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This scoping review aims to synthesize current evidence on the pharmacology, clinical applications, safety, and combination strategies of gepants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A scoping review was conducted following PRISMA\u2010ScR recommendations. A comprehensive search of PubMed\/MEDLINE and Scopus was performed from database inception to July 2025, with an additional search in January 2026 for real\u2010world studies. Data were extracted and summarized narratively without quantitative synthesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Second\u2010 and third\u2010generation gepants, including ubrogepant, rimegepant, atogepant, and zavegepant, overcome the hepatotoxicity and bioavailability limitations of earlier compounds. Pharmacokinetic properties determine their suitability for both acute and preventive use, and their lack of vasoconstrictive activity makes them suitable for patients with cardiovascular comorbidities. Most are metabolized by cytochrome 3A4 and are substrates for efflux transporters, necessitating awareness of drug\u2013drug interactions, although no clinically significant interactions with common migraine preventive medications have been reported. Preclinical and preliminary clinical evidence indicates a low likelihood of gepants inducing medication\u2010overuse headache. Combination therapy with other migraine treatments is mechanistically plausible and supported by early pharmacokinetic and safety data, though robust clinical trial evidence remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Gepants represent an effective and well\u2010tolerated class of CGRP\u2010targeted therapies with flexible use in acute and preventive migraine management. Their pharmacological properties support individualized treatment strategies and potential combination approaches; however, long\u2010term safety, optimal positioning, and the efficacy of combination regimens require further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.70114","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T05:18:42Z","timestamp":1781068722000},"page":"1628-1643","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The pharmacology of gepants in migraine: A scoping review on mechanisms, clinical applications, and combination strategies"],"prefix":"10.1111","volume":"66","author":[{"given":"Luigi Francesco","family":"Iannone","sequence":"first","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia  Modena 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