous injection site.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"Figure E\" src=\"/dailymed/image.cfm?name=zymfentra-18.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span>\n</p>\n<p>\n<span class=\"Bold\"><span>Figure E</span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">6. Wash your hands.</span>\n</p>\n<p>6a. Wash your hands with soap and water and dry them thoroughly (see Figure F).</p>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"Figure F\" src=\"/dailymed/image.cfm?name=zymfentra-19.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span>\n</p>\n<p>\n<span class=\"Bold\"><span>Figure F</span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">7. Clean the injection site.</span>\n</p>\n<p>7a. Clean the injection site with an alcohol swab using a circular motion (see Figure G).<br/> 7b. Let the skin dry before injecting.</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> blow on or touch the injection site again before giving the injection.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"Figure G\" src=\"/dailymed/image.cfm?name=zymfentra-20.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span>\n</p>\n<p>\n<span class=\"Bold\"><span>Figure G</span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Give the injection</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">8. Remove the Cap.</span>\n</p>\n<p>8a. Hold the Prefilled Syringe by the injector body with the Cap on top using one hand. Gently pull the Cap straight off with the other hand.</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> pull back on plunger rod at any time.</li>\n<li>\n<span class=\"Bold\">Do not</span> remove the Cap until you are ready to inject.</li>\n<li>\n<span class=\"Bold\">Do not </span>try to put the Cap back onto the Prefilled Syringe.</li>\n<li>\n<span class=\"Bold\">Do not</span> touch the Needle.</li>\n</ul>\n<p>8b. Throw away (dispose of) the Cap in an FDA cleared sharps container (see Step 12 and Figure H).</p>\n</td><td>\n<p class=\"First\">\n<img alt=\"Figure H\" src=\"/dailymed/image.cfm?name=zymfentra-21.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></p>\n<p>\n<span class=\"Bold\">Figure H</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">9. Insert the Prefilled Syringe into the injection site.</span>\n</p>\n<p>9a. Hold the Prefilled Syringe by its body in one hand between your thumb and index finger.</p>\n<p>9b. Gently pinch a fold of skin at the injection site with one hand.</p>\n<p>9c. With a quick and “dart-like” motion, insert the Needle completely into the fold of the skin at a 45-defree angle (see Figure I).</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not </span>change the position of the Prefilled Syringe after the injection has started.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"Figure I\" src=\"/dailymed/image.cfm?name=zymfentra-22.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span>\n</p>\n<p>\n<span class=\"Bold\"><span>Figure I</span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">10.</span><span class=\"Bold\">Give the injection.</span>\n</p>\n<p>10a. After the Needle is inserted, release the pinched skin.</p>\n<p>10b. Push the Plunger down slowly and as far as it will go until the Prefilled Syringe is empty (See Figure J).</p>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"Figure J\" src=\"/dailymed/image.cfm?name=zymfentra-23.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span>\n</p>\n<p>\n<span class=\"Bold\"><span>Figure J</span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">11. Remove the Prefilled Syringe from the injection site.</span>\n</p>\n<p>11a. Remove the Needle from your skin at the same angle it was inserted (see Figure K).</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> reuse the Prefilled Syringe.</li>\n<li>\n<span class=\"Bold\">Do not </span>try to put the needle cover back on the Prefilled Syringe.</li>\n<li>\n<span class=\"Bold\">Do not </span>touch the Needle.</li>\n<li>Some bleeding may occur.</li>\n<li>\n<span class=\"Bold\">Do not</span> rub the injection site.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"Figure K\" src=\"/dailymed/image.cfm?name=zymfentra-24.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span>\n</p>\n<p>\n<span class=\"Bold\"><span>Figure K</span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">After the injection</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">12. Throw away (dispose of) the Prefilled Syringe.</span>\n</p>\n<p>12a. Put the used Prefilled Syringe in an FDA-cleared sharps disposal container right away after use (see Figure L).</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not </span>try to put the Cap back onto the Prefilled Syringe.</li>\n<li>\n<span class=\"Bold\">Do not</span> throw away (dispose of) the Prefilled Syringe in your household trash.</li>\n<li>If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:<br/> - made of a heavy-duty plastic,<br/> - able to close with a tight-fitting, puncture-resistant lid, without sharps being able to come out,<br/> - upright and stable during use,<br/> - leak-resistant, and<br/> - properly labeled to warn of hazardous waste inside the container.</li>\n<li>When your sharps disposal container is almost full, you will need to follow your community guidelines for right way to disposal of it. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: <a href=\"http://www.fda.gov/safesharpsdisposal\">http://www.fda.gov/safesharpsdisposal</a>.</li>\n<li>\n<span class=\"Bold\">Do not</span> dispose of your sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"Figure L\" src=\"/dailymed/image.cfm?name=zymfentra-25.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span>\n</p>\n<p>\n<span class=\"Bold\"><span>Figure L</span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">13. Care for the injection site.</span>\n</p>\n<p>13a. Treat the injection site by gently pressing a cotton ball or gauze to the site and apply an adhesive bandage, if necessary.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td colspan=\"2\">\n<p class=\"First\">Manufactured by: CELLTRION, Inc., 23, Academy-ro, Yeonsu-gu, Incheon, 22014, Republic of Korea<br/> US License Number 1996</p>\n<p>Distributed by: CELLTRION USA, Inc., 1 Evertrust Plaza Suite 1207, Jersey City, NJ 07302</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Read and follow the Instructions for Use that come with your ZYMFENTRA Prefilled Syringe before you start using it and each time you get a refill. There may be new information. This information dose not take the place of talking to your healthcare provider about your medical condition or treatment.

{ "type": "p", "children": [], "text": "Read and follow the Instructions for Use that come with your ZYMFENTRA Prefilled Syringe before you start using it and each time you get a refill. There may be new information. This information dose not take the place of talking to your healthcare provider about your medical condition or treatment." }

Figure A: Parts of Prefilled Syringe

{ "type": "p", "children": [], "text": "\nFigure A: Parts of Prefilled Syringe\n" }

Caution! Do not remove the Cap until you are ready to inject. Once you remove the Cap, do not recap the Syringe.

{ "type": "p", "children": [], "text": "\nCaution! Do not remove the Cap until you are ready to inject. Once you remove the Cap, do not recap the Syringe.\n" }

Important Information

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

{ "type": "ul", "children": [ "Use the Prefilled Syringe only if your healthcare provider has trained you on the right way to prepare for and to give an injection.", "Ask your healthcare provider how often you will need to give an injection.", "Rotate the injection site each time you give an injection. Each new injection site should be at least 1.2 inches away from the previous injection site.", "\nDo not use Prefilled Syringe if it has been dropped or is visibly damaged.", "\nDo not reuse the Prefilled Syringe.", "\nDo not shake the Prefilled Syringe at any time.", "\nDo not share the Prefilled Syringe with anyone.", "\nDo not pull back on the plunger rod at any time.", "Only use each Prefilled Syringe for one injection." ], "text": "" }

How to store the Prefilled Syringe

{ "type": "p", "children": [], "text": "\nHow to store the Prefilled Syringe\n" }

{ "type": "ul", "children": [ "Store the Prefilled Syringe in a refrigerator between 36°F to 46°F (2°C to 8°C).", "Keep the Prefilled Syringe in the original carton until use to protect it from light.", "\nDo not use the Prefilled Syringe that has been left in direct sunlight.", "\nDo not freeze the Prefilled Syringe. If the Prefilled Pen has been frozen, do not use the Prefilled Syringe even if it is thawed.", "\nDo not warm the Prefilled Syringe using heat sources such as hot water or a microwave. Let the Prefilled Syringe naturally warm at room temperature between 68°F to 77°F (20°C to 25°C) for 30 minutes before giving an injection.", "When the Prefilled Syringe has reached room temperature, do not put it back in the refrigerator. The Prefilled Syringe must be thrown away (discarded) if not used within the 14 days. ", "\nKeep the Prefilled Syringe and all medicines out of the reach of children.\n" ], "text": "" }

Prepare for the Injection

{ "type": "p", "children": [], "text": "\nPrepare for the Injection\n" }

1. Gather the supplies for the injection.

{ "type": "p", "children": [], "text": "\n1. Gather the supplies for the injection.\n" }

1a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area. 1b. Remove 1 Prefilled Syringe from the carton by holding the middle of the Prefilled Syringe Body.

{ "type": "p", "children": [], "text": "1a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area. 1b. Remove 1 Prefilled Syringe from the carton by holding the middle of the Prefilled Syringe Body." }

{ "type": "ul", "children": [ "\nDo not touch the plunger rod." ], "text": "" }

Note: Return the carton with any unused Prefilled Syringe to the refrigerator immediately after taking out one Prefilled Syringe.

{ "type": "p", "children": [], "text": "Note: Return the carton with any unused Prefilled Syringe to the refrigerator immediately after taking out one Prefilled Syringe." }

1c. Make sure you have the following supplies:

{ "type": "p", "children": [], "text": "1c. Make sure you have the following supplies:" }

- Prefilled Syringe - Alcohol swab Not included in the carton: - Cotton ball or gauze - Adhesive bandage - FDA-cleared sharps disposal container

{ "type": "p", "children": [], "text": "- Prefilled Syringe - Alcohol swab\nNot included in the carton:\n - Cotton ball or gauze - Adhesive bandage - FDA-cleared sharps disposal container" }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="99%"> <tbody class="Headless"> <tr class="First"> <td> <p class="First"> <span class="Bold">2. Inspect the Prefilled Syringe.</span> </p> <p>2a. Make sure you have the correct medicine (ZYMFENTRA).</p> <p>2b. Check the expiration (EXP) date on the label of the Prefilled Syringe (See Figure B).</p> <p>2c. Look at the Prefilled Syringe and make sure it is not cracked or damaged.</p> <ul> <li> <span class="Bold">Do not </span>use the Prefilled Syringe if:<br/> - it is cracked or damaged.<br/> - the expiration (EXP) date has passed.</li> </ul> </td><td> <p class="First"> <img alt="Figure B" src="/dailymed/image.cfm?name=zymfentra-27.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></p> <p> <span class="Bold">Figure B</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">3. Inspect the Medicine.</span> </p> <p>3a. Look through the Viewing Window and check that the liquid is clear and colorless to pale brown, and free of particles (see Figure C).</p> <ul> <li> <span class="Bold">Do not</span> use the Prefilled Syringe if the liquid is wrong color, cloudy, or contains particles in it.</li> <li>You may see air bubbles in the liquid. This is normal.</li> </ul> </td><td> <p class="First"> <img alt="Figure C" src="/dailymed/image.cfm?name=zymfentra-28.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></p> <p> <span class="Bold">Figure C</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">4. Wait 30 minutes.</span> </p> <p>4a. Leave the Prefilled Syringe at room temperature 68°F to 77°F (20°C to 25°C) for 30 minutes to allow it to warm up (see Figure D).</p> <ul> <li> <span class="Bold">Do not</span> warm the Prefilled Syringe using heat sources such as hot water or a microwave.</li> </ul> </td><td> <p class="First"></p> <p> <span class="Bold"><span><img alt="Figure D" src="/dailymed/image.cfm?name=zymfentra-29.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span></span> </p> <p> <span class="Bold"><span><span>Figure D</span></span></span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">5. Choose an injection site (see Figure E).</span> </p> <p>5a. You may inject into:</p> <p>- the front of your thighs.</p> <p>- the stomach area (abdomen) except for the 2 inches around the belly button (navel).</p> <p>- the outer area of the upper arm (<span class="Bold">caregiver only</span>).</p> <ul> <li> <span class="Bold">Do not</span> inject into skin that is within 2 inches of your belly button (navel), or is red, hard, tender, damaged, bruised, or scarred.</li> <li> <span class="Bold">Do not</span> inject through your clothes.</li> </ul> <p>5b. <span class="Bold">Rotate the injection site</span> each time you give an injection.</p> <ul> <li> <span class="Bold">Do not</span> injection the same injection site each time you five an injection.</li> <li>Each new injection site should be at least 1.2 inches away from the previous injection site.</li> </ul> </td><td> <p class="First"></p> <p> <span class="Bold"><span><img alt="Figure E" src="/dailymed/image.cfm?name=zymfentra-30.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span></span> </p> <p> <span class="Bold"><span><span>Figure E</span></span></span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">6. Wash your hands.</span> </p> <p>6a. Wash your hands with soap and water and dry them thoroughly (see Figure F).</p> </td><td> <p class="First"></p> <p> <span class="Bold"><span><img alt="Figure F" src="/dailymed/image.cfm?name=zymfentra-31.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span></span> </p> <p> <span class="Bold"><span><span>Figure F</span></span></span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">7. Clean the injection site.</span> </p> <p>7a. Clean the injection site with an alcohol swab (see Figure G).<br/> 7b. Let the skin dry before injecting.</p> <ul> <li> <span class="Bold">Do not</span> blow on or touch the injection site again before giving the injection.</li> </ul> </td><td> <p class="First"></p> <p> <span class="Bold"><span><img alt="Figure G" src="/dailymed/image.cfm?name=zymfentra-32.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span></span> </p> <p> <span class="Bold"><span><span>Figure G</span></span></span> </p> </td> </tr> <tr> <td colspan="2"> <p class="First"> <span class="Bold">Give the injection</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">8. Remove the Cap.</span> </p> <p>8a. Hold the Prefilled Syringe by the injector body with the Cap on top using one hand. Gently pull the Cap straight off with the other hand.</p> <ul> <li> <span class="Bold">Do not</span> pull back on plunger rod at any time.</li> <li> <span class="Bold">Do not</span> remove the Cap until you are ready to inject.</li> <li> <span class="Bold">Do not </span>try to put the Cap back onto the Prefilled Syringe.</li> <li> <span class="Bold">Do not</span> touch the Needle.</li> </ul> <p>8b. Throw away (dispose of) the Cap in an FDA cleared sharps container (see Step 12 and Figure H).</p> </td><td> <p class="First"></p> <p> <span class="Bold"><span><img alt="Figure H" src="/dailymed/image.cfm?name=zymfentra-33.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span></span> </p> <p> <span class="Bold"><span><span>Figure H</span></span></span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">9. Insert the Prefilled Syringe into the injection site.</span> </p> <p>9a. Hold the Prefilled Syringe by its body in one hand between your thumb and index finger.</p> <p>9b. Gently pinch a fold of skin at the injection site with one hand.</p> <p>9c. Witha quick and “dart-like” motion, insert the Needle completely into the fold of the skin at a 45-defree angle (see Figure I).</p> <p>Ÿ   <span class="Bold">Do not </span>change the position of the Prefilled Syringe after the injection has started.</p> </td><td> <p class="First"></p> <p> <span class="Bold"><span><img alt="Figure I" src="/dailymed/image.cfm?name=zymfentra-34.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span></span> </p> <p> <span class="Bold"><span><span>Figure I</span></span></span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">10.</span><span class="Bold">Give the injection.</span> </p> <p>10a. After the Needle is inserted, release the pinched skin.</p> <p>10b. Push the Plunger down slowly and as far as it will go until the Prefilled Syringe is empty (See Figure J).</p> <p>Note: The Needle Guard will not activate unless all the Medicines is injected.</p> </td><td> <p class="First"></p> <p> <span class="Bold"><span><img alt="Figure J" src="/dailymed/image.cfm?name=zymfentra-35.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span></span> </p> <p> <span class="Bold"><span><span>Figure J</span></span></span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">11. Remove the Prefilled Syringe from the injection site.</span> </p> <p>11a. After the Prefilled Syringe is empty, slowly lift your thumb from the Plunger until Needle is completely covered by the Neeld Guard (see Figure K).</p> <ul> <li> <span class="Bold">Do not</span> reuse the Prefilled Syringe.</li> <li> <span class="Bold">Do not </span>touch the Needle.</li> <li>Some bleeding may occur.</li> <li> <span class="Bold">Do not</span> rub the injection site.</li> </ul> </td><td> <p class="First"> <span class="Bold"><img alt="Figure K" src="/dailymed/image.cfm?name=zymfentra-36.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span> </p> <p> <span class="Bold"><span>Figure K</span></span> </p> </td> </tr> <tr> <td colspan="2"> <p class="First"> <span class="Bold">After the injection</span> </p> </td> </tr> <tr> <td> <p class="First"> <span class="Bold">12. Throw away (dispose of) the Prefilled Syringe.</span> </p> <p>12a. Put the used Prefilled Syringe in an FDA-cleared sharps disposal container immediately after use (see Figure L).</p> <ul> <li> <span class="Bold">Do not </span>try to put the Cap back onto the Prefilled Syringe.</li> <li> <span class="Bold">Do not</span> throw away (dispose of) the Prefilled Syringe in your household trash.</li> <li>If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:</li> </ul> <p>- made of a heavy-duty plastic,<br/> - able to closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,<br/> - upright and stable during use,<br/> - leak-resistant, and<br/> - properly labeled to warn of hazardous waste inside the container.</p> <ul> <li>When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to disposal of it. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: <a href="http://www.fda.gov/safesharpsdisposal">http://www.fda.gov/safesharpsdisposal</a>.</li> <li>Do not dispose of your sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.</li> </ul> </td><td> <p class="First"></p> <p> <span class="Bold"><span><img alt="Figure L" src="/dailymed/image.cfm?name=zymfentra-37.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a"/></span></span> </p> <p> <span class="Bold"><span><span>Figure L</span></span></span> </p> </td> </tr> <tr> <td colspan="2"> <p class="First"> <span class="Bold">13. Care for the injection site.</span> </p> <p>13a. Treat the injection site by gently pressing a cotton ball or gauze to the site and apply an adhesive bandage, if necessary.</p> </td> </tr> <tr class="Last"> <td colspan="2"> <p class="First">Manufactured by: CELLTRION, Inc., 23, Academy-ro, Yeonsu-gu, Incheon, 22014, Republic of Korea<br/> US License Number 1996</p> <p>Distributed by: CELLTRION USA, Inc., 1 Evertrust Plaza Suite 1207, Jersey City, NJ 07302</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"99%\">\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<p class=\"First\">\n<span class=\"Bold\">2. Inspect the Prefilled Syringe.</span>\n</p>\n<p>2a. Make sure you have the correct medicine (ZYMFENTRA).</p>\n<p>2b. Check the expiration (EXP) date on the label of the Prefilled Syringe (See Figure B).</p>\n<p>2c. Look at the Prefilled Syringe and make sure it is not cracked or damaged.</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not </span>use the Prefilled Syringe if:<br/> - it is cracked or damaged.<br/> - the expiration (EXP) date has passed.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<img alt=\"Figure B\" src=\"/dailymed/image.cfm?name=zymfentra-27.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></p>\n<p>\n<span class=\"Bold\">Figure B</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">3. Inspect the Medicine.</span>\n</p>\n<p>3a. Look through the Viewing Window and check that the liquid is clear and colorless to pale brown, and free of particles (see Figure C).</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> use the Prefilled Syringe if the liquid is wrong color, cloudy, or contains particles in it.</li>\n<li>You may see air bubbles in the liquid. This is normal.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<img alt=\"Figure C\" src=\"/dailymed/image.cfm?name=zymfentra-28.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></p>\n<p>\n<span class=\"Bold\">Figure C</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">4. Wait 30 minutes.</span>\n</p>\n<p>4a. Leave the Prefilled Syringe at room temperature 68°F to 77°F (20°C to 25°C) for 30 minutes to allow it to warm up (see Figure D).</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> warm the Prefilled Syringe using heat sources such as hot water or a microwave.</li>\n</ul>\n</td><td>\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\"><span><img alt=\"Figure D\" src=\"/dailymed/image.cfm?name=zymfentra-29.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span></span>\n</p>\n<p>\n<span class=\"Bold\"><span><span>Figure D</span></span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">5. Choose an injection site (see Figure E).</span>\n</p>\n<p>5a. You may inject into:</p>\n<p>- the front of your thighs.</p>\n<p>- the stomach area (abdomen) except for the 2 inches around the belly button (navel).</p>\n<p>- the outer area of the upper arm (<span class=\"Bold\">caregiver only</span>).</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> inject into skin that is within 2 inches of your belly button (navel), or is red, hard, tender, damaged, bruised, or scarred.</li>\n<li>\n<span class=\"Bold\">Do not</span> inject through your clothes.</li>\n</ul>\n<p>5b. <span class=\"Bold\">Rotate the injection site</span> each time you give an injection.</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> injection the same injection site each time you five an injection.</li>\n<li>Each new injection site should be at least 1.2 inches away from the previous injection site.</li>\n</ul>\n</td><td>\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\"><span><img alt=\"Figure E\" src=\"/dailymed/image.cfm?name=zymfentra-30.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span></span>\n</p>\n<p>\n<span class=\"Bold\"><span><span>Figure E</span></span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">6. Wash your hands.</span>\n</p>\n<p>6a. Wash your hands with soap and water and dry them thoroughly (see Figure F).</p>\n</td><td>\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\"><span><img alt=\"Figure F\" src=\"/dailymed/image.cfm?name=zymfentra-31.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span></span>\n</p>\n<p>\n<span class=\"Bold\"><span><span>Figure F</span></span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">7. Clean the injection site.</span>\n</p>\n<p>7a. Clean the injection site with an alcohol swab (see Figure G).<br/> 7b. Let the skin dry before injecting.</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> blow on or touch the injection site again before giving the injection.</li>\n</ul>\n</td><td>\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\"><span><img alt=\"Figure G\" src=\"/dailymed/image.cfm?name=zymfentra-32.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span></span>\n</p>\n<p>\n<span class=\"Bold\"><span><span>Figure G</span></span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Give the injection</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">8. Remove the Cap.</span>\n</p>\n<p>8a. Hold the Prefilled Syringe by the injector body with the Cap on top using one hand. Gently pull the Cap straight off with the other hand.</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> pull back on plunger rod at any time.</li>\n<li>\n<span class=\"Bold\">Do not</span> remove the Cap until you are ready to inject.</li>\n<li>\n<span class=\"Bold\">Do not </span>try to put the Cap back onto the Prefilled Syringe.</li>\n<li>\n<span class=\"Bold\">Do not</span> touch the Needle.</li>\n</ul>\n<p>8b. Throw away (dispose of) the Cap in an FDA cleared sharps container (see Step 12 and Figure H).</p>\n</td><td>\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\"><span><img alt=\"Figure H\" src=\"/dailymed/image.cfm?name=zymfentra-33.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span></span>\n</p>\n<p>\n<span class=\"Bold\"><span><span>Figure H</span></span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">9. Insert the Prefilled Syringe into the injection site.</span>\n</p>\n<p>9a. Hold the Prefilled Syringe by its body in one hand between your thumb and index finger.</p>\n<p>9b. Gently pinch a fold of skin at the injection site with one hand.</p>\n<p>9c. Witha quick and “dart-like” motion, insert the Needle completely into the fold of the skin at a 45-defree angle (see Figure I).</p>\n<p>Ÿ   <span class=\"Bold\">Do not </span>change the position of the Prefilled Syringe after the injection has started.</p>\n</td><td>\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\"><span><img alt=\"Figure I\" src=\"/dailymed/image.cfm?name=zymfentra-34.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span></span>\n</p>\n<p>\n<span class=\"Bold\"><span><span>Figure I</span></span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">10.</span><span class=\"Bold\">Give the injection.</span>\n</p>\n<p>10a. After the Needle is inserted, release the pinched skin.</p>\n<p>10b. Push the Plunger down slowly and as far as it will go until the Prefilled Syringe is empty (See Figure J).</p>\n<p>Note: The Needle Guard will not activate unless all the Medicines is injected.</p>\n</td><td>\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\"><span><img alt=\"Figure J\" src=\"/dailymed/image.cfm?name=zymfentra-35.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span></span>\n</p>\n<p>\n<span class=\"Bold\"><span><span>Figure J</span></span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">11. Remove the Prefilled Syringe from the injection site.</span>\n</p>\n<p>11a. After the Prefilled Syringe is empty, slowly lift your thumb from the Plunger until Needle is completely covered by the Neeld Guard (see Figure K).</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not</span> reuse the Prefilled Syringe.</li>\n<li>\n<span class=\"Bold\">Do not </span>touch the Needle.</li>\n<li>Some bleeding may occur.</li>\n<li>\n<span class=\"Bold\">Do not</span> rub the injection site.</li>\n</ul>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\"><img alt=\"Figure K\" src=\"/dailymed/image.cfm?name=zymfentra-36.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span>\n</p>\n<p>\n<span class=\"Bold\"><span>Figure K</span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">After the injection</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">\n<span class=\"Bold\">12. Throw away (dispose of) the Prefilled Syringe.</span>\n</p>\n<p>12a. Put the used Prefilled Syringe in an FDA-cleared sharps disposal container immediately after use (see Figure L).</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not </span>try to put the Cap back onto the Prefilled Syringe.</li>\n<li>\n<span class=\"Bold\">Do not</span> throw away (dispose of) the Prefilled Syringe in your household trash.</li>\n<li>If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:</li>\n</ul>\n<p>- made of a heavy-duty plastic,<br/> - able to closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,<br/> - upright and stable during use,<br/> - leak-resistant, and<br/> - properly labeled to warn of hazardous waste inside the container.</p>\n<ul>\n<li>When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to disposal of it. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: <a href=\"http://www.fda.gov/safesharpsdisposal\">http://www.fda.gov/safesharpsdisposal</a>.</li>\n<li>Do not dispose of your sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.</li>\n</ul>\n</td><td>\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\"><span><img alt=\"Figure L\" src=\"/dailymed/image.cfm?name=zymfentra-37.jpg&amp;setid=93a193ab-9f96-4da6-aa7c-31212e81879a\"/></span></span>\n</p>\n<p>\n<span class=\"Bold\"><span><span>Figure L</span></span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">13. Care for the injection site.</span>\n</p>\n<p>13a. Treat the injection site by gently pressing a cotton ball or gauze to the site and apply an adhesive bandage, if necessary.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td colspan=\"2\">\n<p class=\"First\">Manufactured by: CELLTRION, Inc., 23, Academy-ro, Yeonsu-gu, Incheon, 22014, Republic of Korea<br/> US License Number 1996</p>\n<p>Distributed by: CELLTRION USA, Inc., 1 Evertrust Plaza Suite 1207, Jersey City, NJ 07302</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

NDC 72606-025-01Rx only

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ZymfentraTM infliximab–dyybinjection Subcutaneous use

{ "type": "p", "children": [], "text": "ZymfentraTM\ninfliximab–dyybinjection\nSubcutaneous use\n" }

CELLTRION Inc.

