Age-related differences in hydroxychloroquine-associated adverse events: A pharmacovigilance study based on the FDA Adverse Event Reporting System.

Abstract

Aims: This real-world pharmacovigilance study utilizes FDA Adverse Event Reporting System (FAERS) data (2004-2024) to characterize age-related disparities in hydroxychloroquine (HCQ)-associated adverse events (AEs), addressing gaps in age-stratified risk assessment.

Methods: Disproportionality analysis (reporting odds ratios, RORs) and parametric Weibull modelling were applied to compare AE signals and time-to-onset profiles between paediatric (≤18 years; n = 1744) and geriatric (≥60 years; n = 14 115) populations from 22 249 476 HCQ-related reports.

Results: Paediatric AEs exhibited significantly earlier onset (median 9.5 days vs. 19 days). Ten novel paediatric-specific signals were identified, including COVID-19-related cardiotoxicity (ROR = 3.26, 95% confidence interval [CI] 1.87-6.94) and hypokalaemia complications (ROR = 25.77, 95% CI 18.7-35.52), with distinct reporting patterns compared to geriatric cohorts. Weibull shape parameters revealed divergent risk trajectories: constant hazard profiles in children (α = 0.52, β = 46.68) contrasted with escalating risks in older adults (α = 0.40, β = 93.66), suggesting mechanistic differences in toxicity progression.

Conclusions: Significant age-related variations in HCQ-associated AE profiles, temporal dynamics and risk evolution underscore the necessity for age-stratified pharmacovigilance frameworks. Paediatric-specific cardiotoxic and metabolic risks, coupled with geriatric-specific cumulative toxicity patterns, mandate tailored therapeutic monitoring strategies to optimize safety across age extremes.