Important Safety Information

BOXED WARNINGS: FATAL INFUSION-RELATED REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

• Infusion-Related Reactions: Rituximab product administration can result in serious, including fatal, infusion-related reactions. Deaths within 24 hours of rituximab infusion have occurred. Approximately 80% of fatal infusion-related reactions occurred in association with the first infusion. Monitor patients closely. Discontinue RIABNI™ infusion for severe reactions and provide medical treatment for Grade 3 or 4 infusion-related reactions.
• Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving rituximab products.
• Hepatitis B Virus (HBV) Reactivation: HBV reactivation can occur in patients treated with rituximab products, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with RIABNI™. Discontinue RIABNI™ and concomitant medications in the event of HBV reactivation.
• Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, can occur in patients receiving rituximab products.

Warnings and Precautions

Tumor Lysis Syndrome

• Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, some fatal, can occur within 12−24 hours after the first infusion of RIABNI™ in patients with non-Hodgkin’s lymphoma (NHL). A high number of circulating malignant cells (≥25,000/mm³), or high tumor burden, confers a greater risk of TLS.
• Administer aggressive intravenous hydration and anti-hyperuricemic therapy in patients at high risk for TLS. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated.

Infections

• Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of rituximab product-based therapy. Infections have been reported in some patients with prolonged hypogammaglobulinemia (defined as hypogammaglobulinemia >11 months after rituximab exposure).
• New or reactivated viral infections included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis B and C. Discontinue RIABNI™ for serious infections and institute appropriate anti-infective therapy.
• RIABNI™ is not recommended for use in patients with severe, active infections.

Cardiovascular Adverse Reactions

• Cardiac adverse reactions, including ventricular fibrillation, myocardial infarction, and cardiogenic shock may occur in patients receiving rituximab products. Discontinue infusions for serious or life-threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of RIABNI™ for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina.

Renal Toxicity

• Severe, including fatal, renal toxicity can occur after rituximab product administration in patients with NHL. Renal toxicity has occurred in patients who experience TLS and in patients with NHL administered concomitant cisplatin therapy during clinical trials. The combination of cisplatin and RIABNI™ is not an approved treatment regimen. Monitor closely for signs of renal failure and discontinue RIABNI™ in patients with a rising serum creatinine or oliguria.

Bowel Obstruction and Perforation

• Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving rituximab products in combination with chemotherapy. In postmarketing reports, the mean time to documented gastrointestinal perforation was 6 (range 1−77) days in patients with NHL. Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur.

Immunization

• The safety of immunization with live viral vaccines following rituximab product therapy has not been studied, and vaccination with live virus vaccines is not recommended before or during treatment.
• For patients treated with RIABNI™, physicians should review the patient’s vaccination status and patients should, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating RIABNI™; administer non-live vaccines at least 4 weeks prior to a course of RIABNI™.

Embryo-Fetal Toxicity

• Based on human data, rituximab products can cause fetal harm due to B-cell lymphocytopenia in infants exposed in utero. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception with RIABNI™ and for 12 months after the last dose.

Concomitant Use with Other Biologic Agents and DMARDs other than Methotrexate in RA, GPA, and MPA

• Observe patients closely for signs of infection if biologic agents and/or DMARDs are used concomitantly. Use of concomitant immunosuppressants other than corticosteroids has not been studied in GPA or MPA patients exhibiting peripheral B-cell depletion following treatment with rituximab products.

Use in RA Patients Who Have Not Had Prior Inadequate Response to Tumor Necrosis Factor (TNF) Antagonists

• The use of RIABNI™ in patients with RA who have not had prior inadequate response to one or more TNF antagonists is not recommended.

Most Common Adverse Reactions

• The most common Grade 3 or 4 adverse reactions in clinical trials of NHL and chronic lymphocytic leukemia (CLL) were infusion-related reactions, neutropenia, leukopenia, anemia, thrombocytopenia, and infections. Additionally, lymphopenia and lung disorder were seen in NHL trials; and febrile neutropenia, pancytopenia, hypotension, and hepatitis B were seen in CLL trials.
• The most common adverse reactions (incidence ≥25%) in clinical trials of NHL and CLL were infusion-related reactions. Additionally, fever, lymphopenia, chills, infection, and asthenia were seen in NHL trials; and neutropenia was seen in CLL trials.
• The most common adverse reactions (≥10%) in clinical trials of RA were upper respiratory tract infection, nasopharyngitis, urinary tract infection, and bronchitis. Other important adverse reactions include infusion-related reactions, serious infections, and cardiovascular events.
• The most common adverse reactions (≥15%) in clinical trials of GPA and MPA were infections, nausea, diarrhea, headache, muscle spasms, anemia, peripheral edema, and infusion-related reactions.

Attention Healthcare Provider: Provide Medication Guide to patient prior to RIABNI™ infusion and advise patients to read guide.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Amgen at 1-800-772-6436.

Please see the full Prescribing Information, including BOXED WARNINGS and Medication Guide, for additional Important Safety Information.

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Indications

Non-Hodgkin’s Lymphoma (NHL)

RIABNI™ (rituximab-arrx) is indicated for the treatment of adult patients with:

• Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent.
• Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy.
• Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy.
• Previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens.

Chronic Lymphocytic Leukemia (CLL)

• RIABNI™, in combination with fludarabine and cyclophosphamide (FC), is indicated for the treatment of adult patients with previously untreated and previously treated CD20-positive CLL.

Rheumatoid Arthritis (RA)

• RIABNI™, in combination with methotrexate, is indicated for the treatment of adult patients with moderately- to severely- active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.

Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA)

• RIABNI™, in combination with glucocorticoids, is indicated for the treatment of adult patients with Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA).