Health Canada has issued new warnings on the potentially higher risk of asthma-related deaths from the incorrect use of long-acting beta-2 agonists for treatment of the condition.
The report – which covers GlaxoSmithKline’s asthma drugs Serevent (salmeterol) and Advair (fluticasone propionate/salmeterol), Novartis’ Foradil (formoterol) and AstraZeneca’s Oxeze (formoterol) and Symbicort (budesonide/formoterol) – is based on the agency’s analysis of findings from a clinical trial carried out by GSK.
GSK initiated the SMART (Salmeterol Multi-center Asthma Research Trial) study in 1996 at the request of the US Food and Drug Administration, which had concerns about the regular long-term use of salmeterol in the treatment of asthma.
The trial, involving 30,000 patients, was stopped ahead of schedule in January 2003, following the outcome of an interim analysis that suggested an increased risk of asthma-related death in patients taking Serevent in addition to their usual asthma therapy. However, a review of data by an FDA advisory committee in July this year concluded that the benefits outweighed the risks and a unanimous recommendation saw this class of drugs stay on the market [[14/07/05a]].
Data from SMART indicated 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, although results were not conclusive. The FDA advisory committee noted that higher 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 noted.
Consequently, the agency has issued certain recommendations on the use of asthma drugs, which include: 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.
The prescribing information for Serevent and Advair has been updated, according to the agency, which notes that it is engaged in an ongoing review of these products, as well as a review of safety data for the other long-acting beta-2 agonists.
