Published: 2022-08-24

A short review on atogepant: recently approved first oral calcitonin gene-related peptide receptor antagonist

Akash Agnihotri, M. Kanimozhi, Subhash Samanta, Manjunath Bidarolli, Shailendra Handu


Migraine is the second leading cause of disability in terms of ‘years lived with disability’ and it affects globally about 12% of the general population. Currently available preventive therapies are not specific to migraine. After the discovery of calcitonin gene-related peptide’s (CGRP’s) role in migraine pathophysiology, CGRP receptor antagonist drugs were developed specifically for migraine. Atogepant is the only oral, selective, potent, second-generation CGRP receptor antagonist approved in September 2021 by Food and Drug Administration (FDA) for prophylaxis of episodic migraines and chronic migraines. It acts by blocking the α-CGRP receptor present on the vascular smooth muscle cell membrane of cranial arteries. It has the added advantage of oral administration, less hepatotoxicity, minimal drug–drug interactions (DDIs) with better efficacy, safety, and tolerability profile compared to the other CGRP receptor antagonists. This present review summarizes the physicochemical properties, pharmacokinetics-pharmacodynamics (PK-PD) parameters, uses, and drug-food interactions with the help of available current evidence.



Migraine, Atogepant, CGRP antagonist

Full Text:



Dodick DW. Migraine. Lancet Lond Engl. 2018;391(10127):1315-30.

Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343-9.

Silberstein SD. Migraine. Lancet Lond Engl. 2004;363(9406):381-91.

Safiri S, Pourfathi H, Eagan A, Mansournia MA, Khodayari MT, Sullman MJM, et al. Global, regional, and national burden of migraine in 204 countries and territories, 1990 to 2019. Pain. 2021;163(2):293-309.

Goadsby PJ, Dodick DW, Ailani J, Trugman JM, Finnegan M, Lu K, et al. Safety, tolerability, and efficacy of orally administered atogepant for the prevention of episodic migraine in adults: a double-blind, randomised phase 2b/3 trial. Lancet Neurol. 2020;19(9):727-37.

Peters GL. Migraine overview and summary of current and emerging treatment options. Am J Manag Care. 2019;25(2):23-34.

Charles A. The pathophysiology of migraine: implications for clinical management. Lancet Neurol. 2018;17(2):174-82.

Karnad A, Verghese A. Harrison’s Principles of Internal Medicine. JAMA. 1994;272(8):642.

Charles A, Pozo-Rosich P. Targeting calcitonin gene-related peptide: a new era in migraine therapy. Lancet Lond Engl. 2019;394(10210):1765-74.

Rubio-Beltran E, Chan KY, Danser AJ, MaassenVanDenBrink A, Edvinsson L. Characterisation of the calcitonin gene-related peptide receptor antagonists ubrogepant and atogepant in human isolated coronary, cerebral and middle meningeal arteries. Cephalalgia Int J Headache. 2020;40(4):357-66.

Atogepant. Available at: https://pubchem.ncbi. Accessed on 11 February 2022.

[email protected]: FDA-Approved Drugs. Available at: Accessed on 11 February 2022.

Min KC, Kraft WK, Bondiskey P, Colón-González F, Liu W, Xu J, et al. Atogepant Is Not Associated With Clinically Meaningful Alanine Aminotransferase Elevations in Healthy Adults. Clin Transl Sci. 2021;14(2):599-605.

Rivera-Mancilla E, Villalón CM, MaassenVanDenBrink A. CGRP inhibitors for migraine prophylaxis: a safety review. Expert Opin Drug Saf. 2020;19(10):1237-50.

Boinpally R, Jakate A, Butler M, Borbridge L, Periclou A. Single-Dose Pharmacokinetics and Safety of Atogepant in Adults With Hepatic Impairment: Results From an Open-Label, Phase 1 Trial. Clin Pharmacol Drug Dev. 2021;10(7):726-33.

Ailani J, Lipton RB, Goadsby PJ, Guo H, Miceli R, Severt L, et al. Atogepant for the Preventive Treatment of Migraine. N Engl J Med. 2021;385(8):695-706.

Atogepant. Available at: https://www.uptodate. com/contents/search?search=atogepant&sp=0&searchType=PLAIN_TEXT&source=USER_INPUT&searchControl=TOP_PULLDOWN&searchOffset=1&autoComplete=false&language=&max=0&index=&autoCompleteTerm=&rawSentence. Accessed on 11 February 2022.

Boinpally R, Jakate A, Butler M, Periclou A. Atogepant and sumatriptan: no clinically relevant drug-drug interactions in a randomized, open-label, crossover trial. Pain Manag. 2022;12(4):499-508.

Boinpally R, Spaventa J, Chen K, Butler M. Evaluation of the Pharmacokinetic Interaction and Safety of Atogepant Co-Administered with Acetaminophen or Naproxen in Healthy Participants: A Randomized Trial. Clin Drug Investig. 2021;41(6):557-67.

Ankrom W, Xu J, Vallee M-H, Dockendorf MF, Armas D, Boinpally R, et al. Atogepant Has No Clinically Relevant Effects on the Pharmacokinetics of an Ethinyl Estradiol/Levonorgestrel Oral Contraceptive in Healthy Female Participants. J Clin Pharmacol. 2020;60(9):1157-65.

Boinpally R, McNamee B, Yao L, Butler M, McGeeney D, Borbridge L, et al. A Single Supratherapeutic Dose of Atogepant Does Not Affect Cardiac Repolarization in Healthy Adults: Results From a Randomized, Single-Dose, Phase 1 Crossover Trial. Clin Pharmacol Drug Dev. 2021;10(9):1099-107.

Overview | Headaches in over 12s: diagnosis and management | Guidance | NICE. Available at: Accessed on 11 February 2022.

Lambru G, Andreou AP, Guglielmetti M, Martelletti P. Emerging drugs for migraine treatment: an update. Expert Opin Emerg Drugs. 2018;23(4):301-18.

Ansari H, Ziad S. Drug-Drug Interactions in Headache Medicine. Headache. 2016;56(7):1241-8.

Drug Interactions Checker - For Drugs, Food & Alcohol. Available at: drug_interactions.html. Accessed on 19 February 2022.

Lexicomp® Drug Interactions. Available at: =responsive_home#di-druglist. Accessed on 19 February 2022.