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. |
| Molecular Weight | 387.9 |
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 | Avoid: associated with congenital malformations including oral clefts when used in first trimester (data from flurazepam and other benzodiazepines). |
| 2nd trimester | Avoid: fetal exposure to benzodiazepines in second trimester may contribute to preterm birth or low birth weight. |
| 3rd trimester | Avoid: use in third trimester may cause neonatal withdrawal syndrome, hypotonia, and respiratory depression. |
Clinical note
Comprehensive clinical and safety monograph for DALMANE (DALMANE).
| Placental transfer | Flurazepam and its active metabolites cross the placenta. Cord blood concentrations are similar to maternal serum, indicating significant placental transfer. |
| Breastfeeding | Flurazepam and its active metabolite desalkylflurazepam are excreted into breast milk. Use is not recommended due to potential accumulation in the infant, causing sedation, poor feeding, and weight loss. If essential, use lowest dose for shortest duration. |
■ 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 any benzodiazepineSevere hepatic impairmentNarrow-angle glaucomaMyasthenia gravisSevere respiratory insufficiencySleep apnea syndromeKnown alcohol or drug dependence (with caution in withdrawal)
| 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. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase blood levels of flurazepam. High-fat meals may delay absorption but do not significantly affect efficacy. Alcohol should be strictly avoided. Caffeine intake should be limited as it may counteract the sedative effects. |
Loading safety data…
| Lactation Rating | L4 (Possibly Hazardous) |
| 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. |
| 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. |
| Clinical Pearls | Dalmane (flurazepam) is a long-acting benzodiazepine hypnotic with active metabolites (desalkylflurazepam) that accumulate with repeated dosing, leading to prolonged sedation and increased risk of next-day impairment. Due to its long half-life (40-250 hours), it is not recommended for elderly patients or those with hepatic impairment. It should be used with caution in patients with respiratory depression or sleep apnea. Abrupt discontinuation after prolonged use may precipitate withdrawal or rebound insomnia. |
| Patient Advice | Take Dalmanexactly as prescribed, usually at bedtime, because it can cause drowsiness and impair your ability to drive or operate machinery the next day. · Avoid consuming alcohol or other central nervous system depressants while taking this medication, as it can increase sedative effects. · Do not stop taking suddenly without consulting your doctor, as withdrawal symptoms may occur. · Report any unusual changes in mood, memory problems, or difficulty urinating to your healthcare provider. · This medication is for short-term use only; prolonged use can lead to dependence and tolerance. |