FLURAZEPAM HYDROCHLORIDE
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Positive allosteric modulator of GABA-A receptors, enhancing the inhibitory effects of GABA by increasing the frequency of chloride channel opening.
| Metabolism | Hepatic via N-dealkylation and hydroxylation (CYP2C19, CYP3A4); major active metabolite is N-desalkylflurazepam. |
| Excretion | Renal: 90% (as metabolites, <1% unchanged); Fecal: <10%; Biliary excretion minimal. |
| Half-life | Terminal elimination half-life: 40-114 hours (mean 74 hours); accumulates extensively with repeated dosing, leading to prolonged sedation. |
| Protein binding | 96-97% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 3.0-6.0 L/kg; high Vd indicates extensive tissue distribution, including brain and adipose tissue. |
| Bioavailability | Oral: 80-90% (high due to minimal first-pass metabolism). |
| Onset of Action | Oral: 15-45 minutes; IV: not clinically used due to prolonged action. |
| Duration of Action | 8-12 hours for hypnotic effect, but residual sedation may persist >24 hours due to active metabolites. |
| Molecular Weight | 460.8 |
15-30 mg orally at bedtime as a single dose for insomnia; maximum dose 30 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | Flurazepam is extensively metabolized and not significantly renally cleared. GFR <30 mL/min: use with caution; no specific dose adjustment recommended but monitor for excessive sedation. |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: avoid use due to risk of severe sedation and encephalopathy. |
| Pediatric use | Not recommended for use in pediatric patients due to lack of safety and efficacy data. |
| Geriatric use | Elderly patients: initial dose 15 mg orally at bedtime; may increase to 15-30 mg if needed. Use with caution due to increased sensitivity and risk of falls. |
| 1st trimester | Avoid. Benzodiazepines are associated with congenital malformations (cleft lip/palate) when used in first trimester; recommend alternative therapy. |
| 2nd trimester | Avoid. Consider if benefit outweighs risk, but use with caution due to teratogenicity and fetal growth concerns. |
| 3rd trimester | Avoid near term. Risk of neonatal toxicity, 'floppy infant syndrome' (hypotonia, sedation), and withdrawal if used chronically. |
Clinical note
CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.
| Placental transfer | Flurazepam and its active metabolite cross the placenta. Detectable concentrations in fetal plasma and amniotic fluid have been reported. The degree of transfer is moderate, with fetal:maternal ratio approx. 0.5-1.0. |
| Breastfeeding | Flurazepam and its active metabolite desalkylflurazepam are excreted into breast milk in low concentrations. However, due to the long half-life of the metabolite (40-100 hours), accumulation in the infant is possible, causing sedation and poor feeding. Manufacturer recommends discontinuing breastfeeding or the drug, especially in neonates or when high doses are used. |
■ FDA Black Box Warning
Concomitant use with benzodiazepines or other CNS depressants may cause profound sedation, respiratory depression, coma, and death.
| Common Effects | Sedation |
| Serious Effects |
Known hypersensitivity to flurazepam or any benzodiazepineNarrow-angle glaucomaSevere hepatic impairment (Child-Pugh class C)Sleep apnea syndromeRespiratory insufficiency or depressionMyasthenia gravis
| Precautions | Risk of dependence and withdrawal, Rebound insomnia, CNS depression effects, Respiratory depression risk, Elderly and debilitated patients: increased risk of falls and cognitive impairment, Anterograde amnesia, Suicidal ideation risk |
| Food/Dietary | Avoid grapefruit and grapefruit juice during flurazepam therapy, as they may inhibit CYP3A4-mediated metabolism of flurazepam, increasing its systemic exposure and risk of toxicity. Concurrent use with alcohol is contraindicated due to additive CNS depression. High-fat meals may delay absorption, but no specific dietary restrictions are required beyond moderation of caffeine intake if insomnia persists. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) - Use with caution; monitor infant for sedation. |
| Teratogenic Risk | First trimester: Increased risk of oral clefts. Second and third trimesters: Risk of neonatal withdrawal, hypotonia, and respiratory depression. Avoid use, especially in first trimester. |
| Fetal Monitoring | Monitor for maternal sedation, respiratory depression, and hypotension. fetal monitoring (ultrasound, NST) for growth abnormalities and movement patterns. Neonatal monitoring for withdrawal symptoms, hypotonia, and respiratory depression. |
| Fertility Effects | No specific data. Benzodiazepines may affect menstrual cyclicity; impact on fertility is unknown. |
| Clinical Pearls | Flurazepam is a long-acting benzodiazepine with active metabolites (desalkylflurazepam) that accumulate with repeated dosing, leading to prolonged sedation and hangover effects, especially in elderly patients. Avoid in severe hepatic impairment due to reduced clearance. Onset of action is slower compared to other benzodiazepines (30–60 min), making it less suitable for as-needed use but effective for sleep maintenance insomnia. Tolerance develops to hypnotic effects within 3–14 days. Abrupt discontinuation after prolonged use may precipitate withdrawal symptoms including rebound insomnia and seizures. |
| Patient Advice | Take flurazepam exactly as prescribed, usually 30 minutes before bedtime, and only when you have at least 7–8 hours to dedicate to sleep. · Do not consume alcohol or other CNS depressants while taking this medication, as it increases risk of severe drowsiness, respiratory depression, and accidents. · Avoid driving or operating heavy machinery until you know how flurazepam affects you, as it may cause daytime drowsiness, dizziness, or impaired coordination. · Do not stop taking this medication abruptly; consult your doctor for a gradual dose reduction to prevent withdrawal symptoms. · Inform your healthcare provider if you are pregnant, planning to become pregnant, or breastfeeding, as flurazepam may cause harm to the fetus or infant. |