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Benzodiazepine (short-acting) Pregnancy: Avoid — risk of neonatal floppy infant syndrome, withdrawal symptoms, and possible cleft lip/palate (1st trimester data conflicting).

Alprazolam

Brand names: Xanax (US)

Adult dose

Dose: Anxiety: 250–500 micrograms TDS; max 3 mg/day in divided doses (specialist initiation only).
Route: Oral
Frequency: Three times daily
Max: 3 mg/day
NOT a UK-licensed product; available on private prescription / specialist supply. NICE does not recommend for routine anxiety management — diazepam or lorazepam preferred where benzodiazepine is unavoidable.

Dose adjustments

Renal

Caution; reduce dose in severe impairment.

Hepatic

Reduce dose 50% in moderate impairment; avoid in severe impairment.

Clinical pearls

  • Short half-life (6–12 h) → high inter-dose anxiety rebound and dependence risk; one of the most addictive benzodiazepines.
  • NOT recommended for new prescription in UK — diazepam (long t½, less rebound) preferred if benzodiazepine truly required.
  • Taper slowly when stopping (10% of dose every 2–4 weeks; longer if long-term use) — withdrawal seizures reported even after low-dose chronic use.
  • If switching from chronic alprazolam, convert to equivalent diazepam dose (1 mg alprazolam ≈ 10 mg diazepam) and taper diazepam.
  • Significant illicit/diverted use — explicit safe-prescribing checks essential.

Contraindications

  • Severe respiratory disease
  • Severe sleep apnoea
  • Myasthenia gravis
  • Acute narrow-angle glaucoma
  • Severe hepatic impairment
  • Pregnancy (relative — neonatal effects) and breastfeeding
  • History of benzodiazepine or alcohol dependence

Side effects

  • Drowsiness, sedation, ataxia
  • Anterograde amnesia
  • Respiratory depression (esp. with opioids — black-box warning)
  • Tolerance and dependence (high — short half-life)
  • Severe withdrawal: seizures, delirium, psychosis (taper essential)
  • Paradoxical agitation, disinhibition
  • Falls, fractures (elderly)
  • Cognitive impairment with chronic use

Interactions

  • Opioids: fatal respiratory depression — FDA/MHRA black-box warning
  • Alcohol: additive CNS / respiratory depression
  • CYP3A4 inhibitors (clarithromycin, itraconazole, ritonavir, grapefruit juice): ↑ alprazolam levels markedly
  • CYP3A4 inducers (rifampicin, carbamazepine, phenytoin): ↓ alprazolam levels — withdrawal
  • Other CNS depressants: additive effects

Monitoring

  • Review need for ongoing prescribing every 2–4 weeks
  • Screen for misuse, diversion, and dependence

Reference: BNF 90; NICE CG113 (GAD); MHRA Drug Safety Update Apr 2020 (benzodiazepines + opioids); Ashton Manual on benzodiazepine withdrawal. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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