DIAZEPAM INTENSOL
Clinical safety rating: avoid
CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.
Benzodiazepine that potentiates GABA-A receptor activity by binding to the benzodiazepine site, increasing chloride ion conductance and neuronal inhibition.
| Metabolism | Hepatic via CYP2C19 and CYP3A4 to active metabolite N-desmethyldiazepam; further metabolized to oxazepam and temazepam. |
| Excretion | Renal excretion of metabolites (primarily glucuronide conjugates) accounts for ~70% of elimination; fecal excretion accounts for ~10%; unchanged drug in urine is <1%. |
| Half-life | Terminal elimination half-life is 20–50 hours (mean ~30 hours) in adults, with significant interindividual variability; prolonged in elderly, hepatic impairment, and neonates (up to 100 hours). |
| Protein binding | 98% bound to albumin. |
| Volume of Distribution | 0.8–1.0 L/kg (range 0.6–1.5 L/kg); high Vd indicates extensive tissue distribution, including CNS. |
| Bioavailability | Oral (Intensol): 93–100%. |
| Onset of Action | Oral (Intensol): 15–30 minutes; intramuscular: 15–30 minutes (absorption may be erratic); intravenous: 1–3 minutes. |
| Duration of Action | Oral: 6–8 hours for anxiolytic effect; IV: 20–30 minutes for anticonvulsant effect (due to rapid redistribution). Accumulation occurs with repeated dosing, prolonging duration. |
2 to 10 mg orally 2 to 4 times daily, as needed for anxiety or muscle spasm; 10 mg orally before procedures for sedation. Maximum 40 mg/day.
| Dosage form | CONCENTRATE |
| Renal impairment | No specific dose adjustment required for mild to moderate impairment; use with caution in severe impairment (CrCl <10 mL/min) and consider reducing dose by 50%. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use or use with extreme caution, reduce dose by 75%. |
| Pediatric use | 6 months to 12 years: 0.1-0.3 mg/kg/dose orally every 6-8 hours as needed; maximum 10 mg/day. For status epilepticus: IV/IO/IM: 0.15-0.2 mg/kg/dose, max 10 mg/dose; may repeat once. |
| Geriatric use | Initial dose 2 to 2.5 mg orally 1 to 2 times daily, increase gradually as needed; maximum 20 mg/day. Use lowest effective dose to avoid excessive sedation, ataxia, and falls. Avoid long-term use. |
| 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.
| FDA category | Positive |
| Breastfeeding | Diazepam and its metabolite desmethyldiazepam are excreted into breast milk. M/P ratio approximately 0.1-0.5. Infant serum levels may reach 10-50% of maternal levels. Risk of sedation, poor feeding, and weight loss in the infant. Chronic use is not recommended; single doses may be acceptable with monitoring. |
| Teratogenic Risk |
■ FDA Black Box Warning
Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve co-prescription for patients without alternative treatments.
| Common Effects | alcohol withdrawal |
| Serious Effects |
Hypersensitivity to benzodiazepines; severe respiratory insufficiency; sleep apnea syndrome; narrow-angle glaucoma; myasthenia gravis; pregnancy (high doses near term).
| Precautions | Risk of dependence and withdrawal; respiratory depression especially with IV use; caution in hepatic impairment; avoid abrupt discontinuation; may impair cognitive and motor function. |
Loading safety data…
| First Trimester: Risk of oral clefts (OR 1.8-2.2) and congenital malformations, especially with early exposure. Second/Third Trimester: Risk of hypotonia, respiratory depression, feeding difficulties, and temperature dysregulation in the neonate (floppy infant syndrome) with chronic use. Avoid in first trimester if possible; use lowest effective dose in later trimesters. |
| Fetal Monitoring | Monitor maternal liver function, CBC, and signs of sedation. Fetal monitoring: ultrasound for growth and anatomy. Neonatal monitoring: Apgar scores, signs of withdrawal (e.g., irritability, hypertonia) or oversedation (lethargy, poor suck). |
| Fertility Effects | No direct evidence of impaired fertility in humans. Animal studies show no significant effect on fertility. Diazepam may affect hormonal regulation at high doses, but clinical significance is unknown. |