Calcitonin gene-related peptide (CGRP) is a vasodilatory neuropeptide that plays an essential role in the pathophysiology of migraine, a highly disabling neurovascular disorder characterized by severe headache attacks. Rimegepant is a small-molecule CGRP receptor antagonist that is approved by the FDA for the acute treatment of migraine and currently under investigation for migraine prophylaxis.
The authors summarize the available data on the safety and tolerability of rimegepant and provide our insights on its use for acute migraine treatment.
Rimegepant seems to be well tolerated and superior to placebo for two-hour pain freedom. Moreover, rimegepant does not induce vasoconstriction, and is therefore not contraindicated in patients with cardiovascular disease, nor does it seem to induce medication-overuse headache. However, the therapeutic gain of rimegepant is only small, and since CGRP is a vital rescue molecule during ischemia, blocking the CGRP pathway might be detrimental. Although current evidence on CGRP receptor blockade has shown no cardiovascular adverse events, clinicians should remain critical about the use of rimegepant, as well as other CGRP (receptor) inhibiting drugs. Further research should focus on determining the consequences of long-term CGRP blockade, especially during ischemia or cardiovascular disease, the exact receptors antagonized by rimegepant, and potential effects of combining rimegepant with other antimigraine treatments.