Montelukast: Data from clinical trials in the management of asthma

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of montelukast, a leukotriene receptor antagonist used to treat asthma, and to discuss the therapeutic role of montelukast as lon g-term medication and difficulties associated with the management of asthma . DATA SOURCES: A MEDLINE search (up to May 1999) was conducted to identify r elevant English-language publications, including preclinical studies, clini cal trials, and recent reviews. STUDY SELECTION: All available published reports of controlled, clinical tr ials of montelukast in adults and children with asthma were summarized, inc luding pharmacokinetic and pharmacologic effects of montelukast. DATA EXTRACTION: Information on the safety and efficacy of montelukast was evaluated on the basis of patient selection, study design, methodology, and statistical significance as compared with placebo or inhaled corticosteroi d treatment. DATA SYNTHESIS: Montelukast is approved for the prophylaxis and chronic tre atment of asthma at a dose of 10 mg once daily for adolescents (greater tha n or equal to 15 y) and adults and 5 mg once daily for children (6-14 y). I n placebo-controlled clinical trials, montelukast significantly improved pu lmonary lung function (as measured by forced expiratory volume in 1 sec), s ignificantly reduced beta(2)-agonist use, and significantly improved patien t-reported end points in adults and children (greater than or equal to 6 y) with chronic asthma. In adults, a similar magnitude of improvement in lung function is seen with or without inhaled corticosteroid use; the effects o f montelukast may be additive to those of inhaled corticosteroids and permi t the reduction of the required dose of inhaled corticosteroids. In cases o f exercise-induced asthma (adults and children), montelukast treatment atte nuates the fall in pulmonary function following exercise. It attenuates bot h the early- and late-phase responses of asthma after allergen inhalation. Improvements in asthma control are similar in asthmatic patients who are as pirin-sensitive or not aspirin-sensitive and can be seen within one day of treatment. Tolerance does not develop, and the adverse events do not differ from those of placebo. CONCLUSIONS: Montelukast is indicated for the prophylaxis of chronic asthma in adults and children (greater than or equal to 6 y). It may be considere d for use as first-line therapy in patients with mild persistent asthma or for additional control in patients who are still symptomatic while receivin g treatment with inhaled corticosteroids. It may also be used for additiona l control in aspirin-sensitive asthmatic patients. Consideration may be giv en for using montelukast to allow tapering of the dose of inhaled corticost eroids while maintaining clinical stability. Chronic treatment with montelu kast can provide additional control of symptoms during exercise, but inhale d beta(2)-agonists remain first-line therapy for prophylaxis and treatment.