alprazolam
Alprazolam Intensol, Apo-Alpraz ◆, Novo-Alprazol ◆, Xanax

Available forms
Available by prescription only
Oral solution: 0.1 mg/1 ml
Oral solution (concentrated): 1 mg/1 ml
Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg

Indications and dosages
 Anxiety. Adults: Usual starting dose is 0.25 to 0.5 mg P.O. t.i.d. Increase dose p.r.n. q 3 to 4 days. Maximum total daily dose is 4 mg in divided doses.
≡ Dosage adjustment. For geriatric or debilitated patients or those with hepatic impairment, initial dose is 0.25 mg P.O. b.i.d. or t.i.d.
 Panic disorder. Adults: Initially, 0.5 mg P.O. t.i.d. Increase as needed and tolerated at intervals of 3 to 4 days in increments of 1 mg daily. Most patients require more than 4 mg daily; however, doses from 1 to 10 mg daily have been reported.

Pharmacodynamics
Anxiolytic action: Alprazolam depresses the CNS at the limbic and subcortical levels of the brain. It produces an antianxiety effect by enhancing the effect of the neurotransmitter gamma-aminobutyric acid on its receptor in the ascending reticular activating system, which increases inhibition and blocks both cortical and limbic arousal.

Pharmacokinetics
Absorption: Well absorbed after oral administration.
Distribution: Distributed widely throughout the body. About 80% to 90% bound to plasma protein.
Metabolism: Metabolized in the liver equally to alpha-hydroxyalprazolam and inactive metabolites.
Excretion: Excreted in urine. Half-life of alprazolam is 12 to 15 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other benzodiazepines and in patients with acute angle-closure glaucoma. Use cautiously in patients with hepatic, renal, or pulmonary disease, and in those with a history of drug abuse.

Interactions
Drug-drug. Antidepressants, antihistamines, barbiturates, general anesthetics, MAO inhibitors, narcotics, phenothiazines: Potentiates CNS depressant effects of these drugs. Avoid use together.
Cimetidine, possibly disulfiram: Diminishes hepatic metabolism of alprazolam, increasing its plasma level. Monitor patient carefully.
Digoxin: May increase plasma digoxin level. Monitor serum digoxin level.
Haloperidol: Benzodiazepines may decrease serum haloperidol level. Monitor patient for effect.
Rifampin: May decrease effects of alprazolam. Monitor patient for effect.
Theophylline: May increase sedative effects of alprazolam. Use together cautiously.
Drug-herb. Kava: May induce lethargy, increased CNS effects, or coma. Discourage use together.
Drug-lifestyle. Alcohol use: Potentiates CNS depressant effects of alcohol. Discourage alcohol use.
Heavy smoking: Accelerates alprazolam metabolism, thus lowering clinical effectiveness. Discourage smoking.

Adverse reactions
CNS: drowsiness, light-headedness, minor changes in EEG patterns, headache, confusion, tremor, dizziness, syncope, depression, insomnia, nervousness.
CV: hypotension, tachycardia.
EENT: blurred vision, nasal congestion.
GI: dry mouth, nausea, vomiting, diarrhea, constipation.
Hepatic: liver impairment.
Metabolic: weight gain or loss.
Musculoskeletal: muscle rigidity.
Skin: dermatitis.

Effects on lab test results
• May increase ALT and AST levels.

Overdose and treatment
Signs and symptoms of overdose include somnolence, confusion, coma, hypoactive reflexes, dyspnea, labored breathing, hypotension, bradycardia, slurred speech, unsteady gait, and impaired coordination.
 Support blood pressure and respiration until drug effects subside; monitor vital signs. Flumazenil, a specific benzodiazepine antagonist, may be useful. Mechanical ventilatory assistance via endotracheal tube may be required to maintain a patent airway and support adequate oxygenation. As needed, use I.V. fluids and vasopressors, such as dopamine and phenylephrine, to treat hypotension. If the patient is conscious, induce emesis. Use gastric lavage if ingestion was recent but only if an endotracheal tube is in place to prevent aspiration. After emesis or lavage, administer activated charcoal with a cathartic as a single dose. Dialysis is of limited value. Don’t use barbiturates if excitation occurs because of possible exacerbation of excitation or CNS depression.

Special considerations
• Lower doses are effective in geriatric patients and patients with renal or hepatic dysfunction.
• Anxiety with depression also responds to alprazolam, but patient may need more frequent dosing.
• Paradoxical reaction consisting of excitement, stimulation, and acute rage may occur.
• Monitor patients during prolonged therapy with high doses because they should be weaned from the drug gradually to prevent withdrawal symptoms. A 2- to 3-month withdrawal may be necessary, decreasing at no more than 0.5 mg every 3 days.
• Store drug in a cool, dry place away from direct light.
Breast-feeding patients
• The breast-fed infant of a woman taking alprazolam may become sedated, have feeding difficulties, or lose weight. Avoid use in breast-feeding women.
Pediatric patients
• Closely observe neonate for withdrawal symptoms if mother took alprazolam during pregnancy. Use of alprazolam during labor may cause neonatal flaccidity. Safety hasn’t been established in children or adolescents younger than age 18.
Geriatric patients
• Lower doses are usually effective in geriatric patients because of decreased elimination. During start of therapy or after an increase in dose, geriatric patients who receive drug may need assistance with walking and activities of daily living.

Patient education
• Make sure patient understands potential for physical and psychological dependence with long-term use of alprazolam.
• Instruct patient not to alter drug regimen.
• Warn patient that sudden changes in position can cause dizziness. Advise him to dangle legs for a few minutes before getting out of bed to prevent falls and injury.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use