Safety Profile of Zavegepant in the Treatment of Acute Migraine: Insights from the FDA Adverse Event Monitoring...

Background/Objectives: The recent approval of the first intranasal calcitonin gene-related peptide receptor antagonist (CGRP-RA), zavegepant, has increased the relevance of this drug class in treating acute migraine. However, introducing an alternative delivery method may result in a different real-world safety profile. Thus, the aim of this study was to assess adverse events (AEs) related to zavegepant through a retrospective pharmacovigilance disproportionality analysis. Methods: We analyzed Individual Case Safety Reports (ICSRs) presenting zavegepant as the suspected drug, submitted to the Food and Drug Administration (FDA) Adverse Event Monitoring System (AEMS) database between 1 January 2023 and 31 December 2025. ICSRs were assessed by using descriptive and disproportionality analyses. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were used as disproportionality measures. Results were deemed significant if the ROR 95% CI lower bound was >1 and ≥3 ICSRs were available for each drug-event pair. Results: A total of 509 zavegepant-related ICSRs were identified. Most ICSRs involved female patients (n = 353; 69.4%), with a median (quartile 1, Q1-quartile 3, Q3) age of 45 (34-56) years. The Medical Dictionary for Regulatory Activities (MedDRA^®) Preferred Terms with the highest RORs were nasal discomfort (n = 62; ROR = 298.85; 95%CI [228.91, 390.17]), rhinalgia (10; 126.09; [67.34, 236.09]), dysgeusia (147; 94.72; [78.19, 114.75]), pharyngeal ulceration (3; 79.20; [25.42, 246.75]), and upper-airway cough syndrome (16; 62.87; [38.19, 103.49]). Conclusions: These results suggest a safety profile for zavegepant consistent with previous knowledge regarding CGRP-RAs. However, nasal and/or oropharyngeal AEs, plausibly related to intranasal exposure, may affect perceived tolerability and timely use, warranting further investigation.