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. |
| Molecular Weight | 284.74 |
| 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 | Increased risk of congenital malformations, particularly cleft palate, with first trimester exposure. |
| 2nd trimester | Use only if clearly needed; may cause fetal CNS depression and withdrawal symptoms. |
| 3rd trimester | Risk of neonatal sedation, withdrawal, and floppy infant syndrome; avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for VALIUM (VALIUM).
| Placental transfer | Crosses placenta readily; cord blood levels equal maternal levels. |
| Breastfeeding | Diazepam and its active metabolite excreted into breast milk; may cause sedation, feeding difficulties, and weight loss in infants. Avoid or use lowest dose for shortest duration. |
| Lactation Rating |
■ 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 |
Myasthenia gravisSevere respiratory insufficiencySleep apnea syndromeSevere hepatic dysfunctionAcute narrow-angle glaucomaKnown hypersensitivity to benzodiazepines
| Precautions | Risk of dependence and withdrawal, tolerance, CNS depression, respiratory depression, cognitive impairment, paradoxical reactions, caution in hepatic impairment, elderly, and debilitated patients. |
| Food/Dietary | Avoid or limit grapefruit and grapefruit juice as they may increase diazepam levels. Caffeine may reduce sedative effects. Alcohol potentiates CNS depression and should be avoided. Take with food if gastrointestinal upset occurs. |
Loading safety data…
| L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls | Valium (diazepam) has a long half-life (20-100 hours) and active metabolites (desmethyldiazepam), leading to accumulation with repeated dosing. Avoid in narrow-angle glaucoma. Use with caution in hepatic impairment due to reduced clearance. Administer IV slowly (5 mg/min) to prevent hypotension or respiratory depression. Flumazenil is the reversal agent for overdose. Tolerance develops to sedative effects; withdrawal can be severe including seizures. |
| Patient Advice | Do not drink alcohol while taking Valium as it can increase sedation and risk of overdose. · Avoid driving or operating machinery until you know how Valium affects you; it may cause drowsiness or dizziness. · Take Valium exactly as prescribed; do not increase dose or stop suddenly without consulting your doctor to avoid withdrawal symptoms like anxiety, insomnia, or seizures. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding; Valium may cause harm to the fetus or infant. · Store Valium at room temperature away from moisture and heat, and keep out of reach of children. |