Pharmacovigilance analysis of severe cutaneous adverse reactions associated with antiseizure medications: a FAERS...

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and related conditions, are rare but potentially life-threatening adverse drug reactions. Antiseizure medications (ASMs) are among the most commonly implicated drug classes; however, comparative pharmacovigilance evidence across different ASMs and SCAR phenotypes as well as their time-to-onset (TTO) patterns remain limited. This study aimed to evaluate ASM-associated SCARs using the FDA Adverse Event Reporting System (FAERS) and characterize their TTO patterns.

Reports of ASM-associated SCARs were extracted from the FAERS database (Q1 2004-Q2 2024). Reports in which ASMs were coded as primary or secondary suspect drugs were included. Disproportionality analysis was performed using the reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN). A positive signal was defined as a drug-event pair that met both ROR and BCPNN criteria. Descriptive analyses and TTO analyses were conducted for the positive signal cases. Differences in TTO across SCAR phenotypes and individual ASMs were assessed using the chi-squared test.

A total of 6,212 positive-signal cases associated with ASMs were identified after data cleaning and deduplication, from which 47 positive drug-event associations were detected across 15 ASMs and five SCAR phenotypes. Signals were primarily concentrated in SJS and TEN, with phenytoin-SJS showing the strongest disproportionality signal. Phenytoin, lamotrigine, carbamazepine, zonisamide, and phenobarbital showed relatively strong disproportionality signals, whereas levetiracetam and valproate exhibited comparatively weaker overall signals but were associated with multiple SCAR phenotypes. Lamotrigine and carbamazepine showed positive signals across several phenotypes, indicating broader reporting patterns across SCAR phenotypes. TTO analysis revealed marked early clustering, with 44.3% of cases occurring within 14 days, 71.6% within 30 days, and 85.0% within 60 days; peak onset occurred between 15 and 30 days. TTO differed significantly across the SCAR phenotypes and ASMs (P < 0.001).

ASM-associated SCARs are predominantly concentrated in SJS and TEN and show substantial heterogeneity across individual drugs. Most events occur early after treatment initiation, particularly within the first month, indicating an early period of reporting concentration after ASM initiation. These findings provide hypothesis-generating pharmacovigilance evidence regarding the reporting patterns and time-to-onset characteristics of ASM-associated SCARs and may help inform future risk evaluation and monitoring strategies.