DIASTAT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIASTAT (DIASTAT).
Diazepam enhances the effect of gamma-aminobutyric acid (GABA) at GABA-A receptors, increasing chloride ion conductance and neuronal hyperpolarization, leading to anxiolytic, sedative, muscle relaxant, and anticonvulsant effects.
| Metabolism | Primarily hepatic via CYP2C19 and CYP3A4; active metabolite desmethyldiazepam (with long half-life); minor pathways include glucuronidation. |
| Excretion | Renal (primarily as glucuronide and sulfate conjugates; <5% unchanged), biliary/fecal minimal |
| Half-life | 30–60 hours for diazepam; nordazepam (active metabolite) 50–120 hours. Prolonged in elderly, liver disease, and neonates |
| Protein binding | 98–99%; primarily albumin |
| Volume of Distribution | 0.8–1.0 L/kg; increased in obesity (1.5–2.5 L/kg), redistribution to adipose tissue prolongs half-life |
| Bioavailability | Rectal: 90% (relative to IV, complete absorption). Oral: 100% |
| Onset of Action | Rectal: 2–10 minutes (seizure termination). IV: 1–3 minutes. Oral: 30–60 minutes |
| Duration of Action | Seizure control: 12–24 hours (due to active metabolites). Clinical sedation: 2–4 hours initially, but prolonged with accumulation |
| 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 |
Adult: 0.2 mg/kg (max 20 mg) rectally as a single dose; may repeat once after 4-12 hours if needed. Maximum cumulative dose: 40 mg per 24-hour period.
| Dosage form | GEL |
| Renal impairment | No specific dose adjustment required for renal impairment; however, use with caution in severe impairment (CrCl <10 mL/min) due to prolonged half-life. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50%. Child-Pugh Class C: Reduce dose by 75% or avoid use. |
| Pediatric use | Children 2-5 years: 0.5 mg/kg (max 20 mg) rectally. Children 6-11 years: 0.3 mg/kg (max 20 mg) rectally. Children 12+ years: same as adult dosing. May repeat once after 4-12 hours if needed. Maximum cumulative dose: 40 mg per 24-hour period. |
| Geriatric use | Initiate at lower end of dosing range (e.g., 0.1-0.15 mg/kg, max 10 mg) due to increased sensitivity and risk of falls; monitor for prolonged sedation and respiratory depression. |
| 1st trimester | Diazepam (active metabolite) associated with increased risk of congenital malformations, particularly oral clefts, when used in first trimester. Avoid unless compelling indication. |
| 2nd trimester | Use only if clearly needed; may cause hypotonia, respiratory depression in neonate if given near term. |
| 3rd trimester | Avoid in late third trimester due to risk of neonatal withdrawal, hypotonia, respiratory depression, and poor feeding. |
Clinical note
Comprehensive clinical and safety monograph for DIASTAT (DIASTAT).
| Placental transfer | Diazepam readily crosses the placenta with fetal serum concentrations equal to maternal levels. Active metabolite accumulates in fetal circulation. |
| Breastfeeding | Diazepam and its active metabolite (desmethyldiazepam) are excreted into breast milk in small amounts. Accumulation in infants, especially with prolonged use, may lead to sedation, poor feeding, and weight loss. Use with caution; consider alternative agents. |
■ FDA Black Box Warning
Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.
| Serious Effects |
Hypersensitivity to diazepam or benzodiazepinesMyasthenia gravisSevere respiratory insufficiencySleep apnea syndromeSevere hepatic insufficiencyAcute narrow-angle glaucoma
| Precautions | Risk of respiratory depression, especially with concomitant CNS depressants; tolerance and physical dependence may develop; withdrawal symptoms including seizures after abrupt discontinuation; caution in elderly, debilitated patients, and those with hepatic impairment; may cause drowsiness or dizziness; not recommended for use in pregnancy (neonatal withdrawal). |
| Food/Dietary | No specific food interactions. Avoid grapefruit juice as it may increase diazepam levels. Alcohol can potentiate CNS depression. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | DIASTAT (diazepam) is classified as Pregnancy Category D. First trimester: Increased risk of congenital malformations, particularly cleft lip and palate, when used during the first trimester. Second and third trimesters: Chronic use may lead to fetal dependence and withdrawal symptoms postnatally; risk of floppy infant syndrome (hypotonia, lethargy, sucking difficulties) when administered near term. |
| Fetal Monitoring | Monitor maternal vital signs, sedation level, and respiratory status. In chronic use, monitor fetal growth and development via ultrasound. Neonatal monitoring for signs of floppy infant syndrome (hypotonia, lethargy, respiratory depression) and withdrawal symptoms (irritability, tremors, hypertonicity) after birth. |
| Fertility Effects | No direct evidence of impaired fertility in humans. Animal studies report no significant adverse effects on fertility at therapeutic doses. Diazepam may affect menstrual cycles at high doses, but clinical significance is unclear. |
| Clinical Pearls | DIASTAT (diazepam rectal gel) is a formulation for acute management of seizure clusters. Administer rectally; monitor for respiratory depression, especially with concomitant CNS depressants. Do not exceed 5 doses per month or use for more than 5 episodes per month due to tolerance risk. Have flumazenil available for reversal. |
| Patient Advice | Use only as directed for episodes of increased seizure activity. · Administer rectally; do not reuse diapers/suppositories. · Monitor for drowsiness, dizziness, or breathing problems. · Avoid alcohol and other CNS depressants. · Store at room temperature; protect from light. · Seek emergency care if seizures last longer than usual or breathing is difficult. |