Dosing and uses of Hetlioz (tasimelteon)
Adult dosage forms and strengths
capsule
- 20mg
Non-24-Hour Disorder
Indicated for the treatment of non-24-hour sleep-wake disorder in totally blind
20 mg PO per day taken before bedtime, at the same time every night
Dosage modifications
Renal impairment (all stages): No dosage adjustment necessary
Hepatic impairment
- Mild or moderate: No dosage adjustment necessary
- Severe (Child-Pugh C): Not studied; use not recommended
Dosing Considerations
Because of individual differences in circadian rhythms, drug effect may not occur for weeks or months
Administration
Take on empty stomach without food
Limit activity to preparing for going to bed following administration
Pediatric dosage forms and strengths
Safety and efficacy not established
Hetlioz (tasimelteon) adverse (side) effects
>10%
Headache (17%)
1-10%
Increased ALT (10%)
Nightmares/abnormal dreams (10%)
Upper respiratory infections (7%)
Urinary tract infections (7%)
Warnings
Contraindications
None
Cautions
Somnolence; can impair performance of activities requiring complete mental alertness
Tasimelteon is a CYP1A2 substrate; avoid coadministration with strong CYP1A2 inhibitors because of a potentially large increase in tasimelteon exposure and greater risk of adverse reactions
Smoking causes induction of CYP1A2 levels; tasimelteon exposure in smokers was lower (~40%) than in nonsmokers and therefore the efficacy may be reduced
Tasimelteon is a CYP3A4 substrate: avoid coadministration with CYP3A4 inducers because of a potentially large decrease in tasimelteon exposure with reduced efficacy
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
In clinical trials, coadministration with alcohol showed a trend toward additive sedation
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown if distributed in human breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Hetlioz (tasimelteon)
Mechanism of action
Melatonin receptor agonist with high affinity for MT1 and MT2 receptors in the suprachiasmatic nucleus of the brain; MT1 and MT2 are thought to synchronize the body's melatonin and cortisol circadian rhythms with the day-night cycle in patients with non-24-hour disorder
Absorption
Peak plasma concentration: 0.5-3 hr (fasting)
When administered with a high-fat meal, peak plasma concentration was 44% lower than when given in a fasted state, and the median peak concentration was delayed by approximately 1.75 hr
Oral bioavailability: 38.3%
Distribution
Protein bound: 96%
Vd: 59-126 L
Metabolism
Extensively metabolized primarily by oxidation at multiple sites and oxidative dealkylation resulting in opening of the dihydrofuran ring followed by further oxidation to give a carboxylic acid
CYP1A2 and CYP3A4 are the major isozymes involved
Phenolic glucuronidation is the major phase II metabolic route
Major metabolites had 13-fold or less activity at melatonin receptors compared to tasimelteon
Elimination
Half-life: 1.3 hr; 1.3-3.7 hr (metabolites)
Excretion: 80% urine (<1% as parent compound); 4% feces
