Citation

Chrétien B, Nguyen S, Dolladille C, Morice PM, Heraudeau M, Loilier M, Fedrizzi S, Bourgine J, Cesbron A, Alexandre J, Bocca ML, Freret T, Lelong-Boulouard V. Br. J. Clin. Pharmacol. 2022; ePub(ePub): ePub.

Copyright

(Copyright © 2022, John Wiley and Sons)

DOI

10.1111/bcp.15481

PMID

35939367

Abstract

AIM: Due to their central mechanism of action, anti-seizure medications (ASMs) could lead to adverse effects likely to impair driving skills. Their extended use to neuropsychiatric disorders makes it a class of drugs to monitor for their road traffic accidental (RTA) potential. We aimed to assess the reporting association between ASMs and RTA using the WHO pharmacovigilance database (Vigibas®).

METHODS: We performed a disproportionality analysis to compute adjusted reporting odds ratios (aROR) to evaluate the strength of reporting association between ASMs and RTAs. A univariate analysis using the reporting odds-ratio was used to assess drug-drug interactions (DDI) between ASMs and RTAs.

RESULTS: There were 1,341,509 reports associated with at least one ASM in Vigibase® of whom 2.91‰ were RTAs reports. Eight ASMs were associated with higher reporting of RTAs compared to others (ranging from 1.35 (95% CI 1.11-1.64) for lamotrigine to 4.36 (95% CI 3.56-5.32) for cannabis). Eight significant DDI were found between ASMs and the onset of RTA, mainly involving CYP450 induction.

CONCLUSION: A significant safety signal between RTAs and some ASMs was identified. Association of several ASMs might further increase the occurrence of RTA. ASMs prescription in patients with identified risk factors of RTA should be considered with caution. Study number: ClinicalTrials.gov, NCT04480996.

Language: en

Keywords

road traffic accidents; anti-seizure medications; CYP450 inductors; drug-drug interactions; gabapentinoids; pharmaco-epidemiology