Rituximab

RITUXAN is a CD20-directed cytolytic antibody indicated for the treatment of: Adult patients with Non-Hodgkin's Lymphoma (NHL). 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, and prednisone) (CHOP) or other anthracycline-based chemotherapy regimens.

Rituximab is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, rituximab mediates B-cell lysis. Possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC). B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis. In this setting, B cells may be acting at multiple sites in the autoimmune/inflammatory process, including through production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and/or proinflammatory cytokine production.

Administer only as an intravenous infusion. Do not administer as an intravenous push or bolus. RITUXAN should only be administered by a healthcare professional with appropriate medical support to manage severe infusion-related reactions that can be fatal if they occur. The dose for adult and pediatric B-cell NHL is 375 mg/m 2. The dose for CLL is 375 mg/m 2 in the first cycle and 500 mg/m 2 in cycles 2–6, in combination with FC, administered every 28 days. The dose as a component of Zevalin ® (ibritumomab tiuxetan) Therapeutic Regimen is 250 mg/m 2. The dose for RA in combination with methotrexate is two-1,000 mg intravenous infusions separated by 2 weeks (one course) every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks. Methylprednisolone 100 mg intravenous or equivalent glucocorticoid is recommended 30 minutes prior to each infusion.

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Boxed warning: Fatal infusion-related reactions within 24 hours of RITUXAN infusion, approximately 80% of fatal reactions occurred with first infusion. Monitor patients and discontinue RITUXAN infusion for severe reactions. Severe mucocutaneous reactions, some with fatal outcomes. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Tumor lysis syndrome: Administer aggressive intravenous hydration, anti-hyperuricemic agents, monitor renal function. Infections: Withhold RITUXAN and institute appropriate anti-infective therapy. Cardiac adverse reactions: Discontinue infusions in case of serious or life-threatening events. Renal toxicity: Discontinue in patients with rising serum creatinine or oliguria. Bowel obstruction and perforation: Consider and evaluate for abdominal pain, vomiting, or related symptoms.

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Infusion-related reactions Severe mucocutaneous reactions Hepatitis B reactivation with fulminant hepatitis Progressive multifocal leukoencephalopathy Tumor lysis syndrome Infections Cardiovascular adverse reactions Renal toxicity Bowel obstruction and perforation Most common adverse reactions in clinical trials were: NHL (greater than or equal to 25%): infusion-related reactions, fever, lymphopenia, chills, infection, and asthenia. Pediatric B-NHL/B-AL with chemotherapy (Grade 3 or higher greater than 15%): febrile neutropenia, stomatitis, enteritis, sepsis, alanine aminotransferase increased and hypokalemia. CLL (greater than or equal to 25%): infusion-related reactions and neutropenia.

Formal drug interaction studies have not been performed with RITUXAN. In patients with CLL, RITUXAN did not alter systemic exposure to fludarabine or cyclophosphamide. In clinical trials of patients with RA, concomitant administration of methotrexate or cyclophosphamide did not alter the pharmacokinetics of rituximab. Renal toxicity when used in combination with cisplatin.

Store RITUXAN vials refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. RITUXAN vials should be protected from direct sunlight.