Archived – Important Safety Information Regarding Accolate® (Zafirlukast) and Hepatic Effects – AstraZeneca

Important Safety Information Regarding Accolate® (zafirlukast) and Hepatic Effects

October 7, 2002

Dear Healthcare Professional,

As you may know, Accolate® (zafirlukast) is an oral agent indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. It belongs to a class of drugs called leukotriene receptor antagonists.

Accolate® was first launched globally in 1996 and was launched in Canada in 1997. Since the first approval of Accolate®, the total worldwide exposure to Accolate® is estimated to be more than 1.5 million patient years.

AstraZeneca Canada Inc. would like to update you on important safety information regarding Accolate® based on the extensive post-marketing experience with the product since its launch, particularly with respect to reports of liver dysfunction. (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 Product Monograph for Accolate® has been revised to include more specific recommendations for patient management. Please note the following changes.

Under "Warnings/Hepatic Effects"

Please note that the following section differs from the previous version of the Product Monograph in that it recommends Accolate® be discontinued immediately following any signs or symptoms of liver dysfunction, rather than waiting for the confirmatory test results.

"If liver dysfunction is suspected based on clinical signs or symptoms [e.g., right upper quadrant abdominal pain (enlarged liver), nausea, fatigue, lethargy, pruritus, jaundice, 'flu-like' symptoms and anorexia], Accolate should be discontinued. Liver function tests, in particular serum ALT, should be conducted immediately and the patient managed accordingly. If liver function tests are consistent with hepatic dysfunction, Accolate therapy should not be resumed. Patients in whom Accolate is discontinued due to hepatotoxicity where no other attributable cause is identified, should not be re-exposed to Accolate. Accolate is not recommended for patients with hepatic impairment including hepatic cirrhosis."

Under "Adverse Reactions/Liver Enzymes"

Please note the addition of the following section containing information obtained from post-marketing surveillance as indicated below.

"The following hepatic events (which have occurred predominantly in females) have been reported from post-marketing adverse event surveillance of patients who have received the recommended dose of Accolate (40 mg/day): cases of symptomatic hepatitis (with or without hyperbilirubinemia) without other attributable cause; and rarely, hyperbilirubinemia without other elevated liver function tests. In most, but not all, post-marketing reports, the patient's symptoms abated and the liver enzymes returned to normal or near normal after stopping Accolate. In rare cases, patients have progressed to hepatic failure (See Warnings)."

Under "Information for the Patient/Undesirable Effects That May Be Experienced With Accolate"

Please note the addition of the following sentence:

"Consult your doctor if you experience any of the above signs and symptoms."

AstraZeneca Canada Inc. continues to work closely with Health Canada to monitor adverse event reporting and to ensure that up-to-date information regarding the use of Accolate® is available.

The identification, characterization, and management of drug-related adverse events are dependent on the active participation of healthcare professionals in adverse drug reaction reporting programmes. Healthcare professionals are asked to report any suspected adverse reactions in patients receiving Accolate® to AstraZeneca Canada Inc at the following address:

AstraZeneca Canada Inc.

1004 Middlegate Road

Mississauga, Ontario

L4Y 1M4

Tel: 1-800-433-0733

Fax: 1-800-267-5743

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.

Any questions or requests for the revised Product Monograph may be directed to Medical Information via AstraZeneca Canada Inc. Customer Service at 1-800-668-6000 (English) or 1-800-461-3787 (French).

Sincerely,

original signed by

Kazimierz R. Borkowski, Ph.D.

Vice President, Medical Affairs

AstraZeneca Canada Inc.

Any suspected adverse drug reactions can also be reported to:

Canadian Adverse Drug Reaction Monitoring Program (CADRMP)

Marketed Health Products Directorate

Health Canada

Address Locator: 0201C2

Ottawa, Ontario, K1A 1B9

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