DORAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DORAL (DORAL).
GABAA receptor positive allosteric modulator; enhances the inhibitory effects of GABA by binding to benzodiazepine receptors, increasing chloride channel opening frequency.
| 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. |
| Molecular Weight | 386.86 |
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. |
| 1st trimester | Avoid use due to potential teratogenic effects; benzodiazepines have been associated with cleft lip/palate when used in first trimester. |
| 2nd trimester | Use only if benefit outweighs risk; may cause fetal benzodiazepine exposure and potential for neonatal withdrawal or sedation. |
| 3rd trimester | Avoid use near term; risks include neonatal withdrawal syndrome, floppy infant syndrome, and respiratory depression. |
Clinical note
Comprehensive clinical and safety monograph for DORAL (DORAL).
| Placental transfer | Benzodiazepines, including quazepam, cross the placenta readily, achieving fetal plasma concentrations similar to maternal levels. |
| Breastfeeding | DORAL (quazepam) is excreted into breast milk. Due to the long half-life of its active metabolite, it may accumulate in the nursing infant causing sedation, poor feeding, and weight loss. Alternative agents with shorter half-lives are preferred. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to quazepam or any benzodiazepineMyasthenia gravisSevere respiratory insufficiencySleep apnea syndromeSevere hepatic impairment
| 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 |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase systemic exposure to quazepam. Taking with food may delay absorption; avoid high-fat meals close to administration. No other significant food interactions reported. |
Loading safety data…
| Lactation Rating | L4 (Possibly Hazardous) |
| 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. |
| Fetal Monitoring | Monitor maternal vital signs, sedation level, and respiratory status. For fetal monitoring, perform ultrasound for growth assessment and structural anomalies if inadvertent exposure. In neonates, monitor for hypotonia, respiratory depression, and withdrawal symptoms (irritability, tremors). |
| Fertility Effects | Benzodiazepines may cause menstrual irregularities, anovulation, and decreased libido in females. In males, potential for decreased sperm motility and concentration. Effects are generally reversible upon discontinuation. No dedicated fertility studies for quazepam. |
| Clinical Pearls |
| Doral (quazepam) is a long-acting benzodiazepine with a half-life of 25-41 hours, suitable for insomnia with early morning awakening. Withdrawal symptoms may be delayed due to active metabolites. Avoid in severe hepatic impairment, sleep apnea, and myasthenia gravis. Onset of action is rapid; administer immediately before bedtime. |
| Patient Advice | Take exactly as prescribed, usually just before bedtime. · Do not consume alcohol or other CNS depressants while taking this medication. · Avoid driving or operating heavy machinery until you know how this drug affects you. · Do not stop abruptly; withdrawal symptoms can occur. Taper dose under medical supervision. · Report any unusual changes in mood, thoughts, or behavior, especially suicidal ideation. · Store in a cool, dry place away from children. |