Skip to main content

Tasimelteon (Monograph)

Brand name: Hetlioz
Drug 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

Introduction

Melatonin receptor agonist and circadian rhythm regulator.

Uses for Tasimelteon

Non-24-Hour Sleep-Wake Disorder

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

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. May occur in both sighted and blind individuals, but occurs most often in blind individuals with decreased or no light perception.

Tasimelteon Dosage and Administration

General

Administration

Oral Administration

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

Swallow capsules whole.

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

Dosage

Adults

Non-24-hour Sleep-Wake Disorder
Oral

20 mg once daily.

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

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: Dosage adjustment not necessary.

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

Renal Impairment

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

Geriatric Patients

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

Cautions for Tasimelteon

Contraindications

Warnings/Precautions

Somnolence

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

Abuse Potential and Dependence

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

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

Specific Populations

Pregnancy

Category C.

Lactation

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

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

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

Hepatic Impairment

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

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

Common Adverse Effects

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

Drug Interactions

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

Drugs Affecting Hepatic Microsomal Enzymes

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

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

CYP3A4 inhibitors: No dosage adjustment of tasimelteon necessary.

Drugs Metabolized by Hepatic Microsomal Enzymes

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

Specific Drugs

Drug

Interaction

Comments

Alcohol

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

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; possible reduced efficacy of tasimelteon

Fluvoxamine

Substantially increased AUC and peak concentrations of tasimelteon; possible increased risk of adverse effects

Avoid concomitant use

Ketoconazole

Increased tasimelteon AUC and peak plasma concentration

Dosage adjustment not necessary

Midazolam

No clinically important changes in midazolam exposure

Rifampin

Approximately 90% reduction in tasimelteon exposure; possible reduced efficacy

Avoid concomitant use

Rosiglitazone

No clinically important effect on rosiglitazone exposure

Smoking

Decreased exposure to tasimelteon in smokers; possible reduced efficacy

Tasimelteon Pharmacokinetics

Absorption

Bioavailability

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

Onset

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

Food

High-fat meal reduced peak plasma concentration by 44% and delayed time to peak plasma concentrations by approximately 1.75 hours. (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. Not studied in severe hepatic impairment (Child-Pugh class C). (See Hepatic Impairment under Cautions.)

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

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

Distribution

Extent

Not known whether distributed into human milk.

Plasma Protein Binding

Approximately 90%.

Elimination

Metabolism

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

Elimination Route

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

Half-life

Tasimelteon: Mean elimination half-life of 1.3 hours.

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

Special Populations

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

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

Stability

Storage

Oral

Capsules

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

Actions

Advice to Patients

Preparations

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. Specific availability information is available from the manufacturer by telephone at 844-438-5469 or on the Hetlioz website ([Web]).

Tasimelteon

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

20 mg

Hetlioz

Vanda

AHFS DI Essentials™. © Copyright 2024, Selected Revisions January 6, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

Reload page with references included