HIGHLIGHTS OF PRESCRIBING INFORMATION REMICADE is administered by intravenous infusion over a period of not less These highlights do not include all the information needed to use than 2 hours. REMICADE® safely and effectively. See full prescribing information for Crohn’s Disease (2.1) REMICADE. 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks. Some adult patients who REMICADE (infliximab) initially respond to treatment may benefit from increasing the dose to 10 Lyophilized Concentrate for Injection, for Intravenous Use mg/kg if they later lose their response. Initial U.S. Approval: 1998 Pediatric Crohn’s Disease (2.2) 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks. WARNING: SERIOUS INFECTIONS and MALIGNANCY Ulcerative Colitis (2.3) See full prescribing information for complete boxed warning 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks. SERIOUS INFECTIONS Pediatric Ulcerative Colitis (2.4) Increased risk of serious infections leading to hospitalization or 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks. death, including tuberculosis (TB), bacterial sepsis, invasive fungal Rheumatoid Arthritis (2.5) infections (such as histoplasmosis) and infections due to other In conjunction with methotrexate, 3 mg/kg at 0, 2 and 6 weeks, then every opportunistic pathogens. 8 weeks. Some patients may benefit from increasing the dose up to 10 Discontinue REMICADE if a patient develops a serious infection. mg/kg or treating as often as every 4 weeks. Perform test for latent TB; if positive, start treatment for TB prior to Ankylosing Spondylitis (2.6) starting REMICADE. Monitor all patients for active TB during 5 mg/kg at 0, 2 and 6 weeks, then every 6 weeks. treatment, even if initial latent TB test is negative. (5.1) Psoriatic Arthritis (2.7) and Plaque Psoriasis (2.8) MALIGNANCY 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks. Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor --------------------DOSAGE FORMS AND STRENGTHS---------------------- (TNF) blockers, including REMICADE. 100 mg of lyophilized infliximab in a 20 mL vial for intravenous infusion. (3) Postmarketing cases of fatal hepatosplenic T-cell lymphoma -------------------------------CONTRAINDICATIONS------------------------------ (HSTCL) have been reported in patients treated with TNF blockers REMICADE doses >5 mg/kg in moderate to severe heart failure. (4) including REMICADE. All REMICADE cases were reported in Previous severe hypersensitivity reaction to REMICADE or known patients with Crohn’s disease or ulcerative colitis, the majority of hypersensitivity to inactive components of REMICADE or to any whom were adolescent or young adult males. All had received murine proteins. (4) azathioprine or 6-mercaptopurine concomitantly with REMICADE ---------------------------WARNINGS AND PRECAUTIONS-------------------- at or prior to diagnosis. (5.2) Serious infections – do not give REMICADE during an active infection. -------------------------RECENT MAJOR CHANGES------------------------- If an infection develops, monitor carefully and stop REMICADE if Warnings and Precautions: Malignancies (5.2) 03/2013 infection becomes serious. (5.1) Warnings and Precautions: Concurrent Administration Invasive fungal infections – for patients who develop a systemic illness with other Biological Therapeutics (5.11) 03/2013 on REMICADE, consider empiric antifungal therapy for those who Warnings and Precautions: Live Vaccines/ reside or travel to regions where mycoses are endemic (5.1) Therapeutic Infectious Agents (5.14) 11/2013 Malignancies – the incidence of malignancies including lymphoma was ----------------------------INDICATIONS AND USAGE--------------------------- greater in REMICADE treated patients than in controls. Due to the risk REMICADE is a tumor necrosis factor (TNF) blocker indicated for: of HSTCL carefully assess the risk/benefit especially if the patient has Crohn’s Disease (1.1): Crohn’s disease or ulcerative colitis, is male, and is receiving reducing signs and symptoms and inducing and maintaining clinical azathioprine or 6-mercaptopurine treatment. (5.2) remission in adult patients with moderately to severely active disease Hepatitis B virus reactivation – test for HBV infection before starting who have had an inadequate response to conventional therapy. REMICADE. Monitor HBV carriers during and several months after reducing the number of draining enterocutaneous and rectovaginal therapy. If reactivation occurs, stop REMICADE and begin anti-viral fistulas and maintaining fistula closure in adult patients with fistulizing therapy. (5.3) disease. Hepatotoxicity – rare severe hepatic reactions, some fatal or Pediatric Crohn’s Disease (1.2): necessitating liver transplantation. Stop