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

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 IO-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 een demonstrated in adolescents and adults aged greater than or equal to 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 (FEV1) expressed as percent of predicted normal. Secondary outcomes were FEV1 (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 FEV1 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 less than or equal to 0.045) all efficacy outcomes except asthma-episode score and nights awakened with asthma. However, in the subset of children who had greater than or equal to 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.