A combination of the corticosteroid mometasone furoate (Asmanex) and the long-acting beta₂-agonist (LABA) formoterol (Foradil) has become available in a single metered-dose inhaler (Dulera – Schering) for treatment of asthma in patients ≥12 years old. It is the third corticosteroid/LABA combination inhaler to become available for this indication in the US. None of these combinations should be used for initial treatment of asthma or for acute treatment of asthma symptoms.

A little more than a year ago, The Medical Letter reported the results of an FDA meta-analysis which found that use of a long-acting beta-2 agonist (LABA) such as salmeterol (Severent) or formoterol (Foradil) in patients with asthma was associated with an increased risk of a composite endpoint of asthma-related death, intubation or hospitalization; the highest risk was in children 4-11 years old.There was no significant increase in risk when a long-acting beta-2 agonist was used with an inhaled corticosteroid.The Medical Letter recommended that long-acting beta-2 agonists should not be used as monotherapy for asthma, especially in children, and that long-acting beta-2 agonists should be used for asthma only in combination with an inhaled corticosteroid, preferably in a fixed-dose combination in the same inhaler.1

Now the FDA has issued new Safe Use Requirements2 and labeling requirements for long-acting beta-2 agonists that include the following: “Stop use of the LABA, if possible, once asthma control is achieved and maintain the use of an asthma-controller medication such as an inhaled corticosteroid.”3

It has not been determined that patients taking a longacting beta-2 agonist in a fixed-dose combination with an inhaled corticosteroid have an increased risk of death or that stopping long-acting beta-2 agonists in such patients will improve long-term outcomes. A controlled clinical trial of these new requirements would be welcome.

1. Long-acting beta-2 agonists in asthma. Med Lett Drugs Ther 2009; 51:1.
2. www.fda.gov/safety/medwatch/default.htm
3. BA Chowdhury and G Dal Pan. The FDA and safe use of long-acting beta-agonists in the treatment of asthma. N Engl J Med 2010; Feb 24 (epub).

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Continued use of a long-acting beta-2 agonist for treatment of asthma may cause down-regulation of the beta-2 receptor with loss of the bronchoprotective effect from rescue therapy with a short-acting beta-2 agonist. After a large study (SMART) found an increased risk of asthma-related deaths in patients receiving the long-acting beta-2 agonist salmeterol, a boxed warning was added to the labeling of all medications containing a long-acting beta-2 agonist. Now the FDA has completed a meta-analysis of 110 asthma treatment studies in 60,954 patients taking any of the long-acting beta-2 agonist formulations listed in the table.