REMICADE in cases of reducing signs and symptoms and inducing and maintaining clinical jaundice and/or marked liver enzyme elevations. (5.4) remission in pediatric patients with moderately to severely active disease Heart failure –new onset or worsening symptoms may occur. (4, 5.5) who have had an inadequate response to conventional therapy. Cytopenias – advise patients to seek immediate medical attention if Ulcerative Colitis (1.3): signs and symptoms develop, and consider stopping REMICADE. (5.6) reducing signs and symptoms, inducing and maintaining clinical Hypersensitivity – serious infusion reactions including anaphylaxis or remission and mucosal healing, and eliminating corticosteroid use in serum sickness-like reactions may occur. (5.7) adult patients with moderately to severely active disease who have had Demyelinating disease –exacerbation or new onset may occur. (5.8) an inadequate response to conventional therapy. Lupus-like syndrome – stop REMICADE if syndrome develops. (5.13) Pediatric Ulcerative Colitis (1.4): Live vaccines or therapeutic infectious agents – should not be given with reducing signs and symptoms and inducing and maintaining clinical REMICADE. Bring pediatric patients up to date with all vaccinations remission in pediatric patients with moderately to severely active disease prior to initiating REMICADE. (5.14) who have had an inadequate response to conventional therapy. ------------------------------ADVERSE REACTIONS------------------------------ Rheumatoid Arthritis (1.5) in combination with methotrexate: Most common adverse reactions (>10%) – infections (e.g. upper respiratory, reducing signs and symptoms, inhibiting the progression of structural sinusitis, and pharyngitis), infusion-related reactions, headache, and damage, and improving physical function in patients with moderately to abdominal pain. (6.1) severely active disease. To report SUSPECTED ADVERSE REACTIONS, contact Janssen Ankylosing Spondylitis (1.6): Biotech, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA- reducing signs and symptoms in patients with active disease. 1088 or www.fda.gov/medwatch. Psoriatic Arthritis (1.7): reducing signs and symptoms of active arthritis, inhibiting the ---------------------------------DRUG INTERACTIONS---------------------------- progression of structural damage, and improving physical function. Use with anakinra or abatacept– increased risk of serious infections (7.1) Plaque Psoriasis (1.8): -----------------------USE IN SPECIFIC POPULATIONS----------------------- treatment of adult patients with chronic severe (i.e., extensive and /or Pediatric Use –REMICADE has not been studied in children with disabling) plaque psoriasis who are candidates for systemic therapy and Crohn’s disease or ulcerative colitis<6 years of age. (8.4) when other systemic therapies are medically less appropriate. See 17 for PATIENT COUNSELING INFORMATION and -----------------------DOSAGE AND ADMINISTRATION----------------------- MEDICATION GUIDE. Revised: November 2013 1 Reference ID: 3403013 FULL PRESCRIBING INFORMATION: CONTENTS* 5.14 Live Vaccines/Therapeutic Infectious Agents 6 ADVERSE REACTIONS WARNING: SERIOUS INFECTIONS AND MALIGNANCY 6.1 Clinical Trials Experience 1 INDICATIONS AND USAGE 6.2 Post-marketing Experience 1.1 Crohn’s Disease 7 DRUG INTERACTIONS 1.2 Pediatric Crohn’s Disease 7.1 Use with Anakinra or Abatacept 1.3 Ulcerative Colitis 7.2 Use with Tocilizumab 1.4 Pediatric Ulcerative Colitis 7.3 Use with Other Biological Therapeutics 1.5 Rheumatoid Arthritis 7.4 Methotrexate (MTX) and Other Concomitant Medications 1.6 Ankylosing Spondylitis 7.5 Immunosuppressants 1.7 Psoriatic Arthritis 7.6 Cytochrome P450 Substrates 1.8 Plaque Psoriasis 7.7 Live Vaccines/Therapeutic Infectious Agents 2 DOSAGE AND ADMINISTRATION 8 USE IN SPECIFIC POPULATIONS 2.1 Crohn’s Disease 8.1 Pregnancy 2.2 Pediatric Crohn’s Disease 8.3 Nursing Mothers 2.3 Ulcerative Colitis 8.4 Pediatric Use 2.4 Pediatric Ulcerative Colitis 8.5 Geriatric Use 2.5 Rheumatoid Arthritis 10 OVERDOSAGE 2.6 Ankylosing Spondylitis 11 DESCRIPTION 2.7 Psoriatic Arthritis 12 CLINICAL PHARMACOLOGY 2.8 Plaque Psoriasis 12.1 Mechanism of Action 2.9 Monitoring to Assess Safety 12.2 Pharmacodynamics 2.10 Administration Instructions Regarding Infusion Reactions 12.3 Pharmacokinetics 2.11 General Considerations and Instructions for Preparation and 13 NONCLINICAL TOXICOLOGY Administration 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 3 DOSAGE FORMS AND STRENGTHS 14 CLINICAL STUDIES 4 CONTRAINDICATIONS 14.1 Crohn’s Disease 5 WARNINGS AND PRECAUTIONS (see Boxed WARNINGS) 14.2 Pediatric Crohn’s Disease 5.1 Serious Infections 14.3 Ulcerative Colitis 5.2 Malignancies 14.4 Pediatric Ulcerative Colitis 5.3