2026 Volume 161 Issue 4 Pages 280-290
Migraine is a highly prevalent neurological disorder and is associated with substantial mental, social, and disease burden. Current migraine management comprises acute and preventive treatments; however, conventional acute and preventive medications have been associated with challenges such as contraindications, a delayed onset of efficacy, and adverse drug reactions. Rimegepant is an orally available small molecule calcitonin gene-related peptide (CGRP) receptor antagonist uniquely approved for both acute and preventive treatments. Nonclinical studies have demonstrated its high affinity for the CGRP receptor without inducing vasoconstriction in coronary or intracranial arteries. Consistent with these findings, clinical studies have shown no signals suggestive of cardiovascular risk, indicating a low concern for vasoconstrictive effects as triptans. In Phase 1 studies in healthy Japanese adults, rimegepant showed rapid absorption, supporting a rapid onset of action in acute treatment, and relatively longer half-life (10 h), supporting sustained efficacy. From a preventive perspective, while existing CGRP monoclonal antibodies are administered as injectable formulations, rimegepant can be administered orally as an orally disintegrating (OD) tablet. Drug–drug interaction studies demonstrated co-administration of rimegepant with triptans is possible due to a lack of clinically meaningful blood pressure elevation or pharmacokinetic interactions. Multiple clinical trials have confirmed the efficacy and safety of rimegepant for acute treatment, and every other day (EOD) dosing significantly reduced monthly migraine days. In addition to its favorable safety profile, the flexible use of the same formulation for both acute and preventive treatments represents a clinically meaningful, new option in migraine treatment.
