December 4, 2003

Dear Health Care Professional:

Health Canada, in association with Biogen Idec Canada, Inc., Berlex Canada, Inc., and Serono Canada, Inc., would like to inform you of updated safety information from post-marketing experience with beta-interferon therapy for multiple sclerosis (MS).

The table below describes all beta-interferon products marketed in Canada for MS as well as specific dosage and administration information:

The reported occurrence of post-market cases of serious hepatic injury associated with the beta-interferons is rare (defined as a reporting rate of between 1/1,000 and 1/10,000 patient-years of exposure). In addition to post-marketing cases, serious hepatotoxicity has been reported in the literature for all beta-interferon products, including a Canadian case of hepatic failure requiring liver transplantation^1-5. A total of 3 such hepatic failure cases requiring liver transplantation have been reported worldwide with beta-interferon products.

Post-marketing experience with the beta-interferon class has shown that serious hepatic injury occurs predominantly in the first 6 months of therapy, however cases have been reported in patients on therapy beyond 1 year. It is therefore recommended that liver function testing be conducted monthly for the first 6 months of therapy with monitoring every 6 months thereafter in the absence of symptoms. Upon initiating beta-interferon therapy, physicians are advised to educate patients on the signs and symptoms of hepatic injury, including jaundice, diffuse itching, nausea and vomiting, and easy bruising of the skin. Patients should be instructed to immediately contact their physician should these signs and symptoms occur.

Dose reduction or discontinuation of beta-interferon therapy should also be strongly considered if ALT levels increase 5 times above the upper limit of normal.

Reporting rates determined on the basis of spontaneously reported post-marketing adverse events are generally presumed to underestimate the risks associated with drug treatments. The identification, characterization, and management of drug-related adverse events are dependent on the active participation of health care professionals in adverse drug reaction reporting programmes.

Health care professionals are asked to report any suspected adverse reactions in patients receiving beta-interferons to the relevant companies at the following addresses:

Your professional commitment in this regard has an important role in protecting the well-being of your patients by contributing to early signal detection and informed drug use.

Sincerely,

Avonex^® is a registered trademark of Biogen Idec Inc.
Betaseron^® is a registered trademark of Schering AG.
Rebif^® is a registered trademark of Serono, Inc.

References:
1. Durelli L. 1998. Interferon treatment for multiple sclerosis: autoimmune complications can be lethal. Neurology. 50: 570-571.
2. Duchini A. 2002. Autoimmune hepatitis and Interferon Beta-1a for Multiple Sclerosis. Am J Gastroenterol. 97: 767-768.
3. Yoshida EM et al. 2001. Fulminant hepatic failure during interferon beta treatment for multiple sclerosis. Neurology 56(10): 1416.
4. Yoshida EM et al. 2001. Erratum: Fulminant hepatic failure during interferon beta treatment for multiple sclerosis. Neurology 57(11): 2153.
5. Francis GS et al. 2003. Hepatic reactions during treatment of multiple sclerosis with interferon-b-1a, incidence and clinical significance. Drug Safety 26(11): 815-827.