Full Prescribing Information, including Boxed WARNINGS
Medication Guide (79K/PDF)
Dear Healthcare Provider Letter (PML December 2006) (54K/PDF)
Dear Healthcare Provider Letter (PML September 2008) (646K/PDF)
Dear Healthcare Provider Letter (PML October 2009) (145K/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.

Important Safety Information, including Boxed WARNINGS Rituxan can cause serious side effects, some of which could be life-threatening:

• Progressive Multifocal Leukoencephalopathy (PML)
  PML is a rare brain infection that usually causes death or severe disability. Patients should call their doctor right away if they notice any new or worsening medical problems, such as a new or sudden change in thinking, walking, strength, vision, or other problems that have lasted over several days. PML can occur during treatment with Rituxan or after treatment has finished. There is no known treatment, prevention, or cure for PML.
• Infusion reactions. Patients should tell their doctor or get medical treatment right away if they get hives, swelling, dizziness, blurred vision, drowsiness, headache, cough, wheezing, or have trouble breathing while receiving or after receiving Rituxan.
• Tumor Lysis Syndrome (TLS). TLS is caused by the fast breakdown of certain types of cancer cells. TLS can cause kidney failure and the need for dialysis treatment. Patients receiving Rituxan for Non-Hodgkin's Lymphoma (NHL) may get TLS.
• Severe skin reactions. Patients should tell their doctor or get medical treatment right away if they get any of these symptoms: painful sores on their skin or in their mouth, ulcers, blisters, or peeling skin while receiving or after receiving Rituxan.

Rituxan can cause other serious and life-threatening side effects, including:

• Hepatitis B virus reactivation. Patients should tell their doctor if they had hepatitis B virus or are a carrier of hepatitis B virus. Receiving Rituxan could cause the hepatitis B virus to become an active infection again. This may cause serious liver problems and death. People with active liver disease due to hepatitis B should stop receiving Rituxan.
• Heart problems. Patients should tell their doctor about any heart problems they have including chest pain (angina) and irregular heart beats. Rituxan can cause chest pain and irregular heart beats which may require treatment.
• Infections. Rituxan can increase the chances for getting infections. Patients should call their doctor right away if they have a cough that will not go away, fever, chills, congestion, or any flu-like symptoms while receiving Rituxan. These symptoms may be signs of a serious infection.
• Stomach and bowel problems. Serious stomach and bowel problems have been seen when Rituxan has been used with anti-cancer medicines in some patients with non-Hodgkin's lymphoma. Patients should call their doctor right away if they have any stomach area pain during treatment with Rituxan.

Common side effects during Rituxan infusions include fever, chills and shakes, itching, cough, throat irritation or tightness, headache, nausea, hives, and sneezing. Other side effects with Rituxan include aching joints, upper respiratory tract infection, decreased blood cell counts, and lung problems.

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