Alprazolam

Action

Unclear. Thought to act at limbic, thalamic, and hypothalamic levels of CNS to produce sedative, anxiolytic, skeletal muscle relaxant, and anticonvulsant effects.

Availability

Solution: 1 mg/ml

Tablets (extended-release): 0.5 mg, 1 mg, 2 mg, 3 mg

Tablets (immediate-release): 0.25 mg, 0.5 mg, 1 mg, 2 mg

Tablets (orally disintegrating): 0.25 mg, 0.5 mg, 1 mg, 2 mg

Indications and dosages

➣ Anxiety disorders

Adults: Initially, 0.25 to 0.5 mg P.O. t.i.d. Maximum dosage is 4 mg daily in divided doses.

Elderly patients: Initially, 0.25 mg P.O. two or three times daily. Maximum dosage is 4 mg daily in divided doses.

➣ Panic disorders

Adults: Immediate-release or orally disintegrating tablets-Initially, 0.5 mg P.O. t.i.d. Extended-release tablets-Initially, 0.5 to 1 mg P.O. daily. Usual dosage is 3 to 6 mg daily, with a maximum dosage of 10 mg daily. For all dosage forms, increase by a maximum of 1 mg daily at intervals of 3 to 4 days, with a maximum of 10 mg daily in divided doses.

Dosage adjustment

• Hepatic impairment

Off-label uses

• Agoraphobia

• Depression

• Premenstrual syndrome

Contraindications

• Hypersensitivity to benzodiazepines

• Narrow-angle glaucoma

• Labor and delivery

• Pregnancy or breastfeeding

Precautions

Use cautiously in:

• hepatic dysfunction

• history of attempted suicide or drug dependence

• elderly patients.

Administration

• Don't give with grapefruit juice.

• Make sure patient swallows extended-release tablets whole without chewing or crushing.

• Mix oral solution with liquids or semisolid foods and instruct patient to consume entire amount immediately.

• Administer orally disintegrating tablets by placing tablet on patient's tongue. If only one-half of scored tablet is used, discard unused portion immediately.

☞ Don't withdraw drug suddenly. Seizures and other withdrawal symptoms may occur unless dosage is tapered carefully.

Adverse reactions

CNS: dizziness, drowsiness, depression, fatigue, light-headedness, disorientation, anger, hostility, euphoria, hypomanic episodes, restlessness, confusion, crying, delirium, headache, stupor, rigidity, tremor, paresthesia, vivid dreams, extrapyramidal symptoms

CV: bradycardia, tachycardia, hypertension, hypotension, palpitations, CV collapse

EENT: blurred or double vision, nystagmus, nasal congestion

GI: gastric disorders, dysphagia, anorexia, increased salivation, dry mouth

GU: menstrual irregularities, urinary retention, urinary incontinence, libido changes, gynecomastia

Hematologic: blood dyscrasias such as eosinophilia, agranulocytosis, leukopenia, and thrombocytopenia

Hepatic: hepatic dysfunction (including hepatitis)

Musculoskeletal: muscle rigidity, joint pain

Skin: dermatitis, rash, pruritus, urticaria, increased sweating

Other: weight loss or gain, hiccups, fever, edema, psychological drug dependence, drug tolerance

Interactions

Drug-drug. Antidepressants, antihistamines, opioids, other benzodiazepines: increased CNS depression

Barbiturates, rifampin: increased metabolism and decreased efficacy of alprazolam

Cimetidine, disulfiram, erythromycin, fluoxetine, hormonal contraceptives, isoniazid, ketoconazole, metoprolol, propoxyphene, propranolol, valproic acid: decreased metabolism and increased action of alprazolam

Digoxin: increased risk of digoxin toxicity

Levodopa: decreased antiparkinsonian effect

Theophylline: increased sedative effect

Tricyclic antidepressants (TCAs): increased TCA blood levels

Drug-diagnostic tests. Itraconazole, ketoconazole: increased alprazolam plasma level

Drug-food. Grapefruit juice: decreased drug metabolism and increased blood level

Drug-herbs. Chamomile, hops, kava, skullcap, valerian: increased CNS depression

Drug-behaviors. Alcohol use: increased CNS depression

Smoking: decreased alprazolam efficacy

Patient monitoring

• Watch for excessive CNS depression if patient is concurrently taking antidepressants, other benzodiazepines, antihistamines, or opioids.

• If patient is taking TCAs concurrently, watch for increase in adverse TCA effects.

• Monitor CBC and liver and kidney function test results.

• Monitor vital signs and weight.

• Report signs of drug abuse, including frequent requests for early refills.

Patient teaching

• Instruct patient to swallow extended- release tablets whole without crushing or chewing.

☞ Tell patient that drug may make him more depressed, angry, or hostile. Urge him to contact prescriber immediately if he thinks he's dangerous to himself or others.

• Inform patient that drug may cause tremors, muscle rigidity, and other movement problems. Advise him to report these effects to prescriber.

☞ Caution patient not to stop taking drug suddenly. Withdrawal symptoms, including seizures, may occur unless drug is tapered carefully.

• Advise patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.