OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Daridorexant – Quviviq®

DRUG CLASS

Sedatives and Hypnotics

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Daridorexant	1505484-82-1	C23-H23-ClN6-O2

ANNOTATED BIBLIOGRAPHY

References updated: 05 February 2025

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

  (Expert review of hepatotoxicity published in 1999 before the availability of orexin receptor antagonists).
• Larrey D, Ripault MP. Anxiolytic agents. Hepatotoxicity of psychotropic drugs and drugs of abuse. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, p. 455-6.

  (Review of hepatotoxicity of hypnotics and sedatives discusses benzodiazepines, buspirone and valerian, all of which have been linked to rare cases of liver injury; daridorexant and other orexin receptor antagonists are not discussed).
• Mihic SJ, Mayfield J, Harris RA. Hypnotics and sedatives. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 339-353.

  (Textbook of pharmacology and therapeutics, discusses suvorexant but not daridorexant).
• FDA. Integrated Review. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2022/214985Orig1s000IntegratedR.pdf

  (FDA website with product labels and FDA review of the data on efficacy and safety submitted by the sponsor in support of the approval of daridorexant mentions side effects of somnolence, headache, and fatigue; no mention of ALT elevations or hepatotoxicity, but there was “no indication of any potential effect of daridorexant on laboratory values” including liver function tests).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, no cases were attributed to drugs for insomnia).
• Muehlan C, Heuberger J, Juif PE, Croft M, van Gerven J, Dingemanse J. Accelerated development of the dual orexin receptor antagonist ACT-541468: integration of a microtracer in a first-in-human study. Clin Pharmacol Ther. 2018;104:1022-1029. [PubMed: 29446069]

  (Analysis of the absorption, bioavailability, pharmacokinetics, metabolism, and tolerance of daridorexant in 40 healthy volunteers, in whom side effects were mild-to-moderate only and included somnolence, fatigue, disturbance in concentration, and headache).
• Mignot E, Mayleben D, Fietze I, Leger D, Zammit G, Bassetti CLA, Pain S, et al.; investigators. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol. 2022;21:125-139. [PubMed: 35065036]

  (Among 1854 adults with insomnia treated with daridorexant [10, 25, or 50 mg] or placebo once before bedtime for 3 months, latency to sleep onset and maintenance of sleep increased with the higher doses by an average of 10-20 minutes compared to placebo, while side effects included headache [4%-6% vs 4%), fatigue [2%-4% vs 1%] somnolence [2%-4% vs 2%]; no mention of ALT elevations or hepatotoxicity).
• Daridorexant (Quviviq) for insomnia. Med Lett Drugs Ther. 2022;64:107-110. [PubMed: 35802843]

  (Concise summary of the mechanism of action, clinical efficacy, safety, and costs of daridorexant shortly after its approval as therapy for insomnia in the US mentions adverse events of headache, somnolence, and fatigue [5%-7%] and more rarely daytime sleepiness, sleep paralysis, and hallucinations [<1%]; no mention of ALT elevations or hepatotoxicity).
• Kunz D, Dauvilliers Y, Benes H, García-Borreguero D, Plazzi G, Seboek Kinter D, et al. Long-term safety and tolerability of daridorexant in patients with insomnia disorder. CNS Drugs. 2023;37:93-106. [PMC free article: PMC9829592] [PubMed: 36484969]

  (Among 801 adults with insomnia who participated in a 12-week controlled trial of daridorexant who were enrolled in a 40-week extension trial, improvements in sleep were sustained and adverse events remained mild and infrequent including falls, headache and somnolence in <3%, and dizziness and fatigue <2%, and there were “no clinically significant findings for any changes in hematology or chemistry parameters”).
• Drugs for chronic insomnia. Med Lett Drugs Ther. 2023;65:1-6. [PubMed: 36630579]

  (Concise description of drugs approved for use in chronic insomnia including relative efficacy, safety and costs, mentions that daridorexant like other orexin receptor inhibitors improves latency to falling asleep by 5-10 minutes and duration of sleep to waking by 15 to 25 minutes compared to placebo, and that the most common adverse events are somnolence, fatigue, headache, and abnormal dreams).
• Preskorn SH. Comparative pharmacology of the 3 marketed dual orexin antagonists-daridorexant, lemborexant, and suvorexant-part 2. principal drug metabolizing enzyme, drug-drug interactions, and effects of liver and renal impairment on metabolism. J Psychiatr Pract. 2023;29:38-41. [PubMed: 36649550]

  (Review of the pharmacokinetics of the 3 orexin antagonists in clinical use, including suvo-, lembo-, and darido-rexant, mentions that they have similar chemical structures and similar metabolism by CYP 3A4, with only minor differences in susceptibility to inducers and inhibitors of CYP 3A4).
• Pan B, Ge L, Lai H, Hou L, Tian C, Wang Q, Yang K, et al. The comparative effectiveness and safety of insomnia drugs: a systematic review and network meta-analysis of 153 randomized trials. Drugs. 2023;83:587-619. [PubMed: 36947394]

  (Systematic review of the literature on the safety of drugs for insomnia identified 61 trials with 25,093 patients, and while the frequency of common adverse events varied, “with respect to serious and drug related adverse events, there were no differences among the drugs’; no mention of liver related adverse events).
• Wang Q, Zhou Q, Du Z, Lu R, Jiang Y, Zhu H. Clinical safety of daridorexant in insomnia treatment: Analysis of FDA adverse event reports. J Affect Disord. 2024;362:552-559. [PubMed: 39019232]

  (Among 1854 spontaneous reports to the FDA’s Adverse Event Reporting System between 2022 and 2023 implicating daridorexant, most were for general disorders, psychiatric and neurologic events, only 3 were “hepatobiliary”; no details provided).