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Generic Name: Tasimelteon
Class: Anxiolytics, Sedatives, and Hypnotics; Miscellaneous
- Circadian Rhythm Regulators
- Melatonin Receptor Agonists
VA Class: CN300
Chemical Name: N-[[(1R,2R)-2-(2,3-Dihydro-4-benzofuranyl)cyclopropyl]methyl]-propanamide
Molecular Formula: C15H19NO2
CAS Number: 609799-22-6

Medically reviewed on Jan 7, 2019


Melatonin receptor agonist and circadian rhythm regulator.1 3 5 15

Uses for Hetlioz

Non-24-Hour Sleep-Wake Disorder

Treatment of non-24-hour sleep-wake disorder.1 Designated an orphan drug by FDA for this use.13

Non-24-hour sleep-wake disorder (non-24), also known as free-running or nonentrained rhythm disorder, is a chronic circadian rhythm sleep-wake disorder in which an individual's endogenous circadian rhythm is not synchronized, or entrained, to the 24-hour environment.6 7 8 9 May occur in both sighted and blind individuals, but occurs most often in blind individuals with decreased or no light perception.2 6 7 9

Hetlioz Dosage and Administration


  • Obtain tasimelteon through a specialty pharmacy.14 Contact manufacturer (Vanda) at 844-438-5469 or consult the Hetlioz website ([Web]) for specific availability information.14


Oral Administration

Administer capsules before bedtime, without food, at the same time every night.1 Administration with food may lower drug concentrations and reduce efficacy (see Food under Pharmacokinetics).1

Swallow capsules whole.1

After taking tasimelteon, limit activities to preparing for going to bed.1 (See Somnolence under Cautions and also see Advice to Patients.)



Non-24-hour Sleep-Wake Disorder

20 mg once daily.1

Because of individual differences in circadian rhythms, therapeutic effect may not occur for weeks or months.1

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: Dosage adjustment not necessary.1

Severe hepatic impairment (Child-Pugh class C): Not studied; use not recommended.1 (See Hepatic Impairment under Cautions.)

Renal Impairment

Dosage adjustment not necessary.1 (See Renal Impairment under Cautions.)

Geriatric Patients

Dosage adjustment not necessary.5 (See Geriatric Use under Cautions.)

Cautions for Hetlioz


  • Manufacturer states none known.1



May impair the performance of activities requiring complete mental alertness.1 After taking tasimelteon, limit activities to only those necessary to prepare for bed.1

Abuse Potential and Dependence

Did not produce any abuse-related signals in animal behavioral studies.1 No signs or symptoms indicative of abuse potential observed in clinical studies.1

Discontinuance following chronic administration did not produce withdrawal signs.1 Does not appear to produce physical dependence.1

Specific Populations


Category C.1


Not known whether distributed into human milk.1 Use with caution.1

Pediatric Use

Safety and efficacy not established in pediatric patients.1

Geriatric Use

Higher exposure compared with younger adults (see Absorption: Special Populations, under Pharmacokinetics), which may increase risk of adverse effects.1 2 5 However, dosage adjustment not necessary.5

Hepatic Impairment

Because exposure increased less than twofold in individuals with moderate hepatic impairment, dosage adjustment not necessary in mild or moderate hepatic impairment.1

Not studied in severe hepatic impairment (Child-Pugh class C); use not recommended.1 (See Absorption: Special Populations, under Pharmacokinetics.)

Renal Impairment

Because no apparent relationship demonstrated between oral clearance of tasimelteon and renal function, dosage adjustment not necessary in patients with renal impairment.1 (See Elimination: Special Populations, under Pharmacokinetics.)

