Effectiveness and tolerability of zafirlukast for the treatment of asthma in children

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Objective This study was undertaken to examine the dose-response relationship of zafirlukast (5 to 40 mg BID) and to assess the efficacy and tolerability of the 10-mg BID dose in school-aged children with mild to moderate asthma. Background The efficacy and tolerability of zafirlukast, an oral leukotriene-receptor antagonist, has been demonstrated in adolescents and adults aged ≥12 years. Methods Data from 2 placebo-controlled, parallel-group, multicenter trials (trial 1, 4-week double-blind; trial 2, 6-week double-blind) were integrated. Children aged 5 to 11 years were randomly assigned to receive zafirlukast 5 mg BID (n = 99), 10 mg BID (n = 205), 20 mg BID (n = 105), 40 mg BID (n = 99), or placebo (n = 206). The primary outcome was change from baseline in forced expiratory volume in 1 second (FEV 1) expressed as percent of predicted normal. Secondary outcomes were FEV 1 (L), morning and evening peak expiratory flow, peak flow variability, short-acting beta 2-agonist use, asthma episode score, and nights awakened by asthma. Results Mean baseline FEV 1 was 76.5% of predicted. The greatest improvements were generally seen with zafirlukast 5 mg BID or 10 mg BID, with no additional clinically significant benefits seen at higher doses. The pooled data analysis showed that 10 mg BID compared with placebo significantly improved ( P < 0.045) all efficacy outcomes except asthma-episode score and nights awakened with asthma. However, in the subset of children who had ≥1 night awakened per week at baseline (zafirlukast 10 mg BID = 78; placebo = 86), 10 mg BID significantly reduced nights awakened ( P = 0.009) (mean difference from placebo at end point = −0.81 night/wk). All zafirlukast doses were well tolerated and had tolerability profiles that were clinically indistinguishable from placebo. Conclusion These results support the effectiveness and tolerability of the 10-mg BID dose of zafirlukast for the prophylaxis and chronic treatment of mild to moderate asthma in children.