RESTORIL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for RESTORIL (RESTORIL).

How it works

Temazepam is a benzodiazepine that enhances the effect of gamma-aminobutyric acid (GABA) at the GABA-A receptor, leading to increased chloride ion influx and hyperpolarization of the postsynaptic neuron, resulting in sedation and anxiolysis.

What the body does with it

Metabolism	Primarily hepatic via CYP3A4, glucuronidation; active metabolite (temazepam glucuronide) is renally excreted
Excretion	Renal (approximately 80% as conjugated metabolites, less than 2% unchanged); fecal (approximately 20%).
Half-life	Terminal elimination half-life is approximately 10-15 hours in healthy adults. Clinical context: Half-life may be prolonged in elderly patients and those with hepatic impairment; accumulation may occur with repeated dosing, leading to prolonged sedation.
Protein binding	Approximately 96% bound to plasma proteins, primarily albumin.
Volume of Distribution	Vd is approximately 0.8-1.3 L/kg. Clinical meaning: Indicates moderate tissue distribution; the drug is not extensively sequestered in tissues.
Bioavailability	Oral: 80-90% absorbed, with extensive first-pass metabolism; absolute bioavailability is approximately 80%.
Onset of Action	Oral: 20-30 minutes for hypnotic effect; 30-60 minutes for full sedative effect.
Duration of Action	6-8 hours following a single oral dose. Clinical notes: Duration may be shorter in patients with rapid clearance; residual sedation may occur on awakening, especially with higher doses or in elderly.

Classification & Brands

Dosing & administration

Oral: 15-30 mg once daily at bedtime, as needed for insomnia. Maximum dose: 30 mg/day.

Dosage form	CAPSULE
Renal impairment	No specific dose adjustment recommended for renal impairment. Use with caution in severe renal impairment due to increased sensitivity.
Liver impairment	For mild to moderate hepatic impairment (Child-Pugh A/B): initial dose 15 mg at bedtime; titrate cautiously. Contraindicated in severe hepatic impairment (Child-Pugh C).
Pediatric use	Not recommended for pediatric patients due to lack of safety and efficacy data.
Geriatric use	Initial dose: 15 mg at bedtime. Use lowest effective dose due to increased risk of falls, cognitive impairment, and next-day sedation.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for RESTORIL (RESTORIL).

Breastfeeding	Enters breast milk; M/P ratio approximately 0.6. Use with caution; monitor infant for sedation, poor feeding, respiratory depression. Manufacturer recommends avoiding breastfeeding due to potential accumulation in neonates.
Teratogenic Risk	First trimester: Limited data; increased risk of oral clefts (RR 1.3-2.0) from case-control studies. Second trimester: Possible increased risk of congenital anomalies; avoid chronic use. Third trimester: Known risk of neonatal withdrawal syndrome (hypotonia, respiratory depression, feeding difficulties) and floppy infant syndrome. Chronic use may lead to neonatal sedation.

Warnings & precautions

■ FDA Black Box Warning

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to temazepam or other benzodiazepines; pre-existing CNS depression; narrow-angle glaucoma (relative); severe hepatic impairment; pregnancy (particularly first trimester; risk of congenital malformations); breastfeeding

Clinical Precautions

Precautions

Risk of respiratory depression, especially with concomitant CNS depressants; dependence and withdrawal; amnesia; complex sleep behaviors; worsening of depression or suicidal ideation; anaphylaxis/angioedema; avoid abrupt discontinuation

Clinical Tips & Counseling

Drug interactions

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RESTORIL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for RESTORIL (RESTORIL).

How it works

What the body does with it

Metabolism	Primarily hepatic via CYP3A4, glucuronidation; active metabolite (temazepam glucuronide) is renally excreted
Excretion	Renal (approximately 80% as conjugated metabolites, less than 2% unchanged); fecal (approximately 20%).
Half-life	Terminal elimination half-life is approximately 10-15 hours in healthy adults. Clinical context: Half-life may be prolonged in elderly patients and those with hepatic impairment; accumulation may occur with repeated dosing, leading to prolonged sedation.
Protein binding	Approximately 96% bound to plasma proteins, primarily albumin.
Volume of Distribution	Vd is approximately 0.8-1.3 L/kg. Clinical meaning: Indicates moderate tissue distribution; the drug is not extensively sequestered in tissues.
Bioavailability	Oral: 80-90% absorbed, with extensive first-pass metabolism; absolute bioavailability is approximately 80%.
Onset of Action	Oral: 20-30 minutes for hypnotic effect; 30-60 minutes for full sedative effect.
Duration of Action	6-8 hours following a single oral dose. Clinical notes: Duration may be shorter in patients with rapid clearance; residual sedation may occur on awakening, especially with higher doses or in elderly.

Classification & Brands

Dosing & administration

Oral: 15-30 mg once daily at bedtime, as needed for insomnia. Maximum dose: 30 mg/day.

Dosage form	CAPSULE
Renal impairment	No specific dose adjustment recommended for renal impairment. Use with caution in severe renal impairment due to increased sensitivity.
Liver impairment	For mild to moderate hepatic impairment (Child-Pugh A/B): initial dose 15 mg at bedtime; titrate cautiously. Contraindicated in severe hepatic impairment (Child-Pugh C).
Pediatric use	Not recommended for pediatric patients due to lack of safety and efficacy data.
Geriatric use	Initial dose: 15 mg at bedtime. Use lowest effective dose due to increased risk of falls, cognitive impairment, and next-day sedation.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for RESTORIL (RESTORIL).

Breastfeeding	Enters breast milk; M/P ratio approximately 0.6. Use with caution; monitor infant for sedation, poor feeding, respiratory depression. Manufacturer recommends avoiding breastfeeding due to potential accumulation in neonates.
Teratogenic Risk	First trimester: Limited data; increased risk of oral clefts (RR 1.3-2.0) from case-control studies. Second trimester: Possible increased risk of congenital anomalies; avoid chronic use. Third trimester: Known risk of neonatal withdrawal syndrome (hypotonia, respiratory depression, feeding difficulties) and floppy infant syndrome. Chronic use may lead to neonatal sedation.