Advisory

2005-107
October 4, 2005
For immediate release

Safety information about a class of asthma drugs known as long-acting beta-2 agonists

OTTAWA - Health Canada is advising Canadians of the possible increased risks of asthma-related deaths associated with the use of a class of asthma drugs known as long-acting beta-2 agonists. Further, Health Canada is reminding Canadians of the recommended uses of long-acting beta-2 agonists.

The asthma medications are salmeterol, which is sold under the brand name Serevent; formoterol, sold as Foradil and Oxeze; as well as two combination products containing salmeterol or formoterol in addition to an inhaled corticosteroid. The combination product with salmeterol is sold as Advair, while the formoterol product is sold as Symbicort.

This advisory is based on a Health Canada analysis of findings from an asthma research trial conducted by GlaxoSmithKline, known as the Salmeterol Multi-center Asthma Research Trial, or SMART. The SMART study began in 1996 at the request of the U.S. Food and Drug Administration (FDA), due to increasing safety concerns about regular long-term use of salmeterol in the treatment of asthma. The study of approximately 30,000 patients was prematurely halted in January 2003 after an interim analysis suggested an increased risk of asthma-related death in patients who use Serevent (as compared to a placebo) in addition to their usual asthma therapy. The SMART study data was reviewed by an FDA advisory committee in July 2005 that looked at the safety of these asthma medications. The committee voted unanimously to keep this class of drugs on the market.

Although not conclusive, the SMART study suggests that risks may be higher in African-American patients and in those patients who were not being treated with inhaled corticosteroids at the start of the study. Corticosteroids are a family of drugs with anti-inflammatory effects that are used in asthma treatment, and they are most commonly used in the form of a powder inhaled directly or can be given orally in more severe cases.

Health Canada monitored the FDA advisory committee in July, which noted that increased risks with salmeterol may also apply to other long-acting beta-2 agonist medications such as formoterol, although data to confirm this is not yet available.

Health Canada recommends that:

• Salmeterol and formoterol can only be used with an appropriate dose of inhaled corticosteroid as determined by a physician.
• Long-acting beta-2 agonists are not a substitute for inhaled or oral corticosteroids.
• Serevent, Foradil or Advair should never be used to treat acute or sudden onset of asthma symptoms and attacks.
• Symbicort is not indicated for the treatment of sudden asthma symptoms and attacks.
• Oxeze may be used to treat acute, or the sudden onset of asthma symptoms, in patients 12 years and older.
• Medical attention should be sought if a patient's use of asthma medications becomes less effective, or if more inhalations than usual are required.
• Patients must not stop or reduce their asthma therapy without first consulting their prescribing physician. Abruptly stopping medications may result in deteriorating asthma control, which can be life-threatening.
• Patients with asthma who have any questions about their current prescription or treatment should contact their physician or pharmacist directly.

The prescribing information for Serevent and Advair has been updated. Health Canada is engaged in an ongoing review of these products, and is in the process of reviewing the safety data for the other long-acting beta-2 agonists. Further action may be taken if necessary.

Health Canada has requested that manufacturers of these medications inform physicians of the SMART study findings and of the outcome of the FDA advisory committee meeting. The FDA panel only reviewed data relating to Serevent (salmeterol) and Foradil (formoterol).

Long-acting beta-2 agonists are prescribed as regular treatment to prevent asthma symptoms such as wheezing, shortness of breath and cough. Serevent and Advair are manufactured by GlaxoSmithKline. Foradil is manufactured by Novartis, and Oxeze and Symbicort are manufactured by AstraZeneca.

Managing marketed health product-related adverse reactions depends on health care professionals reporting them. Reporting rates determined on the basis of patient-reported post-marketing adverse events are generally presumed to underestimate the risks associated with drug treatments. Any cases of serious respiratory-related or other serious or unexpected adverse reactions in patients taking salmeterol or formoterol products should be reported to Health Canada at the following address:

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.

Astra Zeneca Canada Inc.
1004 Middlegate Rd.
Mississauga, ON, L4Y 1M4
Tel: (905) 277-7111
1-800-565-5877
Fax: (905)270-3248
1-800-267-5743
www.astrazeneca.ca

Glaxosmithkline Inc.
733 Mississauga Rd. N.
Mississauga ON L5N 6L4
Tel: (905) 819-3000
1-800-268-4600
Fax: (905) 819-3099
http://ca.gsk.com/

Novartis Pharmaceuticals Canada Inc.
385 boul. Bouchard
Dorval, QC H9S 1A9
Tel: (514) 631- 6775
1-877-631-6775
Fax: (514) 631- 1867
www.novartis.ca

-30-

Media Inquiries:
Nathalie Lalonde
Health Canada
(613) 957-1803

Public Inquiries:
(613) 957-2991
1-866 225-0709