DALMANE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DALMANE (DALMANE).
Binds to benzodiazepine site on GABA-A receptor, enhancing GABA inhibitory effects, leading to increased chloride ion influx, hyperpolarization, and sedation.
| Metabolism | Hepatic via CYP450 (CYP3A4, CYP2C9, CYP2D6); major metabolite N-desalkylflurazepam (active, long half-life). |
| Excretion | Renal excretion of metabolites (~90%) and unchanged drug (<1%); fecal excretion (~1-2%). |
| Half-life | Terminal elimination half-life is 47-100 hours (mean 75 h) in adults; prolonged in elderly (up to 160 h) and cirrhosis (up to 200 h). |
| Protein binding | 96-99% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 3-4 L/kg (indicates extensive tissue distribution). |
| Bioavailability | Oral: 30-45% (due to first-pass metabolism); rectal: 50-60%. |
| Onset of Action | Oral: 15-30 minutes; IM: 10-20 minutes. |
| Duration of Action | 7-8 hours (hypnotic effect) but may cause residual sedation due to long half-life; duration of pharmacokinetic effect >24 hours. |
15-30 mg orally at bedtime; maximum 30 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | No specific dose adjustment required; use with caution in severe renal impairment (CrCl <10 mL/min) due to prolonged half-life. |
| Liver impairment | Child-Pugh A: 15 mg at bedtime; Child-Pugh B or C: not recommended due to risk of encephalopathy. |
| Pediatric use | Not recommended for children under 15 years; safety and efficacy not established. |
| Geriatric use | Initiate with 15 mg at bedtime; use lowest effective dose due to increased sensitivity and risk of falls/cognitive impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DALMANE (DALMANE).
| Breastfeeding | Flurazepam and its active metabolite are excreted into breast milk; M/P ratio not established for flurazepam, but similar benzodiazepines have M/P ~0.2-0.5. Potential for infant sedation, poor feeding, and withdrawal; use with caution and monitor infant for drowsiness and weight gain. |
| Teratogenic Risk | First trimester: data limited, but benzodiazepines not strongly associated with major malformations; some studies suggest increased risk of cleft palate (odds ratio ~2-3). Second/third trimester: exposure may cause fetal benzodiazepine intoxication (hypotonia, respiratory depression, hypothermia, poor feeding). Chronic use may lead to neonatal withdrawal. |
■ FDA Black Box Warning
Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death; reserve for patients with inadequate alternative options.
| Serious Effects |
Hypersensitivity to flurazepam or other benzodiazepines; severe respiratory insufficiency; sleep apnea syndrome; severe hepatic impairment; myasthenia gravis; narrow-angle glaucoma; concurrent use with opioids.
| Precautions | Risk of dependence and withdrawal; CNS depression, daytime sedation, impaired psychomotor function; complex sleep behaviors (e.g., sleep-driving); respiratory depression; worsening of depression or suicidal ideation. |
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| Fetal Monitoring | Monitor maternal sedation and respiratory status. Fetal monitoring via ultrasound for growth restriction and amniotic fluid volume during second/third trimester. Neonatal monitoring for withdrawal signs (tremors, hypertonia, irritability) and floppy infant syndrome (hypotonia, poor sucking) postpartum. |
| Fertility Effects | Data limited. Benzodiazepines may disrupt menstrual cyclicity via hypothalamic-pituitary-adrenal axis modulation; no definitive evidence of impaired fertility or decreased conception rates. |