{ "type": "p", "children": [], "text": "\nCELLTRION Inc.\n" }

ZymfentraTM

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infliximab-dyybInjection120 mg/mL

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FOR SUBCUTANEOUS USE ONLY

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ATTENTION: Disponse the enclosed Medication Guide to each patient. 

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NDC 72606-025-01

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Rx ony 

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1 prefilled pen + 2 alcohol preps

{ "type": "p", "children": [], "text": "\n1 prefilled pen + 2 alcohol preps\n" }

1 Single-Dose Prefilled Pen

{ "type": "p", "children": [], "text": "\n1 Single-Dose Prefilled Pen\n" }

CELLTRION USA, Inc.

{ "type": "p", "children": [], "text": "\nCELLTRION USA, Inc.\n" }

NDC 72606-025-09Rx only

{ "type": "p", "children": [], "text": "NDC 72606-025-09Rx only" }

ZymfentraTM infliximab–dyybinjectionSubcutaneous use

{ "type": "p", "children": [], "text": "ZymfentraTM\ninfliximab–dyybinjectionSubcutaneous use" }

CELLTRION, Inc.

{ "type": "p", "children": [], "text": "CELLTRION, Inc.\n" }

ZymfentraTM

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

infliximab-dyybinjection120 mg/mL 

{ "type": "p", "children": [], "text": "infliximab-dyybinjection120 mg/mL " }

FOR SUBCUTANEOUS USE ONLY

{ "type": "p", "children": [], "text": "FOR SUBCUTANEOUS USE ONLY" }

ATTENTION: Dispense the enclosed Medication Guide to each patient. 

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

NDC 72606-025-09

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1 prefilled syringe with needle guard+ 2 alcohol preps

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1 Single-Dose Prefilled Syringe with Needle Guard

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CELLTRION USA, Inc.

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

NDC 72606-025-05Rx only

{ "type": "p", "children": [], "text": "NDC 72606-025-05Rx only" }

ZymfentraTM infliximab–dyybinjectionSubcutaneous use

{ "type": "p", "children": [], "text": "ZymfentraTM\ninfliximab–dyybinjectionSubcutaneous use" }

CELLTRION, Inc. 

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

ZymfentraTM

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

infliximab-dyybinjection120 mg/mL

{ "type": "p", "children": [], "text": "\ninfliximab-dyybinjection120 mg/mL\n" }

FOR SUBCUTANEOUS USE ONLY

{ "type": "p", "children": [], "text": "FOR SUBCUTANEOUS USE ONLY" }

ATTENTION: Dispense the enclosed Medication Guide to each patient. 

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

NDC x72606-025-05

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Rx

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1 prefilled syringe + 2 alcohol preps

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1 Single-Dose Prefilled Syringe CELLTRION USA, Inc.

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REMICADE is indicated for:

REMICADE is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active CD who have had an inadequate response to conventional therapy.

REMICADE is indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response to conventional therapy.

REMICADE is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active UC who have had an inadequate response to conventional therapy.

REMICADE, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis (RA).

REMICADE is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis (AS).

REMICADE is indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in adult patients with psoriatic arthritis (PsA).

REMICADE is indicated for the treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis (Ps) who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. REMICADE should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician [seeBoxed Warning andWarnings and Precautions (5)] .

The recommended dosage of REMICADE is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adults with moderately to severely active CD or fistulizing CD. For adult patients who respond and then lose their response, consideration may be given to treatment with 10 mg/kg every 8 weeks. Patients who do not respond by Week 14 are unlikely to respond with continued dosing and consideration should be given to discontinue REMICADE in these patients.

The recommended dosage of REMICADE for pediatric patients 6 years and older with moderately to severely active CD is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks.

The recommended dosage of REMICADE is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adult patients with moderately to severely active UC.

The recommended dosage of REMICADE for pediatric patients 6 years and older with moderately to severely active UC is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks.

The recommended dosage of REMICADE is 3 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 3 mg/kg every 8 weeks thereafter for the treatment of moderately to severely active RA. REMICADE should be given in combination with methotrexate. For patients who have an incomplete response, consideration may be given to adjusting the dosage up to 10 mg/kg every 8 weeks or treating as often as every 4 weeks bearing in mind that risk of serious infections is increased at higher doses per infusion or more frequent dosing [seeAdverse Reactions (6.1)].

The recommended dosage of REMICADE is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 6 weeks thereafter for the treatment of active AS.

The recommended dosage of REMICADE is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of PsA. REMICADE can be used with or without methotrexate.

The recommended dosage of REMICADE in adult patients is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of chronic severe (i.e., extensive and/or disabling) Ps.

Prior to initiating REMICADE and periodically during therapy, patients should be evaluated for active tuberculosis and tested for latent infection [seeWarnings and Precautions (5.1)] .

Prior to treatment, ensure appropriate personnel and medication are available to treat reactions (e.g., hypersensitivity, other reactions) that occur during infusion and shortly after infusion. Prior to infusion with REMICADE, patients may be premedicated with histamine-1 receptor antagonists, histamine-2 receptor antagonists, acetaminophen, and/or corticosteroids [see Warnings and Precautions (5.7)] .

For mild to moderate reactions during the infusion, consider slowing or stopping the infusion. Upon resolution of these reactions, may reinitiate at a lower infusion rate and/or with histamine-1 receptor antagonists, histamine-2 receptor antagonists, acetaminophen, and/or corticosteroids. Discontinue the infusion if the mild to moderate reactions reoccur.

Discontinue the infusion if severe hypersensitivity reactions occur during the infusion.

REMICADE is intended for use under the guidance and supervision of a healthcare provider. The supplied lyophilized powder must be reconstituted and diluted prior to administration. The infusion solution should be prepared and administered by a trained medical professional using aseptic technique by the following procedure:

No physical biochemical compatibility studies have been conducted to evaluate the co-administration of REMICADE with other agents. REMICADE should not be infused concomitantly in the same intravenous line with other agents.

For injection: 100 mg of infliximab as a white lyophilized powder in a single-dose vial for reconstitution and dilution.

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The use of REMICADE at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure [see Warnings and Precautions (5.5)and Adverse Reactions (6.1)] .

{ "type": "p", "children": [], "text": "The use of REMICADE at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure\n \n [see\n \n Warnings and Precautions (5.5)and\n \n Adverse Reactions (6.1)]\n \n .\n\n " }

REMICADE is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab or any of the inactive ingredients of REMICADE or any murine proteins [severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness] [see Warnings and Precautions (5.7)and Adverse Reactions (6.1)].

{ "type": "p", "children": [], "text": "REMICADE is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab or any of the inactive ingredients of REMICADE or any murine proteins [severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness]\n \n [see\n \n Warnings and Precautions (5.7)and\n \n Adverse Reactions (6.1)].\n \n \n" }

Patients treated with REMICADE are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death.

Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, or parasitic organisms including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, salmonellosis and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease.

Treatment with REMICADE should not be initiated in patients with an active infection, including clinically important localized infections. Patients greater than 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants such as corticosteroids or methotrexate may be at greater risk of infection. The risks and benefits of treatment should be considered prior to initiating therapy in patients:

Tuberculosis

Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving REMICADE, including patients who have previously received treatment for latent or active tuberculosis. Cases of active tuberculosis have also occurred in patients being treated with REMICADE during treatment for latent tuberculosis.

Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating REMICADE and periodically during therapy. Treatment of latent tuberculosis infection prior to therapy with TNF blockers has been shown to reduce the risk of tuberculosis reactivation during therapy. Induration of 5 mm or greater with tuberculin skin testing should be considered a positive test result when assessing if treatment for latent tuberculosis is needed prior to initiating REMICADE, even for patients previously vaccinated with Bacille Calmette-Guérin (BCG).

Anti-tuberculosis therapy should also be considered prior to initiation of REMICADE in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient.

Tuberculosis should be strongly considered in patients who develop a new infection during REMICADE treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis.

Monitoring

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with REMICADE, including the development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. Tests for latent tuberculosis infection may also be falsely negative while on therapy with REMICADE.

REMICADE should be discontinued if a patient develops a serious infection or sepsis. A patient who develops a new infection during treatment with REMICADE should be closely monitored, undergo a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and appropriate antimicrobial therapy should be initiated.

Invasive Fungal Infections

For patients who reside or travel in regions where mycoses are endemic, invasive fungal infection should be suspected if they develop a serious systemic illness. Appropriate empiric antifungal therapy should be considered while a diagnostic workup is being performed. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. When feasible, the decision to administer empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections and should take into account both the risk for severe fungal infection and the risks of antifungal therapy.

Malignancies, some fatal, have been reported among children, adolescents and young adults who received treatment with TNF blockers (initiation of therapy ≤18 years of age), including REMICADE. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months (range 1 to 84 months) after the first dose of TNF blocker therapy. Most of the patients were receiving concomitant immunosuppressants. These cases were reported post-marketing and are derived from a variety of sources, including registries and spontaneous postmarketing reports.

Lymphomas

In the controlled portions of clinical trials of all the TNF blockers, more cases of lymphoma have been observed among patients receiving a TNF blocker compared with control patients. In the controlled and open-label portions of REMICADE clinical trials, 5 patients developed lymphomas among 5707 patients treated with REMICADE (median duration of follow-up 1.0 years) vs. 0 lymphomas in 1600 control patients (median duration of follow-up 0.4 years). In RA patients, 2 lymphomas were observed for a rate of 0.08 cases per 100 patient-years of follow-up, which is approximately three-fold higher than expected in the general population. In the combined clinical trial population for RA, CD, PsA, AS, UC, and Ps, 5 lymphomas were observed for a rate of 0.10 cases per 100 patient-years of follow-up, which is approximately four-fold higher than expected in the general population. Patients with CD, RA or Ps, particularly patients with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF blockers. Cases of acute and chronic leukemia have been reported with postmarketing TNF blocker use in RA and other diseases. Even in the absence of TNF blocker therapy, patients with RA may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia.

Hepatosplenic T-cell Lymphoma (HSTCL)

Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including REMICADE. These cases have had a very aggressive disease course and have been fatal. Almost all patients had received treatment with the immunosuppressants azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. The majority of reported REMICADE cases have occurred in patients with CD or UC and most were in adolescent and young adult males. It is uncertain whether the occurrence of HSTCL is related to TNF blockers or TNF blockers in combination with these other immunosuppressants. When treating patients, consideration of whether to use REMICADE alone or in combination with other immunosuppressants such as azathioprine or 6-mercaptopurine should take into account a possibility that there is a higher risk of HSTCL with combination therapy versus an observed increased risk of immunogenicity and hypersensitivity reactions with REMICADE monotherapy from the clinical trial data [see Warnings and Precautions (5.7)and Adverse Reactions (6.1)] .

Skin Cancer

Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy, including REMICADE [see Adverse Reactions (6.3)] . Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.

Cervical Cancer

A population-based retrospective cohort study using data from Swedish national health registries found a 2 to 3 fold increase in the incidence of invasive cervical cancer in women with RA treated with REMICADE compared to biologics-naïve patients or the general population, particularly those over 60 years of age. A causal relationship between REMICADE and cervical cancer cannot be excluded. Periodic screening should continue in women treated with REMICADE [see Adverse Reactions (6.3)] .

Other Malignancies

In the controlled portions of clinical trials of some TNF blockers including REMICADE, more malignancies (excluding lymphoma and nonmelanoma skin cancer [NMSC]) have been observed in patients receiving those TNF blockers compared with control patients. During the controlled portions of REMICADE trials in patients with moderately to severely active RA, CD, PsA, AS, UC, and Ps, 14 patients were diagnosed with malignancies (excluding lymphoma and NMSC) among 4019 REMICADE-treated patients vs. 1 among 1597 control patients (at a rate of 0.52/100 patient-years among REMICADE-treated patients vs. a rate of 0.11/100 patient-years among control patients), with median duration of follow-up 0.5 years for REMICADE-treated patients and 0.4 years for control patients. Of these, the most common malignancies were breast, colorectal, and melanoma. The rate of malignancies among REMICADE-treated patients was similar to that expected in the general population whereas the rate in control patients was lower than expected.

In a clinical trial exploring the use of REMICADE in patients with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, the majority of lung or head and neck origin, were reported in REMICADE-treated patients compared with control patients. All patients had a history of heavy smoking [see Adverse Reactions (6.1)] . Prescribers should exercise caution when considering the use of REMICADE in patients with moderate to severe COPD.

Ps patients should be monitored for nonmelanoma skin cancers (NMSCs), particularly those patients who have had prior prolonged phototherapy treatment. In the maintenance portion of clinical trials for REMICADE, NMSCs were more common in patients with previous phototherapy [see Adverse Reactions (6.1)] .

The potential role of TNF blockers in the development of malignancies is not known [see Adverse Reactions (6.1)]. Rates in clinical trials for REMICADE cannot be compared to rates in clinical trials of other TNF blockers and may not predict rates observed in a broader patient population. Caution should be exercised in considering REMICADE treatment in patients with a history of malignancy or in continuing treatment in patients who develop malignancy while receiving REMICADE.

Use of TNF blockers, including REMICADE, has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus. In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal. The majority of these reports have occurred in patients concomitantly receiving other medications that suppress the immune system, which may also contribute to HBV reactivation. Patients should be tested for HBV infection before initiating TNF blocker therapy, including REMICADE. For patients who test positive for hepatitis B surface antigen, consultation with a physician with expertise in the treatment of hepatitis B is recommended. Adequate data are not available on the safety or efficacy of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF blocker therapy to prevent HBV reactivation. Patients who are carriers of HBV and require treatment with TNF blockers should be closely monitored for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy. In patients who develop HBV reactivation, TNF blockers should be stopped and antiviral therapy with appropriate supportive treatment should be initiated. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known. Therefore, prescribers should exercise caution when considering resumption of TNF blocker therapy in this situation and monitor patients closely.

Severe hepatic reactions, including acute liver failure, jaundice, hepatitis and cholestasis, have been reported in postmarketing data in patients receiving REMICADE. Autoimmune hepatitis has been diagnosed in some of these cases. Severe hepatic reactions occurred between 2 weeks to more than 1 year after initiation of REMICADE; elevations in hepatic aminotransferase levels were not noted prior to discovery of the liver injury in many of these cases. Some of these cases were fatal or necessitated liver transplantation. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (e.g., ≥5 times the upper limit of normal) develop, REMICADE should be discontinued, and a thorough investigation of the abnormality should be undertaken. In clinical trials, mild or moderate elevations of ALT and AST have been observed in patients receiving REMICADE without progression to severe hepatic injury [see Adverse Reactions (6.1)] .

The use of REMICADE at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure. A randomized, double-blind, placebo-controlled study evaluated the use of REMICADE (5 mg/kg or 10 mg/kg at Weeks 0, 2, and 6) in patients with moderate or severe heart failure [New York Heart Association (NYHA) Functional Class III/IV]. Compared to patients who received placebo, there was a higher rate of mortality and a higher risk of hospitalization at Week 28 due to heart failure in patients who received the 10 mg/kg REMICADE dose, and higher rates of cardiovascular adverse events in patients who received REMICADE doses of 5 mg/kg and 10 mg/kg.

There have been post-marketing reports of new onset and worsening heart failure, with and without identifiable precipitating factors (e.g., pre-existing cardiovascular disease), in REMICADE-treated patients. Some of these patients have been under 50 years of age.

If a decision is made to administer REMICADE (≤ 5 mg/kg) to patients with moderate or severe heart failure or to administer REMICADE (any approved dose) to patients with mild heart failure, they should be closely monitored during therapy, and REMICADE should be discontinued if new or worsening symptoms of heart failure appear [see Contraindications (4)and Adverse Reactions (6.1)] .

Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia, some with a fatal outcome, have been reported in patients receiving REMICADE. The causal relationship to REMICADE therapy remains unclear. Although no high-risk group(s) has been identified, caution should be exercised in patients being treated with REMICADE who have ongoing or a history of significant hematologic abnormalities. All patients should be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever) while on REMICADE. Discontinuation of REMICADE therapy should be considered in patients who develop significant hematologic abnormalities.

REMICADE has been associated with hypersensitivity reactions that vary in their time of onset and required hospitalization in some cases. Most hypersensitivity reactions (including anaphylaxis, urticaria, dyspnea, and/or hypotension), have occurred during or within 2 hours of REMICADE infusion.

However, in some cases, serum sickness-like reactions have been observed in patients after initial REMICADE therapy (i.e., as early as after the second dose), and when REMICADE therapy was reinstituted following an extended period without REMICADE treatment. Symptoms associated with these reactions include fever, rash, headache, sore throat, myalgias, polyarthralgias, hand and facial edema and/or dysphagia. These reactions were associated with a marked increase in antibodies to infliximab, loss of detectable serum concentrations of infliximab, and possible loss of drug efficacy.

REMICADE should be discontinued for severe hypersensitivity reactions. Medications for the treatment of hypersensitivity reactions (e.g., acetaminophen, antihistamines, corticosteroids and/or epinephrine) should be available for immediate use in the event of a reaction [see Dosage and Administration (2.10)and Adverse Reactions (6.1)] .

In RA, CD and Ps clinical trials, re-administration of REMICADE after a period of no treatment resulted in a higher incidence of infusion reactions relative to regular maintenance treatment [see Adverse Reactions (6.1)] . In general, the benefit-risk of re-administration of REMICADE after a period of no-treatment, especially as a re-induction regimen given at weeks 0, 2 and 6, should be carefully considered. In the case where REMICADE maintenance therapy for Ps is interrupted, REMICADE should be reinitiated as a single dose followed by maintenance therapy.

Serious cerebrovascular accidents, myocardial ischemia/infarction (some fatal), hypotension, hypertension, and arrhythmias have been reported during and within 24 hours of initiation of REMICADE infusion. Cases of transient visual loss have been reported during or within 2 hours of infusion of REMICADE. Monitor patients during infusion and if serious reaction occurs, discontinue infusion. Further management of reactions should be dictated by signs and symptoms [see Adverse Reactions (6)] .

REMICADE and other agents that inhibit TNF have been associated with CNS manifestation of systemic vasculitis, seizure and new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Prescribers should exercise caution in considering the use of REMICADE in patients with these neurologic disorders and should consider discontinuation of REMICADE if these disorders develop.

Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and another TNF blocker, etanercept, with no added clinical benefit compared to etanercept alone. Because of the nature of the adverse reactions seen with the concurrent use of etanercept and anakinra therapy, similar toxicities may also result from the concurrent use of anakinra and other TNF blockers. Therefore, the concurrent use of REMICADE and anakinra is not recommended.

In clinical studies, concurrent administration of TNF blockers and abatacept have been associated with an increased risk of infections including serious infections compared with TNF blockers alone, without increased clinical benefit. Therefore, the concurrent use of REMICADE and abatacept is not recommended [see Drug Interactions (7.1)] .

There is insufficient information regarding the concurrent use of REMICADE with other biological products used to treat the same conditions as REMICADE. The concurrent use of REMICADE with these biological products is not recommended because of the possibility of an increased risk of infection [see Drug Interactions (7.1)] .

Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.

Treatment with REMICADE may result in the formation of autoantibodies and in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with REMICADE, treatment should be discontinued [see Adverse Reactions (6.1)] .

Vaccinations

Prior to initiating REMICADE in pediatric and adult patients, update vaccinations in accordance with current vaccination guidelines.

Live Vaccines and Therapeutic Infectious Agents

In patients receiving TNF blockers, limited data are available on the response to vaccination with live vaccines or on the secondary transmission of infection by live vaccines. Use of live vaccines can result in clinical infections, including disseminated infections. The concurrent administration of live vaccines with REMICADE is not recommended.

Fatal outcome due to disseminated BCG infection has been reported in an infant who received a BCG vaccine after in uteroexposure to infliximab. Infliximab is known to cross the placenta and has been detected up to 6 months following birth. At least a six month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in uteroto infliximab.

Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder instillation for the treatment of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious agents not be given concurrently with REMICADE.

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

Adverse Reactions in Adults

The data described herein reflect exposure to REMICADE in 4779 adult patients (1304 patients with RA, 1106 patients with CD, 202 with AS, 293 with PsA, 484 with UC, 1373 with Ps, and 17 patients with other conditions), including 2625 patients exposed beyond 30 weeks and 374 exposed beyond 1 year. [For information on adverse reactions in pediatric patients see Adverse Reactions (6.1)]. One of the most-common reasons for discontinuation of treatment was infusion-related reactions (e.g., dyspnea, flushing, headache and rash).

Infusion-Related Reactions

Adverse Reactions During or Shortly After Infusion

An infusion reaction was defined in clinical trials as any adverse event occurring during an infusion or within 1 hour after an infusion. In all the clinical studies, approximately 20% of REMICADE-treated patients experienced an infusion reaction compared with 10% of placebo-treated patients. Of REMICADE-treated patients who had an infusion reaction during the induction period, 27% experienced an infusion reaction during the maintenance period. Of patients who did not have an infusion reaction during the induction period, 9% experienced an infusion reaction during the maintenance period.

Among all REMICADE infusions, 3% were accompanied by nonspecific symptoms such as fever or chills, 1% were accompanied by cardiopulmonary reactions (primarily chest pain, hypotension, hypertension or dyspnea), and <1% were accompanied by pruritus, urticaria, or the combined symptoms of pruritus/urticaria and cardiopulmonary reactions. Serious infusion reactions occurred in <1% of patients and included anaphylaxis, convulsions, erythematous rash and hypotension. Approximately 3% of patients discontinued REMICADE because of infusion reactions, and all patients recovered with treatment and/or discontinuation of the infusion. REMICADE infusions beyond the initial infusion were not associated with a higher incidence of reactions. The infusion reaction rates remained stable in Ps through 1 year in Ps Study I. In psoriasis Study II, the rates were variable over time and somewhat higher following the final infusion than after the initial infusion. Across the 3 Ps studies, the percent of total infusions resulting in infusion reactions (i.e., an adverse event occurring within 1 hour) was 7% in the 3 mg/kg group, 4% in the 5 mg/kg group, and 1% in the placebo group.

Patients who became positive for antibodies to infliximab were more likely (approximately two-to three-fold) to have an infusion reaction than were those who were negative. Use of concomitant immunosuppressant agents appeared to reduce the frequency of both antibodies to infliximab and infusion reactions [see Adverse Reactions (6.2)and Drug Interactions (7.3)] .

Infusion Reactions Following Re-administration

In a clinical trial of patients with moderate to severe Ps designed to assess the efficacy of long-term maintenance therapy versus re-treatment with an induction regimen of REMICADE following disease flare, 4% (8/219) of patients in the re-treatment induction therapy arm experienced serious infusion reactions versus <1% (1/222) in the maintenance therapy arm. Patients enrolled in this trial did not receive any concomitant immunosuppressant therapy. In this study, the majority of serious infusion reactions occurred during the second infusion at Week 2. Symptoms included, but were not limited to, dyspnea, urticaria, facial edema, and hypotension. In all cases, REMICADE treatment was discontinued and/or other treatment instituted with complete resolution of signs and symptoms.

Delayed Reactions/Reactions Following Re-administration

In Ps studies, approximately 1% of REMICADE-treated patients experienced a possible delayed hypersensitivity reaction, generally reported as serum sickness or a combination of arthralgia and/or myalgia with fever and/or rash. These reactions generally occurred within 2 weeks after repeat infusion.

Infections

In REMICADE clinical studies, treated infections were reported in 36% of REMICADE-treated patients (average of 51 weeks of follow-up) and in 25% of placebo-treated patients (average of 37 weeks of follow-up). The infections most frequently reported were respiratory tract infections (including sinusitis, pharyngitis, and bronchitis) and urinary tract infections. Among REMICADE-treated patients, serious infections included pneumonia, cellulitis, abscess, skin ulceration, sepsis, and bacterial infection. In clinical trials, 7 opportunistic infections were reported; 2 cases each of coccidioidomycosis (1 case was fatal) and histoplasmosis (1 case was fatal), and 1 case each of pneumocystosis, nocardiosis and cytomegalovirus. Tuberculosis (TB) was reported in 14 patients, 4 of whom died due to miliary tuberculosis. Other cases of TB, including disseminated TB, also have been reported post-marketing. Most of these cases of TB occurred within the first 2 months after initiation of therapy with REMICADE and may reflect recrudescence of latent disease [see Warnings and Precautions (5.1)] . In the 1-year placebo-controlled studies RA I and RA II, 5.3% of patients receiving REMICADE every 8 weeks with MTX developed serious infections as compared to 3.4% of placebo patients receiving MTX. Of 924 patients receiving REMICADE, 1.7% developed pneumonia and 0.4% developed TB, when compared to 0.3% and 0.0% in the placebo arm respectively. In a shorter (22-week) placebo-controlled study of 1082 RA patients randomized to receive placebo, 3 mg/kg or 10 mg/kg REMICADE infusions at 0, 2, and 6 weeks, followed by every 8 weeks with MTX, serious infections were more frequent in the 10 mg/kg REMICADE group (5.3%) than the 3 mg/kg or placebo groups (1.7% in both). During the 54-week Crohn's II Study, 15% of patients with fistulizing CD developed a new fistula-related abscess.

