BOXED WARNINGS and Additional Important Safety Information

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

• Infusion-Related Reactions: Rituxan administration can result in serious, including fatal infusion-related 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-related reactions.

• Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan.

• 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. 

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 Rituxan in patients with NHL. Administer aggressive intravenous hydration, anti-hyperuricemic agents, monitor renal function

Infections: Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of Rituxan-based therapy. Withhold Rituxan and institute appropriate anti-infective therapy. Rituxan is not recommended for use in patients with severe, active infections

Cardiovascular Adverse Reactions: Discontinue infusions in case of serious or life-threatening events

Renal Toxicity: Severe, including fatal, renal toxicity can occur after Rituxan administration in patients with NHL. Discontinue in patients with 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. Consider and evaluate for abdominal pain, vomiting, or related symptoms

Immunization: Live virus vaccinations prior to or during Rituxan treatment not recommended

Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception.

Concomitant Use With Biologic Agents and DMARDs Other Than Methotrexate: Patients with RA should be closely observed for signs of infection if biologic agents and/or DMARDs other than methotrexate are used concomitantly. Use of concomitant immunosuppressants other than corticosteroids has not been studied in GPA, MPA, or PV patients exhibiting peripheral B-cell depletion following treatment with Rituxan

Use in Patients With RA Who Had No Prior Inadequate Response to TNF Antagonists: The use of Rituxan 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 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
• The most common adverse reactions (≥15%) in clinical trials of PV were infusion-related reactions, depression, upper respiratory tract infection/nasopharyngitis, and headache. Other important adverse reactions include infections
• The most common (≥15%) Grade 3 or higher adverse reactions in pediatric patients were febrile neutropenia, stomatitis, enteritis, sepsis, alanine aminotransferase increased, and hypokalemia

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

For additional safety information, please see the full Prescribing Information, including BOXED WARNINGS and Medication Guide.

Attention Healthcare Provider: Provide Medication Guide to patient prior to Rituxan infusion.