Severe cutaneous adverse reactions linked to medications in children and adolescents: a pharmacovigilance study based on the FDA Adverse Event Reporting System database

Int J Clin Pharm. 2025 Dec 3. doi: 10.1007/s11096-025-02063-2. Online ahead of print.

ABSTRACT

INTRODUCTION: Severe cutaneous adverse reactions (SCARs) are rare but potentially life-threatening. Children and adolescents are especially vulnerable due to developmental pharmacology, immature immune systems, and limited premarketing safety data. However, large-scale evidence of drug-specific SCAR patterns in pediatric populations remains limited.

AIM: To investigate the epidemiology, clinical features, drug associations, and safety signals of SCARs in children and adolescents using the FDA Adverse Event Reporting System (FAERS).

METHOD: Reports of SCARs in patients aged ≤ 18 years were retrieved from FAERS from Q1 2004 to Q2 2024 and identified using narrow-scope Standardised MedDRA Queries (SMQs). Data cleaning followed the FDA-recommended procedures. Disproportionality analysis was performed using four methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN; yielding Information Component, IC), Multi-item Gamma Poisson Shrinker (MGPS), and empirical Bayes geometric mean (EBGM). Drug-label reviews were used to compare the signal detection results with existing safety warnings.

RESULTS: A total of 7183 pediatric SCAR reports were included. The number of reports has increased over time, with adolescents (13-17 years) and school-aged children (7-12 years) accounting for 68% of cases. The most frequently reported Preferred Terms were drug reaction with eosinophilia and systemic symptoms (DRESS; 32.5%), Stevens-Johnson syndrome (SJS; 27.9%), and toxic epidermal necrolysis (TEN; 19.0%). Hospitalization occurred in 64.5% of cases, and 6.3% were fatal. Among the 2005 cases with available onset time, 82.7% developed within 30 days of drug exposure. Thirty-eight drugs showed positive signals, including lamotrigine, phenytoin, sulfamethoxazole, and phenobarbital. Four drugs, ranitidine, anakinra, clonazepam, and rifampin, showed signals without corresponding warnings in the FDA pediatric labeling.

CONCLUSION: SCARs in children and adolescents show distinct patterns, high hospitalization and mortality, and strong links with antiepileptics and anti-infectives. Strengthening pediatric pharmacovigilance, implementing risk-alert systems, and promoting genotype-guided prescribing may help prevent these severe reactions.

PMID:41335163 | DOI:10.1007/s11096-025-02063-2