In REMICADE clinical studies in patients with UC, infections treated with antimicrobials were reported in 27% of REMICADE-treated patients (average of 41 weeks of follow-up) and in 18% of placebo-treated patients (average 32 weeks of follow-up). The types of infections, including serious infections, reported in patients with UC were similar to those reported in other clinical studies.

The onset of serious infections may be preceded by constitutional symptoms such as fever, chills, weight loss, and fatigue. The majority of serious infections, however, may also be preceded by signs or symptoms localized to the site of the infection.

Autoantibodies/Lupus-like Syndrome

Approximately half of REMICADE-treated patients in clinical trials who were antinuclear antibody (ANA) negative at baseline developed a positive ANA during the trial compared with approximately one-fifth of placebo-treated patients. Anti-dsDNA antibodies were newly detected in approximately one-fifth of REMICADE-treated patients compared with 0% of placebo-treated patients. Reports of lupus and lupus-like syndromes, however, remain uncommon.

Malignancies

In controlled trials, more REMICADE-treated patients developed malignancies than placebo-treated patients [see Warnings and Precautions (5.2)] .

In a randomized controlled clinical trial exploring the use of REMICADE in patients with moderate to severe COPD who were either current smokers or ex-smokers, 157 patients were treated with REMICADE at doses similar to those used in RA and CD. Of these REMICADE-treated patients, 9 developed a malignancy, including 1 lymphoma, for a rate of 7.67 cases per 100 patient-years of follow-up (median duration of follow-up 0.8 years; 95% CI 3.51 – 14.56). There was 1 reported malignancy among 77 control patients for a rate of 1.63 cases per 100 patient-years of follow-up (median duration of follow-up 0.8 years; 95% CI 0.04 – 9.10). The majority of the malignancies developed in the lung or head and neck [see Warnings and Precautions (5.2)] .

Adverse Reactions in Patients with NYHA Class III/IV Heart Failure

In a randomized, double-blind study evaluating REMICADE in moderate or severe heart failure (NYHA Class III/IV; left ventricular ejection fraction ≤35%), 150 patients were randomized to receive treatment with 3 infusions of REMICADE 10 mg/kg, 5 mg/kg, or placebo, at 0, 2, and 6 weeks. Higher incidences of mortality and hospitalization due to worsening heart failure were observed in patients receiving the 10 mg/kg REMICADE dose. At 1 year, 8 patients in the 10 mg/kg REMICADE group had died compared with 4 deaths each in the 5 mg/kg REMICADE and the placebo groups. There were trends toward increased dyspnea, hypotension, angina, and dizziness in both the 10 mg/kg and 5 mg/kg REMICADE treatment groups, versus placebo. REMICADE has not been studied in patients with mild heart failure (NYHA Class I/II) [see Contraindications (4)and Warnings and Precautions (5.5)] .

Hepatotoxicity

Severe liver injury, including acute liver failure and autoimmune hepatitis, has been reported in patients receiving REMICADE [see Warnings and Precautions (5.4)] . Reactivation of hepatitis B virus has occurred in patients receiving TNF blockers, including REMICADE, who are chronic carriers of this virus [see Warnings and Precautions (5.3)] .

In clinical trials in RA, CD, UC, AS, Ps, and PsA, elevations of aminotransferases were observed (ALT more common than AST) in a greater proportion of patients receiving REMICADE than in controls (Table 1), both when REMICADE was given as monotherapy and when it was used in combination with other immunosuppressive agents. In general, patients who developed ALT and AST elevations were asymptomatic, and the abnormalities decreased or resolved with either continuation or discontinuation of REMICADE, or modification of concomitant medications.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: Proportion of Patients with Elevated ALT in Clinical Trials in Adults</span> </caption> <col align="left" valign="top" width="22%"/> <col align="center" valign="top" width="13%"/> <col align="center" valign="top" width="13%"/> <col align="center" valign="top" width="13%"/> <col align="center" valign="top" width="13%"/> <col align="center" valign="top" width="13%"/> <col align="center" valign="top" width="13%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule" rowspan="3"></th><th align="center" class="Rrule" colspan="6">Proportion of patients with elevated ALT</th> </tr> <tr class="Botrule"> <th align="center" class="Lrule Rrule" colspan="2">&gt;1 to &lt;3 × ULN</th><th align="center" class="Rrule" colspan="2">≥3 × ULN</th><th align="center" class="Rrule" colspan="2">≥5 × ULN</th> </tr> <tr class="Last"> <th align="center" class="Lrule Rrule">Placebo</th><th align="center" class="Rrule">REMICADE</th><th align="center" class="Rrule">Placebo</th><th align="center" class="Rrule">REMICADE</th><th align="center" class="Rrule">Placebo</th><th align="center" class="Rrule">REMICADE</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="7"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>Placebo patients received methotrexate while REMICADE patients received both REMICADE and methotrexate. Median follow-up was 58 weeks.</dd> <dt> <a href="#footnote-reference-3" name="footnote-3">†</a> </dt> <dd>Placebo patients in the 2 Phase 3 trials in CD received an initial dose of 5 mg/kg REMICADE at study start and were on placebo in the maintenance phase. Patients who were randomized to the placebo maintenance group and then later crossed over to REMICADE are included in the REMICADE group in ALT analysis. Median follow-up was 54 weeks. </dd> <dt> <a href="#footnote-reference-4" name="footnote-4">‡</a> </dt> <dd>Median follow-up was 30 weeks. Specifically, the median duration of follow-up was 30 weeks for placebo and 31 weeks for REMICADE.</dd> <dt> <a href="#footnote-reference-5" name="footnote-5">§</a> </dt> <dd>Median follow-up was 24 weeks for the placebo group and 102 weeks for the REMICADE group.</dd> <dt> <a href="#footnote-reference-6" name="footnote-6">¶</a> </dt> <dd>Median follow-up was 39 weeks for the REMICADE group and 18 weeks for the placebo group.</dd> <dt> <a href="#footnote-reference-7" name="footnote-7">#</a> </dt> <dd>ALT values are obtained in 2 Phase 3 Ps studies with median follow-up of 50 weeks for REMICADE and 16 weeks for placebo. </dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Rheumatoid arthritis <a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a></td><td align="center" class="Rrule">24%</td><td align="center" class="Rrule">34%</td><td align="center" class="Rrule">3%</td><td align="center" class="Rrule">4%</td><td align="center" class="Rrule">&lt;1%</td><td align="center" class="Rrule">&lt;1%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Crohn's disease <a class="Sup" href="#footnote-3" name="footnote-reference-3">†</a></td><td align="center" class="Rrule">34%</td><td align="center" class="Rrule">39%</td><td align="center" class="Rrule">4%</td><td align="center" class="Rrule">5%</td><td align="center" class="Rrule">0%</td><td align="center" class="Rrule">2%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Ulcerative colitis <a class="Sup" href="#footnote-4" name="footnote-reference-4">‡</a></td><td align="center" class="Rrule">12%</td><td align="center" class="Rrule">17%</td><td align="center" class="Rrule">1%</td><td align="center" class="Rrule">2%</td><td align="center" class="Rrule">&lt;1%</td><td align="center" class="Rrule">&lt;1%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Ankylosing spondylitis <a class="Sup" href="#footnote-5" name="footnote-reference-5">§</a></td><td align="center" class="Rrule">15%</td><td align="center" class="Rrule">51%</td><td align="center" class="Rrule">0%</td><td align="center" class="Rrule">10%</td><td align="center" class="Rrule">0%</td><td align="center" class="Rrule">4%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Psoriatic arthritis <a class="Sup" href="#footnote-6" name="footnote-reference-6">¶</a></td><td align="center" class="Rrule">16%</td><td align="center" class="Rrule">50%</td><td align="center" class="Rrule">0%</td><td align="center" class="Rrule">7%</td><td align="center" class="Rrule">0%</td><td align="center" class="Rrule">2%</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Plaque psoriasis <a class="Sup" href="#footnote-7" name="footnote-reference-7">#</a></td><td align="center" class="Rrule">24%</td><td align="center" class="Rrule">49%</td><td align="center" class="Rrule">&lt;1%</td><td align="center" class="Rrule">8%</td><td align="center" class="Rrule">0%</td><td align="center" class="Rrule">3%</td> </tr> </tbody> </table></div>

Adverse Reactions in Psoriasis Studies

During the placebo-controlled portion across the 3 clinical trials up to Week 16, the proportion of patients who experienced at least 1 serious adverse reaction (SAE; defined as resulting in death, life threatening, requires hospitalization, or persistent or significant disability/incapacity) was 0.5% in the 3 mg/kg REMICADE group, 1.9% in the placebo group, and 1.6% in the 5 mg/kg REMICADE group.

Among patients in the 2 Phase 3 studies, 12.4% of patients receiving REMICADE 5 mg/kg every 8 weeks through 1 year of maintenance treatment experienced at least 1 SAE in Study I. In Study II, 4.1% and 4.7% of patients receiving REMICADE 3 mg/kg and 5 mg/kg every 8 weeks, respectively, through 1 year of maintenance treatment experienced at least 1 SAE.

One death due to bacterial sepsis occurred 25 days after the second infusion of 5 mg/kg REMICADE. Serious infections included sepsis, and abscesses. In Study I, 2.7% of patients receiving REMICADE 5 mg/kg every 8 weeks through 1 year of maintenance treatment experienced at least 1 serious infection. In Study II, 1.0% and 1.3% of patients receiving REMICADE 3 mg/kg and 5 mg/kg, respectively, through 1 year of treatment experienced at least 1 serious infection. The most common serious infection (requiring hospitalization) was abscess (skin, throat, and peri-rectal) reported by 5 (0.7%) patients in the 5 mg/kg REMICADE group. Two active cases of tuberculosis were reported: 6 weeks and 34 weeks after starting REMICADE.

In the placebo-controlled portion of the Ps studies, 7 of 1123 patients who received REMICADE at any dose were diagnosed with at least one NMSC compared to 0 of 334 patients who received placebo.

In the Ps studies, 1% (15/1373) of patients experienced serum sickness or a combination of arthralgia and/or myalgia with fever, and/or rash, usually early in the treatment course. Of these patients, 6 required hospitalization due to fever, severe myalgia, arthralgia, swollen joints, and immobility.

Other Adverse Reactions in Adults

Safety data are available from 4779 REMICADE-treated adult patients, including 1304 with RA, 1106 with CD, 484 with UC, 202 with AS, 293 with PsA, 1373 with Ps and 17 with other conditions. [For information on other adverse reactions in pediatric patients, see Adverse Reactions (6.1)]. Adverse reactions reported in ≥5% of all patients with RA receiving 4 or more infusions are in Table 2. The types and frequencies of adverse reactions observed were similar in REMICADE-treated RA, AS, PsA, Ps, and CD patients except for abdominal pain, which occurred in 26% of REMICADE-treated patients with CD. In the CD studies, there were insufficient numbers and duration of follow-up for patients who never received REMICADE to provide meaningful comparisons.

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 2: Adverse Reactions that Occurred in ≥ 5% of Patients who Received ≥ 4 REMICADE Infusions for RA</span> </caption> <col align="left" valign="top" width="70%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="15%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule">Placebo</th><th align="center" class="Botrule Rrule">REMICADE</th> </tr> <tr class="Botrule"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule">(n=350)</th><th align="center" class="Botrule Rrule">(n=1129)</th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule">Average weeks of follow-up</th><th align="center" class="Botrule Rrule">59 weeks</th><th align="center" class="Botrule Rrule">66 weeks</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Upper respiratory tract infection</td><td align="center" class="Rrule">25%</td><td align="center" class="Rrule">32%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Nausea</td><td align="center" class="Rrule">20%</td><td align="center" class="Rrule">21%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Headache</td><td align="center" class="Rrule">14%</td><td align="center" class="Rrule">18%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Sinusitis</td><td align="center" class="Rrule">8%</td><td align="center" class="Rrule">14%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Diarrhea</td><td align="center" class="Rrule">12%</td><td align="center" class="Rrule">12%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Abdominal pain</td><td align="center" class="Rrule">8%</td><td align="center" class="Rrule">12%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pharyngitis</td><td align="center" class="Rrule">8%</td><td align="center" class="Rrule">12%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Coughing</td><td align="center" class="Rrule">8%</td><td align="center" class="Rrule">12%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Bronchitis</td><td align="center" class="Rrule">9%</td><td align="center" class="Rrule">10%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Rash</td><td align="center" class="Rrule">5%</td><td align="center" class="Rrule">10%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Dyspepsia</td><td align="center" class="Rrule">7%</td><td align="center" class="Rrule">10%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Fatigue</td><td align="center" class="Rrule">7%</td><td align="center" class="Rrule">9%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Urinary tract infection</td><td align="center" class="Rrule">6%</td><td align="center" class="Rrule">8%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pain</td><td align="center" class="Rrule">7%</td><td align="center" class="Rrule">8%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Arthralgia</td><td align="center" class="Rrule">7%</td><td align="center" class="Rrule">8%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pruritus</td><td align="center" class="Rrule">2%</td><td align="center" class="Rrule">7%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Fever</td><td align="center" class="Rrule">4%</td><td align="center" class="Rrule">7%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Hypertension</td><td align="center" class="Rrule">5%</td><td align="center" class="Rrule">7%</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Moniliasis</td><td align="center" class="Rrule">3%</td><td align="center" class="Rrule">5%</td> </tr> </tbody> </table></div>

The most common serious adverse reactions observed in clinical trials were infections [see Adverse Reactions (6.1)] . Other serious, medically relevant adverse reactions ≥0.2% or clinically significant adverse reactions by body system were as follows:

Adverse Reactions in Pediatric Patients

Adverse Reactions in Pediatric Patients with Crohn's Disease

There were some differences in the adverse reactions observed in the pediatric patients receiving REMICADE compared to those observed in adults with CD. These differences are discussed in the following paragraphs.

The following adverse reactions were reported more commonly in 103 randomized pediatric CD patients administered 5 mg/kg REMICADE through 54 weeks than in 385 adult CD patients receiving a similar treatment regimen: anemia (11%), leukopenia (9%), flushing (9%), viral infection (8%), neutropenia (7%), bone fracture (7%), bacterial infection (6%), and respiratory tract allergic reaction (6%).

Infections were reported in 56% of randomized pediatric patients in Study Peds Crohn's and in 50% of adult patients in Study Crohn's I. In Study Peds Crohn's, infections were reported more frequently for patients who received every 8-week as opposed to every 12-week infusions (74% and 38%, respectively), while serious infections were reported for 3 patients in the every 8-week and 4 patients in the every 12-week maintenance treatment group. The most commonly reported infections were upper respiratory tract infection and pharyngitis, and the most commonly reported serious infection was abscess. Pneumonia was reported for 3 patients, (2 in the every 8-week and 1 in the every 12-week maintenance treatment groups). Herpes zoster was reported for 2 patients in the every 8-week maintenance treatment group.

In Study Peds Crohn's, 18% of randomized patients experienced 1 or more infusion reactions, with no notable difference between treatment groups. Of the 112 patients in Study Peds Crohn's, there were no serious infusion reactions, and 2 patients had non-serious anaphylactoid reactions.

Elevations of ALT up to 3 times the upper limit of normal (ULN) were seen in 18% of pediatric patients in CD clinical trials; 4% had ALT elevations ≥3 × ULN, and 1% had elevations ≥5 × ULN. (Median follow-up was 53 weeks).

Adverse Reactions in Pediatric Patients with Ulcerative Colitis

Overall, the adverse reactions reported in the pediatric UC trial and adult UC (Study UC I and Study UC II) studies were generally consistent. In a pediatric UC trial, the most common adverse reactions were upper respiratory tract infection, pharyngitis, abdominal pain, fever, and headache.

Infections were reported in 31 (52%) of 60 treated patients in the pediatric UC trial and 22 (37%) required oral or parenteral antimicrobial treatment. The proportion of patients with infections in the pediatric UC trial was similar to that in the pediatric CD study (Study Peds Crohn's) but higher than the proportion in the adults' UC studies (Study UC I and Study UC II). The overall incidence of infections in the pediatric UC trial was 13/22 (59%) in the every 8 week maintenance treatment group. Upper respiratory tract infection (7/60 [12%]) and pharyngitis (5/60 [8%]) were the most frequently reported respiratory system infections. Serious infections were reported in 12% (7/60) of all treated patients.

Elevations of ALT up to 3 times the upper limit of normal (ULN) were seen in 17% (10/60) of pediatric patients in the pediatric UC trial; 7% (4/60) had ALT elevations ≥3 × ULN, and 2% (1/60) had elevations ≥5 × ULN (median follow-up was 49 weeks).

Overall, 8 of 60 (13%) treated patients experienced one or more infusion reactions, including 4 of 22 (18%) patients in the every 8-week treatment maintenance group. No serious infusion reactions were reported.

In the pediatric UC trial, 45 patients were in the 12 to 17 year age group and 15 in the 6 to 11 year age group. The numbers of patients in each subgroup are too small to make any definitive conclusions about the effect of age on safety events. There were higher proportions of patients with serious adverse events (40% vs. 18%) and discontinuation due to adverse events (40% vs. 16%) in the younger age group than in the older age group. While the proportion of patients with infections was also higher in the younger age group (60% vs. 49%), for serious infections, the proportions were similar in the two age groups (13% in the 6 to 11 year age group vs. 11% in the 12 to 17 year age group). Overall proportions of adverse reactions, including infusion reactions, were similar between the 6 to 11 and 12 to 17 year age groups (13%).

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other infliximab products may be misleading.

Treatment with REMICADE can be associated with the development of antibodies to infliximab. An enzyme immunoassay (EIA) method was originally used to measure anti-infliximab antibodies in clinical studies of REMICADE. The EIA method is subject to interference by serum infliximab, possibly resulting in an underestimation of the rate of patient antibody formation. A separate, drug-tolerant electrochemiluminescence immunoassay (ECLIA) method for detecting antibodies to infliximab was subsequently developed and validated. This method is 60-fold more sensitive than the original EIA. With the ECLIA method, all clinical samples can be classified as either positive or negative for antibodies to infliximab without the need for the inconclusive category.

The incidence of antibodies to infliximab was based on the original EIA method in all clinical studies of REMICADE except for the Phase 3 study in pediatric patients with UC where the incidence of antibodies to infliximab was detected using both the EIA and ECLIA methods.

Immunogenicity in Adult Patients

The incidence of antibodies to infliximab in patients with RA and CD given a 3-dose induction regimen followed by maintenance dosing was approximately 10% as assessed through 1 to 2 years of REMICADE treatment. A higher incidence of antibodies to infliximab was observed in CD patients receiving REMICADE after drug-free intervals >16 weeks. In a PsA study in which 191 patients received 5 mg/kg with or without MTX, antibodies to infliximab occurred in 15% of patients. The majority of antibody-positive patients had low titers. Antibody development was lower among RA and CD patients receiving immunosuppressant therapies such as 6-MP/AZA or MTX. Patients who were antibody-positive were more likely to have higher rates of clearance, have reduced efficacy, and to experience an infusion reaction than were patients who were antibody negative [see Adverse Reactions (6.1)] . In the Ps Study II, which included both the 5 mg/kg and 3 mg/kg doses, antibodies were observed in 36% of patients treated with 5 mg/kg every 8 weeks for 1 year, and in 51% of patients treated with 3 mg/kg every 8 weeks for 1 year.

In the Ps Study III, which also included both the 5 mg/kg and 3 mg/kg doses, antibodies were observed in 20% of patients treated with 5 mg/kg induction (weeks 0, 2 and 6), and in 27% of patients treated with 3 mg/kg induction. Despite the increase in antibody formation, the infusion reaction rates in Studies I and II in patients treated with 5 mg/kg induction followed by every 8 week maintenance for 1 year and in Study III in patients treated with 5 mg/kg induction (14.1%–23.0%) and serious infusion reaction rates (<1%) were similar to those observed in other study populations. The clinical significance of apparent increased immunogenicity on efficacy and infusion reactions in Ps patients as compared to patients with other diseases treated with REMICADE over the long term is not known.

Immunogenicity in Pediatric Patients with Crohn's Disease

In Study Peds Crohn's, in which all patients received stable doses of 6-MP, AZA, or MTX, excluding inconclusive samples, 3 of 24 patients had antibodies to infliximab. Although 105 patients were tested for antibodies to infliximab, 81 patients were classified as inconclusive because they could not be ruled as negative due to assay interference by the presence of infliximab in the sample.

Immunogenicity in Pediatric Patients with Ulcerative Colitis

In the pediatric UC trial, 58 patients were evaluated for antibodies to infliximab using the EIA as well as the drug-tolerant ECLIA. With the EIA, 4 of 58 (7%) patients had antibodies to infliximab. With the ECLIA, 30 of 58 (52%) patients had antibodies to infliximab. The higher incidence of antibodies to infliximab by the ECLIA method was due to the 60-fold higher sensitivity compared to the EIA method. While EIA-positive patients generally had undetectable trough infliximab concentrations, ECLIA-positive patients could have detectable trough concentrations of infliximab because the ECLIA assay is more sensitive and drug-tolerant.

Adverse reactions, some with fatal outcomes, have been identified during post approval use of REMICADE in adult and pediatric patients. 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.

Postmarketing Adverse Reactions in Adults and Pediatric Patients

Postmarketing Serious Adverse Reactions in Pediatric Patients

The following serious adverse reactions have been reported in the post-marketing experience in pediatric patients: infections (some fatal) including opportunistic infections and tuberculosis, infusion reactions, hypersensitivity reactions, malignancies, including hepatosplenic T-cell lymphomas [see Boxed Warningand Warnings and Precautions (5.2)] , transient hepatic enzyme abnormalities, lupus-like syndromes, and the development of autoantibodies.

The combination of REMICADE with other biological products used to treat the same conditions as REMICADE is not recommended [see Warnings and Precautions (5.10)] .

An increased risk of serious infections was seen in clinical studies of other TNF blockers used in combination with anakinra or abatacept, with no added clinical benefit. Because of the nature of the adverse reactions seen with these combinations with TNF blocker therapy, similar toxicities may also result from the combination of anakinra or abatacept with other TNF blockers. Therefore, the combination of REMICADE and anakinra or abatacept is not recommended [see Warnings and Precautions (5.10)] .

The concomitant use of tocilizumab with biological DMARDs such as TNF antagonists, including REMICADE, should be avoided because of the possibility of increased immunosuppression and increased risk of infection.

Specific drug interaction studies, including interactions with methotrexate (MTX), have not been conducted. The majority of patients in RA or CD clinical studies received one or more concomitant medications. In RA, concomitant medications besides MTX were nonsteroidal anti-inflammatory agents (NSAIDs), folic acid, corticosteroids and/or narcotics. Concomitant CD medications were antibiotics, antivirals, corticosteroids, 6-MP/AZA and aminosalicylates. In PsA clinical trials, concomitant medications included MTX in approximately half of the patients as well as NSAIDs, folic acid and corticosteroids. Concomitant MTX use may decrease the incidence of anti-infliximab antibody production and increase infliximab concentrations.

Patients with CD who received immunosuppressants tended to experience fewer infusion reactions compared to patients on no immunosuppressants [see Adverse Reactions (6.1)] . Serum infliximab concentrations appeared to be unaffected by baseline use of medications for the treatment of CD including corticosteroids, antibiotics (metronidazole or ciprofloxacin) and aminosalicylates.

The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (e.g., TNFα, IL-1, IL-6, IL-10, IFN) during chronic inflammation. Therefore, it is expected that for a molecule that antagonizes cytokine activity, such as infliximab, the formation of CYP450 enzymes could be normalized. Upon initiation or discontinuation of REMICADE in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed.

It is recommended that live vaccines not be given concurrently with REMICADE. It is also recommended that live vaccines not be given to infants after in uteroexposure to infliximab for at least 6 months following birth [see Warnings and Precautions (5.13)] .

It is recommended that therapeutic infectious agents not be given concurrently with REMICADE [see Warnings and Precautions (5.13)] .

Risk Summary

Available observational studies in pregnant women exposed to REMICADE showed no increased risk of major malformations among live births as compared to those exposed to non-biologics. However, findings on other birth and maternal outcomes were not consistent across studies of different study design and conduct (see Data) .

Monoclonal antibodies such as infliximab are transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in uteroexposed infant (see Clinical Considerations) . Because infliximab does not cross-react with TNFα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with REMICADE. In a developmental study conducted in mice using an analogous antibody, no evidence of maternal toxicity or fetal harm was observed (see Data) .

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Published data suggest that there is an increased risk of adverse pregnancy outcomes in women with inflammatory bowel disease or rheumatoid arthritis associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2.5 kg) and small for gestational age at birth.

Fetal/Neonatal Adverse Reactions

As with other IgG antibodies, infliximab crosses the placenta. Infliximab has been detected in the serum of infants up to 6 months following birth. Consequently, these infants may be at increased risk of infection, including disseminated infection which can become fatal. At least a six month waiting period following birth is recommended before the administration of live vaccines (e.g., BCG vaccine or other live vaccines, such as the rotavirus vaccine) to these infants [see Warnings and Precautions (5.13)] . Cases of agranulocytosis in infants exposed in uterohave also been reported [see Adverse Reactions (6.3)] .

