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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: March 10, 2015.



Tasimelteon is a melatonin receptor agonist that is used for the treatment of non-24 hour sleep-wake disorder in blind individuals. Tasimelteon therapy is associated with a low rate of serum enzyme elevations, but has not been implicated in cases of clinically apparent liver injury.


Tasimelteon (tas" i mel' tee on) is a synthetic melatonin receptor agonist with affinity for both the melatonin type 1 and type 2 receptors (MT1 and MT2). These receptors are believed to be involved in the maintenance of the circadian rhythm that regulates the normal sleep-wake cycle. Melatonin itself has been proposed as therapy of sleep disturbances including insomnia and jet lag, but systematic reviews and metaanalyses of controlled trials of various melatonin formulations have failed to demonstrate consistent efficacy. In contrast, melatonin receptor agonists such as ramelteon and tasimelteon were found to have effects on the circadian rhythm and sleep patterns. Tasimelteon was approved for use in “non-24 hour sleep-wake disorder” in the United States in 2014, the second melatonin receptor antagonist approved for use in sleep disorders. Whereas ramelteon has been approved for insomnia, tasimelteon is used more for shifting of sleep-wake patterns and may take weeks to have its full effect. Tasimelteon is available in 20 mg capsules under the brand name Hetlioz. The recommended dose is 20 mg taken orally before bedtime at the same time every night. Side effects are few, but may include daytime somnolence, fatigue, dizziness, headache and vivid or abnormal dreams.


In several clinical trials, tasimelteon was found to be well tolerated. Serum enzyme elevations occurred in 10% of tasimelteon treated patients compared to 5% of placebo controls, but instances of clinically apparent liver injury were not reported. Tasimelteon has been available for a limited period of time, but has not been linked to instances of clinically apparent liver injury. Tasimelteon is metabolized by the cytochrome P450 system (predominantly CYP 1A2 and CYP3A4), which can result in significant drug-drug interactions, strong inhibitors of the enzymes increasing serum concentrations of tasimelteon and strong inducers decreasing them.

Drug Class: Sedatives and Hypnotics

Other Drugs in the Subclass, Melatonin and its Analogues: Melatonin, Ramelteon



Tasimelteon – Hetlioz®


Sedatives and Hypnotics


Product labeling at DailyMed, National Library of Medicine, NIH


Suvorexant Chemical Structure


References updated: 10 March 2015

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    (Expert review of hepatotoxicity published in 1999; melatonin, ramelteon and tasimelteon are not discussed).
  • 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; melatonin, ramelteon and tasimelteon are not discussed).
  • Mihic SJ, Harris RA. Hypnotics and sedatives. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 457-80.
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    (Discussion of physiological functions of melatonin and potential clinical uses).
  • Seabra ML, Bignotto M, Pinto LR Jr, Tufik S. Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treatment. J Pineal Res 2000; 29: 193-200. [PubMed: 11068941]
    (Controlled trial of melatonin [10 mg daily] vs placebo for 28 days in 40 volunteers found no changes or abnormalities of serum bilirubin, ALT, AST or Alk P during the 4 weeks of treatment).
  • Buscemi N, Vandermeer B, Hooton N, Pandya R, Tjosvold L, Hartling L, Vohra S, et al. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ 2006; 332: 385-93. [PMC free article: PMC1370968] [PubMed: 16473858]
    (Systematic review of literature on efficacy and safety of melatonin for sleep disorders; in 9 randomized controlled trials there was no overall evidence of benefit; in 10 studies evaluating safety there was no evidence of adverse effects occurring more often than with placebo, with use limited to 3 months).
  • Mayer G, Wang-Weigand S, Roth-Schechter B, Lehmann R, Staner C, Partinen M. Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia. Sleep 2009; 32: 351-60. [PMC free article: PMC2647789] [PubMed: 19294955]
    (Controlled trial of 6 month course of ramelteon vs. placebo in 451 adults with primary chronic insomnia; adverse effects were similar between the two groups; no mention of ALT levels).
  • Rajaratnam SM, Polymeropoulos MH, Fisher DM, Roth T, Scott C, Birznieks G, Klerman EB. Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials. Lancet 2009; 373 (9662): 482-91. [PubMed: 19054552]
    (Controlled trial of 3 doses of tasimelteon vs placebo in 411 patients with transient insomnia found improvements in time to sleep latency and total sleep time, while the “frequency and severity of adverse events were similar across treatment groups”).
  • Morris CJ, Aeschbach D, Scheer FA. Circadian system, sleep and endocrinology. Mol Cell Endocrinol 2012; 349: 91-104. [PMC free article: PMC3242827] [PubMed: 21939733]
    (Review of the biologic basis of circadian rhythm including the role of melatonin).
  • Johnsa JD, Neville MW. Tasimelteon: a melatonin receptor agonist for non-24-hour sleep-wake disorder. Ann Pharmacother 2014; 48: 1636-41. [PubMed: 25204464]
    (Systematic review of published literature on use of tasimelteon mentions that the most common adverse event was headache [<10%] and that “fewer [1% to 10%] patients experienced: increased alanine transaminase…”).
  • Tasimelteon(Hetlioz) for non-24-hour sleep-wake disorder. Med Lett Drugs Ther 2014; 56 (1441): 34-5. [PubMed: 24759294]
    (Concise review of the efficacy, safety and cost of tasimelteon shortly after its approval for use in the US mentions that the most common adverse events are headache [17%], elevated aminotransferase levels [10%], and nightmares or unusual dreams [10%]).


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