Questions and Answers on Rituximab (marketed as Rituxan)

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On December 18, 2006, the Food and Drug Administration (FDA) issued a public health advisory to notify patients and health care providers of emerging evidence regarding the risks of serious viral infections in patients who are currently taking or have recently (within the past year) taken Rituxan (rituximab). Rituxan is a monoclonal antibody for the treatment of patients with several types of non-Hodgkin’s lymphoma and for use with methotrexate in the treatment of patients with rheumatoid arthritis that does not improve or is no longer responding to TNF (tumor necrosis factor) antagonist drugs.

Rituxan received marketing approval on November 26, 1997, for use as a single agent for the treatment of patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin’s lymphoma (NHL). In 2006, Rituxan was approved for the following uses:

In combination with cyclophosphamide, vincristine, and prednisone chemotherapy (CVP) for the initial treatment of slow-growing (follicular) B-cell NHL.

By itself, for patients with low-grade, B-cell NHL whose tumors remain stable or shrink following initial treatment with CVP chemotherapy.

In combination with anthracycline-based combination chemotherapy (e.g., CHOP) for the initial treatment of diffuse large B-cell, NHL.

In combination with methotrexate for treatment of moderately- to severely- active rheumatoid arthritis in adults who have had an inadequate response to one or more TNF antagonist therapies to reduce signs and symptoms of the arthritis.

Rituxan is a powerful immunosuppressant drug which affects one arm of the body’s immune system (the B cells). Normal B cells are one type of white blood cells that help to fight infection. Rituxan is used to treat diseases in which the B cells have become cancerous (non-Hodgkin’s lymphoma) or in which B cells are involved in a process that attacks normal parts of the body (rheumatoid arthritis).

1. What action is the FDA taking with Rituxan today?

The Food and Drug Administration (FDA) yesterday issued a public health advisory and a Dear Health Care Provider information sheet to inform patients, their families, the general public, and the medical community of new reports of a serious viral infection (progressive multifocal leukoencephalopathy or PML) in patients with an autoimmune disease (systemic lupus erythematosus [SLE]), who have been treated with Rituxan. Rituxan is not approved for the treatment of SLE.

2. What is PML?

PML stands for progressive multifocal leukoencephalopathy, which is a rare, progressive, infection of the brain that is caused by reactivation of a virus (the JC virus). Up to 80% of healthy adults have been infected with this virus at some point during childhood but the JC virus normally remains in the body in an inactive (latent) state. However, the JC virus can become active and cause illness when the body’s immune system (natural defenses against infection) is impaired by illness or medications. This is similar to what happens with the chickenpox virus that remains in the body and may become active later in life, causing shingles. In the medical literature, PML has been reported in patients with serious underlying diseases, such as cancers of the blood system (lymphoma, leukemia), HIV infection, or in patients who have had bone marrow, kidney, or heart transplants. In most reports, the patients were also receiving medications that impaired the body’s immune system.

When the JC virus becomes active, it causes PML. Symptoms of PML include mental deterioration, confusion, vision loss, difficulty speaking, and loss of balance. PML usually leads to death or severe disability. There is no way to test for patients who might develop PML. The diagnosis is made by x-rays of the brain and by a spinal tap or brain biopsy. There is no known effective treatment other than to stop drugs that are interfering with the immune system. Rituxan therapy should be stopped in any person who develops PML.

3. Have patients with lymphoma or rheumatoid arthritis (RA) treated with Rituxan developed PML?

There are no confirmed cases of PML occurring in patients with rheumatoid arthritis and no cases of PML reported during clinical trials in which approximately 3000 patients with RA received Rituxan. PML has been reported in approximately 23 patients with cancers of the blood system (non-myeloid lymphoma and leukemia) treated with Rituxan along with other chemotherapy drugs that also affect the body’s immune system. PML was reported in only one patient among more than 1500 patients with lymphoma treated with Rituxan in clinical trials.

4. Why is Rituxan still being marketed?

The decision to take any drug should be carefully considered by patients and physicians, who weigh the possible risks (side effects) and the possible benefits of Rituxan and of alternative treatments, if there are alternatives. Rituxan has been shown to shrink tumors, delay tumor growth and, in some situations, prolong life in patients with non-Hodgkin’s lymphoma, a serious cancer of the blood system. Rituxan has also been shown to reduce the symptoms (painful, swollen joints) of rheumatoid arthritis that has failed standard treatments. The likelihood that a person taking Rituxan will develop PML cannot be determined.

Rituxan has not been proven to be a safe and effective treatment for systemic lupus erythematosus and is not approved by the FDA for this disease.

5. What are other serious risks of taking Rituxan?

There are serious side effects from Rituxan, some of which may be life-threatening. The likelihood of Hepatitis B reactivation is unknown. Other serious side effects of Rituxan occur in less than 1% of patients taking this drug:

Infusion reactions. Hives, swelling dizziness, blurred vision, drowsiness, chills, headache, cough, wheezing, or trouble breathing may occur, usually within 24 hours of infusion.
Infections. Rituxan can increase your chances of developing bacterial and viral infections.
Hepatitis B reactivation. In patients who have been infected with viral hepatitis, Rituxan can cause the virus to become active, causing liver damage and even death.
Severe skin reactions. Painful sores, ulcers, or blisters in the mouth and skin, or skin peeling may appear while or after receiving Rituxan.

Health care professionals should read the full prescribing information for Rituxan.

6. What additional actions are likely to follow?

FDA is discussing strengthening the product labeling with Genentech. FDA and Genentech will be advising investigators of these events so that the investigators can contact and inform their patients and consider whether the risks of the clinical studies outweigh the potential benefits.

7. How should I report cases of PML or other serious side effects in patients who are receiving or have received Rituxan?

The FDA urges health care providers and patients to report adverse event information to the FDA via the MedWatch program by phone (1-800-FDA-1088), by fax (1-800-FDA-0178), by the Internet at http://www.fda.gov/medwatch/report.html, or by returning the postage-paid by mail [to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787. MedWatch forms (FDA form 3500) may be downloaded from www.fda.gov/MedWatch/getforms.html.

Health care professionals should report also any serious adverse events possibly associated with the use of Rituxan to Genentech Drug Safety at 1-888-835-2555.

8. How can consumers get additional information?

Consumers who would like more information or have any questions can talk with their healthcare provider. Consumers can also call the Genentech Medical Information/Communications Department at 1-800-821-8590.

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Date created: December 19, 2006