HETLIOZ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HETLIOZ (HETLIOZ).
Melatonin receptor agonist; selective agonist at MT1 and MT2 receptors in the suprachiasmatic nucleus, regulating circadian rhythms.
| Metabolism | Primarily hepatic via CYP1A2; minor metabolism via CYP3A4. |
| Excretion | Primarily hepatic metabolism; 77-88% excreted in feces as metabolites, 13-23% in urine as metabolites. <1% excreted unchanged. |
| Half-life | Terminal elimination half-life is approximately 1.3-1.5 hours. No clinically relevant accumulation with daily dosing. |
| Protein binding | ~93% bound to serum albumin. |
| Volume of Distribution | Approximately 0.7-1.5 L/kg (based on ~56 L for a 70 kg adult), indicating distribution into tissues. |
| Bioavailability | Absolute oral bioavailability is approximately 10-20% due to extensive first-pass metabolism. |
| Onset of Action | Oral: Onset of sleep-promoting effect occurs within 30-60 minutes post-dose. |
| Duration of Action | Duration of sleep maintenance is approximately 6-8 hours. Clinical effect supports overnight sleep. |
20 mg orally once daily at bedtime, take within 30 minutes of bedtime, with or without food.
| Dosage form | CAPSULE |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m2). |
| Liver impairment | Child-Pugh Class A or B: No dosage adjustment. Child-Pugh Class C: Not recommended (no studies). |
| Pediatric use | Not approved for pediatric patients (no established safety and efficacy). |
| Geriatric use | No specific dosage adjustment recommended, but caution due to potential decreased hepatic/renal function and increased sensitivity to adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HETLIOZ (HETLIOZ).
| Breastfeeding | Not recommended. M/P ratio unknown; present in rat milk. Potential for infant CNS depression or other adverse effects. |
| Teratogenic Risk | Insufficient human data; animal studies show no evidence of teratogenicity at clinically relevant doses. Risk cannot be excluded; use only if benefit outweighs risk. First trimester: limited data, no known malformation pattern. Second/third trimester: no data. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to tasimelteon or any component of the formulation"]
| Precautions | ["May cause somnolence; avoid driving or hazardous activities after taking. Avoid use with strong CYP1A2 inhibitors (e.g., fluvoxamine) or inducers (e.g., smoking). Monitor for angioedema and anaphylaxis. Caution in patients with depression or suicidal ideation."] |
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| Monitor for CNS depression (somnolence, dizziness) in mother. No specific fetal monitoring required beyond routine obstetric care. Assess neonatal respiratory and CNS status if used near term. |
| Fertility Effects | No human data. Animal studies show no effect on fertility at clinically relevant doses. |