DIASTAT ACUDIAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIASTAT ACUDIAL (DIASTAT ACUDIAL).
Binds to GABA-A receptors, enhancing GABA effects and increasing chloride ion conductance, leading to neuronal hyperpolarization and inhibition of seizure activity.
| Metabolism | Hepatic via CYP2C19, CYP3A4, and CYP2B6; major metabolite is N-desmethyldiazepam (active); also forms oxazepam and temazepam. |
| Excretion | Primarily renal (urinary) as glucuronide conjugates and unchanged drug; <2% excreted unchanged in feces. |
| Half-life | Terminal elimination half-life: 20-50 hours in adults; prolonged in elderly and patients with hepatic impairment (up to 100 hours). |
| Protein binding | 97-99% bound primarily to albumin. |
| Volume of Distribution | 0.8-1.4 L/kg (adults); reflects extensive distribution into tissues including brain. |
| Bioavailability | Rectal gel: 80-100% relative to intravenous administration. |
| Onset of Action | Rectal administration: 1-5 minutes for anticonvulsant effect (peak plasma concentrations within 1.5 hours). |
| Duration of Action | Duration of anticonvulsant effect: 6-12 hours for a single dose; clinical effects may persist longer with multiple doses due to accumulation. |
| Molecular Weight | 284.7 |
2.5 mg to 20 mg rectally, as a single dose for acute seizure clusters; may repeat once after 4-12 hours if needed. Maximum: 20 mg per treatment episode.
| Dosage form | GEL |
| Renal impairment | No specific dose adjustment provided in labeling; use with caution in severe renal impairment (CrCl < 10 mL/min) due to propylene glycol content. |
| Liver impairment | Dose reduction may be necessary in Child-Pugh Class C cirrhosis; avoid in severe hepatic impairment due to decreased clearance and propylene glycol accumulation. |
| Pediatric use | 2 to 5 years: 0.5 mg/kg rectally; 6 to 11 years: 0.3 mg/kg; 12 years and older: 0.2 mg/kg. Dose per treatment episode not to exceed 20 mg. |
| Geriatric use | Start at lower end of dosing range (2.5-5 mg) due to increased sensitivity and decreased clearance; monitor for excessive sedation and respiratory depression. |
| 1st trimester | Associated with increased risk of major malformations, particularly oral clefts, when used during first trimester. Avoid unless clearly needed. |
| 2nd trimester | May cause fetal benzodiazepine exposure; risk of developmental toxicity. Use only if benefit outweighs risk. |
| 3rd trimester | High doses near term can cause neonatal respiratory depression, hypotonia, and withdrawal. Avoid chronic use. |
Clinical note
Comprehensive clinical and safety monograph for DIASTAT ACUDIAL (DIASTAT ACUDIAL).
| Placental transfer | Diazepam and its active metabolite, desmethyldiazepam, readily cross the placenta. Fetal levels may approach maternal levels after chronic dosing. |
| Breastfeeding | DIASTAT (diazepam) is excreted into breast milk in low amounts; however, chronic use may lead to accumulation in the infant. Monitor for sedation, poor feeding, and weight loss. The American Academy of Pediatrics considers diazepam to be compatible with breastfeeding, but caution is advised with high doses or prolonged use. |
■ FDA Black Box Warning
Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve for patients with inadequate response to alternatives.
| Serious Effects |
Hypersensitivity to diazepam or any benzodiazepineSevere respiratory insufficiency (e.g., COPD, sleep apnea)Acute narrow-angle glaucomaSevere hepatic impairment (e.g., hepatic encephalopathy)Myasthenia gravisKnown substance use disorder with benzodiazepines
| Precautions | Risk of respiratory depression, particularly with high doses or in elderly/chronically ill; tolerance and dependence; withdrawal symptoms; may impair cognitive and motor functions; should not be abruptly discontinued. |
| Food/Dietary | Grapefruit and grapefruit juice may increase diazepam levels and risk of toxicity; avoid concurrent consumption. Alcohol potentiates CNS depression and should be avoided. No other significant food interactions reported. |
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| Lactation Rating | L3 (Moderately Safe) per Hale's lactation risk categories; some sources list as 'Compatible' with caution. |
| Teratogenic Risk | DIASTAT ACUDIAL (diazepam) crosses the placenta. First trimester exposure is associated with a small increased risk of oral clefts (odds ratio ~1.5). In second and third trimesters, chronic use may lead to fetal benzodiazepine exposure; high doses near term can cause neonatal withdrawal (hypertonia, irritability, tremors, poor feeding) and 'floppy infant syndrome' (hypotonia, lethargy, respiratory depression). No known structural teratogenicity in later trimesters. |
| Fetal Monitoring | Monitor maternal CNS and respiratory status. In pregnant patients, assess fetal heart rate and growth if chronic use. Neonates require observation for 2-3 days post-delivery for signs of withdrawal or sedation. Therapeutic drug monitoring of maternal diazepam levels is not routinely required. |
| Fertility Effects | Animal studies: High-dose diazepam may cause alterations in gonadal hormone levels and spermatogenesis in males; females may experience cycle irregularities. Human data limited; no conclusive evidence of impaired fertility in humans with therapeutic use. |
| Clinical Pearls | DIASTAT ACUDIAL is a diazepam rectal gel formulation used for acute repetitive seizures. Administer rectally; position patient on side to reduce aspiration risk. Do not administer more than 5 doses per month or more than 2 doses per single seizure episode. Monitor respiratory depression, especially with concurrent CNS depressants. Onset of action is 5-15 minutes; if seizure persists beyond 15 minutes, seek emergency medical attention. Avoid use in patients with acute narrow-angle glaucoma or severe liver disease. |
| Patient Advice | Use exactly as prescribed; do not exceed recommended doses. · Insert the rectal gel tip gently and hold buttocks together for 1-2 minutes after administration. · Keep a seizure diary to track episodes and medication use. · Do not drive or operate machinery until you know how this medication affects you. · Avoid alcohol and other CNS depressants while using this drug. · Seek medical help if seizures worsen or if breathing difficulties occur. · Store at room temperature away from light and moisture. |