Data

Human Data

Two prospective cohort studies were conducted assessing birth outcomes as well as the health status of infants up to the age of one year in women exposed to REMICADE compared to non-biologic comparators including methotrexate, azathioprine, 6-mercaptopurine and systemic corticosteroids used for the treatment of similar diseases. The first study was conducted in an IBD pregnancy registry in the United States and assessed pregnancy outcomes in 294 women with inflammatory bowel disease exposed to REMICADE during pregnancy compared with 515 women on a non-biologic treatment. REMICADE exposure was not associated with increased rates of major congenital malformations, miscarriage/stillbirth, infants of low birth weight, small for gestational age, or infection in the first year of life. The second study among IBD and non-IBD patients in Sweden, Finland, and Denmark compared 97, 7, and 166 women exposed to REMICADE to 2,693, 2,499 and 1,268 women on non-biologic systemic therapy, respectively. In this study, comparing pooled data across the three countries, exposure to REMICADE was not associated with increased rates of congenital anomalies or infant death. REMICADE in combination with immunosuppressants (mainly systemic corticosteroids and azathioprine) was associated with increased rates of preterm birth, small for gestational age, low birth weight, and infant hospitalization for infection compared with non-biologic systemic treatment. Although the study did not show any associations with REMICADE monotherapy, the analyses could have been underpowered to detect an association.

There were additional methodological limitations with these studies that may account for the study findings in both studies: the concomitant use of other medications or treatments was not controlled and disease severity was not assessed; in the U.S. study, patient reported outcomes were collected without clinical validation. These methodological limitations hinder interpretation of the study results.

Animal Data

Because infliximab products do not cross-react with TNFα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with infliximab. An embryofetal development study was conducted in pregnant mice using cV1q anti-mouse TNFα, an analogous antibody that selectively inhibits the functional activity of mouse TNFα. This antibody administered in mice, during the period of organogenesis on gestation days (GDs) 6 and 12, at IV doses up to 40 mg/kg produced no evidence of maternal toxicity, fetal mortality, or structural abnormalities. Doses of 10 to 15 mg/kg in pharmacodynamic animal models with the anti-TNF analogous antibody produced maximal pharmacologic effectiveness. Analyses of fetal samples on GD 14 indicated placental transfer of the antibody and exposure of the fetuses during organogenesis. In a peri- and post-natal development study in mice, no maternal toxicity or adverse developmental effects in offspring were observed when dams were administered IV doses of 10 or 40 mg/kg of the analogous antibody on GDs 6, 12 and 18 and lactation days 3, 9 and 15.

Risk Summary

Published literature show that infliximab is present at low levels in human milk. Systemic exposure in a breastfed infant is expected to be low because infliximab is largely degraded in the gastrointestinal tract. A U.S. multi-center study of 168 women treated with infliximab for inflammatory bowel disease (breast milk samples obtained, n=29) showed that infants exposed to infliximab through breast milk had no increase in rates of infections and developed normally. There are no data on the effects of infliximab on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for REMICADE and any potential adverse effects on the breastfed child from REMICADE or from the underlying maternal condition.

The safety and effectiveness of REMICADE have been established in pediatric patients 6 to 17 years of age for induction and maintenance treatment of CD and UC [ see Dosage and Administration (2.2, 2.4)and Adverse Reactions (6.1)] . However, the safety and effectiveness of REMICADE in pediatric patients <6 years of age with CD or UC have not been established. The safety and effectiveness of REMICADE in the treatment of pediatric patients with Ps and juvenile rheumatoid arthritis (JRA) have not been established.

Pediatric Crohn's Disease

The safety and effectiveness of REMICADE have been established for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active CD who have had an inadequate response to conventional therapy. The use of REMICADE for this indication is supported by evidence from a randomized, open-label pediatric CD study in 112 pediatric patients aged 6 years and older [see Clinical Studies (14.2)].

REMICADE has been studied only in combination with conventional immunosuppressive therapy in pediatric CD. The longer term (greater than 1 year) safety and effectiveness of REMICADE in pediatric CD patients have not been established in clinical trials.

Postmarketing cases of HSTCL have been reported in pediatric patients treated with TNF blockers including REMICADE. Due to the risk of HSTCL, a careful risk-benefit assessment should be made when REMICADE is used in combination with other immunosuppressants in pediatric CD patients [see Boxed Warning andWarnings and Precautions (5.2)].

Pediatric Ulcerative Colitis

The safety and effectiveness of REMICADE for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients aged 6 years and older with moderately to severely active UC who have had an inadequate response to conventional therapy have been established. The use of REMICADE for this indication is supported by evidence from adequate and well-controlled studies of REMICADE in adults with additional safety and pharmacokinetic data from an open-label pediatric UC study in 60 pediatric patients aged 6 years and older [see Dosage and Administration (2.4), Adverse Reactions (6.1), and Clinical Studies (14.4)] . The effectiveness of REMICADE in inducing and maintaining mucosal healing in pediatric UC was not established. Although 41 patients had a Mayo endoscopy subscore of 0 or 1 at the Week 8 endoscopy, the induction phase was open-label and lacked a control group. Only 9 patients had an optional endoscopy at Week 54. Approximately half of the patients were on concomitant immunomodulators (AZA, 6-MP, MTX) at study start.

Due to the risk of HSTCL, a careful risk-benefit assessment should be made when REMICADE is used in combination with other immunosuppressants in pediatric UC patients [see Boxed Warningand Warnings and Precautions (5.2)] .

The longer term (greater than 1 year) safety and effectiveness of REMICADE in pediatric UC patients have not been established in clinical trials.

Juvenile Rheumatoid Arthritis (JRA)

The safety and effectiveness of REMICADE in the treatment of pediatric patients with juvenile rheumatoid arthritis (JRA) have notbeen established.

The safety and efficacy of REMICADE in patients with JRA were evaluated in a multicenter, randomized, placebo-controlled, double-blind study for 14 weeks, followed by a double-blind, all-active treatment extension, for a maximum of 44 weeks. Patients with active JRA between the ages of 4 and 17 years who had been treated with MTX for at least 3 months were enrolled. Concurrent use of folic acid, oral corticosteroids (≤0.2 mg/kg/day of prednisone or equivalent), NSAIDs, and/or disease modifying antirheumatic drugs (DMARDs) was permitted.

Doses of 3 mg/kg REMICADE or placebo were administered intravenously at Weeks 0, 2 and 6. Patients randomized to placebo crossed-over to receive 6 mg/kg REMICADE at Weeks 14, 16, and 20, and then every 8 weeks through Week 44. Patients who completed the study continued to receive open-label treatment with REMICADE for up to 2 years in a companion extension study.

The study failed to establish the efficacy of REMICADE in the treatment of JRA. Key observations in the study included a high placebo response rate and a higher rate of immunogenicity than what has been observed in adults. Additionally, a higher rate of clearance of infliximab was observed than had been observed in adults.

Population pharmacokinetic analysis showed that in pediatric patients with JRA with a body weight of up to 35 kg receiving 6 mg/kg REMICADE and pediatric patients with JRA with body weight greater than 35 kg up to adult body weight receiving 3 mg/kg REMICADE, the steady state area under the concentration curve (AUC ss) was similar to that observed in adults receiving 3 mg/kg of REMICADE.

A total of 60 patients with JRA were treated with doses of 3 mg/kg and 57 patients were treated with doses of 6 mg/kg. The proportion of patients with infusion reactions who received 3 mg/kg REMICADE was 35% (21/60) over 52 weeks compared with 18% (10/57) in patients who received 6 mg/kg over 38 weeks. The most common infusion reactions reported were vomiting, fever, headache, and hypotension. In the 3 mg/kg REMICADE group, 4 patients had a serious infusion reaction and 3 patients reported a possible anaphylactic reaction (2 of which were among the serious infusion reactions). In the 6 mg/kg REMICADE group, 2 patients had a serious infusion reaction, 1 of whom had a possible anaphylactic reaction. Two of the 6 patients who experienced serious infusion reactions received REMICADE by rapid infusion (duration of less than 2 hours). Antibodies to infliximab developed in 38% (20/53) of patients who received 3 mg/kg REMICADE compared with 12% (6/49) of patients who received 6 mg/kg.

A total of 68% (41/60) of patients who received 3 mg/kg REMICADE in combination with MTX experienced an infection over 52 weeks compared with 65% (37/57) of patients who received 6 mg/kg REMICADE in combination with MTX over 38 weeks. The most commonly reported infections were upper respiratory tract infection and pharyngitis, and the most commonly reported serious infection was pneumonia. Other notable infections included primary varicella infection in 1 patient and herpes zoster in 1 patient.

Of the total number of REMICADE-treated patients in RA and Ps clinical studies, 256 (9.6%) were 65 years old and over, while 17 (0.6%) were 75 years old and over. In these trials, no overall differences in safety or effectiveness were observed between geriatric patients (patients ≥ 65 years old) and younger adult patients (patients 18 to 65 years old). However, the incidence of serious adverse reactions in geriatric patients was higher in both REMICADE and control groups compared to younger adult patients.

Of the total number of REMICADE-treated patients in CD, UC, AS, and PsA clinical studies, 76 (3.2%) were 65 years old and over, while 9 (0.4%) were 75 years old and over. In the CD, UC, AS, and PsA studies, there were insufficient numbers of geriatric patients to determine whether they respond differently from younger adults .

The incidence of serious infections in REMICADE-treated geriatric patients was greater than in REMICADE-treated younger adult patients; therefore close monitoring of geriatric patients for the development of serious infections is recommended [see Warnings and Precautions (5.1)and Adverse Reactions (6.1)] .

Single doses up to 20 mg/kg have been administered without any direct toxic effect. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects [see Warnings and Precautions (5)] and appropriate symptomatic treatment instituted immediately.

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Infliximab, a tumor necrosis factor (TNF) blocker, is a chimeric IgG1κ monoclonal antibody (composed of human constant and murine variable regions). It has a molecular weight of approximately 149.1 kilodaltons. Infliximab is produced by a recombinant murine myeloma cell line, SP2/0.

{ "type": "p", "children": [], "text": "Infliximab, a tumor necrosis factor (TNF) blocker, is a chimeric IgG1κ monoclonal antibody (composed of human constant and murine variable regions). It has a molecular weight of approximately 149.1 kilodaltons. Infliximab is produced by a recombinant murine myeloma cell line, SP2/0." }

REMICADE ®(infliximab) for injection is supplied as a sterile, preservative-free, white, lyophilized powder for intravenous infusion after reconstitution and dilution. Following reconstitution with 10 mL of Sterile Water for Injection, USP, the final concentration is 10 mg/mL and the resulting pH is approximately 7.2. Each single-dose vial contains 100 mg infliximab, dibasic sodium phosphate, dihydrate (6.1 mg), monobasic sodium phosphate, monohydrate (2.2 mg), polysorbate 80 (0.5 mg), and sucrose (500 mg).

{ "type": "p", "children": [], "text": "REMICADE\n \n ®(infliximab) for injection is supplied as a sterile, preservative-free, white, lyophilized powder for intravenous infusion after reconstitution and dilution. Following reconstitution with 10 mL of Sterile Water for Injection, USP, the final concentration is 10 mg/mL and the resulting pH is approximately 7.2. Each single-dose vial contains 100 mg infliximab, dibasic sodium phosphate, dihydrate (6.1 mg), monobasic sodium phosphate, monohydrate (2.2 mg), polysorbate 80 (0.5 mg), and sucrose (500 mg).\n\n " }

Infliximab neutralizes the biological activity of TNFα by binding with high affinity to the soluble and transmembrane forms of TNFα and inhibits binding of TNFα with its receptors. Infliximab does not neutralize TNFβ (lymphotoxin-α), a related cytokine that utilizes the same receptors as TNFα. Biological activities attributed to TNFα include: induction of pro-inflammatory cytokines such as interleukins (IL) 1 and 6, enhancement of leukocyte migration by increasing endothelial layer permeability and expression of adhesion molecules by endothelial cells and leukocytes, activation of neutrophil and eosinophil functional activity, induction of acute phase reactants and other liver proteins, as well as tissue degrading enzymes produced by synoviocytes and/or chondrocytes. Cells expressing transmembrane TNFα bound by infliximab can be lysed in vitroor in vivo. Infliximab inhibits the functional activity of TNFα in a wide variety of in vitrobioassays utilizing human fibroblasts, endothelial cells, neutrophils, B and T-lymphocytes and epithelial cells. The relationship of these biological response markers to the mechanism(s) by which REMICADE exerts its clinical effects is unknown. Anti-TNFα antibodies reduce disease activity in the cotton-top tamarin colitis model, and decrease synovitis and joint erosions in a murine model of collagen-induced arthritis. Infliximab prevents disease in transgenic mice that develop polyarthritis as a result of constitutive expression of human TNFα, and when administered after disease onset, allows eroded joints to heal.

Elevated concentrations of TNFα have been found in involved tissues and fluids of patients with RA, CD, UC, AS, PsA, and Ps. In RA, treatment with REMICADE reduced infiltration of inflammatory cells into inflamed areas of the joint as well as expression of molecules mediating cellular adhesion [E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)], chemoattraction [IL-8 and monocyte chemotactic protein (MCP-1)] and tissue degradation [matrix metalloproteinase (MMP) 1 and 3]. In CD, treatment with REMICADE reduced infiltration of inflammatory cells and TNFα production in inflamed areas of the intestine, and reduced the proportion of mononuclear cells from the lamina propria able to express TNFα and interferon. After treatment with REMICADE, patients with RA or CD exhibited decreased levels of serum IL-6 and C-reactive protein (CRP) compared to baseline. Peripheral blood lymphocytes from REMICADE-treated patients showed no significant decrease in number or in proliferative responses to in vitromitogenic stimulation when compared to cells from untreated patients. In PsA, treatment with REMICADE resulted in a reduction in the number of T-cells and blood vessels in the synovium and psoriatic skin lesions as well as a reduction of macrophages in the synovium. In Ps, REMICADE treatment may reduce the epidermal thickness and infiltration of inflammatory cells. The relationship between these pharmacodynamic activities and the mechanism(s) by which REMICADE exerts its clinical effects is unknown.

In adults, single intravenous (IV) infusions of 3 mg/kg to 20 mg/kg (two times the maximum recommended dose for any indication) showed a linear relationship between the dose administered and the maximum serum concentration. The volume of distribution at steady state was independent of dose and indicated that infliximab was distributed primarily within the vascular compartment. Pharmacokinetic results for single doses of 3 mg/kg to 10 mg/kg in RA, 5 mg/kg in CD, and 3 mg/kg to 5 mg/kg in Ps indicate that the median terminal half-life of infliximab is 7.7 to 9.5 days.

Following an initial dose of REMICADE, repeated infusions at 2 and 6 weeks resulted in predictable concentration-time profiles following each treatment. No systemic accumulation of infliximab occurred upon continued repeated treatment with 3 mg/kg or 10 mg/kg at 4- or 8-week intervals. Development of antibodies to infliximab increased infliximab clearance. At 8 weeks after a maintenance dose of 3 to 10 mg/kg of REMICADE, median infliximab serum concentrations ranged from approximately 0.5 to 6 mcg/mL; however, infliximab concentrations were not detectable (<0.1 mcg/mL) in patients who became positive for antibodies to infliximab. No major differences in clearance or volume of distribution were observed in patient subgroups defined by age, weight, or gender. It is not known if there are differences in clearance or volume of distribution in patients with marked impairment of hepatic or renal function.

Infliximab pharmacokinetic characteristics (including peak and trough concentrations and terminal half-life) were similar in pediatric (aged 6 to 17 years) and adult patients with CD or UC following the administration of 5 mg/kg of REMICADE.

A 6-month study in CD-1 mice was conducted to assess the tumorigenic potential of cV1q anti-mouse TNFα, an analogous antibody. No evidence of tumorigenicity was observed in mice that received intravenous doses of 10 mg/kg or 40 mg/kg cV1q given weekly. The relevance of this study for human risk is unknown. No impairment of fertility or reproductive performance indices were observed in male or female mice that received cV1q, an analogous mouse antibody, at intravenous doses up to 40 mg/kg given weekly.

Active Crohn's Disease in Adults

The safety and efficacy of single and multiple doses of REMICADE were assessed in 2 randomized, double-blind, placebo-controlled clinical studies in 653 adult patients with moderate to severely active CD [Crohn's Disease Activity Index (CDAI) ≥220 and ≤400] with an inadequate response to prior conventional therapies. Concomitant stable doses of aminosalicylates, corticosteroids and/or immunomodulatory agents were permitted and 92% of patients continued to receive at least one of these medications.

In the single-dose trial of 108 adult patients, 16% (4/25) of placebo patients achieved a clinical response (decrease in CDAI ≥70 points) at Week 4 vs. 81% (22/27) of patients receiving 5 mg/kg REMICADE (p<0.001, two-sided, Fisher's Exact test). Additionally, 4% (1/25) of placebo patients and 48% (13/27) of patients receiving 5 mg/kg REMICADE achieved clinical remission (CDAI<150) at Week 4.

In a multidose trial (ACCENT I [Study Crohn's I]), 545 adult patients received 5 mg/kg at Week 0 and were then randomized to one of three treatment groups; the placebo maintenance group received placebo at Weeks 2 and 6, and then every 8 weeks; the 5 mg/kg maintenance group received 5 mg/kg at Weeks 2 and 6, and then every 8 weeks; and the 10 mg/kg maintenance group received 5 mg/kg at Weeks 2 and 6, and then 10 mg/kg every 8 weeks. Patients in response at Week 2 were randomized and analyzed separately from those not in response at Week 2. Corticosteroid taper was permitted after Week 6.

At Week 2, 57% (311/545) of patients were in clinical response. At Week 30, a significantly greater proportion of these patients in the 5 mg/kg and 10 mg/kg maintenance groups achieved clinical remission compared to patients in the placebo maintenance group (Table 3).

Additionally, a significantly greater proportion of patients in the 5 mg/kg and 10 mg/kg REMICADE maintenance groups were in clinical remission and were able to discontinue corticosteroid use compared to patients in the placebo maintenance group at Week 54 (Table 3).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 3: Clinical Remission and Steroid Withdrawal in Adult Patients with CD (Study Crohn's I)</span> </caption> <col align="left" valign="top" width="50%"/> <col align="center" valign="top" width="23%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="12%"/> <thead> <tr class="First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule">Single 5-mg/kg Dose <a class="Sup" href="#footnote-8" name="footnote-reference-8">*</a></th><th align="center" class="Botrule Rrule" colspan="2">Three-Dose Induction <a class="Sup" href="#footnote-9" name="footnote-reference-9">†</a></th> </tr> <tr> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule">Placebo Maintenance</th><th align="center" class="Botrule Rrule" colspan="2">REMICADE Maintenance <br/> q8 wks </th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule"></th><th align="center" class="Rrule">5 mg/kg</th><th align="center" class="Rrule">10 mg/kg</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-8" name="footnote-8">*</a> </dt> <dd>REMICADE at Week 0 </dd> <dt> <a href="#footnote-reference-9" name="footnote-9">†</a> </dt> <dd>REMICADE 5 mg/kg administered at Weeks 0, 2 and 6</dd> <dt> <a href="#footnote-reference-10" name="footnote-10">‡</a> </dt> <dd>P-values represent pairwise comparisons to placebo </dd> <dt> <a href="#footnote-reference-11" name="footnote-11">§</a> </dt> <dd>Of those receiving corticosteroids at baseline</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule"><span class="Bold">Week 30</span></td><td align="center" class="Rrule">25/102</td><td align="center" class="Rrule">41/104</td><td align="center" class="Rrule">48/105</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Clinical remission</td><td align="center" class="Rrule">25%</td><td align="center" class="Rrule">39%</td><td align="center" class="Rrule">46%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">   <span class="Italics">P</span>-value <a class="Sup" href="#footnote-10" name="footnote-reference-10">‡</a></td><td align="center" class="Rrule"></td><td align="center" class="Rrule">0.022</td><td align="center" class="Rrule">0.001</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Bold">Week 54</span></td><td align="center" class="Rrule">6/54</td><td align="center" class="Rrule">14/56</td><td align="center" class="Rrule">18/53</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Patients in remission able to discontinue corticosteroid use <a class="Sup" href="#footnote-11" name="footnote-reference-11">§</a></td><td align="center" class="Rrule">11%</td><td align="center" class="Rrule">25%</td><td align="center" class="Rrule">34%</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">   <span class="Italics">P</span>-value <a class="Sup" href="#footnote-10">‡</a></td><td align="center" class="Rrule"></td><td align="center" class="Rrule">0.059</td><td align="center" class="Rrule">0.005</td> </tr> </tbody> </table></div>

Patients in the REMICADE maintenance groups (5 mg/kg and 10 mg/kg) had a longer time to loss of response than patients in the placebo maintenance group (Figure 1). At Weeks 30 and 54, significant improvement from baseline was seen among the 5 mg/kg and 10 mg/kg REMICADE-treated groups compared to the placebo group in the disease-specific inflammatory bowel disease questionnaire (IBDQ), particularly the bowel and systemic components, and in the physical component summary score of the general health-related quality of life questionnaire SF-36.

Figure 1: Kaplan-Meier Estimate of the Proportion of Adults with CD Who Had Not Lost Response Through Week 54 (Study Crohn's I)

In a subset of 78 patients who had mucosal ulceration at baseline and who participated in an endoscopic substudy, 13 of 43 patients in the REMICADE maintenance group had endoscopic evidence of mucosal healing compared to 1 of 28 patients in the placebo group at Week 10. Of the REMICADE-treated patients showing mucosal healing at Week 10, 9 of 12 patients also showed mucosal healing at Week 54.

Patients who achieved a response and subsequently lost response were eligible to receive REMICADE on an episodic basis at a dose that was 5 mg/kg higher than the dose to which they were randomized. The majority of such patients responded to the higher dose. Among patients who were not in response at Week 2, 59% (92/157) of REMICADE maintenance patients responded by Week 14 compared to 51% (39/77) of placebo maintenance patients. Among patients who did not respond by Week 14, additional therapy did not result in significantly more responses [see Dosage and Administration (2)] .

Fistulizing Crohn's Disease in Adults

The safety and efficacy of REMICADE were assessed in 2 randomized, double-blind, placebo-controlled studies in adult patients with fistulizing CD with fistula(s) that were of at least 3 months duration. Concurrent use of stable doses of corticosteroids, 5-aminosalicylates, antibiotics, MTX, 6-mercaptopurine (6-MP) and/or azathioprine (AZA) was permitted.

In the first trial, 94 adult patients received 3 doses of either placebo or REMICADE at Weeks 0, 2 and 6. Fistula response (≥50% reduction in number of enterocutaneous fistulas draining upon gentle compression on at least 2 consecutive visits without an increase in medication or surgery for CD) was seen in 68% (21/31) of patients in the 5 mg/kg REMICADE group ( P=0.002) and 56% (18/32) of patients in the 10 mg/kg REMICADE group ( P=0.021) vs. 26% (8/31) of patients in the placebo arm. The median time to onset of response and median duration of response in REMICADE-treated patients was 2 and 12 weeks, respectively. Closure of all fistulas was achieved in 52% of REMICADE-treated patients compared with 13% of placebo-treated patients ( P<0.001).

In the second trial (ACCENT II [Study Crohn's II]), adult patients who were enrolled had to have at least 1 draining enterocutaneous (perianal, abdominal) fistula. All patients received 5 mg/kg REMICADE at Weeks 0, 2 and 6. Patients were randomized to placebo or 5 mg/kg REMICADE maintenance at Week 14. Patients received maintenance doses at Week 14 and then every 8 weeks through Week 46. Patients who were in fistula response (fistula response was defined the same as in the first trial) at both Weeks 10 and 14 were randomized separately from those not in response. The primary endpoint was time from randomization to loss of response among those patients who were in fistula response.

Among the randomized patients (273 of the 296 initially enrolled), 87% had perianal fistulas and 14% had abdominal fistulas. Eight percent also had rectovaginal fistulas. Greater than 90% of the patients had received previous immunosuppressive and antibiotic therapy.

At Week 14, 65% (177/273) of patients were in fistula response. Patients randomized to REMICADE maintenance had a longer time to loss of fistula response compared to the placebo maintenance group (Figure 2). At Week 54, 38% (33/87) of REMICADE-treated patients had no draining fistulas compared with 22% (20/90) of placebo-treated patients ( P=0.02). Compared to placebo maintenance, patients on REMICADE maintenance had a trend toward fewer hospitalizations.

Figure 2: Life Table Estimates of the Proportion of Adult CD Patients Who Had Not Lost Fistula Response Through Week 54 (Study Crohn's II)

Patients who achieved a fistula response and subsequently lost response were eligible to receive REMICADE maintenance therapy at a dose that was 5 mg/kg higher than the dose to which they were randomized. Of the placebo maintenance patients, 66% (25/38) responded to 5 mg/kg REMICADE, and 57% (12/21) of REMICADE maintenance patients responded to 10 mg/kg.

Patients who had not achieved a response by Week 14 were unlikely to respond to additional doses of REMICADE.

Similar proportions of patients in either group developed new fistulas (17% overall) and similar numbers developed abscesses (15% overall).

The safety and efficacy of REMICADE were assessed in a randomized, open-label study (Study Peds Crohn's) in 112 pediatric patients aged 6 to 17 years old with moderately to severely active CD and an inadequate response to conventional therapies. The median age was 13 years and the median Pediatric Crohn's Disease Activity Index (PCDAI) was 40 (on a scale of 0 to 100). All patients were required to be on a stable dose of 6-MP, AZA, or MTX; 35% were also receiving corticosteroids at baseline.

