OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Atogepant – Qulipta®

DRUG CLASS

Migraine Headache Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Atogepant	1374248-81-3	C29-H23-F6-N5-O3

ANNOTATED BIBLIOGRAPHY

References updated: 12 January 2025

Abbreviations: CGRP, calcitonin gene-related peptide.

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Review of hepatotoxicity published in 1999 before the availability of CGRP antagonists).
• FDA. Integrated Review. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2021/215206Orig1s000IntegratedR.pdf

  (FDA Drug Approvals website that has product labels [package inserts], letters of approval and full FDA integrated scientific review of the atogepant application including specific discussion of hepatic adverse events among 1319 patients treated with atogepant focusing on 2 instances of ALT or AST elevations considered “probable” and 4 “possible” liver injury, despite similar rate elevations above 3 times ULN between drug vs placebo groups [1.0% vs 1.8%]; all suspected cases were asymptomatic, without bilirubin elevations, and resolving rapidly once drug was stopped).
• Ho TW, Connor KM, Zhang Y, Pearlman E, Koppenhaver J, Fan X, Lines C, et al. Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention. Neurology 2014; 83: 958-66. [PubMed: 25107879]

  (Among 660 patients with migraine enrolled in a controlled trial of telcagepant [140 or 280 mg] vs placebo twice daily for 12 weeks, 13 patients on telcagepant developed ALT elevations above 3 times ULN, generally between weeks 4 and 6 of treatment, and in two instances rising to 33 and 39 times ULN accompanied by symptoms but not jaundice leading to prompt discontinuation and to early termination of the trial because of the risk of significant hepatotoxicity).
• Tfelt-Hansen P, Loder E. The emperor's new gepants: are the effects of the new oral CGRP antagonists clinically meaningful? Headache 2019; 59: 113-7. [PubMed: 30451300]

  (Commentary on the relative efficacy of two oral CGRP receptor antagonists, ubrogepant and rimegepant, which show only modest efficacy in acute migraine [therapeutic gain of 5-8%] and only when compared to placebo as compared to well-known effective therapies such as aspirin and other nonsteroidal antiinflammatory agents [8-14%] and the triptans [16-32%]).
• Drugs for migraine. Med Lett Drugs Ther 2020; 62: 153-60. [PubMed: 33434187]

  (Concise summary of the relative clinical efficacy, safety, and costs of drugs to treat acute migraine headache [such as analgesics, opiates, triptans, ergots and oral CGRP receptor antagonists] and to prevent migraines [such as anticonvulsants, beta blockers, antidepressants, and the monoclonal antibodies to CGRP and its receptor]).
• Goadsby PJ, Dodick DW, Ailani J, Trugman JM, Finnegan M, Lu K, Szegedi A. 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;19:727-737. [PubMed: 32822633]

  (Among 825 adults with chronic migraine headaches treated with 5 doses of atogepant [10, 30, or 60 mg once or twice daily] vs placebo, reduction in migraine days per month was similar across all dose regimens [-3.8 to -4.1] and higher than with placebo [-2.9], while adverse event rates with slightly higher [58 to 66% vs 49%] and ALT elevations above 3 times ULN were uncommon and similar in rate to those with placebo [1 to 2% vs 1%], and were all without symptoms or jaundice).
• Min KC, Kraft WK, Bondiskey P, Colón-González F, Liu W, Xu J, Panebianco D, et al. Atogepant Is not associated with clinically meaningful alanine aminotransferase elevations in healthy adults. Clin Transl Sci. 2021;14:599-605. [PMC free article: PMC7993278] [PubMed: 33142014]

  (Among 34 healthy adults treated with atogepant [170 mg] or placebo once daily for 28 days, adverse events in atogepant treated subjects were mild and included nausea, fatigue, dizziness and decreased appetite, while mean ALT levels decreased and remained within the normal range with no individual value rising about 3 times ULN).
• Ailani J, Lipton RB, Goadsby PJ, Guo H, Miceli R, Severt L, Finnegan M, Trugman JM; ADVANCE Study Group. Atogepant for the preventive treatment of migraine. N Engl J Med. 2021;385:695-706. [PubMed: 34407343]

  (Among 873 adults with episodic migraine headaches treated with atogepant [10, 30, or 60 mg] or placebo once daily for 12 weeks, mean difference from placebo with atogepant ranged from -1.2 to -1.7 days per month, while adverse events rates were similar with ALT elevations above 3 times ULN being lower with atogepant [0.4 to 0.9%] vs placebo [2.7%], no ALT elevation being associated with jaundice).
• Atogepant (Qulipta) for migraine prevention. Med Lett Drugs Ther. 2021;63:169-171. [PubMed: 35085204]

  (Concise review of the mechanism of action, clinical efficacy, safety, and costs of atogepant discusses minor adverse events of nausea, constipation, and fatigue but does not mention ALT elevations or hepatoxicity).
• Robbins MS. Diagnosis and management of headache: a review. JAMA 2021; 325: 1874-85. [PubMed: 33974014]