Common Adverse Effects

Headache,1 increased ALT concentrations,1 nightmares or abnormal dreams,1 upper respiratory tract infection,1 urinary tract infection.1

Interactions for Hetlioz

Extensively metabolized, principally by CYP isoenzymes 1A2 and 3A4.1 Other than CYP1A2- and CYP3A4-mediated drug interactions, clinically important pharmacokinetic drug interactions unlikely.1

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP1A2 inhibitors: Possible pharmacokinetic interaction (substantially increased tasimelteon exposure and greater risk of adverse effects).1 Avoid concomitant use.1

CYP3A4 inducers: Possible pharmacokinetic interaction (substantially decreased tasimelteon exposure and reduced efficacy).1 5 Avoid concomitant use.1

CYP3A4 inhibitors: No dosage adjustment of tasimelteon necessary.5

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP isoenzymes 3A4, 1A2, 2A6, 2C8, 2C9, 2C19, 2D6, or 2E1: Clinically important pharmacokinetic interaction unlikely.1 5

Specific Drugs





Small increase (10–25%) in tasimelteon exposure;5 possible additive CNS effects1

β-Adrenergic blocking agents (e.g., atenolol, metoprolol, propranolol)

β-adrenergic blocking agents can markedly reduce endogenous melatonin secretion and cause insomnia and other sleep disturbances;10 12 17 possible reduced efficacy of tasimelteon1


Substantially increased AUC and peak concentrations of tasimelteon; possible increased risk of adverse effects1 2 5

Avoid concomitant use1


Increased tasimelteon AUC and peak plasma concentration1

Dosage adjustment not necessary5


No clinically important changes in midazolam exposure1 5


Approximately 90% reduction in tasimelteon exposure;1 5 possible reduced efficacy1

Avoid concomitant use1


No clinically important effect on rosiglitazone exposure1


Decreased exposure to tasimelteon in smokers; possible reduced efficacy1

Hetlioz Pharmacokinetics



Peak plasma concentrations occur about 0.5–3 hours after fasting oral administration.1


Therapeutic effect may not occur for weeks or months due to individual differences in circadian rhythms.1


High-fat meal reduced peak plasma concentration by 44% and delayed time to peak plasma concentrations by approximately 1.75 hours.1 (See Oral Administration under Dosage and Administration.)

Special Populations

In individuals with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment, AUC increased by 43 and 110%, respectively; peak concentrations 20% higher in individuals with mild or moderate hepatic impairment compared with healthy individuals.5 Not studied in severe hepatic impairment (Child-Pugh class C).1 (See Hepatic Impairment under Cautions.)

Higher exposure in geriatric individuals (peak concentrations and AUC increased by approximately twofold) than in younger adults.1 2 5 (See Geriatric Use under Cautions.)

Approximately 20–30% higher exposure in females than in males.1



Not known whether distributed into human milk.1

Plasma Protein Binding

Approximately 90%.1



Extensively metabolized primarily by oxidation at multiple sites and oxidative dealkylation, followed by further oxidation.1 Metabolized principally by CYP1A2 and 3A4.1 Glucuronidation is the major phase II metabolic route.1 Major metabolites 13-fold or less active than tasimelteon.1

Elimination Route

Excreted in urine (80%) and feces (approximately 4%); <1% excreted in urine as unchanged drug.1


Tasimelteon: Mean elimination half-life of 1.3 hours.1

Principal metabolites: Mean terminal elimination half lives of 1.3–3.7 hours.1

Special Populations

No apparent relationship between oral clearance of tasimelteon and renal function.1 Tasimelteon and the majority of its principal metabolites are cleared by hemodialysis.1 (See Renal Impairment under Cautions.)

Exposure decreased by approximately 40% in smokers compared with nonsmokers.1 2 (See Specific Drugs under Interactions.)