All patients received induction dosing of 5 mg/kg REMICADE at Weeks 0, 2, and 6. At Week 10, 103 patients were randomized to a maintenance regimen of 5 mg/kg REMICADE given either every 8 weeks or every 12 weeks.

At Week 10, 88% of patients were in clinical response (defined as a decrease from baseline in the PCDAI score of ≥15 points and total PCDAI score of ≤30 points), and 59% were in clinical remission (defined as PCDAI score of ≤10 points).

The proportion of pediatric patients achieving clinical response at Week 10 compared favorably with the proportion of adults achieving a clinical response in Study Crohn's I. The study definition of clinical response in Study Peds Crohn's was based on the PCDAI score, whereas the CDAI score was used in the adult Study Crohn's I.

At both Week 30 and Week 54, the proportion of patients in clinical response was greater in the every 8-week treatment group than in the every 12-week treatment group (73% vs. 47% at Week 30, and 64% vs. 33% at Week 54). At both Week 30 and Week 54, the proportion of patients in clinical remission was also greater in the every 8-week treatment group than in the every 12-week treatment group (60% vs. 35% at Week 30, and 56% vs. 24% at Week 54), (Table 4).

For patients in Study Peds Crohn's receiving corticosteroids at baseline, the proportion of patients able to discontinue corticosteroids while in remission at Week 30 was 46% for the every 8-week maintenance group and 33% for the every 12-week maintenance group. At Week 54, the proportion of patients able to discontinue corticosteroids while in remission was 46% for the every 8-week maintenance group and 17% for the every 12-week maintenance group.

<div class="scrollingtable"><table width="85%"> <caption> <span>Table 4: Response and Remission in Study Peds Crohn's</span> </caption> <col align="left" valign="top" width="60%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <thead> <tr class="First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule" colspan="2">5 mg/kg REMICADE</th> </tr> <tr> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule">Every 8 Week</th><th align="center" class="Botrule Rrule">Every 12 Week</th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">Treatment Group</th><th align="center" class="Rrule">Treatment Group</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-12" name="footnote-12">*</a> </dt> <dd>Defined as a decrease from baseline in the PCDAI score of ≥15 points and total score of ≤30 points.</dd> <dt> <a href="#footnote-reference-13" name="footnote-13">†</a> </dt> <dd>P-value &lt;0.01 </dd> <dt> <a href="#footnote-reference-14" name="footnote-14">‡</a> </dt> <dd>Defined as a PCDAI score of ≤10 points.</dd> <dt> <a href="#footnote-reference-15" name="footnote-15">§</a> </dt> <dd>P-value &lt;0.05 </dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule"><span class="Bold">Patients randomized</span></td><td align="center" class="Rrule">52</td><td align="center" class="Rrule">51</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Clinical Response</span><a class="Sup" href="#footnote-12" name="footnote-reference-12">*</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Week 30</td><td align="center" class="Rrule">73% <a class="Sup" href="#footnote-13" name="footnote-reference-13">†</a></td><td align="center" class="Rrule">47%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Week 54</td><td align="center" class="Rrule">64% <a class="Sup" href="#footnote-13">†</a></td><td align="center" class="Rrule">33%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Clinical Remission</span><a class="Sup" href="#footnote-14" name="footnote-reference-14">‡</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Week 30</td><td align="center" class="Rrule">60% <a class="Sup" href="#footnote-15" name="footnote-reference-15">§</a></td><td align="center" class="Rrule">35%</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">  Week 54</td><td align="center" class="Rrule">56% <a class="Sup" href="#footnote-13">†</a></td><td align="center" class="Rrule">24%</td> </tr> </tbody> </table></div>

The safety and efficacy of REMICADE were assessed in 2 randomized, double-blind, placebo-controlled clinical studies in 728 adult patients with moderately to severely active UC (Mayo score 6 to 12 [of possible range 0 to 12], Endoscopy subscore ≥2) with an inadequate response to conventional oral therapies (Studies UC I and UC II). Concomitant treatment with stable doses of aminosalicylates, corticosteroids and/or immunomodulatory agents was permitted. Corticosteroid taper was permitted after Week 8. Patients were randomized at week 0 to receive either placebo, 5 mg/kg REMICADE or 10 mg/kg REMICADE at Weeks 0, 2, 6, and every 8 weeks thereafter through Week 46 in Study UC I, and at Weeks 0, 2, 6, and every 8 weeks thereafter through Week 22 in Study UC II. In Study UC II, patients were allowed to continue blinded therapy to Week 46 at the investigator's discretion.

Adult patients in Study UC I had failed to respond or were intolerant to oral corticosteroids, 6-MP, or AZA. Adult patients in Study UC II had failed to respond or were intolerant to the above treatments and/or aminosalicylates. Similar proportions of patients in Studies UC I and UC II were receiving corticosteroids (61% and 51%, respectively), 6-MP/AZA (49% and 43%) and aminosalicylates (70% and 75%) at baseline. More patients in Study UC II than UC I were taking solely aminosalicylates for UC (26% vs. 11%, respectively). Clinical response was defined as a decrease from baseline in the Mayo score by ≥30% and ≥3 points, accompanied by a decrease in the rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0 or 1.

Clinical Response, Clinical Remission, and Mucosal Healing

In both Study UC I and Study UC II, greater percentages of patients in both REMICADE groups achieved clinical response, clinical remission and mucosal healing than in the placebo group. Each of these effects was maintained through the end of each trial (Week 54 in Study UC I, and Week 30 in Study UC II). In addition, a greater proportion of patients in REMICADE groups demonstrated sustained response and sustained remission than in the placebo groups (Table 5).

Of patients on corticosteroids at baseline, greater proportions of adult patients in the REMICADE treatment groups were in clinical remission and able to discontinue corticosteroids at Week 30 compared with the patients in the placebo treatment groups (22% in REMICADE treatment groups vs. 10% in placebo group in Study UC I; 23% in REMICADE treatment groups vs. 3% in placebo group in Study UC II). In Study UC I, this effect was maintained through Week 54 (21% in REMICADE treatment groups vs. 9% in placebo group). The REMICADE-associated response was generally similar in the 5 mg/kg and 10 mg/kg dose groups.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 5: Response, Remission and Mucosal Healing in Adult UC Studies (Studies UC I and UC II)</span> </caption> <col align="left" valign="top" width="16%"/> <col align="center" valign="top" width="12%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="12%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="15%"/> <thead> <tr class="First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule" colspan="3">Study UC I</th><th align="center" class="Botrule Rrule" colspan="3">Study UC II</th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule" valign="bottom">Placebo</th><th align="center" class="Rrule" valign="bottom">5 mg/kg REMICADE</th><th align="center" class="Rrule" valign="bottom">10 mg/kg REMICADE</th><th align="center" class="Rrule" valign="bottom">Placebo</th><th align="center" class="Rrule" valign="bottom">5 mg/kg REMICADE</th><th align="center" class="Rrule" valign="bottom">10 mg/kg REMICADE</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="7"> <dl class="Footnote"> <dt> <a href="#footnote-reference-16" name="footnote-16">*</a> </dt> <dd>Defined as a decrease from baseline in the Mayo score by ≥30% and ≥3 points, accompanied by a decrease in the rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0 or 1. (The Mayo score consists of the sum of four subscores: stool frequency, rectal bleeding, physician's global assessment and endoscopy findings).</dd> <dt> <a href="#footnote-reference-17" name="footnote-17">†</a> </dt> <dd>Patients who had a prohibited change in medication, had an ostomy or colectomy, or discontinued study infusions due to lack of efficacy are considered to not be in clinical response, clinical remission or mucosal healing from the time of the event onward.</dd> <dt> <a href="#footnote-reference-18" name="footnote-18">‡</a> </dt> <dd>P&lt;0.001, </dd> <dt> <a href="#footnote-reference-19" name="footnote-19">§</a> </dt> <dd>P&lt;0.01 </dd> <dt> <a href="#footnote-reference-20" name="footnote-20">¶</a> </dt> <dd>Defined as a Mayo score ≤2 points, no individual subscore &gt;1.</dd> <dt> <a href="#footnote-reference-21" name="footnote-21">#</a> </dt> <dd>Defined as a 0 or 1 on the endoscopy subscore of the Mayo score.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule"><span class="Bold">Patients randomized</span></td><td align="center" class="Rrule">121</td><td align="center" class="Rrule">121</td><td align="center" class="Rrule">122</td><td align="center" class="Rrule">123</td><td align="center" class="Rrule">121</td><td align="center" class="Rrule">120</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">Clinical Response</span><a class="Sup" href="#footnote-16" name="footnote-reference-16">*</a><span class="Sup">,</span><a class="Sup" href="#footnote-17" name="footnote-reference-17">†</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Week 8</td><td align="center" class="Rrule">37%</td><td align="center" class="Rrule">69% <a class="Sup" href="#footnote-18" name="footnote-reference-18">‡</a></td><td align="center" class="Rrule">62% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">29%</td><td align="center" class="Rrule">65% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">69% <a class="Sup" href="#footnote-18">‡</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Week 30</td><td align="center" class="Rrule">30%</td><td align="center" class="Rrule">52% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">51% <a class="Sup" href="#footnote-19" name="footnote-reference-19">§</a></td><td align="center" class="Rrule">26%</td><td align="center" class="Rrule">47% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">60% <a class="Sup" href="#footnote-18">‡</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Week 54</td><td align="center" class="Rrule">20%</td><td align="center" class="Rrule">45% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">44% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">NA</td><td align="center" class="Rrule">NA</td><td align="center" class="Rrule">NA</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">Sustained Response</span><a class="Sup" href="#footnote-17">†</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  (Clinical response at both Weeks 8 and 30)</td><td align="center" class="Rrule">23%</td><td align="center" class="Rrule">49% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">46% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">15%</td><td align="center" class="Rrule">41% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">53% <a class="Sup" href="#footnote-18">‡</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  (Clinical response at Weeks 8, 30, and 54)</td><td align="center" class="Rrule">14%</td><td align="center" class="Rrule">39% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">37% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">NA</td><td align="center" class="Rrule">NA</td><td align="center" class="Rrule">NA</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">Clinical Remission</span><a class="Sup" href="#footnote-20" name="footnote-reference-20">¶</a><span class="Sup">,</span><a class="Sup" href="#footnote-17">†</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Week 8</td><td align="center" class="Rrule">15%</td><td align="center" class="Rrule">39% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">32% <a class="Sup" href="#footnote-19">§</a></td><td align="center" class="Rrule">6%</td><td align="center" class="Rrule">34% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">28% <a class="Sup" href="#footnote-18">‡</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Week 30</td><td align="center" class="Rrule">16%</td><td align="center" class="Rrule">34% <a class="Sup" href="#footnote-19">§</a></td><td align="center" class="Rrule">37% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">11%</td><td align="center" class="Rrule">26% <a class="Sup" href="#footnote-19">§</a></td><td align="center" class="Rrule">36% <a class="Sup" href="#footnote-18">‡</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Week 54</td><td align="center" class="Rrule">17%</td><td align="center" class="Rrule">35% <a class="Sup" href="#footnote-19">§</a></td><td align="center" class="Rrule">34% <a class="Sup" href="#footnote-19">§</a></td><td align="center" class="Rrule">NA</td><td align="center" class="Rrule">NA</td><td align="center" class="Rrule">NA</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">Sustained Remission</span><a class="Sup" href="#footnote-17">†</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  (Clinical remission at both Weeks 8 and 30)</td><td align="center" class="Rrule">8%</td><td align="center" class="Rrule">23% <a class="Sup" href="#footnote-19">§</a></td><td align="center" class="Rrule">26% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">2%</td><td align="center" class="Rrule">15% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">23% <a class="Sup" href="#footnote-18">‡</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  (Clinical remission at Weeks 8, 30 and 54)</td><td align="center" class="Rrule">7%</td><td align="center" class="Rrule">20% <a class="Sup" href="#footnote-19">§</a></td><td align="center" class="Rrule">20% <a class="Sup" href="#footnote-19">§</a></td><td align="center" class="Rrule">NA</td><td align="center" class="Rrule">NA</td><td align="center" class="Rrule">NA</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">Mucosal Healing</span><a class="Sup" href="#footnote-21" name="footnote-reference-21">#</a><span class="Sup">,</span><a class="Sup" href="#footnote-17">†</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Week 8</td><td align="center" class="Rrule">34%</td><td align="center" class="Rrule">62% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">59% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">31%</td><td align="center" class="Rrule">60% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">62% <a class="Sup" href="#footnote-18">‡</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Week 30</td><td align="center" class="Rrule">25%</td><td align="center" class="Rrule">50% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">49% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">30%</td><td align="center" class="Rrule">46% <a class="Sup" href="#footnote-19">§</a></td><td align="center" class="Rrule">57% <a class="Sup" href="#footnote-18">‡</a></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">  Week 54</td><td align="center" class="Rrule">18%</td><td align="center" class="Rrule">45% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">47% <a class="Sup" href="#footnote-18">‡</a></td><td align="center" class="Rrule">NA</td><td align="center" class="Rrule">NA</td><td align="center" class="Rrule">NA</td> </tr> </tbody> </table></div>

The improvement with REMICADE was consistent across all Mayo subscores through Week 54 (Study UC I shown in Table 6; Study UC II through Week 30 was similar).

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 6: Proportion of Adult UC Patients in Study UC I with Mayo Subscores Indicating Inactive or Mild Disease Through Week 54</span> </caption> <col align="left" valign="top" width="55%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="15%"/> <thead> <tr class="First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule" colspan="3">Study UC I</th> </tr> <tr> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule"></th><th align="center" class="Botrule Rrule" colspan="2">REMICADE</th> </tr> <tr> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule">Placebo</th><th align="center" class="Botrule Rrule">5 mg/kg</th><th align="center" class="Botrule Rrule">10 mg/kg</th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">(n=121)</th><th align="center" class="Rrule">(n=121)</th><th align="center" class="Rrule">(n=122)</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Stool frequency</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Baseline</td><td align="center" class="Rrule">17%</td><td align="center" class="Rrule">17%</td><td align="center" class="Rrule">10%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">    Week 8</td><td align="center" class="Rrule">35%</td><td align="center" class="Rrule">60%</td><td align="center" class="Rrule">58%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">    Week 30</td><td align="center" class="Rrule">35%</td><td align="center" class="Rrule">51%</td><td align="center" class="Rrule">53%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">    Week 54</td><td align="center" class="Rrule">31%</td><td align="center" class="Rrule">52%</td><td align="center" class="Rrule">51%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Rectal bleeding</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Baseline</td><td align="center" class="Rrule">54%</td><td align="center" class="Rrule">40%</td><td align="center" class="Rrule">48%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">    Week 8</td><td align="center" class="Rrule">74%</td><td align="center" class="Rrule">86%</td><td align="center" class="Rrule">80%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">    Week 30</td><td align="center" class="Rrule">65%</td><td align="center" class="Rrule">74%</td><td align="center" class="Rrule">71%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">    Week 54</td><td align="center" class="Rrule">62%</td><td align="center" class="Rrule">69%</td><td align="center" class="Rrule">67%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Physician's Global Assessment</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Baseline</td><td align="center" class="Rrule">4%</td><td align="center" class="Rrule">6%</td><td align="center" class="Rrule">3%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">    Week 8</td><td align="center" class="Rrule">44%</td><td align="center" class="Rrule">74%</td><td align="center" class="Rrule">64%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">    Week 30</td><td align="center" class="Rrule">36%</td><td align="center" class="Rrule">57%</td><td align="center" class="Rrule">55%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">    Week 54</td><td align="center" class="Rrule">26%</td><td align="center" class="Rrule">53%</td><td align="center" class="Rrule">53%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Endoscopy findings</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Baseline</td><td align="center" class="Rrule">0%</td><td align="center" class="Rrule">0%</td><td align="center" class="Rrule">0%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">    Week 8</td><td align="center" class="Rrule">34%</td><td align="center" class="Rrule">62%</td><td align="center" class="Rrule">59%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">    Week 30</td><td align="center" class="Rrule">26%</td><td align="center" class="Rrule">51%</td><td align="center" class="Rrule">52%</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">    Week 54</td><td align="center" class="Rrule">21%</td><td align="center" class="Rrule">50%</td><td align="center" class="Rrule">51%</td> </tr> </tbody> </table></div>

The safety and effectiveness of REMICADE for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients aged 6 years and older with moderately to severely active UC who have had an inadequate response to conventional therapy are supported by evidence from adequate and well-controlled studies of REMICADE in adults. Additional safety and pharmacokinetic data were collected in an open-label pediatric UC trial in 60 pediatric patients aged 6 through 17 years (median age 14.5 years) with moderately to severely active UC (Mayo score of 6 to 12; Endoscopic subscore ≥2) and an inadequate response to conventional therapies. At baseline, the median Mayo score was 8, 53% of patients were receiving immunomodulator therapy (6-MP/AZA/MTX), and 62% of patients were receiving corticosteroids (median dose 0.5 mg/kg/day in prednisone equivalents). Discontinuation of immunomodulators and corticosteroid taper were permitted after Week 0.

All patients received induction dosing of 5 mg/kg REMICADE at Weeks 0, 2, and 6. Patients who did not respond to REMICADE at Week 8 received no further REMICADE and returned for safety follow-up. At Week 8, 45 patients were randomized to a maintenance regimen of 5 mg/kg REMICADE given either every 8 weeks through Week 46 or every 12 weeks through Week 42. Patients were allowed to change to a higher dose and/or more frequent administration schedule if they experienced loss of response.

Clinical response at Week 8 was defined as a decrease from baseline in the Mayo score by ≥30% and ≥3 points, including a decrease in the rectal bleeding subscore by ≥1 points or achievement of a rectal bleeding subscore of 0 or 1.

Clinical remission at Week 8 was measured by the Mayo score, defined as a Mayo score of ≤2 points with no individual subscore >1. Clinical remission was also assessed at Week 8 and Week 54 using the Pediatric Ulcerative Colitis Activity Index (PUCAI) 1score and was defined by a PUCAI score of <10 points.

Endoscopies were performed at baseline and at Week 8. A Mayo endoscopy subscore of 0 indicated normal or inactive disease and a subscore of 1 indicated mild disease (erythema, decreased vascular pattern, or mild friability).

Of the 60 patients treated, 44 were in clinical response at Week 8. Of 32 patients taking concomitant immunomodulators at baseline, 23 achieved clinical response at Week 8, compared to 21 of 28 of those not taking concomitant immunomodulators at baseline. At Week 8, 24 of 60 patients were in clinical remission as measured by the Mayo score and 17 of 51 patients were in remission as measured by the PUCAI score.

At Week 54, 8 of 21 patients in the every 8-week maintenance group and 4 of 22 patients in the every 12-week maintenance group achieved remission as measured by the PUCAI score.

During maintenance phase, 23 of 45 randomized patients (9 in the every 8-week group and 14 in the every 12-week group) required an increase in their dose and/or increase in frequency of REMICADE administration due to loss of response. Nine of the 23 patients who required a change in dose had achieved remission at Week 54. Seven of those patients received the 10 mg/kg every 8-week dosing.

The safety and efficacy of REMICADE in adult patients with RA were assessed in 2 multicenter, randomized, double-blind, pivotal trials: ATTRACT (Study RA I) and ASPIRE (Study RA II). Concurrent use of stable doses of folic acid, oral corticosteroids (≤10 mg/day) and/or non-steroidal anti-inflammatory drugs (NSAIDs) was permitted.

Study RA I was a placebo-controlled study of 428 patients with active RA despite treatment with MTX. Patients enrolled had a median age of 54 years, median disease duration of 8.4 years, median swollen and tender joint count of 20 and 31 respectively, and were on a median dose of 15 mg/wk of MTX. Patients received either placebo+MTX or one of 4 doses/schedules of REMICADE+MTX: 3 mg/kg or 10 mg/kg of REMICADE by IV infusion at Weeks 0, 2 and 6 followed by additional infusions every 4 or 8 weeks in combination with MTX.

Study RA II was a placebo-controlled study of 3 active treatment arms in 1004 MTX naive patients of 3 or fewer years' duration active RA. Patients enrolled had a median age of 51 years with a median disease duration of 0.6 years, median swollen and tender joint count of 19 and 31 , respectively, and >80% of patients had baseline joint erosions. At randomization, all patients received MTX (optimized to 20 mg/wk by Week 8) and either placebo, 3 mg/kg or 6 mg/kg REMICADE at Weeks 0, 2, and 6 and every 8 weeks thereafter.

Data on use of REMICADE without concurrent MTX are limited [see Adverse Reactions (6.1)] .

Clinical Response

In Study RA I, all doses/schedules of REMICADE+MTX resulted in improvement in signs and symptoms as measured by the American College of Rheumatology response criteria (ACR 20) with a higher percentage of patients achieving an ACR 20, 50 and 70 compared to placebo+MTX (Table 7). This improvement was observed at Week 2 and maintained through Week 102. Greater effects on each component of the ACR 20 were observed in all patients treated with REMICADE+MTX compared to placebo+MTX (Table 8). More patients treated with REMICADE reached a major clinical response than placebo-treated patients (Table 7).

In Study RA II, after 54 weeks of treatment, both doses of REMICADE+MTX resulted in statistically significantly greater response in signs and symptoms compared to MTX alone as measured by the proportion of patients achieving ACR 20, 50 and 70 responses (Table 7). More patients treated with REMICADE reached a major clinical response than placebo-treated patients (Table 7).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 7: ACR Response (percent of patients) in Adult RA Patients (Studies RA I and RA II)</span> </caption> <col align="left" valign="top" width="12%"/> <col align="center" valign="top" width="11%"/> <col align="center" valign="top" width="11%"/> <col align="center" valign="top" width="11%"/> <col align="center" valign="top" width="11%"/> <col align="center" valign="top" width="11%"/> <col align="center" valign="top" width="11%"/> <col align="center" valign="top" width="11%"/> <col align="center" valign="top" width="11%"/> <thead> <tr class="First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule" colspan="5">Study RA I</th><th align="center" class="Botrule Rrule" colspan="3">Study RA II</th> </tr> <tr> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule"></th><th align="center" class="Botrule Rrule" colspan="4" valign="bottom">REMICADE+MTX</th><th align="center" class="Rrule"></th><th align="center" class="Botrule Rrule" colspan="2">REMICADE+MTX</th> </tr> <tr class="Botrule"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule"></th><th align="center" class="Rrule" colspan="2">3 mg/kg</th><th align="center" class="Rrule" colspan="2">10 mg/kg</th><th align="center" class="Rrule"></th><th align="center" class="Rrule">3 mg/kg</th><th align="center" class="Rrule">6 mg/kg</th> </tr> <tr class="Botrule"> <th align="left" class="Lrule Rrule">Response</th><th align="center" class="Rrule" valign="bottom">Placebo+MTX</th><th align="center" class="Rrule" valign="bottom">q8 wks</th><th align="center" class="Rrule" valign="bottom">q4 wks</th><th align="center" class="Rrule" valign="bottom">q8 wks</th><th align="center" class="Rrule" valign="bottom">q4 wks</th><th align="center" class="Rrule" valign="bottom">Placebo+MTX</th><th align="center" class="Rrule" valign="bottom">q8 wks</th><th align="center" class="Rrule" valign="bottom">q8 wks</th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">(n=88)</th><th align="center" class="Rrule">(n=86)</th><th align="center" class="Rrule">(n=86)</th><th align="center" class="Rrule">(n=87)</th><th align="center" class="Rrule">(n=81)</th><th align="center" class="Rrule">(n=274)</th><th align="center" class="Rrule">(n=351)</th><th align="center" class="Rrule">(n=355)</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="9"> <dl class="Footnote"> <dt> <a href="#footnote-reference-22" name="footnote-22">*</a> </dt> <dd>P≤0.001 </dd> <dt> <a href="#footnote-reference-23" name="footnote-23">†</a> </dt> <dd>P&lt;0.05 </dd> <dt> <a href="#footnote-reference-24" name="footnote-24">‡</a> </dt> <dd>P&lt;0.01 </dd> <dt> <a href="#footnote-reference-25" name="footnote-25">§</a> </dt> <dd>A major clinical response was defined as a 70% ACR response for 6 consecutive months (consecutive visits spanning at least 26 weeks) through Week 102 for Study RA I and Week 54 for Study RA II.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">ACR 20</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Week 30</td><td align="center" class="Rrule">20%</td><td align="center" class="Rrule">50% <a class="Sup" href="#footnote-22" name="footnote-reference-22">*</a></td><td align="center" class="Rrule">50% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">52% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">58% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">N/A</td><td align="center" class="Rrule">N/A</td><td align="center" class="Rrule">N/A</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Week 54</td><td align="center" class="Rrule">17%</td><td align="center" class="Rrule">42% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">48% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">59% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">59% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">54%</td><td align="center" class="Rrule">62% <a class="Sup" href="#footnote-23" name="footnote-reference-23">†</a></td><td align="center" class="Rrule">66% <a class="Sup" href="#footnote-22">*</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">ACR 50</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Week 30</td><td align="center" class="Rrule">5%</td><td align="center" class="Rrule">27% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">29% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">31% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">26% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">N/A</td><td align="center" class="Rrule">N/A</td><td align="center" class="Rrule">N/A</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Week 54</td><td align="center" class="Rrule">9%</td><td align="center" class="Rrule">21% <a class="Sup" href="#footnote-23">†</a></td><td align="center" class="Rrule">34% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">40% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">38% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">32%</td><td align="center" class="Rrule">46% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">50% <a class="Sup" href="#footnote-22">*</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">ACR 70</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Week 30</td><td align="center" class="Rrule">0%</td><td align="center" class="Rrule">8% <a class="Sup" href="#footnote-24" name="footnote-reference-24">‡</a></td><td align="center" class="Rrule">11% <a class="Sup" href="#footnote-24">‡</a></td><td align="center" class="Rrule">18% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">11% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">N/A</td><td align="center" class="Rrule">N/A</td><td align="center" class="Rrule">N/A</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Week 54</td><td align="center" class="Rrule">2%</td><td align="center" class="Rrule">11% <a class="Sup" href="#footnote-23">†</a></td><td align="center" class="Rrule">18% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">26% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">19% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">21%</td><td align="center" class="Rrule">33% <a class="Sup" href="#footnote-24">‡</a></td><td align="center" class="Rrule">37% <a class="Sup" href="#footnote-22">*</a></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Major clinical response <a class="Sup" href="#footnote-25" name="footnote-reference-25">§</a></td><td align="center" class="Rrule">0%</td><td align="center" class="Rrule">7% <a class="Sup" href="#footnote-23">†</a></td><td align="center" class="Rrule">8% <a class="Sup" href="#footnote-24">‡</a></td><td align="center" class="Rrule">15% <a class="Sup" href="#footnote-22">*</a></td><td align="center" class="Rrule">6% <a class="Sup" href="#footnote-23">†</a></td><td align="center" class="Rrule">8%</td><td align="center" class="Rrule">12%</td><td align="center" class="Rrule">17% <a class="Sup" href="#footnote-22">*</a></td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 8: Components of ACR 20 at Baseline and 54 Weeks (Study RA I)</span> </caption> <col align="left" valign="top" width="52%"/> <col align="center" valign="top" width="12%"/> <col align="center" valign="top" width="12%"/> <col align="center" valign="top" width="12%"/> <col align="center" valign="top" width="12%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule" colspan="2">Placebo+MTX</th><th align="center" class="Rrule" colspan="2">REMICADE+MTX <a class="Sup" href="#footnote-26" name="footnote-reference-26">*</a></th> </tr> <tr class="Botrule"> <th align="left" class="Lrule Rrule">Parameter (medians)</th><th align="center" class="Rrule" colspan="2">(n=88)</th><th align="center" class="Rrule" colspan="2">(n=340)</th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">Baseline</th><th align="center" class="Rrule">Week 54</th><th align="center" class="Rrule">Baseline</th><th align="center" class="Rrule">Week 54</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-26" name="footnote-26">*</a> </dt> <dd>All doses/schedules of REMICADE+MTX</dd> <dt> <a href="#footnote-reference-27" name="footnote-27">†</a> </dt> <dd>Visual Analog Scale (0=best, 10=worst)</dd> <dt> <a href="#footnote-reference-28" name="footnote-28">‡</a> </dt> <dd>Health Assessment Questionnaire, measurement of 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities (0=best, 3=worst)</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">No. of Tender Joints</td><td align="center" class="Rrule">24</td><td align="center" class="Rrule">16</td><td align="center" class="Rrule">32</td><td align="center" class="Rrule">8</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">No. of Swollen Joints</td><td align="center" class="Rrule">19</td><td align="center" class="Rrule">13</td><td align="center" class="Rrule">20</td><td align="center" class="Rrule">7</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pain <a class="Sup" href="#footnote-27" name="footnote-reference-27">†</a></td><td align="center" class="Rrule">6.7</td><td align="center" class="Rrule">6.1</td><td align="center" class="Rrule">6.8</td><td align="center" class="Rrule">3.3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Physician's Global Assessment <a class="Sup" href="#footnote-27">†</a></td><td align="center" class="Rrule">6.5</td><td align="center" class="Rrule">5.2</td><td align="center" class="Rrule">6.2</td><td align="center" class="Rrule">2.1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Patient's Global Assessment <a class="Sup" href="#footnote-27">†</a></td><td align="center" class="Rrule">6.2</td><td align="center" class="Rrule">6.2</td><td align="center" class="Rrule">6.3</td><td align="center" class="Rrule">3.2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Disability Index (HAQ-DI) <a class="Sup" href="#footnote-28" name="footnote-reference-28">‡</a></td><td align="center" class="Rrule">1.8</td><td align="center" class="Rrule">1.5</td><td align="center" class="Rrule">1.8</td><td align="center" class="Rrule">1.3</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">CRP (mg/dL)</td><td align="center" class="Rrule">3.0</td><td align="center" class="Rrule">2.3</td><td align="center" class="Rrule">2.4</td><td align="center" class="Rrule">0.6</td> </tr> </tbody> </table></div>

