Adverse drug reaction patterns associated with potentially inappropriate medications in children: insights from two global pharmacovigilance databases

Background Advances in pediatric pharmacotherapy have improved clinical outcomes but are accompanied by increased vulnerability to adverse drug reactions (ADRs), owing to developmental pharmacokinetics and frequent off-label use. Key potentially inappropriate drugs in pediatrics (KIDs) are medications that warrant caution due to unfavorable risk-benefit profiles in children. However, the real-world pattern of ADRs associated with these drugs remains incompletely characterized. The current study aimed to determine how frequently the ADRs specified in the KIDs list are reported for the corresponding medications using two large pharmacovigilance databases. Method In this study, we conducted a retrospective analysis of ADRs reported from 2020 to 2025 in the United States FDA Adverse Event Reporting System and European EudraVigilance databases, focusing on KIDs in patients under 18 years of age. A drug was considered to have been potentially causative of the ADR if it was reported as a primary or secondary suspect medication. For each KID, we noted the total number of ICSRs containing the specific drug as a primary or secondary suspect, the total number of ADRs reported in these ICSRs, and the number of ICSRs reporting the specific “ADR of interest” for each KID. “ADR of interest” was the specific adverse event(s) for which a particular drug has been labeled as potentially inappropriate in a specific age group as per the KIDs list. A complementary approach of use of two large pharmacovigilance databases was adopted to enable a more comprehensive assessment of reporting patterns. Results Following deduplication, 8276 and 9114 ICSRs were available in FAERS and EudraVigilance, respectively, with the 12–17-year age group accounting for 54.42% and 42.03% of reports. Predefined ADRs of interest were reported in 1,427 reports (17.24%) in FAERS and 521 (5.72%) in EudraVigilance. Across both databases, central nervous system-acting drugs, particularly atypical antipsychotics, accounted for the majority of reported ADRs. Metabolic disturbances and extrapyramidal symptoms were most frequently observed, with hyperprolactinemia, weight gain, and dyslipidemia emerging as prominent findings. Among the non-CNS drugs, montelukast contributed substantially to reports of sleep disturbance. Serious ADRs, including reports of fatal outcomes, involving neurological, respiratory, metabolic, and hematological systems were also observed. Conclusion The findings, supported by consistent ADR patterns across complementary pharmacovigilance databases, underscore the vulnerability of pediatric patients to ADRs from potentially inappropriate medications. The results highlight the need for judicious prescribing, close monitoring, and strengthened pharmacovigilance to improve medication safety in children.