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) in combination with methotrexate is indicated for the treatment of adult patients with moderately- to severely-active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.

Status Rituxan (Rituximab) received U.S. Food and Drug Administration approval in November 1997 for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma (NHL). In April 2001, a supplemental Biologics License Application was approved for Rituxan for these additional uses: 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 February 2006, the FDA approved Rituxan for the first-line treatment of diffuse large B-cell, CD20-positive, non-Hodgkin's lymphoma (DLBCL- a type of NHL) in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or other anthracycline-based chemotherapy regimens. Also in February 2006, the FDA approved Rituxan in combination with methotrexate for the treatment of moderately- to severely-active rheumatoid arthritis in patients who have had an inadequate response to one or more TNF antagonist therapies.

For additional detailed information, please see the Rituxan RA Fact Sheet.

Important Safety Information, including Boxed WARNINGS Rituxan can cause serious side effects including:

• Progressive Multifocal Leukoencephalopathy (PML)
  
  • PML is a rare brain infection.
  • PML 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 usually happens in patients with weakened immune systems.
  • 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. 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 the skin or in the 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.

Common side effects during Rituxan infusions include fever, headache, chills and shakes, nausea, itching, hives, cough, sneezing, throat irritation or tightness.

Other side effects with Rituxan include aching joints, upper respiratory tract infection, decreased blood cell counts, and lung problems.

These are not all of the possible side effects with Rituxan. Patients should tell their doctor about any side effect that bother them or that do not go away.

Patients should read the Rituxan Full Prescribing Information including Boxed WARNINGS, and the Medication Guide.

Proposed Mechanism of Action Rituxan binds to 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 within several months.

Rheumatoid Arthritis RA is a systemic debilitating autoimmune disease that occurs when the immune system inappropriately attacks joint tissue, causing painful chronic inflammation and irreversible destruction of cartilage, tendons and bones, that often results in chronic pain, loss of function and disability, and can also lead to cardiovascular and pulmonary complications. Additionally, since RA is a systemic disease, it can have effects on other tissues and organs such as the lungs, eyes and bone marrow.