Radiographic Response

Structural damage in both hands and feet was assessed radiographically at Week 54 by the change from baseline in the van der Heijde-modified Sharp (vdH-S) score, a composite score of structural damage that measures the number and size of joint erosions and the degree of joint space narrowing in hands/wrists and feet.

In Study RA I, approximately 80% of patients had paired X-ray data at 54 weeks and approximately 70% at 102 weeks. The inhibition of progression of structural damage was observed at 54 weeks (Table 9) and maintained through 102 weeks.

In Study RA II, >90% of patients had at least 2 evaluable X-rays. Inhibition of progression of structural damage was observed at Weeks 30 and 54 (Table 9) in the REMICADE+MTX groups compared to MTX alone. Patients treated with REMICADE+MTX demonstrated less progression of structural damage compared to MTX alone, whether baseline acute-phase reactants (ESR and CRP) were normal or elevated: patients with elevated baseline acute-phase reactants treated with MTX alone demonstrated a mean progression in vdH-S score of 4.2 units compared to patients treated with REMICADE+MTX who demonstrated 0.5 units of progression; patients with normal baseline acute phase reactants treated with MTX alone demonstrated a mean progression in vdH-S score of 1.8 units compared to REMICADE+MTX who demonstrated 0.2 units of progression. Of patients receiving REMICADE+MTX, 59% had no progression (vdH-S score ≤0 unit) of structural damage compared to 45% of patients receiving MTX alone. In a subset of patients who began the study without erosions, REMICADE+MTX maintained an erosion-free state at 1 year in a greater proportion of patients than MTX alone, 79% (77/98) vs. 58% (23/40), respectively ( P<0.01). Fewer patients in the REMICADE+MTX groups (47%) developed erosions in uninvolved joints compared to MTX alone (59%).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 9: Radiographic Change from Baseline to Week 54 in Adult RA Patients (Studies RA I and RA II)</span> </caption> <col align="left" valign="bottom" width="34%"/> <col align="center" valign="top" width="11%"/> <col align="center" valign="top" width="11%"/> <col align="center" valign="top" width="11%"/> <col align="center" valign="top" width="11%"/> <col align="center" valign="top" width="11%"/> <col align="center" valign="top" width="11%"/> <thead> <tr class="First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule" colspan="3">Study RA I</th><th align="center" class="Botrule Rrule" colspan="3">Study RA II</th> </tr> <tr> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule"></th><th align="center" class="Botrule Rrule" colspan="2">REMICADE+MTX</th><th align="center" class="Rrule"></th><th align="center" class="Botrule Rrule" colspan="2">REMICADE+MTX</th> </tr> <tr> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule"></th><th align="center" class="Botrule Rrule">3 mg/kg</th><th align="center" class="Botrule Rrule">10 mg/kg</th><th align="center" class="Botrule Rrule"></th><th align="center" class="Botrule Rrule">3 mg/kg</th><th align="center" class="Botrule Rrule">6 mg/kg</th> </tr> <tr> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule" valign="bottom">Placebo+MTX</th><th align="center" class="Botrule Rrule" valign="bottom">q8 wks</th><th align="center" class="Botrule Rrule" valign="bottom">q8 wks</th><th align="center" class="Botrule Rrule" valign="bottom">Placebo+MTX</th><th align="center" class="Botrule Rrule" valign="bottom">q8 wks</th><th align="center" class="Botrule Rrule" valign="bottom">q8 wks</th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">(n=64)</th><th align="center" class="Rrule">(n=71)</th><th align="center" class="Rrule">(n=77)</th><th align="center" class="Rrule">(n=282)</th><th align="center" class="Rrule">(n=359)</th><th align="center" class="Rrule">(n=363)</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="7"> <dl class="Footnote"> <dt> <a href="#footnote-reference-29" name="footnote-29">*</a> </dt> <dd>P&lt;0.001 for each outcome against placebo.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">Total Score</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7">Baseline</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Mean</td><td align="center" class="Rrule">79</td><td align="center" class="Rrule">78</td><td align="center" class="Rrule">65</td><td align="center" class="Rrule">11.3</td><td align="center" class="Rrule">11.6</td><td align="center" class="Rrule">11.2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Median</td><td align="center" class="Rrule">55</td><td align="center" class="Rrule">57</td><td align="center" class="Rrule">56</td><td align="center" class="Rrule">5.1</td><td align="center" class="Rrule">5.2</td><td align="center" class="Rrule">5.3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7">Change from baseline</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Mean</td><td align="center" class="Rrule">6.9</td><td align="center" class="Rrule">1.3 <a class="Sup" href="#footnote-29" name="footnote-reference-29">*</a></td><td align="center" class="Rrule">0.2 <a class="Sup" href="#footnote-29">*</a></td><td align="center" class="Rrule">3.7</td><td align="center" class="Rrule">0.4 <a class="Sup" href="#footnote-29">*</a></td><td align="center" class="Rrule">0.5 <a class="Sup" href="#footnote-29">*</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Median</td><td align="center" class="Rrule">4.0</td><td align="center" class="Rrule">0.5</td><td align="center" class="Rrule">0.5</td><td align="center" class="Rrule">0.4</td><td align="center" class="Rrule">0.0</td><td align="center" class="Rrule">0.0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">Erosion Score</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7">Baseline</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Mean</td><td align="center" class="Rrule">44</td><td align="center" class="Rrule">44</td><td align="center" class="Rrule">33</td><td align="center" class="Rrule">8.3</td><td align="center" class="Rrule">8.8</td><td align="center" class="Rrule">8.3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Median</td><td align="center" class="Rrule">25</td><td align="center" class="Rrule">29</td><td align="center" class="Rrule">22</td><td align="center" class="Rrule">3.0</td><td align="center" class="Rrule">3.8</td><td align="center" class="Rrule">3.8</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7">Change from baseline</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Mean</td><td align="center" class="Rrule">4.1</td><td align="center" class="Rrule">0.2 <a class="Sup" href="#footnote-29">*</a></td><td align="center" class="Rrule">0.2 <a class="Sup" href="#footnote-29">*</a></td><td align="center" class="Rrule">3.0</td><td align="center" class="Rrule">0.3 <a class="Sup" href="#footnote-29">*</a></td><td align="center" class="Rrule">0.1 <a class="Sup" href="#footnote-29">*</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Median</td><td align="center" class="Rrule">2.0</td><td align="center" class="Rrule">0.0</td><td align="center" class="Rrule">0.5</td><td align="center" class="Rrule">0.3</td><td align="center" class="Rrule">0.0</td><td align="center" class="Rrule">0.0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7"><span class="Bold">JSN Score</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7">Baseline</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Mean</td><td align="center" class="Rrule">36</td><td align="center" class="Rrule">34</td><td align="center" class="Rrule">31</td><td align="center" class="Rrule">3.0</td><td align="center" class="Rrule">2.9</td><td align="center" class="Rrule">2.9</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Median</td><td align="center" class="Rrule">26</td><td align="center" class="Rrule">29</td><td align="center" class="Rrule">24</td><td align="center" class="Rrule">1.0</td><td align="center" class="Rrule">1.0</td><td align="center" class="Rrule">1.0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="7">Change from baseline</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Mean</td><td align="center" class="Rrule">2.9</td><td align="center" class="Rrule">1.1 <a class="Sup" href="#footnote-29">*</a></td><td align="center" class="Rrule">0.0 <a class="Sup" href="#footnote-29">*</a></td><td align="center" class="Rrule">0.6</td><td align="center" class="Rrule">0.1 <a class="Sup" href="#footnote-29">*</a></td><td align="center" class="Rrule">0.2</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">  Median</td><td align="center" class="Rrule">1.5</td><td align="center" class="Rrule">0.0</td><td align="center" class="Rrule">0.0</td><td align="center" class="Rrule">0.0</td><td align="center" class="Rrule">0.0</td><td align="center" class="Rrule">0.0</td> </tr> </tbody> </table></div>

Physical Function Response

Physical function and disability were assessed using the Health Assessment Questionnaire (HAQ-DI) and the general health-related quality of life questionnaire SF-36.

In Study RA I, all doses/schedules of REMICADE+MTX showed significantly greater improvement from baseline in HAQ-DI and SF-36 physical component summary score averaged over time through Week 54 compared to placebo+MTX, and no worsening in the SF-36 mental component summary score. The median (interquartile range) improvement from baseline to Week 54 in HAQ-DI was 0.1 (-0.1, 0.5) for the placebo+MTX group and 0.4 (0.1, 0.9) for REMICADE+MTX (p<0.001). Both HAQ-DI and SF-36 effects were maintained through Week 102. Approximately 80% of patients in all doses/schedules of REMICADE+MTX remained in the trial through 102 weeks.

In Study RA II, both REMICADE treatment groups showed greater improvement in HAQ-DI from baseline averaged over time through Week 54 compared to MTX alone; 0.7 for REMICADE+MTX vs. 0.6 for MTX alone ( P≤0.001). No worsening in the SF-36 mental component summary score was observed.

The safety and efficacy of REMICADE were assessed in a randomized, multicenter, double-blind, placebo-controlled study in 279 adult patients with active AS. Patients were between 18 and 74 years of age, and had AS, as defined by the modified New York criteria for Ankylosing Spondylitis. Patients were to have had active disease as evidenced by both a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score >4 (possible range 0–10) and spinal pain >4 (on a Visual Analog Scale [VAS] of 0–10). Patients with complete ankylosis of the spine were excluded from study participation, and the use of Disease Modifying Anti-Rheumatic Drugs (DMARDs) and systemic corticosteroids were prohibited. Doses of REMICADE 5 mg/kg or placebo were administered intravenously at Weeks 0, 2, 6, 12 and 18.

At 24 weeks, improvement in the signs and symptoms of AS, as measured by the proportion of patients achieving a 20% improvement in ASAS response criteria (ASAS 20), was seen in 60% of patients in the REMICADE-treated group vs. 18% of patients in the placebo group (p<0.001). Improvement was observed at Week 2 and maintained through Week 24 (Figure 3 and Table 10).

Figure 3: Proportion of Adult AS Patients Who Achieved a ASAS 20 Response

At 24 weeks, the proportions of patients achieving a 50% and a 70% improvement in the signs and symptoms of AS, as measured by ASAS response criteria (ASAS 50 and ASAS 70, respectively), were 44% and 28%, respectively, for patients receiving REMICADE, compared to 9% and 4%, respectively, for patients receiving placebo ( P<0.001, REMICADE vs. placebo). A low level of disease activity (defined as a value <20 [on a scale of 0–100 mm] in each of the 4 ASAS response parameters) was achieved in 22% of REMICADE-treated patients vs. 1% in placebo-treated patients ( P<0.001).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 10: Components of AS Disease Activity</span> </caption> <col align="left" valign="bottom" width="30%"/> <col align="center" valign="top" width="14%"/> <col align="center" valign="top" width="14%"/> <col align="center" valign="top" width="14%"/> <col align="center" valign="top" width="14%"/> <col align="center" valign="top" width="14%"/> <thead> <tr class="First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule" colspan="2">Placebo <br/> (n=78) </th><th align="center" class="Botrule Rrule" colspan="2">REMICADE 5 mg/kg <br/> (n=201) </th><th align="center" class="Botrule Rrule"></th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">Baseline</th><th align="center" class="Rrule">24 Weeks</th><th align="center" class="Rrule">Baseline</th><th align="center" class="Rrule">24 Weeks</th><th align="center" class="Rrule"><span class="Italics">P</span>-value </th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-30" name="footnote-30">*</a> </dt> <dd>Measured on a VAS with 0="none" and 10="severe"</dd> <dt> <a href="#footnote-reference-31" name="footnote-31">†</a> </dt> <dd>Bath Ankylosing Spondylitis Functional Index (BASFI), average of 10 questions</dd> <dt> <a href="#footnote-reference-32" name="footnote-32">‡</a> </dt> <dd>Inflammation, average of last 2 questions on the 6-question BASDAI</dd> <dt> <a href="#footnote-reference-33" name="footnote-33">§</a> </dt> <dd>CRP normal range 0–1.0 mg/dL</dd> <dt> <a href="#footnote-reference-34" name="footnote-34">¶</a> </dt> <dd>Spinal mobility normal values: modified Schober's test: &gt;4 cm; chest expansion:&gt;6 cm; tragus to wall: &lt;15 cm; lateral spinal flexion: &gt;10 cm</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="6"><span class="Bold">ASAS 20 response</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="6"><span class="Bold">Criteria (Mean)</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Patient Global Assessment <a class="Sup" href="#footnote-30" name="footnote-reference-30">*</a></td><td align="center" class="Rrule">6.6</td><td align="center" class="Rrule">6.0</td><td align="center" class="Rrule">6.8</td><td align="center" class="Rrule">3.8</td><td align="center" class="Rrule">&lt;0.001</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Spinal pain <a class="Sup" href="#footnote-30">*</a></td><td align="center" class="Rrule">7.3</td><td align="center" class="Rrule">6.5</td><td align="center" class="Rrule">7.6</td><td align="center" class="Rrule">4.0</td><td align="center" class="Rrule">&lt;0.001</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  BASFI <a class="Sup" href="#footnote-31" name="footnote-reference-31">†</a></td><td align="center" class="Rrule">5.8</td><td align="center" class="Rrule">5.6</td><td align="center" class="Rrule">5.7</td><td align="center" class="Rrule">3.6</td><td align="center" class="Rrule">&lt;0.001</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Inflammation <a class="Sup" href="#footnote-32" name="footnote-reference-32">‡</a></td><td align="center" class="Rrule">6.9</td><td align="center" class="Rrule">5.8</td><td align="center" class="Rrule">6.9</td><td align="center" class="Rrule">3.4</td><td align="center" class="Rrule">&lt;0.001</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="6"><span class="Bold">Acute Phase Reactants</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Median CRP <a class="Sup" href="#footnote-33" name="footnote-reference-33">§</a>(mg/dL) </td><td align="center" class="Rrule">1.7</td><td align="center" class="Rrule">1.5</td><td align="center" class="Rrule">1.5</td><td align="center" class="Rrule">0.4</td><td align="center" class="Rrule">&lt;0.001</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="6"><span class="Bold">Spinal Mobility (cm, Mean)</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Modified Schober's test <a class="Sup" href="#footnote-34" name="footnote-reference-34">¶</a></td><td align="center" class="Rrule">4.0</td><td align="center" class="Rrule">5.0</td><td align="center" class="Rrule">4.3</td><td align="center" class="Rrule">4.4</td><td align="center" class="Rrule">0.75</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Chest expansion <a class="Sup" href="#footnote-34">¶</a></td><td align="center" class="Rrule">3.6</td><td align="center" class="Rrule">3.7</td><td align="center" class="Rrule">3.3</td><td align="center" class="Rrule">3.9</td><td align="center" class="Rrule">0.04</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Tragus to wall <a class="Sup" href="#footnote-34">¶</a></td><td align="center" class="Rrule">17.3</td><td align="center" class="Rrule">17.4</td><td align="center" class="Rrule">16.9</td><td align="center" class="Rrule">15.7</td><td align="center" class="Rrule">0.02</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">  Lateral spinal flexion <a class="Sup" href="#footnote-34">¶</a></td><td align="center" class="Rrule">10.6</td><td align="center" class="Rrule">11.0</td><td align="center" class="Rrule">11.4</td><td align="center" class="Rrule">12.9</td><td align="center" class="Rrule">0.03</td> </tr> </tbody> </table></div>

The median improvement from baseline in the general health-related quality-of-life questionnaire SF-36 physical component summary score at Week 24 was 10.2 for the REMICADE group vs. 0.8 for the placebo group ( P<0.001). There was no change in the SF-36 mental component summary score in either the REMICADE group or the placebo group.

Results of this study were similar to those seen in a multicenter double-blind, placebo-controlled study of 70 patients with AS.

Safety and efficacy of REMICADE were assessed in a multicenter, double-blind, placebo-controlled study in 200 adult patients with active PsA despite DMARD or NSAID therapy (≥5 swollen joints and ≥5 tender joints) with 1 or more of the following subtypes: arthritis involving DIP joints (n=49), arthritis mutilans (n=3), asymmetric peripheral arthritis (n=40), polyarticular arthritis (n=100), and spondylitis with peripheral arthritis (n=8). Patients also had Ps with a qualifying target lesion ≥2 cm in diameter. Forty-six percent of patients continued on stable doses of methotrexate (≤25 mg/week). During the 24-week double-blind phase, patients received either 5 mg/kg REMICADE or placebo at Weeks 0, 2, 6, 14, and 22 (100 patients in each group). At Week 16, placebo patients with <10% improvement from baseline in both swollen and tender joint counts were switched to REMICADE induction (early escape). At Week 24, all placebo-treated patients crossed over to REMICADE induction. Dosing continued for all patients through Week 46.

Clinical Response

Treatment with REMICADE resulted in improvement in signs and symptoms, as assessed by the ACR criteria, with 58% of REMICADE-treated patients achieving ACR 20 at Week 14, compared with 11% of placebo-treated patients ( P<0.001). The response was similar regardless of concomitant use of methotrexate. Improvement was observed as early as Week 2. At 6 months, the ACR 20/50/70 responses were achieved by 54%, 41%, and 27%, respectively, of patients receiving REMICADE compared to 16%, 4%, and 2%, respectively, of patients receiving placebo. Similar responses were seen in patients with each of the subtypes of PsA, although few patients were enrolled with the arthritis mutilans and spondylitis with peripheral arthritis subtypes.

Compared to placebo, treatment with REMICADE resulted in improvements in the components of the ACR response criteria, as well as in dactylitis and enthesopathy (Table 11). The clinical response was maintained through Week 54. Similar ACR responses were observed in an earlier randomized, placebo-controlled study of 104 PsA patients, and the responses were maintained through 98 weeks in an open-label extension phase.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 11: Components of ACR 20 and Percentage of Adult PsA Patients with 1 or More Joints with Dactylitis and Percentage of Adult PsA Patients with Enthesopathy at Baseline and Week 24</span> </caption> <col align="left" valign="top" width="40%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="15%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule" colspan="2">Placebo</th><th align="center" class="Rrule" colspan="2">REMICADE 5 mg/kg <a class="Sup" href="#footnote-35" name="footnote-reference-35">*</a></th> </tr> <tr class="Botrule"> <th align="left" class="Lrule Rrule">Patients Randomized</th><th align="center" class="Rrule" colspan="2">(n=100)</th><th align="center" class="Rrule" colspan="2">(n=100)</th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">Baseline</th><th align="center" class="Rrule">Week 24</th><th align="center" class="Rrule">Baseline</th><th align="center" class="Rrule">Week 24</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-35" name="footnote-35">*</a> </dt> <dd>P&lt;0.001 for percent change from baseline in all components of ACR 20 at Week 24, P&lt;0.05 for % of patients with dactylitis, and P=0.004 for % of patients with enthesopathy at Week 24 </dd> <dt> <a href="#footnote-reference-36" name="footnote-36">†</a> </dt> <dd>Scale 0–68</dd> <dt> <a href="#footnote-reference-37" name="footnote-37">‡</a> </dt> <dd>Scale 0–66</dd> <dt> <a href="#footnote-reference-38" name="footnote-38">§</a> </dt> <dd>Visual Analog Scale (0=best, 10=worst)</dd> <dt> <a href="#footnote-reference-39" name="footnote-39">¶</a> </dt> <dd>Health Assessment Questionnaire, measurement of 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities (0=best, 3=worst)</dd> <dt> <a href="#footnote-reference-40" name="footnote-40">#</a> </dt> <dd>Normal range 0–0.6 mg/dL</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Parameter (medians)</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">No. of Tender Joints <a class="Sup" href="#footnote-36" name="footnote-reference-36">†</a></td><td align="center" class="Rrule">24</td><td align="center" class="Rrule">20</td><td align="center" class="Rrule">20</td><td align="center" class="Rrule">6</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">No. of Swollen Joints <a class="Sup" href="#footnote-37" name="footnote-reference-37">‡</a></td><td align="center" class="Rrule">12</td><td align="center" class="Rrule">9</td><td align="center" class="Rrule">12</td><td align="center" class="Rrule">3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pain <a class="Sup" href="#footnote-38" name="footnote-reference-38">§</a></td><td align="center" class="Rrule">6.4</td><td align="center" class="Rrule">5.6</td><td align="center" class="Rrule">5.9</td><td align="center" class="Rrule">2.6</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Physician's Global Assessment <a class="Sup" href="#footnote-38">§</a></td><td align="center" class="Rrule">6.0</td><td align="center" class="Rrule">4.5</td><td align="center" class="Rrule">5.6</td><td align="center" class="Rrule">1.5</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Patient's Global Assessment <a class="Sup" href="#footnote-38">§</a></td><td align="center" class="Rrule">6.1</td><td align="center" class="Rrule">5.0</td><td align="center" class="Rrule">5.9</td><td align="center" class="Rrule">2.5</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Disability Index (HAQ-DI) <a class="Sup" href="#footnote-39" name="footnote-reference-39">¶</a></td><td align="center" class="Rrule">1.1</td><td align="center" class="Rrule">1.1</td><td align="center" class="Rrule">1.1</td><td align="center" class="Rrule">0.5</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">CRP (mg/dL) <a class="Sup" href="#footnote-40" name="footnote-reference-40">#</a></td><td align="center" class="Rrule">1.2</td><td align="center" class="Rrule">0.9</td><td align="center" class="Rrule">1.0</td><td align="center" class="Rrule">0.4</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">% Patients with 1 or more digits with dactylitis</td><td align="center" class="Rrule">41</td><td align="center" class="Rrule">33</td><td align="center" class="Rrule">40</td><td align="center" class="Rrule">15</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">% Patients with enthesopathy</td><td align="center" class="Rrule">35</td><td align="center" class="Rrule">36</td><td align="center" class="Rrule">42</td><td align="center" class="Rrule">22</td> </tr> </tbody> </table></div>

Improvement in Psoriasis Area and Severity Index (PASI) in PsA patients with baseline body surface area (BSA) ≥3% (n=87 placebo, n=83 REMICADE) was achieved at Week 14, regardless of concomitant methotrexate use, with 64% of REMICADE-treated patients achieving at least 75% improvement from baseline vs. 2% of placebo-treated patients; improvement was observed in some patients as early as Week 2. At 6 months, the PASI 75 and PASI 90 responses were achieved by 60% and 39%, respectively, of patients receiving REMICADE compared to 1% and 0%, respectively, of patients receiving placebo. The PASI response was generally maintained through Week 54. [see Clinical Studies (14.8)] .

