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
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
- Mental Health: Meds and CommunicationBenzodiazepines and sedative withdrawal: Diazepam: Up to 48 h; metabolite up to 100 h: Self-tapers; accumulates in older adults
- 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
- Sedation, Pain and Delirium ScalesAlcohol withdrawal in the ICU: Benzodiazepines are first-line, cross-tolerant with alcohol at GABA-A. CIWA-Ar symptom-triggered dosing needs a patient who can talk, so in intubated or delirious patients titrate to RASS. Benzodiazepine resistance is commonly defined as needing more than about 50 mg diazepam in the first hour or 200 mg in 3–4 hours; definitions vary.
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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 the order, the label and your institution's protocols.