What is the half-life of alprazolam (Xanax)?

Half-Life of Alprazolam (Xanax)

The half-life of alprazolam is approximately 11.2 hours (range: 6.3-26.9 hours) in healthy adults, according to the FDA drug label. 1

Pharmacokinetic Profile

Alprazolam, a triazolobenzodiazepine, has the following pharmacokinetic characteristics:

• Absorption: Rapidly absorbed after oral administration with peak plasma concentrations occurring in 1-2 hours 1
• Distribution: Volume of distribution is 0.8-1.3 L/kg 2
• Protein binding: Approximately 80% bound to serum proteins, primarily albumin 1
• Metabolism: Extensively metabolized by cytochrome P450 3A4 (CYP3A4) to two major metabolites:
  • 4-hydroxyalprazolam
  • α-hydroxyalprazolam
  • Both metabolites have lower potency than the parent compound and appear in plasma at less than 10% of alprazolam concentrations 1, 2
• Elimination: Primarily excreted in urine 1

Factors Affecting Half-Life

The half-life of alprazolam varies significantly in certain populations:

• Elderly patients: Mean half-life increases to 16.3 hours (range: 9.0-26.9 hours) 1
• Alcoholic liver disease: Half-life ranges between 5.8-65.3 hours (mean: 19.7 hours) 1
• Obesity: Half-life ranges between 9.9-40.4 hours (mean: 21.8 hours) 1
• Race: Half-life is approximately 25% higher in Asians compared to Caucasians 1
• Smoking: Alprazolam concentrations may be reduced by up to 50% in smokers 1

Drug Interactions Affecting Half-Life

Several medications can significantly alter alprazolam's half-life through CYP3A4 inhibition or induction:

• CYP3A4 inhibitors (increase alprazolam concentrations):

  • Ketoconazole (3.98-fold increase in AUC)
  • Itraconazole (2.70-fold increase)
  • Nefazodone (1.98-fold increase)
  • Fluvoxamine (1.96-fold increase)
  • Erythromycin (1.61-fold increase) 1

• CYP3A4 inducers (decrease alprazolam concentrations):

  • Carbamazepine can shorten the elimination half-life from 17.1 to 7.7 hours 1

Clinical Implications

The relatively long half-life of alprazolam has important clinical implications:

• Less frequent dosing may be required compared to shorter-acting benzodiazepines
• Risk of accumulation with repeated dosing, particularly in elderly patients or those with hepatic impairment
• Potential for withdrawal symptoms if discontinued abruptly after prolonged use
• Dosage adjustments are necessary for elderly patients and those with hepatic impairment

Understanding alprazolam's half-life is crucial for appropriate dosing, especially when considering its use in special populations or with concomitant medications that may affect its metabolism.