Medication Guide (79K/PDF)
Full Prescribing Information
Dear Healthcare Provider Letter (PML December 2006) (54K/PDF)
Dear Healthcare Provider Letter (PML September 2008) (646K/PDF)

Rituxan® (Rituximab) is indicated for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma (NHL) as a single agent; for previously untreated diffuse large B-cell, CD20-positive, NHL in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or other anthracycline-based chemotherapy regimens; for previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP (cyclophosphamide, vincristine and prednisolone) chemotherapy; and for the treatment of non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent, after first-line CVP chemotherapy.

Status Approved by the U.S. Food and Drug Administration (FDA) in November 1997, Rituxan was the first therapeutic antibody approved for treating cancer in the United States.

A supplemental Biological License Application (sBLA) was approved for Rituxan in April 2001, adding several new uses including:

• retreatment of patients with Rituxan who have relapsed following initial Rituxan therapy
• use of eight weekly doses (compared to original four) per course of treatment
• treatment of patients with bulky disease (lesions > 10 cm).

In September 2006, the FDA approved two additional uses for Rituxan for patients with CD-20 positive, B-Cell NHL.

Rituxan's safety and efficacy have been documented in more than 200 Phase II and Phase III clinical studies over the past 10 years. For additional detailed information please see the Rituxan Fact Sheet.

WARNINGS FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) 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. Carefully monitor patients during infusions. Discontinue Rituxan infusion and provide medical treatment for Grade 3 or 4 infusion reactions (see Warnings and Precautions, Adverse Reactions). Tumor Lysis Syndrome (TLS) Acute renal failure requiring dialysis with instances of fatal outcome can occur in the setting of TLS following treatment of non-Hodgkin's lymphoma (NHL) patients with Rituxan (see Warnings and Precautions, Adverse Reactions). Severe Mucocutaneous Reactions Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan (see Warnings and Precautions, Adverse Reactions). Progressive Multifocal Leukoencephalopathy (PML) JC virus infection resulting in PML and death can occur in patients receiving Rituxan (see Warnings and Precautions, Adverse Reactions).

Proposed Mechanism of Action Rituxan works by binding to a particular protein (the CD20 antigen) on the surface of normal and malignant B-cells. From there, it recruits the body's natural defenses to attack and kill the marked B-cells. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B-cells to regenerate after treatment and return to normal levels.

Non-Hodgkin's Lymphoma Non-Hodgkin's lymphoma (NHL) is a cancer that develops in the lymphatic system. A vital part of the immune system, the lymphatic system is a network of thin vessels that branch into tissues throughout the body and help fight disease and infection.

Along the network, small organs called lymph nodes are clustered in the abdomen, chest, groin, and neck. A colorless and watery fluid called lymph circulates through the system carrying infection-fighting cells called lymphocytes. When these cells divide and multiply uncontrollably, malignant tumors can form. Since lymph is carried throughout the body, NHL may form anywhere and can spread easily to other parts of the lymphatic system, including the tonsils, stomach, skin, intestines and bone marrow.

• More than 66,000 Americans are expected to be diagnosed with NHL in 2008
• Approximately 360,000 Americans are diagnosed and living with NHL