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Bedside Snapshot
  • Core dose: Seizures: 0.15–0.2 mg/kg IV (max 10 mg) at ≤5 mg/min, may repeat once; agitation: 2–10 mg IV titrated to effect; alcohol withdrawal: 10–20 mg IV/PO every 5–15 min until calm; rectal 0.5 mg/kg (max 20 mg) if no IV
  • Onset/duration: IV onset 1–3 min, rectal 5–10 min; anticonvulsant effect ~15–30 min after single IV bolus due to redistribution; elimination half-life 20–50 h (active metabolites 30–100+ h)
  • Key danger: Respiratory depression/apnea (especially with opioids or alcohol); hypotension; accumulation with repeated dosing (long-acting metabolites); paradoxical agitation (rare); avoid IM (erratic absorption)
  • Special: Benzodiazepine (GABA_A positive allosteric modulator); high lipophilicity → rapid CNS penetration but redistributes quickly; can use rectal route if no IV; flumazenil is reversal agent (use cautiously in seizure patients); propylene glycol vehicle
Brand & Generic Names
  • Generic Name: diazepam (oral/IV/rectal)
  • Brand Names: Valium (PO/IV), Diastat/Diastat AcuDial (rectal gel)
Medication Class

Benzodiazepine; anticonvulsant, anxiolytic, sedative-hypnotic, muscle relaxant

Pharmacology

Mechanism of Action:

  • Positive allosteric modulator of GABA_A receptors at the benzodiazepine site
  • Rapid CNS penetration due to high lipophilicity
  • Anticonvulsant effect is fast but redistributes from brain to peripheral tissues within ~15–30 min after IV dose

Pharmacokinetics (clinically relevant):

  • Onset: IV 1–3 min; PR ~5–10 min; IM is erratic/slow—avoid for emergencies
  • Duration (anticonvulsant): ~15–30 min after single IV bolus due to redistribution (despite long elimination half-life)
  • Half-life: diazepam ~20–50 h; active metabolite desmethyldiazepam (nordiazepam) 30–100+ h → accumulation with repeated dosing, especially elderly/hepatic impairment
  • Metabolism: hepatic (CYP2C19, CYP3A4) to desmethyldiazepam, temazepam, oxazepam
  • Protein binding: highly protein bound (~98–99%)
  • Elimination: hepatic/biliary; renal excretion of metabolites. Not dialyzable in overdose to any meaningful degree
Indications
  • Status epilepticus/acute repetitive seizures
  • Sedation and agitation control in hyperadrenergic states (e.g., stimulant toxicity), serotonin syndrome (adjunct), and tetanus
  • Alcohol withdrawal/DTs (symptom-triggered or loading strategies)
  • Muscle spasm (e.g., severe back spasm) and spasticity (adjunct)
  • Chemical agent/nerve agent seizure control (CANA auto-injector; military/CBRN protocols)
Conditions Treated
  • Status epilepticus
  • Acute repetitive seizures
  • Stimulant toxicity (agitation control)
  • Serotonin syndrome
  • Alcohol withdrawal syndrome / Delirium tremens
  • Severe muscle spasm and spasticity
  • Tetanus
  • Nerve agent exposure (seizure control)
Dosing & Administration

Available Forms:

  • Injection: 5 mg/mL (2 mL = 10 mg; 10 mL = 50 mg)
  • Rectal gel (Diastat): weight-based prefilled doses (2.5–20 mg)
  • Oral tablets: 2 mg, 5 mg, 10 mg

Adult Dosing:

Indication Dose Notes
Status epilepticus/active seizure 0.15–0.2 mg/kg IV (max 10 mg) at ≤5 mg/min May repeat once after 5–10 min. If IV unavailable, PR 0.5 mg/kg (max 20 mg)
Acute agitation/hyperadrenergic toxicity 2–10 mg IV Repeat titrated to effect and BP/respiratory status
Alcohol withdrawal 10–20 mg IV/PO every 5–15 min until calm but arousable Then scheduled/PRN per CIWA or ICU protocol; high cumulative doses may be required
Muscle spasm 2–10 mg PO/IV every 6–8 h as needed Use lowest effective dose

