Full Prescribing Information, including Boxed WARNINGS and Medication Guide
Dear Healthcare Provider Letter (PML December 2006)
Dear Healthcare Provider Letter (PML September 2008)
Dear Healthcare Provider Letter (PML October 2009)

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. Rituxan with glucocorticoids is used to treat adults with Wegener's Granulomatosis (WG) and Microscopic Polyangiitis (MPA).

People with serious infections should not receive Rituxan.

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.
• Additionally, in February 2010 Rituxan was approved in combination with fludarabine and cyclophosphamide (FC) for people with previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL).

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

Important Safety Information

• Rituxan can cause serious side effects that can lead to death, including: infusion reactions, tumor lysis syndrome (TLS; kidney failure due to fast breakdown of cancer cells), severe skin and mouth reactions, and progressive multifocal leukoencephalopathy (PML; a rare, serious brain infection).
• Infusion Reactions: Serious infusion reactions can happen during the infusion or within 24 hours of receiving Rituxan. The doctor should give the patient medicines before the infusion of Rituxan to decrease the patients' chance of having a severe infusion reaction. If a serious reaction occurs, the infusion may be stopped and the patient should receive medical care. Patients must tell their doctor or get medical help right away if they get any of these symptoms: hives or rash, itching, swelling of the lips, tongue, throat, or face, sudden cough, shortness of breath, difficulty breathing or wheezing, weakness, dizziness or feeling faint, palpitations, or chest pain.
• Tumor Lysis Sydrome (TLS): TLS is caused by the fast breakdown of cancer cells and can occur after treatment with Rituxan. TLS can cause a person to have kidney failure and the need for dialysis treatment. TLS may also cause abnormal heart rhythm. The doctor may give the patient medicines to prevent TLS and do blood tests to check the patient for TLS.
• Severe Skin and Mouth Reactions: Severe skin and mouth reactions can occur in patients who receive Rituxan.
• Progressive Multifocal Leukoencephalopathy (PML): PML is a rare, serious brain infection caused by a virus. People with a weakened immune system can get PML. Patients must tell their doctor right away if they have any of the following symptoms: confusion or problems thinking, loss of balance, change in the way they walk or talk, decreased strength or weakness on one side of their body, blurred vision or loss of vision.
• Other serious, potentially life-threatening side effects are: hepatitis B infection that may become active again, other infections, heart problems, and low blood cell counts.
• 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.
• The most common side effects seen in patients with RA were upper respiratory tract infection, nasopharyngitis (nose and throat inflammation), urinary tract infection, and bronchitis.
• The most common side effects seen in patients with WG and MPA were infections, nausea, diarrhea, headache, muscle spasms, anemia, peripheral edema (swollen hands and feet).
• These are not all of the possible side effects with Rituxan. Patients should tell their doctor about any side effects that bother them or that do not go away.

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

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.