  (Review of the diagnosis and management of headache including use of calcitonin gene-related peptide antagonists for acute migraine attacks, which have uncommon side effects of dry mouth and dizziness; no mention of ALT elevations or hepatotoxicity).
• Deeks ED. Atogepant: First approval. Drugs. 2022;82:65-70. [PubMed: 34813050]

  (Summary of the mechanism of action, history of development, pharmacology, clinical efficacy, and safety of atogepant shortly after its approval for prevention of episodic migraine mentions that rates of ALT elevations above 3 times ULN were less frequent with atogepant than placebo [1.0 vs 1.8% in short term and 2.4 vs 3.2% in longer term studies], and no patient with ALT elevations developed symptoms or jaundice and abnormalities resolved rapidly with discontinuation).
• Woodhead JL, Siler SQ, Howell BA, Watkins PB, Conway C. Comparing the liver safety profiles of 4 next-generation CGRP receptor antagonists to the hepatotoxic CGRP inhibitor telcagepant using quantitative systems toxicology modeling. Toxicol Sci. 2022;188:108-116. [PMC free article: PMC9237996] [PubMed: 35556143]

  (Mechanism simulation of hepatotoxicity indicated that telcagepant had multiple potential adverse effects on liver function compared to the more recently developed CGRP antagonists, rimegepant, ubrogepant, atogepant, and zavegepant).
• Drugs for migraine. Med Lett Drugs Ther. 2023;65:89-96. [PubMed: 37266987]

  (Concise summary of the relative clinical efficacy, safety, and costs of drugs to treat and to prevent migraine headaches, states that systemic adverse effects are uncommon with use of oral CGRP receptor antagonists, but that nausea and somnolence can occur; no mention of ALT elevations or hepatotoxicity).
• Zavegepant (Zavzpret) for acute treatment of migraine. Med Lett Drugs Ther. 2023;65:116-118. [PubMed: 37460143]

  (Concise review of the mechanism of action, clinical efficacy, safety, and costs of zavegepant mentions adverse events of dysgeusia, nausea, nasal discomfort, and vomiting as well as hypersensitivity reactions [facial swelling, urticaria], but does not mention ALT elevations or hepatoxicity).
• Pozo-Rosich P, Ailani J, Ashina M, Goadsby PJ, Lipton RB, Reuter U, Guo H, et al. Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;402(10404):775-785. [PubMed: 37516125]

  (Among 755 adults with chronic migraine treated with atogepant [30 mg twice or 60 mg once daily] vs placebo for 12 weeks, reduction of days with migraine headaches was greater with drug [-7.5 and -6.9 vs -5.1 days per month] and adverse events were generally mild and included constipation, nausea, fatigue, and weight loss, while ALT or AST elevations above 3 times ULN arose in 0.8% on atogepant vs 0.4% on placebo and no patient had concurrent symptoms or jaundice).
• Tassorelli C, Nagy K, Pozo-Rosich P, Lanteri-Minet M, Sacco S, Nežádal T, Guo H, et al. Safety and efficacy of atogepant for the preventive treatment of episodic migraine in adults for whom conventional oral preventive treatments have failed (ELEVATE): a randomised, placebo-controlled, phase 3b trial. Lancet Neurol. 2024;23:382-392. [PubMed: 38364831]

  (Among 315 adults with refractory, episodic migraines treated with atogepant [60 mg] or placebo once daily for 12 weeks, the mean decrease in migraine days per month decreased more with drug [-4.1] than placebo [-1.9], while adverse events of atogepant included constipation [10%], nausea [7%], and decreased appetite [3%], but no patient developed ALT or AST elevations above 3 times ULN or any elevation with jaundice).
• Liang Q, Liao X, Wu H, Huang Y, Liang T, Li H. Real-world study of adverse events associated with gepant use in migraine treatment based on the VigiAccess and U.S. Food and Drug Administration's adverse event reporting system databases. Front Pharmacol. 2024;15:1431562. [PMC free article: PMC11322337] [PubMed: 39144633]

  (Search of two large registry databases on spontaneous reports of adverse events due to -gepants [rimegepant, ubrogepant, and atogepant] identified 23,542 reports, but only 0.09% to 0.27% were liver related, attesting to the lack of severe liver injury due to the currently available oral CGRP receptor antagonists).
• Zhang Y, Sun S, Wang Y. Adverse events associated with atogepant: a FAERS-based pharmacovigilance analysis. Expert Opin Drug Saf. 2024 Sep 12:1-7. Epub ahead of print. [PubMed: 39242080]

  (Search of atogepant adverse event reports made to the FDA’s Adverse Event Reporting System [FAERS] from 2021 through 2023, identified 3015 reports involving 27 body systems, most commonly neurologic [1651], general [1282], and gastrointestinal [1003], but very few related to hepatobiliary disorders [8]).