Adverse drug reactions of leukotriene receptor antagonists in children with asthma: a systematic review

BACKGROUND: Asthma is the most common chronic condition of childhood. Leukotriene receptor antagonists (LTRAs) are included in international guidelines for children and young people (CYP), but there have been highly publicised concerns about potential adverse effects. The aim was to identify and understand the reported frequency of adverse drug reactions (ADRs) attributed to LTRAs in CYP with asthma. METHODS: Embase, MEDLINE, PubMed and CINAHL were searched up to October 2020. Reference lists of eligible papers were manually screened. Eligible studies identified adverse events attributed to an LTRA in individuals aged between 0 and 18 years diagnosed with asthma. Four different tools were used to assess risk of bias or quality of data to accommodate the papers assessed. RESULTS: The search identified 427 papers after deduplication; 15 were included (7 case reports, 7 case–controlled or cohort studies and 1 randomised control trial (RCT)). 7012 patients were recorded, of which 6853 received an LTRA. 13 papers examined the ADRs attributed to montelukast, one to pranlukast and one to unspecified LTRAs. After language standardisation, 48 ADRs were found, 20 of which were psychiatric disorders. Across all studies, the most commonly reported ADRs were ‘anxiety’, ‘sleep disorders’ and ‘mood disorders’. The frequency of ADRs could be calculated in seven of the eight studies. Applying standardised frequency terms to the prospective studies and RCT, there were 14 ‘common’ and ‘uncommon’ ADRs. ‘Common’ ADRs included ‘agitation/hyperactivity/irritability/nervousness’, ‘aggression’ and ‘headache’. The case reports showed a similar pattern, describing 46 different ADRs experienced by a total of eight patients. CONCLUSIONS: LTRAs have a wide range of suspected ADRs in CYP, predominantly gastrointestinal and neuropsychiatric disorders. Careful monitoring of CYP with asthma is required, both to assess and manage ADRs and to step treatment down when clinically stable. PROSPERO REGISTRATION NUMBER: CRD42020209627.