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. |
| Molecular Weight | 284.74 |
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 | Risk of congenital malformations, particularly cleft palate, with first trimester exposure. Use only if clearly needed. |
| 2nd trimester | Use with caution; may cause maternal sedation and hypotension. Low doses preferred. |
| 3rd trimester | Risk of neonatal withdrawal, floppy infant syndrome (hypotonia, lethargy, respiratory depression). Avoid near term. |
Clinical note
CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.
| FDA category | Positive |
| Placental transfer | Crosses placenta readily; fetal serum levels equal or exceed maternal levels. |
| Breastfeeding |
■ 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 diazepam or any componentSevere respiratory insufficiencyMyasthenia gravisSevere hepatic impairmentAcute narrow-angle glaucomaSleep apnea syndrome
| 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. |
| Food/Dietary | Avoid alcohol and grapefruit juice. Alcohol potentiates CNS depression and can cause severe sedation and respiratory depression. Grapefruit juice may increase diazepam absorption and peak concentration, leading to enhanced effects. No other significant food interactions; however, taking with food may slow absorption but does not affect overall bioavailability. |
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| Diazepam and its active metabolite desmethyldiazepam are excreted into breast milk. Infant serum levels can reach up to 10% of maternal levels. Monitor for sedation, poor feeding, and weight gain. |
| Lactation Rating | L3 |
| Teratogenic Risk | 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. |
| Clinical Pearls | DIAZEPAM INTENSOL is a concentrated oral solution (5 mg/mL) for patients who require precise, low-volume dosing or cannot swallow tablets. Use a calibrated dropper; do not dilute in large volumes to avoid precipitation. Onset of action is rapid (15–30 minutes) due to liquid formulation. Caution in elderly and hepatic impairment; reduce dose by 50%. Avoid abrupt discontinuation to prevent withdrawal seizures. Monitor for respiratory depression, especially in combination with opioids or alcohol. |
| Patient Advice | Use only the dropper provided to measure your dose; do not use a household spoon. · Mix the dose with a small amount of water, juice, or soft food (like applesauce) and take it right away. · Do not drink alcohol while taking this medication; it can increase side effects like drowsiness and breathing problems. · This medication can cause drowsiness, dizziness, and blurred vision; do not drive or operate machinery until you know how it affects you. · Do not stop taking this medication suddenly; your doctor will tell you how to slowly decrease the dose to avoid withdrawal symptoms. · Keep this medicine out of reach of children; it can cause severe sedation and breathing problems if accidentally taken. · Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. |