Clinical Research and Knowledge Transfer Unit on Childhood Asthma, Research Centre, CHU Sainte-Justine, Montreal, QC, Canada.
Dept of Pediatrics, University of Montreal, Montreal, QC, Canada.
Eur Respir J. 2017 Aug 17;50(2). doi: 10.1183/13993003.00148-2017. Print 2017 Aug.
Although montelukast is generally well tolerated, postmarketing studies have reported serious neuropsychiatric adverse drug reactions (ADRs) leading to a United States Food and Drug Administration black box warning. The objective of this study was to determine the incidence of neuropsychiatric ADRs leading to discontinuation of montelukast in asthmatic children.We conducted a retrospective cohort study in children aged 1-17 years initiated on montelukast. In a nested cohort study, children initiated on montelukast as monotherapy or adjunct therapy to inhaled corticosteroids (ICS) were matched to those initiated on ICS monotherapy. A non-leading parental interview served to ascertain the occurrence of any ADRs with any asthma medication, and circumstances related to, and evolution of, the event.Out of the 106 participants who initiated montelukast, most were male (58%), Caucasian (62%) with a median (interquartile range) age of 5 (3-8) years. The incidence (95% CI) of drug cessation due to neuropsychiatric ADRs was 16 (10-26)%, mostly occurring within 2 weeks. Most frequent ADRs were irritability, aggressiveness and sleep disturbances. The relative risk of neuropsychiatric ADRs associated with montelukast ICS was 12 (2-90).In the real-life setting, asthmatic children initiated on montelukast experienced a notable risk of neuropsychiatric ADRs leading to drug cessation, that is significantly higher than that associated with ICS.
虽然孟鲁司特通常具有良好的耐受性，但上市后研究报告称其会引起严重的神经精神不良药物反应（ADR），导致美国食品和药物管理局发出黑框警告。本研究旨在确定导致孟鲁司特在哮喘儿童中停药的神经精神 ADR 的发生率。我们对 1 至 17 岁接受孟鲁司特治疗的儿童进行了回顾性队列研究。在一项嵌套队列研究中，将接受孟鲁司特单药治疗或联合吸入皮质激素（ICS）治疗的儿童与接受 ICS 单药治疗的儿童相匹配。非主要的父母访谈用于确定任何与任何哮喘药物相关的 ADR 的发生情况，以及与该事件相关的情况及其演变。在 106 名开始接受孟鲁司特治疗的参与者中，大多数为男性（58%），白种人（62%），中位数（四分位距）年龄为 5（3-8）岁。由于神经精神 ADR 而停药的发生率（95%CI）为 16（10-26）%，大多数发生在 2 周内。最常见的 ADR 为易怒、攻击性和睡眠障碍。孟鲁司特联合 ICS 发生神经精神 ADR 的相对风险为 12（2-90）。在真实环境中，开始接受孟鲁司特治疗的哮喘儿童经历了显著的神经精神 ADR 停药风险，显著高于与 ICS 相关的风险。
