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What is known and objectives: Migraine is a disabling disorder that affects individuals of all ages. To date, there are multiple limitations to using guidelines‐recommended treatments and preventive therapies. The goal of this review was to provide a comprehensive clinical review of the safety, efficacy and prescribing information of the emerging calcitonin gene‐related peptide (CGRP) antagonists. Agents in this new pharmacologic class were approved by the US Food and Drug Administration (FDA) for the treatment of acute migraine attack pain and the management of episodic and chronic migraine. Methods: A total of 12 randomized, placebo‐controlled clinical trials were identified and included in the review utilizing databases such as clinicaltrial.gov, PubMed and EMBASE. The trials collectively evaluated six CGRP antagonists starting from the orally administered CGRPs such as rimegepant and ubrogepant, to the quarterly IV administered CGRP such as eptinezumab, and the monthly/quarterly subcutaneously administered agents such as erenumab, fremanezumab and galcanezumab. Results and discussion: All agents displayed significant efficacy compared with placebo, measured by reduction in mean monthly migraine days (MMD). In addition, CGRP antagonists displayed a great tolerability profile with few adverse effects. These medications were neither associated with any cardiovascular‐related adverse effects, nor do they currently have specific contraindications to pre‐existing cardiovascular conditions. This can present a safe alternative to a wide range of patients who cannot be appropriately treated with first‐line treatments such as triptans. No treatment‐related death was reported in any of the clinical trials outlined and discussed. What is new and conclusion: Calcitonin gene‐related peptide antagonists are safe and efficacious medications both in treating acute migraine headache pain and the management of episodic and chronic migraine. Head‐to‐head comparative studies with current guideline‐recommended treatments are needed. However, CGRP antagonists are promising agents that present an alternative solution for patients living with migraine. [ABSTRACT FROM AUTHOR]