Archived – Possible Association Between RITUXAN® (Rituximab) and the Recurrence of Hepatitis B – Hoffmann-La Roche Limited – For the Public

Public Advisory

Health Canada Endorsed Important Safety Information on RITUXAN (rituximab)

July 30, 2004

Subject: Possible association between RITUXAN and the recurrence of hepatitis B

Hoffmann-La Roche Limited, in consultation with Health Canada, has informed Canadian healthcare professionals of important new safety information concerning RITUXAN (rituximab). This drug is used to treat some types of lymphomas (cancers of the lymph nodes) either alone or with chemotherapy. Please note the following new safety information for the use of RITUXAN:

• Very rare cases of recurrence of hepatitis B virus infection have been reported, occasionally leading to liver failure and death. Most of these cases occurred in patients who were also receiving chemotherapy.
• Patients at risk for hepatitis B infection should have a blood test before starting RITUXAN to determine if they are carrying or have had a previous infection with the hepatitis B virus. Patients in doubt of their risk for hepatitis B should talk to their Health Care Provider.
• Carriers of the hepatitis B virus and patients who have previously been infected with hepatitis B should be closely monitored for signs and symptoms of recurrence of active hepatitis B infection for up to a year after RITUXAN therapy.

Hoffmann-La Roche Limited has continued to gather information on the safety and efficacy of RITUXAN since RITUXAN was introduced to the market.

If hepatitis B infection re-occurs, RITUXAN and any associated chemotherapy should be discontinued and appropriate treatment should be prescribed.

Signs and symptoms of hepatitis B include:

• yellowing of the skin or eyes (jaundice)
• feeling of sickness
• tiredness
• loss of appetite
• joint pain
• abdominal pain

Patients who experience any of these symptoms should contact their physician immediately.

This advisory is in addition to a letter issued to healthcare professionals discussing the above-mentioned safety information. This letter can be accessed at Health Canada's web site at: http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2004/index-eng.php

The identification, characterization, and management of marketed health product-related adverse reactions are dependent on the active participation of healthcare professionals in adverse reaction reporting programmes. Any recurrences of hepatitis B virus infection or other 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:

Hoffmann-La Roche Limited

Drug Information and Safety Department

2455 Meadowpine Boulevard

Mississauga, ON L5N 6L7

or call toll-free at 1-888-762-4388

Any suspected adverse reaction can also be reported to:

Canadian Adverse Drug Reaction Monitoring Program (CADRMP)

Marketed Health Products Directorate

Health Canada

Address Locator: 0701C

Ottawa, Ontario, K1A 0K9

Tel: (613) 957-0337 or Fax: (613) 957-0335

To report an Adverse Reaction, consumers and health professionals may call toll free:

Tel: 866 234-2345

Fax: 866 678-6789

cadrmp@hc-sc.gc.ca

For other inquiries: please refer to contact information.

The AR Reporting Form and the AR Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.

original signed by

Lorenzo Biondi

Vice President,

Medical and Regulatory Affairs