Radiographic Response

Structural damage in both hands and feet was assessed radiographically by the change from baseline in the van der Heijde-Sharp (vdH-S) score, modified by the addition of hand DIP joints. The total modified vdH-S score is a composite score of structural damage that measures the number and size of joint erosions and the degree of joint space narrowing (JSN) in the hands and feet. At Week 24, REMICADE-treated patients had less radiographic progression than placebo-treated patients (mean change of -0.70 vs. 0.82, P<0.001). REMICADE-treated patients also had less progression in their erosion scores (-0.56 vs 0.51) and JSN scores (-0.14 vs 0.31). The patients in the REMICADE group demonstrated continued inhibition of structural damage at Week 54. Most patients showed little or no change in the vdH-S score during this 12-month study (median change of 0 in both patients who initially received REMICADE or placebo). More patients in the placebo group (12%) had readily apparent radiographic progression compared with the REMICADE group (3%).

Physical Function

Physical function status was assessed using the HAQ Disability Index (HAQ-DI) and the SF-36 Health Survey. REMICADE-treated patients demonstrated significant improvement in physical function as assessed by HAQ-DI (median percent improvement in HAQ-DI score from baseline to Week 14 and 24 of 43% for REMICADE-treated patients vs 0% for placebo-treated patients).

During the placebo-controlled portion of the trial (24 weeks), 54% of REMICADE-treated patients achieved a clinically meaningful improvement in HAQ-DI (≥0.3 unit decrease) compared to 22% of placebo-treated patients. REMICADE-treated patients also demonstrated greater improvement in the SF-36 physical and mental component summary scores than placebo-treated patients. The responses were maintained for up to 2 years in an open-label extension study.

The safety and efficacy of REMICADE were assessed in 3 randomized, double-blind, placebo-controlled studies in patients 18 years of age and older with chronic, stable Ps involving ≥10% BSA, a minimum PASI score of 12, and who were candidates for systemic therapy or phototherapy. Patients with guttate, pustular, or erythrodermic psoriasis were excluded from these studies. No concomitant anti-psoriatic therapies were allowed during the study, with the exception of low-potency topical corticosteroids on the face and groin after Week 10 of study initiation.

Study I (EXPRESS) evaluated 378 patients who received placebo or REMICADE at a dose of 5 mg/kg at Weeks 0, 2, and 6 (induction therapy), followed by maintenance therapy every 8 weeks. At Week 24, the placebo group crossed over to REMICADE induction therapy (5 mg/kg), followed by maintenance therapy every 8 weeks. Patients originally randomized to REMICADE continued to receive REMICADE 5 mg/kg every 8 weeks through Week 46. Across all treatment groups, the median baseline PASI score was 21 and the baseline Static Physician Global Assessment (sPGA) score ranged from moderate (52% of patients) to marked (36%) to severe (2%). In addition, 75% of patients had a BSA >20%. Seventy-one percent of patients previously received systemic therapy, and 82% received phototherapy.

Study II (EXPRESS II) evaluated 835 patients who received placebo or REMICADE at doses of 3 mg/kg or 5 mg/kg at Weeks 0, 2, and 6 (induction therapy). At Week 14, within each REMICADE dose group, patients were randomized to either scheduled (every 8 weeks) or as needed (PRN) maintenance treatment through Week 46. At Week 16, the placebo group crossed over to REMICADE induction therapy (5 mg/kg), followed by maintenance therapy every 8 weeks. Across all treatment groups, the median baseline PASI score was 18, and 63% of patients had a BSA >20%. Fifty-five percent of patients previously received systemic therapy, and 64% received a phototherapy.

Study III (SPIRIT) evaluated 249 patients who had previously received either psoralen plus ultraviolet A treatment (PUVA) or other systemic therapy for their psoriasis. These patients were randomized to receive either placebo or REMICADE at doses of 3 mg/kg or 5 mg/kg at Weeks 0, 2, and 6. At Week 26, patients with a sPGA score of moderate or worse (greater than or equal to 3 on a scale of 0 to 5) received an additional dose of the randomized treatment. Across all treatment groups, the median baseline PASI score was 19, and the baseline sPGA score ranged from moderate (62% of patients) to marked (22%) to severe (3%). In addition, 75% of patients had a BSA >20%. Of the enrolled patients, 114 (46%) received the Week 26 additional dose.

In Studies I, II and III, the primary endpoint was the proportion of patients who achieved a reduction in score of at least 75% from baseline at Week 10 by the PASI (PASI 75). In Study I and Study III, another evaluated outcome included the proportion of patients who achieved a score of "cleared" or "minimal" by the sPGA. The sPGA is a 6-category scale ranging from "5 = severe" to "0 = cleared" indicating the physician's overall assessment of the psoriasis severity focusing on induration, erythema, and scaling. Treatment success, defined as "cleared" or "minimal," consisted of none or minimal elevation in plaque, up to faint red coloration in erythema, and none or minimal fine scale over <5% of the plaque.

Study II also evaluated the proportion of patients who achieved a score of "clear" or "excellent" by the relative Physician's Global Assessment (rPGA). The rPGA is a 6-category scale ranging from "6 = worse" to "1 = clear" that was assessed relative to baseline. Overall lesions were graded with consideration to the percent of body involvement as well as overall induration, scaling, and erythema. Treatment success, defined as "clear" or "excellent," consisted of some residual pinkness or pigmentation to marked improvement (nearly normal skin texture; some erythema may be present). The results of these studies are presented in Table 12.

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 12: Adult Psoriasis Studies I, II, and III, Percentage of Patients who Achieved PASI 75 and Percentage who Achieved Treatment "Success" with Physician's Global Assessment at Week 10</span> </caption> <col align="left" valign="top" width="55%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="15%"/> <thead> <tr class="First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Botrule Rrule">Placebo</th><th align="center" class="Botrule Rrule" colspan="2">REMICADE</th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule"></th><th align="center" class="Rrule">3 mg/kg</th><th align="center" class="Rrule">5 mg/kg</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-41" name="footnote-41">*</a> </dt> <dd>Patients with missing data at Week 10 were considered as nonresponders.</dd> <dt> <a href="#footnote-reference-42" name="footnote-42">†</a> </dt> <dd>P&lt;0.001 compared with placebo </dd> <dt> <a href="#footnote-reference-43" name="footnote-43">‡</a> </dt> <dd>Patients with missing data at Week 10 were imputed by last observation.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Psoriasis Study I - patients randomized <a class="Sup" href="#footnote-41" name="footnote-reference-41">*</a></td><td align="center" class="Rrule">77</td><td align="center" class="Rrule">—</td><td align="center" class="Rrule">301</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  PASI 75</td><td align="center" class="Rrule">2 (3%)</td><td align="center" class="Rrule">—</td><td align="center" class="Rrule">242 (80%) <a class="Sup" href="#footnote-42" name="footnote-reference-42">†</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  sPGA</td><td align="center" class="Rrule">3 (4%)</td><td align="center" class="Rrule">—</td><td align="center" class="Rrule">242 (80%) <a class="Sup" href="#footnote-42">†</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Psoriasis Study II - patients randomized <a class="Sup" href="#footnote-41">*</a></td><td align="center" class="Rrule">208</td><td align="center" class="Rrule">313</td><td align="center" class="Rrule">314</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  PASI 75</td><td align="center" class="Rrule">4 (2%)</td><td align="center" class="Rrule">220 (70%) <a class="Sup" href="#footnote-42">†</a></td><td align="center" class="Rrule">237 (75%) <a class="Sup" href="#footnote-42">†</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  rPGA</td><td align="center" class="Rrule">2 (1%)</td><td align="center" class="Rrule">217 (69%) <a class="Sup" href="#footnote-42">†</a></td><td align="center" class="Rrule">234 (75%) <a class="Sup" href="#footnote-42">†</a></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Psoriasis Study III - patients randomized <a class="Sup" href="#footnote-43" name="footnote-reference-43">‡</a></td><td align="center" class="Rrule">51</td><td align="center" class="Rrule">99</td><td align="center" class="Rrule">99</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  PASI 75</td><td align="center" class="Rrule">3 (6%)</td><td align="center" class="Rrule">71 (72%) <a class="Sup" href="#footnote-42">†</a></td><td align="center" class="Rrule">87 (88%) <a class="Sup" href="#footnote-42">†</a></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">  sPGA</td><td align="center" class="Rrule">5 (10%)</td><td align="center" class="Rrule">71 (72%) <a class="Sup" href="#footnote-42">†</a></td><td align="center" class="Rrule">89 (90%) <a class="Sup" href="#footnote-42">†</a></td> </tr> </tbody> </table></div>

In Study I, in the subgroup of patients with more extensive Ps who had previously received phototherapy, 85% of patients on 5 mg/kg REMICADE achieved a PASI 75 at Week 10 compared with 4% of patients on placebo.

In Study II, in the subgroup of patients with more extensive Ps who had previously received phototherapy, 72% and 77% of patients on 3 mg/kg and 5 mg/kg REMICADE achieved a PASI 75 at Week 10 respectively compared with 1% on placebo. In Study II, among patients with more extensive Ps who had failed or were intolerant to phototherapy, 70% and 78% of patients on 3 mg/kg and 5 mg/kg REMICADE achieved a PASI 75 at Week 10 respectively, compared with 2% on placebo.

Maintenance of response was studied in a subset of 292 and 297 REMICADE-treated patients in the 3 mg/kg and 5 mg/kg groups; respectively, in Study II. Stratified by PASI response at Week 10 and investigational site, patients in the active treatment groups were re-randomized to either a scheduled or as needed maintenance (PRN) therapy, beginning on Week 14.

The groups that received a maintenance dose every 8 weeks appear to have a greater percentage of patients maintaining a PASI 75 through Week 50 as compared to patients who received the as-needed or PRN doses, and the best response was maintained with the 5 mg/kg every 8-week dose. These results are shown in Figure 4. At Week 46, when REMICADE serum concentrations were at trough level, in the every 8-week dose group, 54% of patients in the 5 mg/kg group compared to 36% in the 3 mg/kg group achieved PASI 75. The lower percentage of PASI 75 responders in the 3 mg/kg every 8-week dose group compared to the 5 mg/kg group was associated with a lower percentage of patients with detectable trough serum infliximab levels. This may be related in part to higher antibody rates [see Adverse Reactions (6.1)] . In addition, in a subset of patients who had achieved a response at Week 10, maintenance of response appears to be greater in patients who received REMICADE every 8 weeks at the 5 mg/kg dose. Regardless of whether the maintenance doses are PRN or every 8 weeks, there is a decline in response in a subpopulation of patients in each group over time. The results of Study I through Week 50 in the 5 mg/kg every 8 weeks maintenance dose group were similar to the results from Study II.

Figure 4: Proportion of Adult Ps Patients Who Achieved ≥75% Improvement in PASI from Baseline through Week 50 (patients randomized at Week 14)

Efficacy and safety of REMICADE treatment beyond 50 weeks have not been evaluated in patients with Ps.

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How Supplied

REMICADE ®(infliximab) for injection is supplied in a carton containing one single-dose vial (NDC 57894-030-01).

Each single-dose vial contains 100 mg of infliximab as a sterile, preservative-free, white lyophilized powder for reconstitution and dilution (more than one vial may be needed for a full dose) [see Dosage and Administration (2.11)].

Storage and Handling

Store unopened REMICADE ®vials in a refrigerator at 2°C to 8°C (36°F to 46°F).

If needed, unopened REMICADE vials may be stored at room temperatures up to a maximum of 30°C (86°F) for a single period of up to 6 months but not exceeding the original expiration date. The new expiration date must be written in the space provided on the carton. Once removed from the refrigerator, REMICADE cannot be returned to the refrigerator.

For storage conditions of the reconstituted and diluted product for administration, see Dosage and Administration (2.11).

Infections

Inform patients that REMICADE increases the risk for developing serious infections. Instruct patients of the importance of contacting their healthcare provider if they develop any symptoms of an infection, including tuberculosis, invasive fungal infections, and reactivation of hepatitis B virus infections [see Warnings and Precautions (5.1, 5.3)] .

Malignancies

Malignancies have been reported among children, adolescents and young adults who received treatment with TNF blockers. Patients should be counseled about the risk of lymphoma and other malignancies while receiving REMICADE [see Warnings and Precautions (5.2)] .

Hepatotoxicity

Instruct patients to seek medical attention if they develop signs or symptoms of hepatotoxicity (e.g., jaundice) [see Warnings and Precautions (5.4)].

Heart Failure

Instruct patients to seek medical attention and consult their prescriber if they develop signs or symptoms of heart failure [see Contraindications (4)and Warnings and Precautions (5.5)] .

Hematologic Reactions

Instruct patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever) while on REMICADE [see Warnings and Precautions (5.6)] .

Hypersensitivity

Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.7)].

Cardiovascular and Cerebrovascular Reactions During and After Infusion

Advise patients to seek immediate medical attention if they develop any new or worsening symptoms of cardiovascular and cerebrovascular reactions which have been reported during and within 24 hours of initiation of REMICADE infusion [see Warnings and Precautions (5.8)].

Neurologic Reactions

Advise patients to seek medical attention if they develop signs or symptoms of neurologic reactions [see Warnings and Precautions (5.9)].

Live Vaccines/Therapeutic Infectious Agents

Instruct REMICADE-treated patients to avoid receiving live vaccines or therapeutic infectious agents [see Warnings and Precautions (5.13)].

