Tasimelteon

Tasimelteon
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];

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Overview

Tasimelteon is a central nervous system agent that is FDA approved for the treatment of non-24-hour sleep-wake disorder. Common adverse reactions include headache, urinary tract infection, upper respiratory tract infection, abnormal dreams, increased liver enzymes.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

• HETLIOZ is indicated for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24).

Dosage

• The recommended dosage of HETLIOZ is 20 mg per day taken before bedtime, at the same time every night.

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

DOSAGE FORMS AND STRENGTHS

• Capsules: 20 mg size 1 dark blue opaque, hard gelatin capsules printed with “VANDA 20 mg” in white.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

• There is limited information regarding Off-Label Guideline-Supported Use of Tasimelteon in adult patients.

Non–Guideline-Supported Use

• There is limited information regarding Off-Label Non–Guideline-Supported Use of Tasimelteon in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

• There is limited information regarding FDA-Labeled Use of Tasimelteon in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

• There is limited information regarding Off-Label Guideline-Supported Use of Tasimelteon in pediatric patients.

Non–Guideline-Supported Use

• There is limited information regarding Off-Label Non–Guideline-Supported Use of Tasimelteon in pediatric patients.

Contraindications

• None

Warnings

Somnolence

• After taking HETLIOZ, patients should limit their activity to preparing for going to bed. HETLIOZ can potentially impair the performance of activities requiring complete mental alertness.

Adverse Reactions

Clinical Trials Experience

• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

• A total of 1346 subjects were treated with at least one dose of HETLIOZ, of which 139 were treated for > 26 weeks and 93 were treated for > 1 year.

• A 26-week, parallel-arm placebo-controlled study (Study 1) evaluated HETLIOZ (n=42) compared to placebo (n=42) in patients with Non-24. A randomized-withdrawal, placebo- controlled study of 8 weeks duration (Study 2) also evaluated HETLIOZ (n=10), compared to placebo (n=10), in patients with Non-24.

• In placebo-controlled studies, 6% of patients exposed to HETLIOZ discontinued treatment due to an adverse event, compared with 4% of patients who received placebo.

• TABLE 1 shows the incidence of adverse reactions from Study 1.

This image is provided by the National Library of Medicine.

Postmarketing Experience

• There is limited information regarding Postmarketing Experience of Tasimelteon in the drug label.

Drug Interactions

Strong CYP1A2 Inhibitors (e.g., fluvoxamine)

• Avoid use of HETLIOZ in combination with fluvoxamine or other strong CYP1A2 inhibitors because of a potentially large increase in tasimelteon exposure and greater risk of adverse reactions [see Clinical Pharmacology (12.3)].

Strong CYP3A4 Inducers (e.g., rifampin)

• Avoid use of HETLIOZ in combination with rifampin or other CYP3A4 inducers because of a potentially large decrease in tasimelteon exposure with reduced efficacy.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): Pregnancy Category C

• There are no adequate and well-controlled studies of HETLIOZ in pregnant women. In animal studies, administration of tasimelteon during pregnancy resulted in developmental toxicity (embryofetal mortality, neurobehavioral impairment, and decreased growth and development in offspring) at doses greater than those used clinically. HETLIOZ should be used during pregnancy only if the potential benefit justifies the potential risks.

• In pregnant rats administered tasimelteon at oral doses of 5, 50, or 500 mg/kg/day during the period of organogenesis, there were no effects on embryofetal development. The highest dose tested is approximately 240 times the recommended human dose (RHD) of 20 mg/day, on a mg/m2 basis.

• In pregnant rabbits administered tasimelteon at oral doses of 5, 30, or 200 mg/kg/day during the period of organogenesis, embryolethality and embryofetal toxicity (reduced fetal body weight and delayed ossification) were observed at the highest dose tested. The highest dose not associated with adverse effects (30 mg/kg/day) is approximately 30 times the RHD on a mg/m2 basis.

• Oral administration of tasimelteon (50, 150, or 450 mg/kg/day) to rats throughout organogenesis and lactation resulted in persistent reductions in body weight, delayed sexual maturation and physical development, and neurobehavioral impairment in offspring at the highest dose tested. Reduced body weight in offspring was also observed at the mid-dose. The no effect dose (50 mg/kg/day) is approximately 25 times the RHD on a mg/m2 basis.

Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Tasimelteon in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Tasimelteon during labor and delivery.

Nursing Mothers

• It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when HETLIOZ is administered to a nursing woman.

Pediatric Use

• Safety and effectiveness in pediatric patients have not been established.

Geriatic Use

• The risk of adverse reactions may be greater in elderly (>65 years) patients than younger patients because exposure to tasimelteon is increased by approximately 2-fold compared with younger patients.

Gender

There is no FDA guidance on the use of Tasimelteon with respect to specific racial populations.

Race

There is no FDA guidance on the use of Tasimelteon with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Tasimelteon in patients with renal impairment.

Hepatic Impairment

• Dose adjustment is not necessary in patients with mild or moderate hepatic impairment. HETLIOZ has not been studied in patients with severe hepatic impairment (Child-Pugh Class C). Therefore, HETLIOZ is not recommended for use in patients with severe hepatic impairment

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Tasimelteon in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Tasimelteon in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

• Intravenous

Monitoring

There is limited information regarding Monitoring of Tasimelteon in the drug label.

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Tasimelteon in the drug label.

Overdosage

• There is limited premarketing clinical experience with the effects of an overdosage of HETLIOZ.

• As with the management of any overdose, general symptomatic and supportive measures should be used, along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. Respiration, pulse, blood pressure, and other appropriate vital signs should be monitored, and general supportive measures employed.

• While hemodialysis was effective at clearing HETLIOZ and the majority of its major metabolites in patients with renal impairment, it is not known if hemodialysis will effectively reduce exposure in the case of overdose.

• As with the management of any overdose, the possibility of multiple drug ingestion should be considered. Contact a poison control center for current information on the management of overdose.

Pharmacology

There is limited information regarding Tasimelteon Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Tasimelteon Mechanism of Action in the drug label.

Structure

HETLIOZ (tasimelteon) is a melatonin receptor agonist, chemically designated as (1R, 2R)-N-[2-(2,3-dihydrobenzofuran-4-yl)cyclopropylmethyl]propanamide, containing two chiral centers. The molecular formula is C15H19NO2, and the molecular weight is 245.32. The structural formula is:

This image is provided by the National Library of Medicine.

• Tasimelteon is a white to off-white crystalline powder. It is very slightly soluble in cyclohexane, slightly soluble in water and 0.1 N hydrochloric acid, and freely soluble or very soluble in methanol, 95% ethanol, acetonitrile, isopropanol, polyethylene glycol 300, propylene glycol and ethyl acetate.

• HETLIOZ is available in 20 mg strength capsules for oral administration. Inactive ingredients are: lactose anhydrous, microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate. Each hard gelatin capsule consists of gelatin, titanium dioxide, FD&C Blue #1, FD&C Red #3, and FD&C Yellow #6.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Tasimelteon in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Tasimelteon in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Tasimelteon in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Tasimelteon in the drug label.

How Supplied

Storage

There is limited information regarding Tasimelteon Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Tasimelteon in the drug label.

Precautions with Alcohol

• Alcohol-Tasimelteon interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• ®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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