RITUXAN Prescribing Information - Genentech

1 HIGHLIGHTS OF Prescribing Information The dose for RA in combination with methotrexate is two-1000 mg These highlights do not include all the Information needed to use intravenous infusions separated by 2 weeks (one course) every 24 weeks RITUXAN safely and effectively. See full Prescribing Information for or based on clinical evaluation, but not sooner than every 16 weeks. RITUXAN . Methylprednisolone 100 mg intravenous or equivalent glucocorticoid is recommended 30 minutes prior to each infusion ( ). RITUXAN (rituximab) injection, for intravenous use . The dose for GPA and MPA in combination with glucocorticoids is Initial Approval: 1997 375 mg/m once weekly for 4 weeks ( ). 2. The dose for PV is two-1000 mg intravenous infusions separated by 2. WARNING: FATAL INFUSION REACTIONS, SEVERE weeks in combination with a tapering course of glucocorticoids, then a MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS 500 mg intravenous infusion at Month 12 and every 6 months thereafter or REACTIVATION and PROGRESSIVE MULTIFOCAL based on clinical evaluation.

2 Dose upon relapse is a 1000 mg intravenous LEUKOENCEPHALOPATHY infusion with considerations to resume or increase the glucocorticoid dose See full Prescribing Information for complete boxed warning. based on clinical evaluation. Subsequent infusions may be no sooner than 16 weeks after the previous infusion ( ). Methylprednisolone 100 mg Fatal infusion reactions within 24 hours of RITUXAN infusion; intravenous or equivalent glucocorticoid is recommended 30 minutes prior approximately 80% of fatal reactions occurred with first infusion. to each infusion ( ). Monitor patients and discontinue RITUXAN infusion for severe reactions ( ). ---------------------DOSAGE FORMS AND STRENGTHS------------------- Severe mucocutaneous reactions, some with fatal outcomes ( ). Injection: 100 mg/10 mL and 500 mg/50 mL solution in a single-use vial Hepatitis B virus (HBV) reactivation, in some cases resulting in (3).

3 Fulminant hepatitis, hepatic failure, and death ( ). Progressive multifocal leukoencephalopathy (PML) resulting in death ------------------------------CONTRAINDI CATIONS--------------------------- ( ). None (4). --------------------------RECENT MAJOR CHANGES------------------------- -----------------------WARNINGS AND PRECAUTIONS------------------- Indications and Usage ( ) 06/2018 Tumor lysis syndrome: Administer aggressive intravenous hydration, Dosage and Administration ( ) 06/2018 anti-hyperuricemic agents, monitor renal function ( ). Warnings and Precautions, Embryo-Fetal Toxicity ( ) 04/2018 Infections: Withhold RITUXAN and institute appropriate anti-infective therapy ( ). ---------------------------INDICATIONS AND USAGE------------------------- Cardiac adverse reactions: Discontinue infusions in case of serious or life- RITUXAN (rituximab) is a CD20-directed cytolytic antibody indicated for the threatening events ( ).

4 Treatment of adult patients with: Renal toxicity: Discontinue in patients with rising serum creatinine or Non-Hodgkin's Lymphoma (NHL) ( ). oliguria ( ). o Relapsed or refractory, low grade or follicular, CD20-positive B- Bowel obstruction and perforation: Consider and evaluate for abdominal cell NHL as a single agent. pain, vomiting, or related symptoms ( ). o Previously untreated follicular, CD20-positive, B-cell NHL in Immunizations: Live virus vaccinations prior to or during RITUXAN . combination with first line chemotherapy and, in patients achieving treatment not recommended ( ). a complete or partial response to RITUXAN in combination with Embryo-Fetal toxicity: Can cause neonatal harm. Advise of potential risk chemotherapy, as single-agent maintenance therapy. to neonates and use of effective contraception ( ). o Non-progressing (including stable disease), low-grade, CD20- positive, B-cell NHL as a single agent after first-line ------------------------------ADVERSE REACTIONS---------------------------- cyclophosphamide , vincristine , and prednisone (CVP) Most common adverse reactions in clinical trials were: chemotherapy.

5 NHL ( 25%): infusion reactions, fever, lymphopenia, chills, infection and o Previously untreated diffuse large B-cell, CD20-positive NHL in asthenia ( ). combination with ( cyclophosphamide , doxorubicin , vincristine , CLL ( 25%): infusion reactions and neutropenia ( ). and prednisone ) (CHOP) or other anthracycline-based RA ( 10%): upper respiratory tract infection, nasopharyngitis, urinary chemotherapy regimens. tract infection, and bronchitis (other important adverse reactions include Chronic Lymphocytic Leukemia (CLL) ( ). infusion reactions, serious infections, and cardiovascular events) ( ). o Previously untreated and previously treated CD20-positive CLL in GPA and MPA ( 15 %): infections, nausea, diarrhea, headache, muscle combination with fludarabine and cyclophosphamide (FC). spasms, anemia, peripheral edema (other important adverse reactions Rheumatoid Arthritis (RA) in combination with methotrexate in adult include infusion reactions) ( ).

