Post-marketing safety of antiseizure medications: Focus on serious adverse effects including drug reaction with eosinophilia and systemic symptoms (DRESS)

Purpose

On November 28, 2023, the U.S. FDA issued a Drug Safety Communication, warning that antiseizure medications (ASMs) levetiracetam and clobazam can cause a rare but serious reaction, drug reaction with eosinophilia and systemic symptoms (DRESS). However, the risk of DRESS from other ASMs remains unclear. This observational study examined post-marketing safety of ASMs focusing on serious adverse events (AEs) reporting including DRESS.

Methods

This retrospective, cross-sectional study analyzed the U.S. FDA Adverse Event Reporting System (FAERS) data from January 1, 2004, to March 31, 2024. Ten older (valproic acid, carbamazepine, oxcarbazepine, phenytoin, and phenobarbital) and newer (zonisamide, topiramate, lamotrigine, lacosamide, and brivaracetam) frequently used ASMs and three benzodiazepines (lorazepam, chlordiazepoxide, and diazepam) in clinical practice as alternative treatments were examined together with levetiracetam and clobazam, respectively. Disproportionality analysis, reporting odds ratio (ROR), was used to detect reporting risk signals of DRESS along with serious AE, hospitalization, death, and Stevens-Johnson Syndrome (SJS) for levetiracetam/clobazam and alternative treatments. A statistically significant reporting risk signal was detected when the lower boundary of the 95 % confidence interval for the RORs exceeded 1.

Results

Levetiracetam had significant reporting risks of serious AE, hospitalization, DRESS, and SJS. Older ASMs including valproic acid, carbamazepine, oxcarbazepine, phenytoin, and phenobarbital all had significant reporting risks of DRESS and SJS. Newer ASMs including zonisamide and lamotrigine had significant reporting risks of DRESS and SJS, while topiramate, lacosamide, and brivaracetam did not exhibit reporting risk for DRESS. Clobazam had significant reporting risks of serious AE, DRESS, and SJS. Lorazepam, chlordiazepoxide, and diazepam did not exhibit reporting risks for DRESS or SJS.

Conclusions

Findings highlighted reporting risk signals of DRESS for levetiracetam/clobazam and alternative ASMs. Given the limitations from passive surveillance nature of FAERS, further surveillance and longitudinal studies are essential to evaluate and confirm our findings.