Serious liver injury with TEBRAZID (pyrazinamide) or PMS-pyrazinamide and rifampin for the treatment of latent tuberculosis - ICN Canada Limited and Pharmascience Inc.

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Contact : MHPD DPSC

IMPORTANT SAFETY INFORMATION REGARDING TEBRAZID^® (PYRAZINAMIDE) AND PMS-PYRAZINAMIDE FOR THE TREATMENT OF LATENT TUBERCULOSIS INFECTION

December 22, 2003

Dear Health Care Professional,

SUBJECT: Important safety information regarding serious liver injury associated with the combined use of Tebrazid^® (pyrazinamide) or pms-Pyrazinamide and rifampin for latent tuberculosis (TB) infection.

A recent report from the Centers for Disease Control and Prevention (CDC) of the US describes high rates of hospitalization and death from liver injury following the combined use of pyrazinamide and rifampin for the treatment of latent TB. As a result, the American Thoracic Society and the CDC now recommend that this regimen not be offered as a first-line treatment to persons with latent TB infection.

ICN Canada and Pharmascience recognize the risk of pyrazinamide-associated hepatotoxicity as pointed out in the prescribing information for the treatment of clinical TB.

After consultation with Health Canada, ICN Canada and Pharmascience Inc. recommend that the combination regimen of pyrazinamide and rifampin not be used for the first-line treatment of latent TB, because of a higher risk of hepatotoxicity. The CDC's revised drug regimen for the treatment of latent TB infection in adults can be viewed at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5231a4.htm

Recommendations for the treatment of active TB remain unchanged. The Canadian Tuberculosis Standards recommendations for the treatment of active TB disease can be viewed at: http://www.phac-aspc.gc.ca/tbpc-latb/pubs_e.html

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 is 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 pyrazinamide to ICN, Pharmascience, or to the Marketed Health Products Directorate at the following addresses or telephone numbers:

Any suspected adverse incident 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
Toll free for consumers and health professionals:
Tel: 866 234-2345, Fax: 866 678-6789
cadrmp@hc-sc.gc.ca

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

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.

original signed by

ICN Canada Limited
Joseph Awad, M.B.Ch.B.
Director, Medical and Regulatory Affairs

Pharmascience Inc.
Len Neirinck, Ph. D.
Vice President Scientific Affairs