Benzodiazepine · Antiepileptic · Alcohol withdrawal
Diazepam (Valium)
Also called Valium
Indications
- Status epilepticus, first-line IV alongside lorazepam and IM midazolam (AES 2016)
- Seizure clusters without IV access, as rectal gel or nasal spray
- Acute alcohol withdrawal (label), including front-loading in severe cases
- Muscle spasm and tetanus (label)
- Sedation for endoscopy or cardioversion (label)
- Stimulant toxicity (off-label)
Dosing
| Where | Dose |
|---|---|
| Seizures and neuro | Diazepam: 0.15–0.2 mg/kg IV (max 10 mg), repeat once |
| Benzodiazepine equivalence | Diazepam: 5 mg (fast IV onset; long active metabolites) |
On the quick cards
- Diazepam (Valium, Diastat)EMS Field Drugs: Neuro and seizure: IV or rectal benzodiazepine
- Benzodiazepine equivalenceEquivalents and Conversions: Approximate equal doses
Mechanism of action
Diazepam binds the benzodiazepine site between an α subunit (α1, α2, α3 or α5) and the γ2 subunit in the extracellular domain of the GABA-A receptor. It raises the receptor's affinity for GABA so the chloride channel opens more often, and it needs GABA to work. Spinal GABA-A receptors with α2 and α3 subunits mediate its muscle relaxation. Its active metabolites act at the same site, which extends its effect and stacks it with repeated doses.
Pharmacology
- CNS: rapid anticonvulsant, anxiolytic and sedative effect; the anticonvulsant effect fades in 20–30 min as the drug moves into fat, so seizures can recur
- Respiratory: dose-related depression and apnea, worse with opioids, alcohol and stacked doses
- Cardiovascular: little effect at usual doses; hypotension with rapid injection or large doses
- Other: centrally mediated muscle relaxation; the propylene glycol and ethanol vehicle causes pain, phlebitis and venous thrombosis
Pharmacokinetics
| Onset | IV 1–3 min; IM slow and erratic |
|---|---|
| Duration | Anticonvulsant effect 20–30 min after an IV dose, ended by redistribution |
| Half-life | Terminal up to 48 h (label); longer with age and 2–5 times longer in cirrhosis |
| Distribution | Vd 0.8–1.0 L/kg; very lipophilic with a large fat reservoir; crosses the placenta |
| Protein binding | 98% |
| Metabolism | CYP2C19 and CYP3A4 N-demethylation to desmethyldiazepam; CYP3A4 hydroxylation to temazepam; both become oxazepam (all three active), then glucuronides |
| Clearance | Low, 20–30 mL/min in young adults (label) |
| Elimination | Urine, mainly as glucuronides |
| Active metabolite | Desmethyldiazepam: half-life up to 100 h (label); it builds up over days and outlasts diazepam |
| Routes | IV, rectal gel, nasal spray and oral (over 90% absorbed); avoid IM |
Chemistry
- 7-chloro-1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, the prototype benzodiazepine; removing the N1-methyl group yields desmethyldiazepam
- pKa 3.4: un-ionized at body pH and very lipophilic, which explains the fast onset, rapid redistribution and fat reservoir
- Insoluble in water: the injection is 5 mg/mL in 40% propylene glycol, 10% ethanol, benzoate buffer and 1.5% benzyl alcohol, pH 6.2–6.9
- Do not dilute or mix it, because it precipitates; PVC bags and tubing absorb it, so infusions are impractical
Adverse effects and cautions
In the one-pagers
- Behavioral Emergencies, Agitation and AbuseSedation: the full NASEMSO list and BETA rationale: NASEMSO adult doses and onsets: diazepam 5 mg IV (2-5 min) or 10 mg IM (15-30 min); lorazepam 2 mg IV (2-5 min) or 4 mg IM (15-30 min); midazolam 5 mg IV (3-5 min), IM (10-15 min) or IN (3-5 min); droperidol 2.5 mg IV (10 min) or 5-10 mg IM (20 min), an option for high violence risk; haloperidol 5 mg IV (5-10 min) or 5-10 mg IM (10-20 min), limit
- Neuro: ICP and StrokeStatus epilepticus: IV alternative: Diazepam 0.15 mg/kg, max 10 mg
- Obstetric EmergenciesPreeclampsia with severe features, eclampsia and HELLP: Collaborative Eclampsia Trial 1995: 1,680 with eclampsia: Recurrence 52% lower than diazepam, 67% than phenytoin
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In the algorithms
Other benzodiazepine drugs
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Sources
- FDA label: Diazepam injection (Hospira, 2023)
- FDA label: Valium (2026)
- PubChem: diazepam
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow your local protocols and medical direction.