Safety analysis of gepants for migraine treatment: A pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) database.

BACKGROUND

Gepants, a novel class of calcitonin gene-related peptide (CGRP) receptor antagonists, are increasingly used for acute and preventive migraine treatment; however, comprehensive real-world safety data are limited. This study is a retrospective disproportionality analysis that evaluates the safety profile of rimegepant, ubrogepant, atogepant, and zavegepant by analyzing adverse events (AEs) reports from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database in patients with migraine.

METHODS

AE reports for rimegepant, ubrogepant, atogepant, and zavegepant from January 2020 to March 2025 were retrieved from the FAERS database using standardized drug names and migraine-related indications. Disproportionality analyses were employed to detect AE signals, classified by system organ class (SOC) and Preferred Term (PT) using MedDRA 27.0.

RESULTS

A total of 84, 55, 80, and 31 AE signals were identified for rimegepant, ubrogepant, atogepant, and zavegepant, respectively. Nausea, a gastrointestinal disorder, was the only AE common to all four gepants (4.07%-5.2%). Oral gepants (rimegepant, ubrogepant, atogepant) primarily showed gastrointestinal and nervous system AEs, including constipation (atogepant, reporting odds ratio {ROR} = 11.39 [95% confidence interval {CI}: 10.21-12.71]) and dizziness. Zavegepant was associated with respiratory AEs, notably nasal discomfort (ROR = 718.38 [95% CI: 552.33-934.35]). Potential signals related to pregnancy outcomes were detected for rimegepant and ubrogepant, warranting cautious interpretation and further investigation.

CONCLUSION

Gepants display distinct AE profiles, with oral agents linked to gastrointestinal and neurological effects and intranasal zavegepant associated with respiratory irritation. Continued post-marketing surveillance is essential to inform personalized migraine management and guide future CGRP-targeted drug development.