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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The FDA has approved the marketing of the corticosteroid ciclesonide (Alvesco - Sepracor) in a hydrofluoroalkane (HFA) metered-dose inhaler formulation for maintenance treatment of asthma in patients >12 years old. Ciclesonide is also available in the US as a nasal spray for allergic rhinitis (Omnaris), and has been available for asthma in Europe since 2003.

Patients with mild, infrequent asthma symptoms may require only intermittent, asneeded use of an inhaled short-acting beta2-adrenergic agonist. Use of a short-acting beta2-agonist more than twice weekly, other than for exercise-induced bronchospasm, indicates a need for anti-inflammatory treatment. Inhaled corticosteroids are the most effective anti-inflammatory medication; leukotriene modifiers are less effective alternatives. If regular use of an inhaled corticosteroid in a low dose does not prevent symptoms, a long-acting beta2-agonist should be added; addition of a second drug is more effective than raising the dose of the inhaled steroid. A leukotriene modifier can also be used as the second drug. Omalizumab may be considered as adjunctive therapy for patients more than 12 years old who have allergic asthma not controlled by other drugs. A short course of oral corticosteroids may be useful for acute exacerbations. Treatment of acute severe asthma as a medical emergency is not included here; it has been reviewed elsewhere (ER McFadden Jr, Am J Respir Crit Care Med 2003; 168:740).

Montelukast sodium (Singulair - Merck), a leukotriene receptor antagonist, has been approved by the US Food and Drug Administration (FDA) for oral prophylaxis and chronic treatment of asthma in adults and children at least 6 years old. It is the third 'leukotriene modifier' to become available in the USA; zafirlukast (Accolate - Medical Letter, 38:111, 1996) and zileuton (Zyflo - Medical Letter, 39:18, 1997) were marketed previously. Neither zafirlukast nor zileuton has been approved by the FDA for use in children less than 12 years old. Leukotriene modifiers are not recommended for treatment of an acute asthma attack (Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma, Bethesda: NIH, 1997; www.nhlbi.NIH.gov/nhlbi/lung/ asthma/prof/asthgdln.htm).

The FDA has approved marketing of the corticosteroid budesonide in an oral inhalatoin powder formulation (Pulmicort Turbuhaler - Astra) for maintenance treatment of asthma in adults and children at least six years old. Budesonide has been available in the USA as an intranasal spray (Rhinocort) for treatment of allergic rhinitis since 1994 and has been used for inhalation treatment of asthma in Canada and Europe for ten years.