DORAL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DORAL (DORAL).

How it works

GABAA receptor positive allosteric modulator; enhances the inhibitory effects of GABA by binding to benzodiazepine receptors, increasing chloride channel opening frequency.

What the body does with it

Metabolism	Hepatic via CYP3A4 and CYP2C19; major metabolites include N-desalkylflurazepam (active).
Excretion	Renal (primarily as metabolites; <1% unchanged). Biliary/fecal: minor.
Half-life	Terminal elimination half-life: 40-120 hours (long-acting benzodiazepine). Accumulation occurs with repeated dosing, especially in elderly or hepatic impairment.
Protein binding	97-99% bound to albumin.
Volume of Distribution	0.5-2.6 L/kg (large Vd indicates extensive tissue distribution, particularly adipose tissue).
Bioavailability	Oral: ~100% (well absorbed).
Onset of Action	Oral: 30-60 minutes (hypnotic effect).
Duration of Action	6-8 hours for hypnotic effect; prolonged sedation may occur due to long half-life and active metabolites.

Classification & Brands

Dosing & administration

15-30 mg orally at bedtime, maximum 60 mg/day.

Dosage form	TABLET
Renal impairment	CrCl 10-50 mL/min: reduce dose by 50%; CrCl <10 mL/min: use with caution, reduce dose by 75%.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated.
Pediatric use	Not recommended for pediatric patients; safety and efficacy not established.
Geriatric use	Initiate at 7.5 mg orally at bedtime; titrate cautiously to maximum 15 mg/day due to increased sensitivity and risk of falls.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DORAL (DORAL).

Breastfeeding	Quazepam and its active metabolite (2-oxoquazepam) are excreted in breast milk. The milk-to-plasma ratio is approximately 0.2-0.5 based on limited data. Potential for infant sedation and feeding difficulties. Breastfeeding is not recommended during therapy.
Teratogenic Risk	DORAL (quazepam) is a benzodiazepine classified as FDA Pregnancy Category X. First trimester use is associated with a 2-3 fold increased risk of oral clefts. Second and third trimester exposure may cause fetal CNS depression, hypotonia, and withdrawal symptoms (floppy infant syndrome). Use contraindicated in all trimesters.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to benzodiazepines","Severe respiratory insufficiency","Myasthenia gravis","Severe hepatic impairment","Pregnancy (first trimester and labor)"]

Clinical Precautions

Precautions

["Risk of dependence and withdrawal","CNS depressant effects and next-day impairment","Elderly patients: increased risk of falls and cognitive impairment","Respiratory depression in patients with compromised respiratory function","Anterograde amnesia"]

Clinical Tips & Counseling

Drug interactions

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DORAL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DORAL (DORAL).

How it works

GABAA receptor positive allosteric modulator; enhances the inhibitory effects of GABA by binding to benzodiazepine receptors, increasing chloride channel opening frequency.

What the body does with it

Metabolism	Hepatic via CYP3A4 and CYP2C19; major metabolites include N-desalkylflurazepam (active).
Excretion	Renal (primarily as metabolites; <1% unchanged). Biliary/fecal: minor.
Half-life	Terminal elimination half-life: 40-120 hours (long-acting benzodiazepine). Accumulation occurs with repeated dosing, especially in elderly or hepatic impairment.
Protein binding	97-99% bound to albumin.
Volume of Distribution	0.5-2.6 L/kg (large Vd indicates extensive tissue distribution, particularly adipose tissue).
Bioavailability	Oral: ~100% (well absorbed).
Onset of Action	Oral: 30-60 minutes (hypnotic effect).
Duration of Action	6-8 hours for hypnotic effect; prolonged sedation may occur due to long half-life and active metabolites.

Classification & Brands

Dosing & administration

15-30 mg orally at bedtime, maximum 60 mg/day.

Dosage form	TABLET
Renal impairment	CrCl 10-50 mL/min: reduce dose by 50%; CrCl <10 mL/min: use with caution, reduce dose by 75%.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated.
Pediatric use	Not recommended for pediatric patients; safety and efficacy not established.
Geriatric use	Initiate at 7.5 mg orally at bedtime; titrate cautiously to maximum 15 mg/day due to increased sensitivity and risk of falls.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DORAL (DORAL).

Breastfeeding	Quazepam and its active metabolite (2-oxoquazepam) are excreted in breast milk. The milk-to-plasma ratio is approximately 0.2-0.5 based on limited data. Potential for infant sedation and feeding difficulties. Breastfeeding is not recommended during therapy.
Teratogenic Risk	DORAL (quazepam) is a benzodiazepine classified as FDA Pregnancy Category X. First trimester use is associated with a 2-3 fold increased risk of oral clefts. Second and third trimester exposure may cause fetal CNS depression, hypotonia, and withdrawal symptoms (floppy infant syndrome). Use contraindicated in all trimesters.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to benzodiazepines","Severe respiratory insufficiency","Myasthenia gravis","Severe hepatic impairment","Pregnancy (first trimester and labor)"]