INDICATIONS & IMPORTANT SAFETY INFORMATION
BOXED WARNINGS and Additional Important Safety Information
Infusion Reactions: Rituxan administration can result in serious, including fatal infusion reactions. Deaths within 24 hours of Rituxan infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Monitor patients closely. Discontinue Rituxan infusion for severe reactions and provide medical treatment for Grade 3 or 4 infusion reactions.
Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan. Discontinue Rituxan in patients who experience a severe mucocutaneous reaction. The safety of readministration of Rituxan to patients with severe mucocutaneous reactions has not been determined.
Hepatitis B Virus (HBV) Reactivation: HBV reactivation can occur in patients treated with Rituxan, 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 Rituxan. Discontinue Rituxan and concomitant medications in the event of HBV reactivation.
Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, can occur in patients receiving Rituxan. Discontinue Rituxan and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML.
Warnings and Precautions
Tumor Lysis Syndrome (TLS): Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, sometimes fatal, can occur within 12-24 hours after the first infusion of Rituxan in patients with Non-Hodgkin’s Lymphoma (NHL). 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 Rituxan-based therapy. Discontinue Rituxan for serious infections and institute appropriate anti-infective therapy. Rituxan is not recommended for use in patients with severe, active infections.
Cardiovascular Adverse Reactions: Discontinue infusions for serious or life-threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of Rituxan 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 Rituxan administration in patients with Non-Hodgkin’s Lymphoma (NHL). Monitor closely for signs of renal failure and discontinue Rituxan 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 Rituxan in combination with chemotherapy. Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur.
Immunization: The safety of immunization with live viral vaccines following Rituxan therapy has not been studied, and vaccination with live vaccines is not recommended before or during treatment.
Embryo-Fetal Toxicity: Rituxan can cause fetal harm due to B-cell lymphocytopenia in infants exposed to Rituxan in-utero. Advise pregnant women of the risk to a fetus. Females of childbearing potential should use effective contraception while receiving Rituxan and for 12 months following the last dose of Rituxan.
Concomitant Use With Biologic Agents and DMARDs Other Than Methotrexate: 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 PV patients exhibiting peripheral B-cell depletion following treatment with Rituxan.
Clinical Trials Experience in Pemphigus Vulgaris (PV)
Adverse reactions reported in ≥10% of patients treated with the Ritux 3 regimen† vs patients treated with prednisone monotherapy were infusion reactions (58% vs N/A), depression (18% vs 11%), herpes simplex (13% vs 3%), and alopecia (13% vs 0%).
Infusion reactions were the most commonly reported adverse drug reactions (58%). All infusion reactions were mild to moderate (Grade 1 or 2) except one Grade 3 serious infusion reaction (arthralgia) associated with the Month 12 maintenance infusion. No patients were withdrawn from treatment due to infusion reactions.
Fourteen patients (37%) treated with the Ritux 3 regimen experienced treatment-related infections compared to 15 patients (42%) treated with prednisone monotherapy. The most common infections in the patients treated with the Ritux 3 regimen were herpes simplex, herpes zoster, bronchitis, urinary tract infection, fungal infection, and conjunctivitis. Three patients (8%) treated with the Ritux 3 regimen experienced a total of 5 serious infections and 1 patient (3%) treated with prednisone monotherapy experienced 1 serious infection.
Using a new ELISA assay, a total of 19/34 (56%) patients with PV treated with the Ritux 3 regimen tested positive for anti-rituximab antibodies by 18 months. The clinical relevance of anti-rituximab antibody formation in Rituxan treated PV patients is unclear.
For additional Important Safety Information, please see the Rituxan full Prescribing Information, including BOXED WARNINGS.
†Ritux 3 regimen=Roche-manufactured, EU-approved rituximab product
- Rituxan is indicated for the treatment of adult patients with moderate to severe pemphigus vulgaris