Montelukast - A review of its therapeutic potential in persistent asthma

Montelukast is a cysteinyl leukotriene receptor antagonist used to treat pe rsistent asthma in patients aged greater than or equal to 6 years. The drug has a rapid onset of action. Improvements in lung function and red uctions in as-needed beta(2)-agonist usage are apparent within 1 day of ini tiating montelukast treatment in adults and adolescents (aged greater than or equal to 15 years treated with 10 mg/day) or children (aged 6 to 14 year s treated with 5 mg/day) with persistent asthma as shown in clinical trials . In two 12-week, multicentre, randomised, double-blind studies in adults and adolescents aged greater than or equal to 15 years with persistent asthma [forced expiratory volume in 1 second(FEV1) = 50 to 85% predicted] there wa s significantly (p less than or equal to 0.05) greater improvement in FEV1, symptom scores, peak expiratory now (PEF), as-needed beta(2)-agonist use, peripheral eosinophil counts and health-related quality of life (QOL) in pa tients treated with montelukast 10 mg/day than in recipients of placebo. Im provements were significantly greater in patients treated with inhaled becl omethasone 400 mu g/day than in recipients of montelukast 10 mg/day in 1 of these studies. Nonetheless, 42% of montelukast recipients experienced grea ter than or equal to 11% improvement in FEV1, the median improvement in thi s parameter in beclomethasone-treated patients. In an 8-week multicentre, randomised, double-blind, study in children aged 6 to 14 years with persistent asthma (FEV1 50 to 85% predicted), montelulia st 5 mg/day produced significantly greater improvements in FEV1, clinic PEF , as-needed beta(2)-agonist use, peripheral eosinophil counts, asthma exace rbations and QOL scores than placebo. The combination of montelukast 10 md/day plus inhaled beclomethasone 200 mu g twice daily provided significantly better asthma control than inhaled be clomethasone 200 mu g twice daily in adults with poorly controlled asthma ( mean FEV1 = 72% predicted) despite 4 weeks treatment with inhaled beclometh asone. Patients receiving the combination experienced significant improveme nts in FEV 1 and morning PEF, significant reductions in daytime symptom sco res, as-needed beta(2) agonist usage and night-time awakenings with asthma, and had significantly lower peripheral blood eosinophil counts after 16 we eks in this multicentre, randomised, double-blind, placebo-controlled study . Among adults (FEV(1)greater than or equal to 70%) treated with montelukast 10 mg/day for 12 weeks, inhaled corticosteroid dosages were titrated downwa rd by 47% (Its 30% in placebo recipients), 40% of patients were tapered off of inhaled corticosteroids (vs 29%), and significantly fewer patients (16 vs 30%) experienced failed corticosteroid rescues in a muldcentre, randomis ed, double-blind study. During clinical studies, the frequency of adverse events in montelukast-tre ated adults, adolescents and children was similar to that in placebo recipi ents. In conclusion, montelukast is well tolerated and effective in adults and ch ildren aged greater than or equal to 6 years with persistent asthma includi ng those with exercise-induced bronchoconstriction and/or aspirin sensitivi ty. Furthermore, montelukast has glucocorticoid sparing properties. Hence, montelukast, as monotherapy in patients with mild persistent asthma, or as an adjunct to inhaled corticosteroids is useful across a broad spectrum of patients with persistent asthma.