General

Pronunciation:
tas-i-mel-tee-on

Trade Name(s)

• Hetlioz
• Hetlioz LQ

Ther. Class.

sedative/hypnotics

Pharm. Class.

melatonin receptor agonists

Indications

• Non-24-hour sleep-wake disorder (a circadian rhythm disorder more common in totally blind patients).
• Nighttime sleep disturbances in Smith-Magenis Syndrome.

Action

Acts as an agonist at melatonin MT₁  and MT₂  receptor sites, which are involved in regulation or circadian rhythm.

Therapeutic Effect(s):

Improved circadian rhythm with improved sleep/wake patterns.

Pharmacokinetics

Absorption: 38% absorbed following oral administration, plasma concentrations ↑ in female patients.

Distribution: Unknown.

Metabolism and Excretion: Primarily metabolized by the liver via the CYP1A2 and CYP3A4 isoenzymes. Primarily excreted in urine as metabolites.

Half-life: 1.3 hr.

TIME/ACTION PROFILE (establishment of circadian rhythm/sleep cycle)

Contraindication/Precautions

Contraindicated in:

• Severe hepatic impairment.

Use Cautiously in:

• OB:  Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
• Pedi:  Safety and effectiveness not established in children;
• Geri:  Older adults have ↑ risk of adverse reactions.

Adverse Reactions/Side Effects

GI: ↑ liver enzymes

Neuro: headache, nightmares/unusual dreams

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• Concurrent use of  strong CYP1A2 inhibitors, including  fluvoxamine, may ↑ levels and risk of toxicity.
• Concurrent use of  strong CYP1A2 inducers, including  rifampin  and  cigarette smoke , may ↓ levels and effectiveness.
•  Strong CYP3A4 inhibitors, including  ketoconazole, may ↑ levels and risk of toxicity.
•  Alcohol  may ↑ CNS depression.

Route/Dosage

Capsules are not interchangeable with the oral suspension.

Non-24-Hour Sleep-Wake Disorder

PO (Adults): Capsules: 20 mg one hr before bedtime, taken at the same time every night.

Nighttime Sleep Disturbances in Smith-Magenis Syndrome

PO (Adults and Children ≥16 yr): Capsules: 20 mg one hr before bedtime, taken at the same time every night.

PO (Children 3–15 yr and >28 kg): Oral suspension: 20 mg one hr before bedtime, taken at the same time every night.

PO (Children 3–15 yr and ≤28 kg): Oral suspension: 0.7 mg/kg one hr before bedtime, taken at the same time every night.

Availability (generic available)

Capsules (Hetlioz): 20 mg

Oral suspension (Hetlioz LQ) (cherry flavor): 4 mg/mL

Assessment

• Assess mental status, sleep patterns, and frequency of daytime naps prior and periodically during therapy.

Lab Test Considerations:

May cause ↑ transaminases.

Implementation

• PO Administer without food before bedtime at the same time each night.  DNC: Swallow capsule whole; do not open, dissolve, crush, or chew. 
  • Shake oral suspension for ≥30 sec before administering. Store suspension in refrigerator. Discard refrigerated suspension after 5 wk (for 48 mL bottle) and after 8 wk (for 158 mL bottle).
  • Oral capsules and suspension are not interchangeable.

Patient/Family Teaching

• Instruct patient to take tasimelteon as directed at the same time each day. If unable to take at approximately the same time on a given night, skip dose and resume following night. After taking, advise patient to limit activity to preparing to go to bed.
• Pedi:  Teach parents or caregivers to calculate and measure doses accurately. Reinforce importance of using measuring device supplied by pharmacy or with product, not household items.
• Caution patient tasimelteon can impair performance of activities requiring complete mental alertness. Advise patient to avoid driving and other activities requiring alertness after taking tasimelteon.
• Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

Improved circadian rhythm with improved sleep/wake patterns. Due to differences in circadian rhythms, may require daily use for several wk or mo before benefit from tasimelteon is noticeable.