25°C (may be exposed to 15–30°C).1 Protect from light and moisture.1


  • Precise mechanism of action not fully elucidated, but thought to be related to tasimelteon's ability to entrain or synchronize pathological circadian rhythms to the 24-hour clock through its actions in the suprachiasmatic nucleus (SCN) of the hypothalamus.1 2

  • Agonist at melatonin MT1 and MT2 receptors.1 2 Demonstrates greater affinity for MT2 receptors than MT1 receptors.1 2

Advice to Patients

  • Importance of instructing patients to take tasimelteon before bedtime, at the same time every night.1 Importance of advising patients to swallow tasimelteon capsules whole and to take the drug without food for better absorption.1

  • Importance of advising patients to skip the tasimelteon dose if they cannot take the drug at approximately the same time on any given night.1

  • Risk of somnolence.1 Importance of advising patients to limit their activities to preparing for going to bed after taking tasimelteon since the drug can potentially impair performance of activities requiring complete mental alertness (e.g., driving, operating machinery).1

  • Importance of informing patients that tasimelteon's therapeutic effect may not occur for weeks or months because of individual differences in circadian rhythms.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 16

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., fluvoxamine, rifampin) and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1 16

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Tasimelteon can only be obtained through a specialty pharmacy.14 Specific availability information is available from the manufacturer by telephone at 844-438-5469 or on the Hetlioz website ([Web]).14



Dosage Forms


Brand Names




20 mg



AHFS DI Essentials™. © Copyright 2019, Selected Revisions January 6, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.


1. Vanda Pharmaceuticals, Inc. Hetlioz (tasimelteon) capsules prescribing information. Washington, DC; 2014 Jan.

2. Vanda Pharmaceuticals, Inc. Submission of clinical and economic data supporting formulary consideration of Hetlioz (tasimelteon) capsules 20 mg. Washington, DC; 2014 Mar 7.

3. Lockley SW, Dressman MA, Xiao C, et al. Tasimelteon treatment entrains the circadian clock and demonstrates a clinically meaningful benefit in totally blind individuals with non-24-hour circadian rhythms. Poster presented at the Endocrine Society's 95th annual meeting; 2013 Jun 15–18; San Francisco, CA.

4. Lockley SW, Dressman MA, Xiao C, et al. RESET study demonstrates that tasimelteon maintains entrainment of melatonin and cortisol in totally blind individuals with non-24-hour circadian rhythms. Poster presented at the Endocrine Society's 95th annual meeting; 2013 Jun 15–18; San Francisco, CA.

5. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 205677: Clinical pharmacology and biopharmaceutics review(s). From FDA website. Accessed 2014 Apr 24.

6. Lockley SW, Arendt J, Skene DJ. Visual impairment and circadian rhythm disorders. Dialogues Clin Neurosci. 2007; 9:301-14.

7. American Psychiatric Association. DSM-5: diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013:361-422.

8. Sack RL, Brandes RW, Kendall AR et al. Entrainment of free-running circadian rhythms by melatonin in blind people. N Engl J Med. 2000; 343:1070-7.

9. Zee PC, Attarian H, Videnovic A. Circadian rhythm abnormalities. Continuum (Minneap Minn). 2013; 19:132-47.

10. Brown GM. Light, melatonin and the sleep-wake cycle. J Psychiatry Neurosci. 1994; 19:345-53.

11. Dubocovich ML. Melatonin receptors: role on sleep and circadian rhythm regulation. Sleep Med. 2007; 8 Suppl 3:34-42.

12. Stoschitzky K, Sakotnik A, Lercher P et al. Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol. 1999; 55:111-5.

13. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Rockville, MD. From FDA website. Accessed 2014 Apr 23.

14. Vanda Pharmaceuticals, Inc. HetliozSolutions prescription and service request form. Washington, DC. Accessed 2014 Apr 29.

15. Anon. Tasimelteon (Hetlioz) for non-24-hour sleep-wake disorder. Med Lett Drugs Ther. 2014; 56:34-5.

16. Vanda Pharmaceuticals, Inc. Here's important safety information for Hetlioz (tasimelteon). Washington, DC. Accessed 2014 Aug 25.

17. Novartis. Lopressor (metoprolol tartrate) tablets and injection prescribing information. East Hanover, NJ; 2013 Mar.