6 Patients with moderately-to severely-active RA who have inadequate PV ( 15%): infusion reactions, depression (other important adverse response to one or more TNF antagonist therapies ( ). reactions include infections) ( ). Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA) in adult patients in combination with To report SUSPECTED ADVERSE REACTIONS, contact Genentech at glucocorticoids ( ). 1-888-835-2555 or FDA at 1-800-FDA-1088 or Moderate to severe Pemphigus Vulgaris (PV) in adult patients ( ). -------------------------------DRUG INTERACTIONS--------------------------- Renal toxicity when used in combination with cisplatin ( ). ------------------------DOSAGE AND ADMINISTRATION------------------- Administer only as an intravenous infusion. -----------------------USE IN SPECIFIC POPULATIONS--------------------- Do not administer as an intravenous push or bolus.

7 Lactation: Advise not to breastfeed ( ). RITUXAN should only be administered by a healthcare professional with Geriatric Use: In CLL patients older than 70 years of age, exploratory appropriate medical support to manage severe infusion reactions that can analyses suggest no benefit with the addition of RITUXAN to FC ( ). be fatal if they occur. The dose for NHL is 375 mg/m ( ). 2. See 17 for PATIENT COUNSELING Information and Medication The dose for CLL is 375 mg/m in the first cycle and 500 mg/m in 2 2 Guide. cycles 2-6, in combination with FC, administered every 28 days ( ). Revised: 06/2018. The dose as a component of Zevalin (ibritumomab tiuxetan) Therapeutic Regimen is 250 mg/m ( ). 2. FULL Prescribing Information : CONTENTS* Use in RA Patients Who Have Not Had Prior Inadequate Response to Tumor Necrosis Factor WARNING: FATAL INFUSION REACTIONS, SEVERE.

8 (TNF) Antagonists MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS. Retreatment in Patients with Granulomatosis with REACTIVATION and PROGRESSIVE MULTIFOCAL. Polyangiitis (GPA) (Wegener's Granulomatosis) and LEUKOENCEPHALOPATHY (PML). Microscopic Polyangiitis (MPA). 1 INDICATIONS AND USAGE. 6 ADVERSE REACTIONS. Non-Hodgkin's Lymphoma (NHL). Clinical Trials Experience in Lymphoid Malignancies Chronic Lymphocytic Leukemia (CLL). Clinical Trials Experience in Rheumatoid Arthritis Rheumatoid Arthritis (RA). Clinical Trials Experience in Granulomatosis with Granulomatosis with Polyangiitis (GPA) (Wegener's Polyangiitis (GPA) (Wegener's Granulomatosis) and Granulomatosis) and Microscopic Polyangiitis (MPA). Microscopic Polyangiitis (MPA). Pemphigus Vulgaris (PV). Clinical Trials Experience in Pemphigus Vulgaris 2 DOSAGE AND ADMINISTRATION. (PV). Important Dosing Information Immunogenicity Recommended Dose for Non-Hodgkin's Lymphoma Postmarketing Experience (NHL).

9 7 DRUG INTERACTIONS. Recommended Dose for Chronic Lymphocytic 8 USE IN SPECIFIC POPULATIONS. Leukemia (CLL). Pregnancy Recommended Dose as a Component of Zevalin for Lactation treatment of NHL. Females and Males of Reproductive Potential Recommended Dose for Rheumatoid Arthritis (RA). Pediatric Use Recommended Dose for Granulomatosis with Geriatric Use Polyangiitis (GPA) (Wegener's Granulomatosis) and 11 DESCRIPTION. Microscopic Polyangiitis (MPA). 12 CLINICAL PHARMACOLOGY. Recommended Dose for Pemphigus Vulgaris (PV). Mechanism of Action Recommended Dose for Premedication and Pharmacodynamics Prophylactic Medications Pharmacokinetics Administration and Storage 13 NONCLINICAL TOXICOLOGY. 3 DOSAGE FORMS AND STRENGTHS. Carcinogenesis, Mutagenesis, Impairment of Fertility 4 CONTRAINDICATIONS. 14 CLINICAL STUDIES. 5 WARNINGS AND PRECAUTIONS. Relapsed or Refractory, Low-Grade or Follicular, Infusion Reactions CD20-Positive, B-Cell NHL.

10 Severe Mucocutaneous Reactions Previously Untreated, Low-Grade or Follicular, Hepatitis B Virus (HBV) Reactivation CD20-Positive, B-Cell NHL. Progressive Multifocal Leukoencephalopathy (PML). Diffuse Large B-Cell NHL (DLBCL). Tumor Lysis Syndrome (TLS). Ninety-Minute Infusions in Previously Untreated Infections Follicular NHL and DLBCL. Cardiovascular Adverse Reactions Chronic Lymphocytic Leukemia (CLL). Renal Toxicity Rheumatoid Arthritis (RA). Bowel Obstruction and Perforation Granulomatosis with Polyangiitis (GPA) (Wegener's Immunization Granulomatosis) and Microscopic Polyangiitis (MPA). Embryo-Fetal Toxicity Pemphigus Vulgaris (PV). Concomitant Use with Other Biologic Agents and 16 HOW SUPPLIED/STORAGE AND HANDLING. DMARDS other than Methotrexate in RA, GPA and 17 PATIENT COUNSELING Information . MPA, PV. Sections or subsections omitted from the full Prescribing Information are *.