DIASTAT ACUDIAL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DIASTAT ACUDIAL (DIASTAT ACUDIAL).

How it works

Binds to GABA-A receptors, enhancing GABA effects and increasing chloride ion conductance, leading to neuronal hyperpolarization and inhibition of seizure activity.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DIASTAT ACUDIAL (DIASTAT ACUDIAL).

Breastfeeding

Diazepam is excreted into breast milk; M/P ratio is approximately 0.1-0.3. Relative infant dose estimated at 1-10% of maternal weight-adjusted dose. Neonatal accumulation possible due to long half-life (50-100 hours in preterm neonates). Breastfeeding is not recommended during chronic use due to risks of sedation, poor feeding, and withdrawal. Short-term, single-dose use may be acceptable with monitoring.

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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to diazepam or benzodiazepines; narrow-angle glaucoma; severe respiratory insufficiency; myasthenia gravis; concomitant use with opioids (except for palliative care).

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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DIASTAT ACUDIAL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DIASTAT ACUDIAL (DIASTAT ACUDIAL).

How it works

Binds to GABA-A receptors, enhancing GABA effects and increasing chloride ion conductance, leading to neuronal hyperpolarization and inhibition of seizure activity.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DIASTAT ACUDIAL (DIASTAT ACUDIAL).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to diazepam or benzodiazepines; narrow-angle glaucoma; severe respiratory insufficiency; myasthenia gravis; concomitant use with opioids (except for palliative care).