Pediatric Dosing:

  • Seizure: IV/IO 0.2 mg/kg (max 10 mg), may repeat once; PR 0.5 mg/kg (max 20 mg)
  • Rectal gel (Diastat) rescue: 0.2–0.5 mg/kg with rounding to prefilled strengths; one repeat dose after 4–12 h per labeling/protocol

Administration:

  • Administer undiluted IV push into a large vein; avoid mixing with other drugs/fluids
  • Injection is nonaqueous and incompatible with many solutions—administer via slow IV push into a running line
  • Do not mix with other medications
Contraindications

Contraindications:

  • Acute narrow-angle glaucoma
  • Severe respiratory insufficiency without ventilatory support
  • Hypersensitivity to benzodiazepines

Boxed Warnings:

  • Concomitant use with opioids may cause profound sedation, respiratory depression, coma, and death
  • Risk of abuse, misuse, and addiction
  • Physical dependence and withdrawal reactions

Precautions:

  • Use caution in hepatic impairment (risk of oversedation/encephalopathy)
  • Elderly (falls, delirium)
  • Sleep apnea
  • Myasthenia gravis
  • Substance use disorders
  • Pregnancy (neonatal CNS/respiratory depression if used near delivery)
  • Avoid routine IM route (erratic absorption, tissue irritation)
Opioid Combination: Concomitant use with opioids increases risk of profound sedation, respiratory depression, coma, and death.
Adverse Effects

Dose-related CNS Depression:

  • Somnolence
  • Ataxia
  • Confusion
  • Anterograde amnesia
  • Paradoxical agitation (rare)

Cardiorespiratory:

  • Respiratory depression, especially with other CNS depressants or rapid IV push
  • Hypotension

Local:

  • Pain, thrombophlebitis
  • Propylene glycol–containing injection can cause hypotension/metabolic acidosis with high cumulative dosing
Drug Interactions
  • Opioids, alcohol, antihistamines, antipsychotics, other sedatives: Additive CNS/respiratory depression
  • CYP3A4/CYP2C19 inhibitors (fluconazole, fluoxetine, omeprazole, cimetidine, clarithromycin): May increase diazepam levels
  • CYP inducers (rifampin, carbamazepine): May decrease effect
  • Clozapine: Avoid during acute titration (respiratory/circulatory collapse reported); monitor closely if necessary
Clinical Pearls
Status Epilepticus: Follow diazepam with a longer-acting antiepileptic (e.g., levetiracetam, fosphenytoin, valproate) because anticonvulsant effect of a single bolus is short (redistribution).
Route Selection: Prefer IV/IO or rectal over IM for emergencies. If only IM route is available, midazolam is preferred.
Alcohol Withdrawal: Titrate using symptom-triggered protocols when possible; diazepam's long half-life smooths rebound between doses.
Flumazenil Caution: Avoid flumazenil in undifferentiated overdose or chronic benzodiazepine users—can precipitate refractory seizures; reserve for select iatrogenic cases with airway secured.
Stimulant Toxicity/Serotonin Syndrome: Benzodiazepines are first-line to control agitation and autonomic hyperactivity; treat hyperthermia with external cooling (avoid antipsychotics in severe stimulant toxicity).
Administration Compatibility: Injection is nonaqueous and incompatible with many solutions—administer undiluted via slow IV push into a running line; do not mix with other medications.
References
  • 1. Papadopoulos, J. (2008). Pocket guide to critical care pharmacotherapy. Humana Press.
  • 2. Medscape. (n.d.). Diazepam (Valium, Diastat) – drug monograph & dosing. Retrieved 2025-11-12, from https://reference.medscape.com
  • 3. Medscape. (n.d.). Status epilepticus: Treatment & management. Retrieved 2025-11-12, from https://emedicine.medscape.com
  • 4. Medscape. (n.d.). Alcohol withdrawal syndrome: Treatment. Retrieved 2025-11-12, from https://emedicine.medscape.com
  • 5. DrugBank Online. (n.d.). Diazepam (DB00829). Retrieved 2025-11-12, from https://go.drugbank.com/drugs/DB00829
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