Adverse events associated with gepants: a pharmacovigilance analysis based on the FDA adverse event reporting system

Gepants have demonstrated notable benefits in migraine therapy, yet their safety profiles are not thoroughly investigated. This study comprehensively analyzed the adverse event (AE) risk signals of the currently approved gepants using the U.S. Food and Drug Administration Adverse Event Reporting System database, aiming to gain better understanding of their post-marketing safety features and potential risks.

All data of the gepants (rimegepant, atogepant, ubrogepant, and zavegepant) from January 1st 2020 to December 31st 2024 were retrieved from the database. Descriptive analysis was conducted to characterize the features of gepant-associated AEs. Disproportionality analysis and subsequent sensitivity analysis were employed to evaluate the risk signals of the gepants utilizing the algorithms of reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC).

A total of 7766 reports of rimegepant, 3672 reports of atogepant, 1958 reports of ubrogepant, and 463 reports of zavegepant were identified after data processing. Most AEs were occurred within 30 days after gepant administration. The integration of disproportionality analysis and sensitivity analysis indicated that "feeling abnormal" was the most reported AE of rimegepant (n = 185, 6.81%, ROR₀₂₅ = 6.46, IC₀₂₅ = 2.59, PRR = 7.24, χ² = 998.58), while "constipation" was the most common AE of atogepant (n = 288, 16.09%, ROR₀₂₅ = 19.99, IC₀₂₅ = 4.10, PRR = 20.72, χ² = 5418.12). The most prevalent AE of ubrogepant was "fatigue" (n = 60, 7.19%, ROR₀₂₅ = 1.88, IC₀₂₅ = 0.84, PRR = 2.38, χ² = 48.82), whereas "dysgeusia" was the most frequently observed AE of zavegepant (n = 150, 45.18%, ROR₀₂₅ = 212.07, IC₀₂₅ = 6.10, PRR = 181.96, χ² = 26,975.74). Comparative analysis of AEs revealed that two AEs were shared among all gepants and zavegepant had the largest collection of unique AEs (n = 15).

The present pharmacovigilance study systematically revealed the significant risk signals of gepants. The common AEs and unique AEs of the four gepants were also identified and explored. Our results would provide valuable reference for the safe use of gepants, guiding personalized drug selection in clinical practice.