Print | Need Larger Text? | Share

Important Safety Information on RITUXAN (rituximab) - For Health Professionals

Help on accessing alternative formats, such as Portable Document Format (PDF), Microsoft Word and PowerPoint (PPT) files, can be obtained in the alternate format help section.

(PDF Version - 387 K)

Contact MHPD

August 8, 2007

Subject: Reports of Progressive Multifocal Leukoencephalopathy (PML) following RITUXAN use in Systemic Lupus Erythematosus and Vasculitis (off-label use)

Dear Health Care Professional:

Hoffmann-La Roche Limited, in consultation with Health Canada, would like to inform you of important new safety data that have implications for the use of RITUXAN (rituximab).

RITUXAN^® is a recombinant chimeric anti-CD20 monoclonal antibody indicated for the treatment of B-cell non-Hodgkin's Lymphoma (NHL) and Rheumatoid Arthritis (RA). It is estimated that over one million patients have been administered RITUXAN worldwide.

Progressive multifocal leukoencephalopathy (PML) is a rare, progressive, demyelinating disease of the central nervous system that usually leads to death or severe disability. PML is caused by activation of the JC virus, a polyomavirus that resides in latent form in up to 80% of healthy adults. JC virus usually remains latent, typically only causing PML in immunocompromised patients. The factors leading to activation of the latent infection are not fully understood.

PML has been reported in HIV positive patients, immunosuppressed cancer patients, transplantation patients and patients with autoimmune disease including SLE. Abnormalities in T cells have been described as important for activation of JC virus and PML. Very rare (<1/10,000) cases of PML have been described in NHL patients receiving chemotherapy alone or receiving RITUXAN; in the majority of cases this occurred in combination with chemotherapy or as part of hematopoietic stem cell transplant.

JC virus infection with resultant PML and death has been reported in 2 patients with SLE treated with RITUXAN. Both of these patients had longstanding SLE with multiple courses of immunosuppressant use prior to receiving RITUXAN. These patients were diagnosed with PML within 12 months of their last infusion of RITUXAN. JC virus infection with resultant PML has also been reported in 1 patient with ANCA-negative Vasculitis/Cyroglobulinemia (Hepatitis C negative). The patient received immunosuppressive (including cytotoxic) therapy prior to receiving RITUXAN, and continued to receive immunosuppressive therapy in combination with RITUXAN. PML was diagnosed within 12 months of the first exposure to RITUXAN and the patient is currently undergoing treatment.

PML has been reported in patients with SLE and also in patients with Vasculitis receiving other immunosuppressants without concomitant RITUXAN. A causal relationship between RITUXAN and PML has not been established. The overall incidence of PML in patients with SLE or Vasculitis is not known. There have been no reports of PML in patients with autoimmune diseases receiving RITUXAN in Canada. We continue to follow this closely and any new information will be promptly communicated.

Physicians treating patients with autoimmune diseases or lymphoid malignancies should consider the diagnosis of PML in any patient presenting with new onset neurologic manifestations. Consultation with a neurologist, brain MRI and lumbar puncture may be considered as clinically indicated. There is no currently accepted screening test for PML.

In patients who develop PML, RITUXAN should be discontinued and reductions or discontinuation in concomitant immunosuppressive therapy and appropriate treatment should be considered. There are no known interventions that can reliably prevent PML or adequately treat PML if it occurs.

The  Canadian Product Monograph (CPM) has been revised to include information on PML. Managing marketed health product related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any occurrence of serious and/or unexpected adverse reactions in patients receiving RITUXAN should be reported to Hoffmann-La Roche Limited, or Health Canada at the following addresses:

Should you have any questions or require additional information regarding the use of RITUXAN, please contact the Drug Information Department at Hoffmann-La Roche Limited at 1-888-762-4388 from 8:30 a.m. to 4:30 p.m. Monday to Friday Eastern Standard Time.

Sincerely,

original signed by

Lorenzo Biondi
Vice President, Medical and Regulatory Affairs
Hoffmann-La Roche Limited