Manufactured by: Janssen Biotech, Inc. Horsham, PA 19044

U.S. License No. 1864

© Johnson & Johnson and its affiliates 1998-2025

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="2%"/> <col align="left" valign="top" width="30%"/> <col align="left" valign="top" width="35%"/> <col align="left" valign="top" width="33%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="3">                This Medication Guide has been approved by the U.S. Food and Drug Administration</td><td align="right">Revised: 2/2025</td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="4"><span class="Bold">MEDICATION GUIDE <br/> REMICADE <span class="Sup">®</span>(Rem-eh-kaid) <br/> (infliximab) <br/> for injection, for intravenous use </span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4">Read the Medication Guide that comes with REMICADE before you receive the first treatment, and before each time you get a treatment of REMICADE. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment. <br/> <span class="Bold">What is the most important information I should know about REMICADE?</span> <br/> REMICADE may cause serious side effects, including: <br/> <span class="Bold">1. Risk of infection</span> <br/> REMICADE is a medicine that affects your immune system. REMICADE can lower the ability of your immune system to fight infections. Serious infections have happened in patients receiving REMICADE. These infections include tuberculosis (TB) and infections caused by viruses, fungi or bacteria that have spread throughout the body. Some patients have died from these infections. <br/> <ul> <li>Your doctor should test you for TB before starting REMICADE.</li> <li>Your doctor should monitor you closely for signs and symptoms of TB during treatment with REMICADE.</li> </ul> <span class="Bold">Before starting REMICADE, tell your doctor if you:</span> <ul> <li>think you have an infection. You should not start receiving REMICADE if you have any kind of infection.</li> <li>are being treated for an infection.</li> <li>have signs of an infection, such as a fever, cough, flu-like symptoms.</li> <li>have any open cuts or sores on your body.</li> <li>get a lot of infections or have infections that keep coming back.</li> <li>have diabetes or an immune system problem. People with these conditions have a higher chance for infections.</li> <li>have TB, or have been in close contact with someone with TB.</li> <li>live or have lived in certain parts of the country (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis). These infections may develop or become more severe if you receive REMICADE. If you do not know if you have lived in an area where histoplasmosis, coccidioidomycosis, or blastomycosis is common, ask your doctor.</li> <li>have or have had hepatitis B.</li> <li>use the medicines KINERET (anakinra), ORENCIA (abatacept), ACTEMRA (tocilizumab), or other medicines called biologics used to treat the same conditions as REMICADE.</li> </ul> <span class="Bold">After starting REMICADE</span>, if you have an infection, any sign of an infection including a fever, cough, flu-like symptoms, or have open cuts or sores on your body, call your doctor right away. REMICADE can make you more likely to get infections or make any infection that you have worse. <br/> <span class="Bold">2. Risk of Cancer</span> <ul> <li>There have been cases of unusual cancers in children and teenage patients using tumor necrosis factor (TNF) blocker medicines.</li> <li>For children and adults receiving TNF blocker medicines, including REMICADE, the chances of getting lymphoma or other cancers may increase.</li> <li>Some people receiving TNF blockers, including REMICADE, developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. Most of these people were male teenagers or young men. Also, most people were being treated for Crohn's disease or ulcerative colitis with a TNF blocker and another medicine called azathioprine or 6-mercaptopurine.</li> <li>People who have been treated for rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis for a long time may be more likely to develop lymphoma. This is especially true for people with very active disease.</li> <li>Some people treated with REMICADE have developed certain kinds of skin cancer. If any changes in the appearance of your skin or growths on your skin occur during or after your treatment with REMICADE, tell your doctor.</li> <li>Patients with Chronic Obstructive Pulmonary Disease (COPD), a specific type of lung disease, may have an increased risk for getting cancer while being treated with REMICADE.</li> <li>Some women being treated for rheumatoid arthritis with REMICADE have developed cervical cancer. For women receiving REMICADE, including those over 60 years of age, your doctor may recommend that you continue to be regularly screened for cervical cancer.</li> <li>Tell your doctor if you have ever had any type of cancer. Discuss with your doctor any need to adjust medicines you may be taking.</li> </ul>See the section " <span class="Bold"><a href="#SE">What are the possible side effects of REMICADE?</a></span>" below for more information. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">What is REMICADE?</span> <br/> REMICADE is a prescription medicine that is approved for patients with: <ul> <li>Rheumatoid Arthritis - adults with moderately to severely active rheumatoid arthritis, along with the medicine methotrexate.</li> <li>Crohn's Disease - children 6 years and older and adults with Crohn's disease who have not responded well to other medicines.</li> <li>Ankylosing Spondylitis in adults</li> <li>Psoriatic Arthritis in adults</li> <li>Plaque Psoriasis - adult patients with plaque psoriasis that is chronic (does not go away), severe, extensive, and/or disabling.</li> <li>Ulcerative Colitis - children 6 years and older and adults with moderately to severely active ulcerative colitis who have not responded well to other medicines.</li> </ul>REMICADE blocks the action of a protein in your body called tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is made by your body's immune system. People with certain diseases have too much TNF-alpha that can cause the immune system to attack normal healthy parts of the body. REMICADE can block the damage caused by too much TNF-alpha. <br/> <span class="Bold">It is not known if REMICADE is safe and effective in children under 6 years of age.</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Who should not receive REMICADE?</span> <br/> You should not receive REMICADE if you have: <ul> <li>heart failure, unless your doctor has examined you and decided that you are able to receive REMICADE. Talk to your doctor about your heart failure.</li> <li>had an allergic reaction to REMICADE, or any of the other ingredients in REMICADE. See the end of this Medication Guide for a complete list of ingredients in REMICADE.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">What should I tell my doctor before starting treatment with REMICADE?</span> <br/> Your doctor will assess your health before each treatment. <br/> Tell your doctor about all of your medical conditions, including if you: <ul> <li>have an infection (see " <span class="Bold"><a href="#important">What is the most important information I should know about REMICADE?</a></span>"). </li> <li>have other liver problems including liver failure.</li> <li>have heart failure or other heart conditions. If you have heart failure, it may get worse while you receive REMICADE.</li> <li>have or have had any type of cancer.</li> <li>have had phototherapy (treatment with ultraviolet light or sunlight along with a medicine to make your skin sensitive to light) for psoriasis. You may have a higher chance of getting skin cancer while receiving REMICADE.</li> <li>have COPD, a specific type of lung disease. Patients with COPD may have an increased risk of getting cancer while receiving REMICADE.</li> <li>have or have had a condition that affects your nervous system such as: <ul class="Circle"> <li>multiple sclerosis, or Guillain-Barré syndrome, or</li> <li>if you experience any numbness or tingling, or</li> <li>if you have had a seizure.</li> </ul> </li> <li>have recently received or are scheduled to receive a vaccine. <span class="Bold">Adults and children receiving REMICADE should not receive live vaccines (for example, the Bacille Calmette-Guérin [BCG] vaccine) or treatment with a weakened bacteria</span>(such as BCG for bladder cancer). Adults and children should have all of their vaccines brought up to date before starting treatment with REMICADE. </li> <li>are pregnant or plan to become pregnant, are breastfeeding or plan to breastfeed. You and your doctor should decide if you should receive REMICADE while you are pregnant or breastfeeding.</li> </ul>If you have a baby and you were receiving REMICADE during your pregnancy, it is important to tell your baby's doctor and other health care professionals about your REMICADE use so they can decide when your baby should receive any vaccine. Certain vaccinations can cause infections. <br/> If you received REMICADE while you were pregnant, your baby may be at higher risk for getting an infection. If your baby receives a live vaccine within 6 months after birth, your baby may develop infections with serious complications that can lead to death. This includes live vaccines such as the BCG, rotavirus, or any other live vaccines. For other types of vaccines, talk with your doctor. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">How should I receive REMICADE?</span> <ul> <li>You will be given REMICADE through a needle placed in a vein (IV or intravenous infusion) in your arm.</li> <li>Your doctor may decide to give you medicine before starting the REMICADE infusion to prevent or lessen side effects.</li> <li>Only a healthcare professional should prepare the medicine and administer it to you.</li> <li>REMICADE will be given to you over a period of about 2 hours.</li> <li>If you have side effects from REMICADE, the infusion may need to be adjusted or stopped. In addition, your healthcare professional may decide to treat your symptoms.</li> <li>A healthcare professional will monitor you during the REMICADE infusion and for a period of time afterward for side effects. Your doctor may do certain tests while you are receiving REMICADE to monitor you for side effects and to see how well you respond to the treatment.</li> <li>Your doctor will determine the right dose of REMICADE for you and how often you should receive it. Make sure to discuss with your doctor when you will receive infusions and to come in for all your infusions and follow-up appointments.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">What should I avoid while receiving REMICADE?</span> <br/> Do not take REMICADE together with medicines such as KINERET (anakinra), ORENCIA (abatacept), ACTEMRA (tocilizumab), or other medicines called biologics that are used to treat the same conditions as REMICADE. <br/> <span class="Bold">Tell your doctor about all the medicines you take</span>, including prescription and over-the-counter medicines, vitamins, and herbal supplements. These include any other medicines to treat Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or psoriasis. <br/> Know the medicines you take. Keep a list of your medicines and show them to your doctor and pharmacist when you get a new medicine. </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">What are the possible side effects of REMICADE?</span> <br/> REMICADE can cause serious side effects, including: <br/> See " <span class="Bold"><a href="#important">What is the most important information I should know about REMICADE?</a></span>" <br/> <span class="Bold">Serious Infections</span> <ul> <li>Some patients, especially those 65 years and older have had serious infections while receiving REMICADE. These serious infections include TB and infections caused by viruses, fungi, or bacteria that have spread throughout the body or cause infections in certain areas (such as skin). Some patients die from these infections. If you get an infection while receiving treatment with REMICADE your doctor will treat your infection and may need to stop your REMICADE treatment.</li> <li>Tell your doctor right away if you have any of the following signs of an infection while receiving or after receiving REMICADE:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"> </td><td align="left"> <ul class="Circle"> <li>a fever</li> <li>feel very tired</li> <li>have a cough</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Circle"> <li>have flu-like symptoms</li> <li>warm, red, or painful skin</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <ul> <li>Your doctor will examine you for TB and perform a test to see if you have TB. If your doctor feels that you are at risk for TB, you may be treated with medicine for TB before you begin treatment with REMICADE and during treatment with REMICADE.</li> <li>Even if your TB test is negative, your doctor should carefully monitor you for TB infections while you are receiving REMICADE. Patients who had a <span class="Bold">negative</span>TB skin test before receiving REMICADE have developed active TB. </li> <li>If you are a chronic carrier of the hepatitis B virus, the virus can become active while you are being treated with REMICADE. In some cases, patients have died as a result of hepatitis B virus being reactivated. Your doctor should do a blood test for hepatitis B virus before you start treatment with REMICADE and occasionally while you are being treated. Tell your doctor if you have any of the following symptoms:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"> </td><td align="left"> <ul class="Circle"> <li>feel unwell</li> <li>poor appetite</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Circle"> <li>tiredness (fatigue)</li> <li>fever, skin rash, or joint pain</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Heart Failure</span> <br/> If you have a heart problem called congestive heart failure, your doctor should check you closely while you are receiving REMICADE. Your congestive heart failure may get worse while you are receiving REMICADE. Be sure to tell your doctor of any new or worse symptoms including: </td> </tr> <tr> <td align="left" class="Lrule"> </td><td align="left"> <ul class="Disc"> <li>shortness of breath</li> <li>swelling of ankles or feet</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>sudden weight gain</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4">Treatment with REMICADE may need to be stopped if you get new or worse congestive heart failure. <br/> <span class="Bold">Other Heart Problems</span> <br/> Some patients have experienced a heart attack (some of which led to death), low blood flow to the heart, or abnormal heart rhythm within 24 hours of beginning their infusion of REMICADE. Symptoms may include chest discomfort or pain, arm pain, stomach pain, shortness of breath, anxiety, lightheadedness, dizziness, fainting, sweating, nausea, vomiting, fluttering or pounding in your chest, and/or a fast or a slow heartbeat. Tell your doctor right away if you have any of these symptoms. <br/> <span class="Bold">Liver Injury</span> <br/> Some patients receiving REMICADE have developed serious liver problems. Tell your doctor if you have: </td> </tr> <tr> <td align="left" class="Lrule"> </td><td align="left"> <ul class="Disc"> <li>jaundice (skin and eyes turning yellow)</li> <li>dark brown-colored urine</li> <li>pain on the right side of your stomach area (right-sided abdominal pain)</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>fever</li> <li>extreme tiredness (severe fatigue)</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Blood Problems</span> <br/> In some patients receiving REMICADE, the body may not make enough of the blood cells that help fight infections or help stop bleeding. Tell your doctor if you: </td> </tr> <tr> <td align="left" class="Lrule"> </td><td align="left"> <ul class="Disc"> <li>have a fever that does not go away</li> <li>bruise or bleed very easily</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>look very pale</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Nervous System Disorders</span> <br/> Some patients receiving REMICADE have developed problems with their nervous system. Tell your doctor if you have: </td> </tr> <tr> <td align="left" class="Lrule"> </td><td align="left"> <ul class="Disc"> <li>changes in your vision</li> <li>numbness or tingling in any part of your body</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>seizures</li> <li>weakness in your arms or legs</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4">Some patients have experienced a stroke within approximately 24 hours of their infusion with REMICADE. Tell your doctor right away if you have symptoms of a stroke which may include: numbness or weakness of the face, arm or leg, especially on one side of the body; sudden confusion, trouble speaking or understanding; sudden trouble seeing in one or both eyes, sudden trouble walking, dizziness, loss of balance or coordination or a sudden, severe headache. <br/> <span class="Bold">Allergic Reactions</span> <br/> Some patients have had allergic reactions to REMICADE. Some of these reactions were severe. These reactions can happen while you are getting your REMICADE treatment or shortly afterward. Your doctor may need to stop or pause your treatment with REMICADE and may give you medicines to treat the allergic reaction. Signs of an allergic reaction can include: </td> </tr> <tr> <td align="left" class="Lrule"> </td><td align="left"> <ul class="Disc"> <li>hives (red, raised, itchy patches of skin)</li> <li>difficulty breathing</li> <li>chest pain</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>high or low blood pressure</li> <li>fever</li> <li>chills</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4">Some patients treated with REMICADE have had delayed allergic reactions. The delayed reactions occurred 3 to 12 days after receiving treatment with REMICADE. Tell your doctor right away if you have any of these signs of delayed allergic reaction to REMICADE:</td> </tr> <tr> <td align="left" class="Lrule"> </td><td align="left"> <ul class="Disc"> <li>fever</li> <li>rash</li> <li>headache</li> <li>sore throat</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>muscle or joint pain</li> <li>swelling of the face and hands</li> <li>difficulty swallowing</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Lupus-like Syndrome</span> <br/> Some patients have developed symptoms that are like the symptoms of Lupus. If you develop any of the following symptoms, your doctor may decide to stop your treatment with REMICADE. </td> </tr> <tr> <td align="left" class="Lrule"> </td><td align="left"> <ul class="Disc"> <li>chest discomfort or pain that does not go away</li> <li>shortness of breath</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>joint pain</li> <li>rash on the cheeks or arms that gets worse in the sun</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Psoriasis</span> <br/> Some people receiving REMICADE had new psoriasis or worsening of psoriasis they already had. Tell your doctor if you develop red scaly patches or raised bumps on the skin that are filled with pus. Your doctor may decide to stop your treatment with REMICADE. <br/> <span class="Bold">The most common side effects of REMICADE include:</span></td> </tr> <tr> <td align="left" class="Lrule"> </td><td align="left"> <ul class="Disc"> <li>respiratory infections, such as sinus infections and sore throat</li> <li>headache</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>coughing</li> <li>stomach pain</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4">Infusion reactions can happen up to 2 hours after your infusion of REMICADE. Symptoms of infusion reactions may include:</td> </tr> <tr> <td align="left" class="Lrule"> </td><td align="left"> <ul class="Disc"> <li>fever</li> <li>chills</li> <li>chest pain</li> </ul> </td><td align="left"> <ul class="Disc"> <li>low blood pressure or high blood pressure</li> <li>shortness of breath</li> </ul> </td><td align="left" class="Rrule"> <ul class="Disc"> <li>rash</li> <li>itching</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4">Children who received REMICADE in studies for Crohn's disease showed some differences in side effects compared with adults who received REMICADE for Crohn's disease. The side effects that happened more in children were: anemia (low red blood cells), leukopenia (low white blood cells), flushing (redness or blushing), viral infections, neutropenia (low neutrophils, the white blood cells that fight infection), bone fracture, bacterial infection and allergic reactions of the breathing tract. Among patients who received REMICADE for ulcerative colitis in clinical studies, more children had infections as compared with adults. <br/> Tell your doctor about any side effect that bothers you or does not go away. <br/> These are not all of the side effects with REMICADE. Ask your doctor or pharmacist for more information. <br/> Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">General information about REMICADE</span> <br/> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. <br/> You can ask your doctor or pharmacist for information about REMICADE that is written for health professionals. <br/> For more information go to www.remicade.com, or call 1-800-526-7736. </td> </tr> <tr class="Botrule Last"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">What are the ingredients in REMICADE?</span> <br/> The active ingredient is Infliximab. <br/> The inactive ingredients in REMICADE include: dibasic sodium phosphate dihydrate, monobasic sodium phosphate monohydrate, polysorbate 80, and sucrose. No preservatives are present. <br/> Manufactured by: Janssen Biotech, Inc., Horsham, PA 19044  © Johnson &amp; Johnson and its affiliates 2025 U.S. License No. 1864 </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"2%\"/>\n<col align=\"left\" valign=\"top\" width=\"30%\"/>\n<col align=\"left\" valign=\"top\" width=\"35%\"/>\n<col align=\"left\" valign=\"top\" width=\"33%\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"3\">                This Medication Guide has been approved by the U.S. Food and Drug Administration</td><td align=\"right\">Revised: 2/2025</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">MEDICATION GUIDE \n <br/> REMICADE\n \n <span class=\"Sup\">®</span>(Rem-eh-kaid) \n <br/> (infliximab) \n <br/> for injection, for intravenous use\n \n </span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">Read the Medication Guide that comes with REMICADE before you receive the first treatment, and before each time you get a treatment of REMICADE. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment. \n <br/>\n<span class=\"Bold\">What is the most important information I should know about REMICADE?</span>\n<br/> REMICADE may cause serious side effects, including: \n <br/>\n<span class=\"Bold\">1. Risk of infection</span>\n<br/> REMICADE is a medicine that affects your immune system. REMICADE can lower the ability of your immune system to fight infections. Serious infections have happened in patients receiving REMICADE. These infections include tuberculosis (TB) and infections caused by viruses, fungi or bacteria that have spread throughout the body. Some patients have died from these infections. \n <br/>\n<ul>\n<li>Your doctor should test you for TB before starting REMICADE.</li>\n<li>Your doctor should monitor you closely for signs and symptoms of TB during treatment with REMICADE.</li>\n</ul>\n<span class=\"Bold\">Before starting REMICADE, tell your doctor if you:</span>\n<ul>\n<li>think you have an infection. You should not start receiving REMICADE if you have any kind of infection.</li>\n<li>are being treated for an infection.</li>\n<li>have signs of an infection, such as a fever, cough, flu-like symptoms.</li>\n<li>have any open cuts or sores on your body.</li>\n<li>get a lot of infections or have infections that keep coming back.</li>\n<li>have diabetes or an immune system problem. People with these conditions have a higher chance for infections.</li>\n<li>have TB, or have been in close contact with someone with TB.</li>\n<li>live or have lived in certain parts of the country (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis). These infections may develop or become more severe if you receive REMICADE. If you do not know if you have lived in an area where histoplasmosis, coccidioidomycosis, or blastomycosis is common, ask your doctor.</li>\n<li>have or have had hepatitis B.</li>\n<li>use the medicines KINERET (anakinra), ORENCIA (abatacept), ACTEMRA (tocilizumab), or other medicines called biologics used to treat the same conditions as REMICADE.</li>\n</ul>\n<span class=\"Bold\">After starting REMICADE</span>, if you have an infection, any sign of an infection including a fever, cough, flu-like symptoms, or have open cuts or sores on your body, call your doctor right away. REMICADE can make you more likely to get infections or make any infection that you have worse. \n <br/>\n<span class=\"Bold\">2. Risk of Cancer</span>\n<ul>\n<li>There have been cases of unusual cancers in children and teenage patients using tumor necrosis factor (TNF) blocker medicines.</li>\n<li>For children and adults receiving TNF blocker medicines, including REMICADE, the chances of getting lymphoma or other cancers may increase.</li>\n<li>Some people receiving TNF blockers, including REMICADE, developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. Most of these people were male teenagers or young men. Also, most people were being treated for Crohn's disease or ulcerative colitis with a TNF blocker and another medicine called azathioprine or 6-mercaptopurine.</li>\n<li>People who have been treated for rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis for a long time may be more likely to develop lymphoma. This is especially true for people with very active disease.</li>\n<li>Some people treated with REMICADE have developed certain kinds of skin cancer. If any changes in the appearance of your skin or growths on your skin occur during or after your treatment with REMICADE, tell your doctor.</li>\n<li>Patients with Chronic Obstructive Pulmonary Disease (COPD), a specific type of lung disease, may have an increased risk for getting cancer while being treated with REMICADE.</li>\n<li>Some women being treated for rheumatoid arthritis with REMICADE have developed cervical cancer. For women receiving REMICADE, including those over 60 years of age, your doctor may recommend that you continue to be regularly screened for cervical cancer.</li>\n<li>Tell your doctor if you have ever had any type of cancer. Discuss with your doctor any need to adjust medicines you may be taking.</li>\n</ul>See the section \"\n \n <span class=\"Bold\"><a href=\"#SE\">What are the possible side effects of REMICADE?</a></span>\" below for more information.\n \n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">What is REMICADE?</span>\n<br/> REMICADE is a prescription medicine that is approved for patients with:\n \n <ul>\n<li>Rheumatoid Arthritis - adults with moderately to severely active rheumatoid arthritis, along with the medicine methotrexate.</li>\n<li>Crohn's Disease - children 6 years and older and adults with Crohn's disease who have not responded well to other medicines.</li>\n<li>Ankylosing Spondylitis in adults</li>\n<li>Psoriatic Arthritis in adults</li>\n<li>Plaque Psoriasis - adult patients with plaque psoriasis that is chronic (does not go away), severe, extensive, and/or disabling.</li>\n<li>Ulcerative Colitis - children 6 years and older and adults with moderately to severely active ulcerative colitis who have not responded well to other medicines.</li>\n</ul>REMICADE blocks the action of a protein in your body called tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is made by your body's immune system. People with certain diseases have too much TNF-alpha that can cause the immune system to attack normal healthy parts of the body. REMICADE can block the damage caused by too much TNF-alpha. \n <br/>\n<span class=\"Bold\">It is not known if REMICADE is safe and effective in children under 6 years of age.</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Who should not receive REMICADE?</span>\n<br/> You should not receive REMICADE if you have:\n \n <ul>\n<li>heart failure, unless your doctor has examined you and decided that you are able to receive REMICADE. Talk to your doctor about your heart failure.</li>\n<li>had an allergic reaction to REMICADE, or any of the other ingredients in REMICADE. See the end of this Medication Guide for a complete list of ingredients in REMICADE.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">What should I tell my doctor before starting treatment with REMICADE?</span>\n<br/> Your doctor will assess your health before each treatment. \n <br/> Tell your doctor about all of your medical conditions, including if you:\n \n <ul>\n<li>have an infection (see \"\n \n <span class=\"Bold\"><a href=\"#important\">What is the most important information I should know about REMICADE?</a></span>\").\n \n </li>\n<li>have other liver problems including liver failure.</li>\n<li>have heart failure or other heart conditions. If you have heart failure, it may get worse while you receive REMICADE.</li>\n<li>have or have had any type of cancer.</li>\n<li>have had phototherapy (treatment with ultraviolet light or sunlight along with a medicine to make your skin sensitive to light) for psoriasis. You may have a higher chance of getting skin cancer while receiving REMICADE.</li>\n<li>have COPD, a specific type of lung disease. Patients with COPD may have an increased risk of getting cancer while receiving REMICADE.</li>\n<li>have or have had a condition that affects your nervous system such as:\n \n <ul class=\"Circle\">\n<li>multiple sclerosis, or Guillain-Barré syndrome, or</li>\n<li>if you experience any numbness or tingling, or</li>\n<li>if you have had a seizure.</li>\n</ul>\n</li>\n<li>have recently received or are scheduled to receive a vaccine.\n \n <span class=\"Bold\">Adults and children receiving REMICADE should not receive live vaccines (for example, the Bacille Calmette-Guérin [BCG] vaccine) or treatment with a weakened bacteria</span>(such as BCG for bladder cancer). Adults and children should have all of their vaccines brought up to date before starting treatment with REMICADE.\n \n </li>\n<li>are pregnant or plan to become pregnant, are breastfeeding or plan to breastfeed. You and your doctor should decide if you should receive REMICADE while you are pregnant or breastfeeding.</li>\n</ul>If you have a baby and you were receiving REMICADE during your pregnancy, it is important to tell your baby's doctor and other health care professionals about your REMICADE use so they can decide when your baby should receive any vaccine. Certain vaccinations can cause infections. \n <br/> If you received REMICADE while you were pregnant, your baby may be at higher risk for getting an infection. If your baby receives a live vaccine within 6 months after birth, your baby may develop infections with serious complications that can lead to death. This includes live vaccines such as the BCG, rotavirus, or any other live vaccines. For other types of vaccines, talk with your doctor.\n \n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">How should I receive REMICADE?</span>\n<ul>\n<li>You will be given REMICADE through a needle placed in a vein (IV or intravenous infusion) in your arm.</li>\n<li>Your doctor may decide to give you medicine before starting the REMICADE infusion to prevent or lessen side effects.</li>\n<li>Only a healthcare professional should prepare the medicine and administer it to you.</li>\n<li>REMICADE will be given to you over a period of about 2 hours.</li>\n<li>If you have side effects from REMICADE, the infusion may need to be adjusted or stopped. In addition, your healthcare professional may decide to treat your symptoms.</li>\n<li>A healthcare professional will monitor you during the REMICADE infusion and for a period of time afterward for side effects. Your doctor may do certain tests while you are receiving REMICADE to monitor you for side effects and to see how well you respond to the treatment.</li>\n<li>Your doctor will determine the right dose of REMICADE for you and how often you should receive it. Make sure to discuss with your doctor when you will receive infusions and to come in for all your infusions and follow-up appointments.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">What should I avoid while receiving REMICADE?</span>\n<br/> Do not take REMICADE together with medicines such as KINERET (anakinra), ORENCIA (abatacept), ACTEMRA (tocilizumab), or other medicines called biologics that are used to treat the same conditions as REMICADE. \n <br/>\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. These include any other medicines to treat Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or psoriasis. \n <br/> Know the medicines you take. Keep a list of your medicines and show them to your doctor and pharmacist when you get a new medicine.\n \n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">What are the possible side effects of REMICADE?</span>\n<br/> REMICADE can cause serious side effects, including: \n <br/> See \"\n \n <span class=\"Bold\"><a href=\"#important\">What is the most important information I should know about REMICADE?</a></span>\" \n <br/>\n<span class=\"Bold\">Serious Infections</span>\n<ul>\n<li>Some patients, especially those 65 years and older have had serious infections while receiving REMICADE. These serious infections include TB and infections caused by viruses, fungi, or bacteria that have spread throughout the body or cause infections in certain areas (such as skin). Some patients die from these infections. If you get an infection while receiving treatment with REMICADE your doctor will treat your infection and may need to stop your REMICADE treatment.</li>\n<li>Tell your doctor right away if you have any of the following signs of an infection while receiving or after receiving REMICADE:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"> </td><td align=\"left\">\n<ul class=\"Circle\">\n<li>a fever</li>\n<li>feel very tired</li>\n<li>have a cough</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>have flu-like symptoms</li>\n<li>warm, red, or painful skin</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul>\n<li>Your doctor will examine you for TB and perform a test to see if you have TB. If your doctor feels that you are at risk for TB, you may be treated with medicine for TB before you begin treatment with REMICADE and during treatment with REMICADE.</li>\n<li>Even if your TB test is negative, your doctor should carefully monitor you for TB infections while you are receiving REMICADE. Patients who had a\n \n <span class=\"Bold\">negative</span>TB skin test before receiving REMICADE have developed active TB.\n \n </li>\n<li>If you are a chronic carrier of the hepatitis B virus, the virus can become active while you are being treated with REMICADE. In some cases, patients have died as a result of hepatitis B virus being reactivated. Your doctor should do a blood test for hepatitis B virus before you start treatment with REMICADE and occasionally while you are being treated. Tell your doctor if you have any of the following symptoms:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"> </td><td align=\"left\">\n<ul class=\"Circle\">\n<li>feel unwell</li>\n<li>poor appetite</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>tiredness (fatigue)</li>\n<li>fever, skin rash, or joint pain</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Heart Failure</span>\n<br/> If you have a heart problem called congestive heart failure, your doctor should check you closely while you are receiving REMICADE. Your congestive heart failure may get worse while you are receiving REMICADE. Be sure to tell your doctor of any new or worse symptoms including:\n \n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"> </td><td align=\"left\">\n<ul class=\"Disc\">\n<li>shortness of breath</li>\n<li>swelling of ankles or feet</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>sudden weight gain</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">Treatment with REMICADE may need to be stopped if you get new or worse congestive heart failure. \n <br/>\n<span class=\"Bold\">Other Heart Problems</span>\n<br/> Some patients have experienced a heart attack (some of which led to death), low blood flow to the heart, or abnormal heart rhythm within 24 hours of beginning their infusion of REMICADE. Symptoms may include chest discomfort or pain, arm pain, stomach pain, shortness of breath, anxiety, lightheadedness, dizziness, fainting, sweating, nausea, vomiting, fluttering or pounding in your chest, and/or a fast or a slow heartbeat. Tell your doctor right away if you have any of these symptoms. \n <br/>\n<span class=\"Bold\">Liver Injury</span>\n<br/> Some patients receiving REMICADE have developed serious liver problems. Tell your doctor if you have:\n \n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"> </td><td align=\"left\">\n<ul class=\"Disc\">\n<li>jaundice (skin and eyes turning yellow)</li>\n<li>dark brown-colored urine</li>\n<li>pain on the right side of your stomach area (right-sided abdominal pain)</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>fever</li>\n<li>extreme tiredness (severe fatigue)</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Blood Problems</span>\n<br/> In some patients receiving REMICADE, the body may not make enough of the blood cells that help fight infections or help stop bleeding. Tell your doctor if you:\n \n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"> </td><td align=\"left\">\n<ul class=\"Disc\">\n<li>have a fever that does not go away</li>\n<li>bruise or bleed very easily</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>look very pale</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Nervous System Disorders</span>\n<br/> Some patients receiving REMICADE have developed problems with their nervous system. Tell your doctor if you have:\n \n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"> </td><td align=\"left\">\n<ul class=\"Disc\">\n<li>changes in your vision</li>\n<li>numbness or tingling in any part of your body</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>seizures</li>\n<li>weakness in your arms or legs</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">Some patients have experienced a stroke within approximately 24 hours of their infusion with REMICADE. Tell your doctor right away if you have symptoms of a stroke which may include: numbness or weakness of the face, arm or leg, especially on one side of the body; sudden confusion, trouble speaking or understanding; sudden trouble seeing in one or both eyes, sudden trouble walking, dizziness, loss of balance or coordination or a sudden, severe headache. \n <br/>\n<span class=\"Bold\">Allergic Reactions</span>\n<br/> Some patients have had allergic reactions to REMICADE. Some of these reactions were severe. These reactions can happen while you are getting your REMICADE treatment or shortly afterward. Your doctor may need to stop or pause your treatment with REMICADE and may give you medicines to treat the allergic reaction. Signs of an allergic reaction can include:\n \n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"> </td><td align=\"left\">\n<ul class=\"Disc\">\n<li>hives (red, raised, itchy patches of skin)</li>\n<li>difficulty breathing</li>\n<li>chest pain</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>high or low blood pressure</li>\n<li>fever</li>\n<li>chills</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">Some patients treated with REMICADE have had delayed allergic reactions. The delayed reactions occurred 3 to 12 days after receiving treatment with REMICADE. Tell your doctor right away if you have any of these signs of delayed allergic reaction to REMICADE:</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"> </td><td align=\"left\">\n<ul class=\"Disc\">\n<li>fever</li>\n<li>rash</li>\n<li>headache</li>\n<li>sore throat</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>muscle or joint pain</li>\n<li>swelling of the face and hands</li>\n<li>difficulty swallowing</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Lupus-like Syndrome</span>\n<br/> Some patients have developed symptoms that are like the symptoms of Lupus. If you develop any of the following symptoms, your doctor may decide to stop your treatment with REMICADE.\n \n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"> </td><td align=\"left\">\n<ul class=\"Disc\">\n<li>chest discomfort or pain that does not go away</li>\n<li>shortness of breath</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>joint pain</li>\n<li>rash on the cheeks or arms that gets worse in the sun</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Psoriasis</span>\n<br/> Some people receiving REMICADE had new psoriasis or worsening of psoriasis they already had. Tell your doctor if you develop red scaly patches or raised bumps on the skin that are filled with pus. Your doctor may decide to stop your treatment with REMICADE. \n <br/>\n<span class=\"Bold\">The most common side effects of REMICADE include:</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"> </td><td align=\"left\">\n<ul class=\"Disc\">\n<li>respiratory infections, such as sinus infections and sore throat</li>\n<li>headache</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>coughing</li>\n<li>stomach pain</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">Infusion reactions can happen up to 2 hours after your infusion of REMICADE. Symptoms of infusion reactions may include:</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"> </td><td align=\"left\">\n<ul class=\"Disc\">\n<li>fever</li>\n<li>chills</li>\n<li>chest pain</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>low blood pressure or high blood pressure</li>\n<li>shortness of breath</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Disc\">\n<li>rash</li>\n<li>itching</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">Children who received REMICADE in studies for Crohn's disease showed some differences in side effects compared with adults who received REMICADE for Crohn's disease. The side effects that happened more in children were: anemia (low red blood cells), leukopenia (low white blood cells), flushing (redness or blushing), viral infections, neutropenia (low neutrophils, the white blood cells that fight infection), bone fracture, bacterial infection and allergic reactions of the breathing tract. Among patients who received REMICADE for ulcerative colitis in clinical studies, more children had infections as compared with adults. \n <br/> Tell your doctor about any side effect that bothers you or does not go away. \n <br/> These are not all of the side effects with REMICADE. Ask your doctor or pharmacist for more information. \n <br/> Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">General information about REMICADE</span>\n<br/> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. \n <br/> You can ask your doctor or pharmacist for information about REMICADE that is written for health professionals. \n <br/> For more information go to www.remicade.com, or call 1-800-526-7736.\n \n </td>\n</tr>\n<tr class=\"Botrule Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">What are the ingredients in REMICADE?</span>\n<br/> The active ingredient is Infliximab. \n <br/> The inactive ingredients in REMICADE include: dibasic sodium phosphate dihydrate, monobasic sodium phosphate monohydrate, polysorbate 80, and sucrose. No preservatives are present. \n <br/> Manufactured by: Janssen Biotech, Inc., Horsham, PA 19044  © Johnson &amp; Johnson and its affiliates 2025 U.S. License No. 1864\n \n </td>\n</tr>\n</tbody>\n</table></div>" }

NDC 57894-030-01

{ "type": "p", "children": [], "text": "NDC 57894-030-01" }

Remicade ® (infliximab) For Injection 100 mg per vial

{ "type": "p", "children": [], "text": "Remicade \n ®\n\n(infliximab)\n \nFor Injection\n \n100 mg per vial\n " }

Single-dose vial Discard unused portion

{ "type": "p", "children": [], "text": "Single-dose vial\n \nDiscard unused portion\n " }

Each patient is required to receive the enclosed Medication Guide.

{ "type": "p", "children": [], "text": "Each patient is required to\n \nreceive the enclosed\n \nMedication Guide.\n " }

Must Reconstitute and Dilute Before Intravenous Infusion. Must infuse over at least 2 hours with an in-line filter.

{ "type": "p", "children": [], "text": "Must Reconstitute and Dilute Before\n \nIntravenous Infusion.\n \nMust infuse over at least 2 hours\n \nwith an in-line filter.\n " }

Rx only

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