VALIUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VALIUM (VALIUM).
Benzodiazepine that enhances the effect of GABA at GABA-A receptors, increasing chloride ion conductance and producing neuronal hyperpolarization.
| Metabolism | Hepatic via CYP3A4 and CYP2C19 to active metabolites (nordiazepam, temazepam, oxazepam); excreted renally. |
| Excretion | Renal: <1% unchanged; hepatic metabolism to active metabolites (desmethyldiazepam, temazepam, oxazepam); metabolites excreted renally as glucuronides. Fecal: minor. |
| Half-life | Terminal elimination half-life of diazepam: 20–50 hours; active metabolite desmethyldiazepam half-life: 36–200 hours (accumulates with chronic dosing, prolonging clinical effects). |
| Protein binding | 98–99% bound to albumin. |
| Volume of Distribution | 0.8–1.5 L/kg; large Vd indicates extensive tissue distribution, including brain and adipose tissue. |
| Bioavailability | Oral: 90–100%; IM: 80–90% (variable due to injection site absorption); rectal: 80–90%. |
| Onset of Action | IV: 1–3 minutes; IM: 15–30 minutes (erratic absorption); oral: 30–60 minutes; rectal: 10–30 minutes. |
| Duration of Action | IV: 15–30 minutes for single dose (rapid redistribution); oral: 3–6 hours for single dose; chronic dosing leads to prolonged duration due to active metabolites. |
| Action Class | Benzodiazepines |
| Brand Substitutes | Zepose 10mg Tablet, Repam 10mg Tablet, Alzepam 10mg Tablet, Dipax 10mg Tablet, D P M 10mg Tablet, Osopose 2mg Tablet, Microdep 2mg Tablet, Equipam 2mg Tablet, Silprex 2mg Tablet, Peptica Tablet |
Oral: 2-10 mg 2-4 times daily. IV/IM: 5-10 mg, repeat in 3-4 hours if needed; max 30 mg in 8 hours.
| Dosage form | TABLET |
| Renal impairment | eGFR 10-50 mL/min: reduce dose by 25-50%; eGFR <10 mL/min: avoid or use with caution. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid. |
| Pediatric use | Neonates: 0.1-0.8 mg/kg/day IM/IV; Children: 0.1-0.3 mg/kg/day oral, 0.2-0.5 mg/kg IV; Max: 10 mg. |
| Geriatric use | Initial dose 2.5 mg once or twice daily; titrate slowly; avoid doses >10 mg daily. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VALIUM (VALIUM).
| Breastfeeding | Diazepam is excreted into breast milk; M/P ratio ≈ 0.1-0.3. Relative infant dose ≈ 4-6% of maternal weight-adjusted dose. May cause sedation, poor feeding, and weight loss in neonates. Avoid use during breastfeeding, especially in preterm infants. |
| Teratogenic Risk | First trimester: Increased risk of cleft lip/palate (OR 1.8-2.3) with oral use; IM/IV use limited data. Second and third trimesters: Risk of hypotonia, respiratory depression, withdrawal symptoms (floppy infant syndrome). Avoid near term/ delivery due to risk of neonatal sedation and withdrawal. |
■ FDA Black Box Warning
Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve for patients without alternative options.
| Serious Effects |
Hypersensitivity to benzodiazepines, severe respiratory insufficiency, sleep apnea syndrome, severe hepatic impairment, acute narrow-angle glaucoma, myasthenia gravis.
| Precautions | Risk of dependence and withdrawal, tolerance, CNS depression, respiratory depression, cognitive impairment, paradoxical reactions, caution in hepatic impairment, elderly, and debilitated patients. |
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| Fetal Monitoring |
| Monitor maternal vital signs, respiratory rate, level of sedation. Fetal monitoring (non-stress test or biophysical profile) for prolonged use. Assess neonatal withdrawal symptoms (e.g., hypertonia, hyperreflexia, poor feeding) after delivery. |
| Fertility Effects | No conclusive evidence of impaired fertility in humans. Animal studies show dose-dependent effects on estrous cycle, mating behavior, and implantation. High doses may disrupt ovulation. |