DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20201768

Rimegepant: first novel oral calcitonin gene-related peptide inhibitor for migraine

Saravana Kumar Ramasubbu, Senkadhirdasan Dakshinamurthy, Sarika Palepu, Arkapal Bandyopadhyay, Sathish Kumar Rajendran

Abstract


Migraine is a neurological condition characterized by intense, debilitating headaches. Symptoms may include nausea, vomiting, numbness or tingling, sensitivity to light and sound. There are multitude of drugs available to treat migraine like triptans, non-steroidal anti-inflammatory drugs, ergots and opioids. But these drugs are associated with adverse effects especially triptans causing cardiovascular effects limiting its use. During last decade, calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for management of migraine. CGRP has been shown to release during episode of migraine attack and it may play a causative role in induction of migraine. Rimegepant is a novel CGRP antagonist has been approved by FDA for treatment of acute migraine. Rimegepant is a first oral CGRP antagonist compared to other gepants. The oral bioavailability of Rimegepant is 64% and high fat meal can decrease the Cmax, Tmax and area under the curve. This drug is mainly metabolized by CYP3A4 and to lesser extent by CYP2C9. Most common adverse reactions associated with this drug were nausea and urinary tract infection. Clinical trials for Rimegepant have been positive, and results suggest that the drug may be a new safe and effective option for treatment of acute migraine.


Keywords


Calcitonin gene-related peptide, Migraine, Rimegepant, Triptans

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References


Reuter U. GBD 2016: still no improvement in the burden of migraine. Lancet Neurol. 2018;17(11):929-30.

Perry CM, Markham A. Sumatriptan. Drugs. 1998;55(6):889-922.

Géraud G, Keywood C, Senard JM. Migraine headache recurrence: relationship to clinical, pharmacological, and pharmacokinetic properties of triptans. Headache J Head Face Pain. 2003;43(4):376-88.

Derry CJ, Derry S, Moore RA. Sumatriptan (oral route of administration) for acute migraine attacks in adults. Cochrane Database Syst Rev. 2012;(2).

Lipton RB, Croop R, Stock EG, Stock DA, Morris BA, Frost M, et al. Rimegepant, an oral calcitonin gene–related peptide receptor antagonist, for migraine. N Engl J Med. 2019;381(2):142-9.

Naot D, Cornish J. The role of peptides and receptors of the calcitonin family in the regulation of bone metabolism. Bone. 2008;43(5):813-8.

Edvinsson L. Rimegepant oral disintegrating tablet for migraine. Lancet Lond Engl. 2019;394(10200):711.

Storer RJ, Akerman S, Goadsby PJ. Calcitonin gene-related peptide (CGRP) modulates nociceptive trigeminovascular transmission in the cat. Br J Pharmacol. 2004;142(7):1171-81.

Negro A, Martelletti P. Gepants for the treatment of migraine. Expert Opin Investig Drugs. 2019;28(6):555-67.

Xu F, Sun W. Network meta-analysis of calcitonin gene-related peptide (CGRP) receptor antagonists for the acute treatment of migraine. Front Pharmacol. 2019;10:795.

Martelletti P, Giamberardino MA. Advances in orally administered pharmacotherapy for the treatment of migraine. Expert Opin Pharmacother. 2019;20(2):209-18.

Marcus R, Goadsby PJ, Dodick D, Stock D, Manos G, Fischer TZ. BMS-927711 for the acute treatment of migraine: A double-blind, randomized, placebo controlled, dose-ranging trial. Cephalalgia. 2014;34(2):114-25.

Croop R, Goadsby PJ, Stock DA, Conway CM, Forshaw M, Stock EG, et al. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Lancet. 2019;394(10200):737-45.