Melatonin Receptor Agonist

Hetlioz

Approved 31 Jan 2014OralCapsule

Indications

HETLIOZ is a melatonin receptor agonist. HETLIOZ capsules are indicated for the treatment of: Non-24-Hour Sleep-Wake Disorder (Non-24) in adults ( 1 ) Nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) in patients 16 years of age and older ( 1 ) HETLIOZ LQ oral suspension is indicated for the treatment of: Nighttime sleep disturbances in SMS in pediatric patients 3 years to 15 years of age ( 1 )

1.1Non-24-Hour Sleep-Wake Disorder (Non-24)

HETLIOZ capsules are indicated for the treatment of Non-24 in adults.

1.2Nighttime Sleep Disturbances in Smith-Magenis Syndrome (SMS)

HETLIOZ capsules are indicated for the treatment of nighttime sleep disturbances in SMS in patients 16 years of age and older. HETLIOZ LQ oral suspension is indicated for the treatment of nighttime sleep disturbances in SMS in pediatric patients 3 to 15 years of age.

Contraindications

None. None ( 4 )

Warnings and precautions

May cause somnolence: After taking HETLIOZ, patients should limit their activity to preparing for going to bed, because HETLIOZ can impair the performance of activities requiring complete mental alertness ( 5.1 )

5.1Somnolence

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.

Interactions

Strong CYP1A2 inhibitors (e.g., fluvoxamine): Avoid use of HETLIOZ in combination with strong CYP1A2 inhibitors because of increased exposure ( 7.1 , 12.3 ) Strong CYP3A4 inducers (e.g., rifampin): Avoid use of HETLIOZ in combination with rifampin or other CYP3A4 inducers, because of decreased exposure ( 7.2 , 12.3 )

7.1Strong CYP1A2 Inhibitors

At a glance

Brand name: Hetlioz
Active substance: tasimelteon
Pharmacologic class: Melatonin Receptor Agonist
Route: Oral
Dosage form: Capsule
Applicant: Vanda Pharms Inc
Status: Prescription
FDA approval: 31 Jan 2014
Application: NDA205677-001

Indications

1.1Non-24-Hour Sleep-Wake Disorder (Non-24)

HETLIOZ capsules are indicated for the treatment of Non-24 in adults.

1.2Nighttime Sleep Disturbances in Smith-Magenis Syndrome (SMS)

Warnings and precautions

5.1Somnolence

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.

Interactions

7.1Strong CYP1A2 Inhibitors

Adverse reactions

The most common adverse reactions (incidence >5% and at least twice as high on HETLIOZ than on placebo) were headache, increased alanine aminotransferase, nightmares or unusual dreams, and upper respiratory or urinary tract infection ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Vanda Pharmaceuticals Inc. at 1-844-438-5469 or www.hetlioz.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical 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. More than 2080 subjects have been treated with at least one dose of HETLIOZ, of which more than 380 have been treated for > 26 weeks and more than 170 have been treated for > 1 year.

Non-24-Hour Sleep-Wake Disorder (Non-24) 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 2 shows the incidence of adverse reactions from Study 1. *Adverse reactions with an incidence > 5% and at least twice as high on HETLIOZ than on placebo are displayed. Table 2: Adverse Reactions in Study 1 HETLIOZ N=42 Placebo N=42 Headache 17 % 7 % Alanine aminotransferase increased 10 % 5 % Nightmare/abnormal dreams 10 % 0 % Upper respiratory tract infection 7 % 0 % Urinary tract infection 7 % 2 % Nighttime Sleep Disturbances in Smith-Magenis Syndrome (SMS) A 9-week, double-blind, randomized, placebo-controlled, two-period crossover study evaluated HETLIOZ (capsules and oral suspension; n=25) compared to placebo (n=26) in the treatment of nighttime sleep disturbances in patients with Smith-Magenis Syndrome.

Pediatric patients (n=11, age 3 to 15 years) received HETLIOZ LQ oral suspension, and patients ≥16 years of age (n=14) received HETLIOZ capsules. Adverse reactions were similar in patients treated for Non-24 and patients with Smith-Magenis syndrome treated for nighttime sleep disturbances. Adverse reactions were also similar in pediatric patients (3 years to 15 years) who received HETLIOZ LQ oral suspension, and patients ≥16 years of age who received HETLIOZ capsules.

Hetlioz

Indications

1.1Non-24-Hour Sleep-Wake Disorder (Non-24)

1.2Nighttime Sleep Disturbances in Smith-Magenis Syndrome (SMS)

Contraindications

Warnings and precautions

5.1Somnolence

Interactions

7.1Strong CYP1A2 Inhibitors

At a glance

Two medicines in one question?

Hetlioz

Indications

1.1Non-24-Hour Sleep-Wake Disorder (Non-24)

1.2Nighttime Sleep Disturbances in Smith-Magenis Syndrome (SMS)

Contraindications

Warnings and precautions

5.1Somnolence

Interactions

7.1Strong CYP1A2 Inhibitors

At a glance

Two medicines in one question?

7.2Strong CYP3A4 Inducers

7.3Beta-adrenergic Receptor Antagonists

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

Composition

Official product information