New Safety Information on Long-Acting Beta-2 Agonists

By Dodoo, Alex

Canada – Health Canada has advised of a possible increased risk of asthma-related deaths associated with long-acting beta-2 agonists.

The medications involved are salmeterol, (SerevenKD), formoterol, (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 AdvairR, while the formoterol product is sold as Symbicort. Long-acting beta-2 agonists are prescribed as regular treatment to prevent asthma symptoms such as wheezing, shortness of breath and cough.

This advisory is based on a Health Canada analysis of findings from an asthma research trial known as the Salmeterol Multi-center Asthma Research Trial, or SMART. The SMART study began in 1996 at the request of the US 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 salmeterol (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.

Table 1: Reports submitted to Health Canada of amnesia* suspected of being associated with statins from date marketed in Canada to 31 May 2005[dagger]

Although not conclusive, the SMART study suggests that risks may be higher in AfricanAmerican patients and in those patients who were not being treated with inhaled corticosteroids at the start of the study.

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.

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.

Reference: Health Canada Advisory, 2005-107.4 October 2005

Copyright World Health Organization 2005