HETLIOZ LQ

Clinical safety rating: caution

Comprehensive clinical and safety monograph for HETLIOZ LQ (HETLIOZ LQ).

How it works

Melatonin receptor agonist; selectively binds to and activates MT1 and MT2 receptors in the suprachiasmatic nucleus, regulating circadian rhythms and promoting sleep.

What the body does with it

Metabolism	Primarily hepatic via CYP1A2 (major) and CYP3A4 (minor); undergoes extensive first-pass metabolism.
Excretion	Primarily hepatic metabolism (CYP1A2, CYP3A4) with renal excretion of metabolites; unchanged tasimelteon in urine <1%; fecal excretion accounts for approximately 80% of total clearance.
Half-life	Terminal elimination half-life is approximately 1.5-2.0 hours; clinical context: dosing at bedtime aligns with short half-life to avoid residual daytime sedation.
Protein binding	~90-92% bound to serum proteins, primarily albumin.
Volume of Distribution	Vd/F is approximately 55-90 L (0.79-1.29 L/kg for 70 kg adult); large Vd indicates extensive tissue distribution.
Bioavailability	Oral absolute bioavailability is approximately 40-50% due to first-pass metabolism (CYP1A2, CYP3A4).
Onset of Action	Oral: Onset of sleep induction occurs within 30-60 minutes, with maximal melatonin receptor occupancy at 1 hour post-dose.
Duration of Action	Duration of sleep promotion is approximately 4-6 hours; clinical note: short duration minimizes next-morning sedation, suitable for sleep onset maintenance.

Classification & Brands

Dosing & administration

20 mg orally once daily at bedtime, taken within 30 minutes of bedtime with or without food. For delayed sleep-wake phase disorder: 0.5 mg/kg (up to 20 mg) once daily at bedtime.

Dosage form	SUSPENSION
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended for severe renal impairment (CrCl <30 mL/min) or end-stage renal disease due to lack of data.
Liver impairment	Mild hepatic impairment (Child-Pugh A): No dose adjustment. Moderate hepatic impairment (Child-Pugh B): Reduce dose to 10 mg once daily. Severe hepatic impairment (Child-Pugh C): Not recommended due to lack of data.
Pediatric use	Approved for non-24-hour sleep-wake disorder in children ≥16 years: 20 mg once daily at bedtime. For off-label use (e.g., delayed sleep-wake phase disorder) in children ≥6 years: 0.5 mg/kg (max 20 mg) once daily at bedtime based on limited data.
Geriatric use	No specific dose adjustment required based on age alone. However, elderly patients may have decreased renal function; monitor CrCl and adjust if severe impairment. Start at lower end of dosing range due to potential increased sensitivity to side effects (e.g., dizziness, somnolence).

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for HETLIOZ LQ (HETLIOZ LQ).

Breastfeeding	No data on presence in human milk, effects on breastfed infant, or milk production. Excreted in rat milk at concentrations up to 80% of maternal plasma; M/P ratio not determined in humans. Caution advised; consider developmental and health benefits of breastfeeding along with mother's clinical need and potential adverse effects.
Teratogenic Risk	Pregnancy Category C. In animal studies, tasimelteon administration resulted in embryofetal mortality and reduced fetal body weight at maternal toxic doses. No adequate well-controlled studies in pregnant women. First trimester: potential risk based on animal data; second and third trimesters: unknown; use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to tasimelteon or any excipients.","Severe hepatic impairment (Child-Pugh class C).","Concomitant use with strong CYP1A2 inhibitors (e.g., fluvoxamine)."]

Clinical Precautions

Precautions

["May impair daytime wakefulness and cause somnolence; avoid driving or hazardous activities within 5 hours of dosing.","Angioedema, anaphylaxis, and other hypersensitivity reactions reported; discontinue if signs occur.","Suicidal ideation or worsening depression observed; monitor for mood changes.","Caution in hepatic impairment (avoid in severe impairment).","Avoid use with strong CYP1A2 inhibitors (e.g., fluvoxamine) or inducers (e.g., smoking, rifampin)."]

Clinical Tips & Counseling

Drug interactions

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HETLIOZ LQ

Clinical safety rating: caution

Comprehensive clinical and safety monograph for HETLIOZ LQ (HETLIOZ LQ).

How it works

Melatonin receptor agonist; selectively binds to and activates MT1 and MT2 receptors in the suprachiasmatic nucleus, regulating circadian rhythms and promoting sleep.

What the body does with it

Metabolism	Primarily hepatic via CYP1A2 (major) and CYP3A4 (minor); undergoes extensive first-pass metabolism.
Excretion	Primarily hepatic metabolism (CYP1A2, CYP3A4) with renal excretion of metabolites; unchanged tasimelteon in urine <1%; fecal excretion accounts for approximately 80% of total clearance.
Half-life	Terminal elimination half-life is approximately 1.5-2.0 hours; clinical context: dosing at bedtime aligns with short half-life to avoid residual daytime sedation.
Protein binding	~90-92% bound to serum proteins, primarily albumin.
Volume of Distribution	Vd/F is approximately 55-90 L (0.79-1.29 L/kg for 70 kg adult); large Vd indicates extensive tissue distribution.
Bioavailability	Oral absolute bioavailability is approximately 40-50% due to first-pass metabolism (CYP1A2, CYP3A4).
Onset of Action	Oral: Onset of sleep induction occurs within 30-60 minutes, with maximal melatonin receptor occupancy at 1 hour post-dose.
Duration of Action	Duration of sleep promotion is approximately 4-6 hours; clinical note: short duration minimizes next-morning sedation, suitable for sleep onset maintenance.

Classification & Brands

Dosing & administration

20 mg orally once daily at bedtime, taken within 30 minutes of bedtime with or without food. For delayed sleep-wake phase disorder: 0.5 mg/kg (up to 20 mg) once daily at bedtime.

Dosage form	SUSPENSION
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended for severe renal impairment (CrCl <30 mL/min) or end-stage renal disease due to lack of data.
Liver impairment	Mild hepatic impairment (Child-Pugh A): No dose adjustment. Moderate hepatic impairment (Child-Pugh B): Reduce dose to 10 mg once daily. Severe hepatic impairment (Child-Pugh C): Not recommended due to lack of data.
Pediatric use	Approved for non-24-hour sleep-wake disorder in children ≥16 years: 20 mg once daily at bedtime. For off-label use (e.g., delayed sleep-wake phase disorder) in children ≥6 years: 0.5 mg/kg (max 20 mg) once daily at bedtime based on limited data.
Geriatric use	No specific dose adjustment required based on age alone. However, elderly patients may have decreased renal function; monitor CrCl and adjust if severe impairment. Start at lower end of dosing range due to potential increased sensitivity to side effects (e.g., dizziness, somnolence).

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for HETLIOZ LQ (HETLIOZ LQ).

Breastfeeding	No data on presence in human milk, effects on breastfed infant, or milk production. Excreted in rat milk at concentrations up to 80% of maternal plasma; M/P ratio not determined in humans. Caution advised; consider developmental and health benefits of breastfeeding along with mother's clinical need and potential adverse effects.
Teratogenic Risk	Pregnancy Category C. In animal studies, tasimelteon administration resulted in embryofetal mortality and reduced fetal body weight at maternal toxic doses. No adequate well-controlled studies in pregnant women. First trimester: potential risk based on animal data; second and third trimesters: unknown; use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to tasimelteon or any excipients.","Severe hepatic impairment (Child-Pugh class C).","Concomitant use with strong CYP1A2 inhibitors (e.g., fluvoxamine)."]