Tasimelteon

HETLIOZ

What it isMT1 and MT2 melatonin receptor agonist; non-24-hour sleep-wake disorder in blind patients.

Why this oneIt entrains the circadian clock in people with no light perception, which nothing else does.

What limits itEntrainment takes weeks to months. CYP1A2 and CYP3A4 dependent; avoid with fluvoxamine.

FDA-approved for

FDA dosing	Population	Start	Target	Max
Non-24-hour sleep-wake disorder	Adults (capsules)	20 mg QHS	20 mg QHS	20 mg QHS
Nighttime sleep disturbances in Smith-Magenis syndrome	≥16 yr (capsules)	20 mg QHS	20 mg QHS	20 mg QHS
Nighttime sleep disturbances in Smith-Magenis syndrome, ≤28 kg	Pediatric 3-15 yr (oral suspension)	0.7 mg/kg QHS	0.7 mg/kg QHS	0.7 mg/kg QHS
Nighttime sleep disturbances in Smith-Magenis syndrome, >28 kg	Pediatric 3-15 yr (oral suspension)	20 mg QHS	20 mg QHS	20 mg QHS

Renal Undefined

Hepatic Severe: not studied, not recommended

Take one hour before bedtime, at the same time every night
Take without food
Capsules and LQ oral suspension are not substitutable
If unable to take at about the same time, skip that dose and take next as scheduled
Non-24: drug effect may take weeks to months

Somnolence — after dosing, limit activity to preparing for bed; impairs mental-alertness tasks

Pregnancy Insufficient human data; no embryofetal toxicity in rats at tested exposures

Lactation No human or animal milk data

NO BOXED WARNINGS

Principal riskEntrainment takes weeks to months

Cost, est. cash$10–$300/month

Generic entry2022

Therapeutic safety burden1 / 4

Overdose danger1 / 4

Weight-gain liability0 / 4

Sedation liability3 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryC

Defining liabilitySomnolence, headache and hepatic enzyme elevations; acute toxicity is generally limited.

CYP1A2 substrate