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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.
| Breastfeeding | Flurazepam and its active metabolite are excreted in breast milk. M/P ratio not established. Neonatal accumulation may lead to sedation and feeding difficulties. Breastfeeding not recommended. |
| 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 |
■ 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 |
["Hypersensitivity to flurazepam or other benzodiazepines","Narrow-angle glaucoma","Severe respiratory insufficiency","Myasthenia gravis","Severe hepatic impairment","Pregnancy (especially first and third trimesters)","Concurrent use with opioids or other severe CNS depressants"]
| 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"] |
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| 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. |