BLACK BOX WARNING
- concomitant use with opioids: concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death
alprazolam
Brand: Xanax, Xanax XR, Niravam
⚠ BBW Beers Criteria Prototype: diazepam
Drug Class: benzodiazepine
Drug Family: benzodiazepine
Subclass: short-to-intermediate acting benzodiazepine
Organ Systems: cns
Mechanism of Action
Binds the benzodiazepine site (alpha subunit/gamma subunit interface) on GABA-A receptors, increasing the FREQUENCY of chloride channel opening in response to GABA, enhancing inhibitory neurotransmission. Produces anxiolytic, sedative, anticonvulsant, and muscle-relaxant effects.
GABA-A receptor (benzodiazepine site)
Indications
- generalized anxiety disorder (GAD)
- panic disorder
- anxiety associated with depression
Contraindications
- acute narrow-angle glaucoma
- concurrent ketoconazole or itraconazole
- pregnancy
- severe hepatic impairment
Adverse Effects
Common
- sedation
- drowsiness
- cognitive impairment
- coordination difficulty
- anterograde amnesia
Serious
- physical dependence and severe withdrawal
- respiratory depression (with opioids)
- paradoxical disinhibition (rage)
- suicidal ideation
Pharmacokinetics (ADME)
| Absorption | oral; bioavailability ~80–90% |
| Distribution | 80% protein bound |
| Metabolism | hepatic via CYP3A4 to inactive metabolites |
| Excretion | renal |
| Half-life | 6–26 hours |
| Onset | 15–30 minutes |
| Peak | 1–2 hours |
| Duration | 4–6 hours |
| Protein Binding | 80% |
| Vd | 0.8–1.2 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| opioids | additive CNS and respiratory depression; risk of fatal respiratory arrest | major |
| CYP3A4 inhibitors (ketoconazole) | dramatically increase alprazolam levels — ketoconazole 3.98-fold; contraindicated | major |
| alcohol | additive CNS depression | major |
Nursing Considerations
- Assess respiratory rate and level of sedation before administration; do not administer if respiratory rate <12/min.
- Instruct patients never to combine with alcohol or opioids; this combination can be fatal.
- Tolerance and dependence develop rapidly with regular use; NOT recommended for long-term anxiety management.
- Discontinue by tapering slowly (no more than 0.5 mg decrease every 3 days); abrupt withdrawal can cause life-threatening seizures.
Clinical Pearls
- Alprazolam has one of the highest abuse and dependence potentials among benzodiazepines due to its rapid onset and short half-life, which produce pronounced pharmacological reinforcement.
- The FDA's black box warning for concurrent opioid use reflects epidemic numbers of overdose deaths from benzodiazepine-opioid combinations; if both must be prescribed, prescribe lowest doses and monitor closely.
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.