BLACK BOX WARNING
- concurrent use with opioids increases risk of profound sedation, respiratory depression, coma, and death
diazepam
Brand: Valium, Diastat, Valtoco
⚠ BBW ISMP High Alert Beers Criteria Prototype Drug
Drug Class: benzodiazepine
Drug Family: benzodiazepine
Subclass: long-acting benzodiazepine
Organ Systems: cns
Mechanism of Action
Positive allosteric modulator of GABA-A receptors; binds the benzodiazepine site between alpha and gamma subunits, increasing the frequency of chloride channel opening and enhancing inhibitory neurotransmission.
GABA-A receptor (benzodiazepine binding site)
Indications
- anxiety disorders
- acute alcohol withdrawal
- muscle spasm
- status epilepticus (IV/rectal)
- preoperative sedation
Contraindications
- myasthenia gravis
- severe respiratory insufficiency
- sleep apnea
- severe hepatic insufficiency
- acute narrow-angle glaucoma
Adverse Effects
Common
- sedation
- dizziness
- ataxia
- anterograde amnesia
- muscle weakness
Serious
- respiratory depression
- coma
- paradoxical reactions (agitation, aggression)
- dependence and withdrawal
Pharmacokinetics (ADME)
| Absorption | Well absorbed orally (~93%); IM absorption erratic |
| Distribution | Highly lipophilic; Vd 0.8–1.0 L/kg; crosses BBB rapidly; extensive distribution to adipose tissue |
| Metabolism | Hepatic via CYP2C19 and CYP3A4 to active metabolites including desmethyldiazepam (t1/2 36–200 h) and oxazepam |
| Excretion | Renal as glucuronide conjugates |
| Half-life | 20–100 hours (parent); active metabolites 36–200 hours |
| Onset | IV: 1–3 minutes; oral: 30–60 minutes |
| Peak | 1–2 hours (oral) |
| Duration | Variable (prolonged due to active metabolites) |
| Protein Binding | ~98% |
| Vd | 0.8–1.0 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| opioids | additive CNS/respiratory depression; boxed warning combination | major |
| alcohol | additive CNS depression | major |
| flumazenil | competitive antagonist reverses benzodiazepine effects | moderate |
Nursing Considerations
- IV administration: inject slowly (<5 mg/min in adults); have resuscitation equipment available; monitor respiratory rate and oxygen saturation continuously
- Assess fall risk before administration, especially in elderly patients; Beers Criteria drug — avoid for chronic use in older adults
- Monitor for paradoxical reactions (more common in children, elderly, and patients with brain damage) — increased anxiety, agitation, aggression
- Counsel patients about dependence risk; do not abruptly discontinue after prolonged use — taper over weeks to months to prevent withdrawal seizures
Clinical Pearls
- Diazepam's long half-life and active metabolites make it particularly useful for alcohol withdrawal (self-tapering) but problematic in the elderly due to accumulation
- In status epilepticus, IV lorazepam is often preferred over diazepam due to its longer CNS duration of action despite diazepam's faster onset
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.