alprazolam

Pregnancy Category D

Controlled Substance C-IV

Drug classes

Benzodiazepine

Anxiolytic

Therapeutic actions

Exact mechanisms of action not understood; main sites of action may be the limbic system and reticular formation; increases the effects of gamma-aminobutyrate, an inhibitory neurotransmitter; anxiety blocking effects occur at doses well below those necessary to cause sedation, ataxia.

Indications

· Management of anxiety disorders, short-term relief of symptoms of anxiety; anxiety associated with depression.

· Treatment of panic attacks with or without agoraphobia

· Unlabeled uses: Social phobia, premenstrual syndrome, depression

Contraindications and cautions

· Contraindicated with hypersensitivity to benzodiazepines, psychoses, acute narrow-angle glaucoma, shock, coma, acute alcoholic intoxication with depression of vital signs, pregnancy (crosses the placenta; risk of congenital malformations, neonatal withdrawal syndrome), labor and delivery ("floppy infant" syndrome), lactation (secreted in breast milk; infants become lethargic and lose weight).

· Use cautiously with impaired liver or kidney function, debilitation.

Available forms

Tablets—0.25, 0.5, 1, 2 mg; XR tablets—0.5, 1, 2, 3 mg; intensol solution—1 mg/mL

Dosages

Individualize dosage; increase dosage gradually to avoid adverse effects.

ADULTS

· Anxiety disorders: Initially, 0.25–0.5 mg PO tid; adjust to maximum daily dose of 4 mg/day in divided doses or extended-release form once per day in the AM once dosage is established.

· Panic disorder: Initially, 0.5 mg PO tid; increase dose at 3- to 4-day intervals in increments of no more than 1 mg/day; ranges of 1–10 mg/day have been needed; extended-release form once per day in AM once dosage is established.

· Social phobia: 2–8 mg/day PO.

· Premenstrual syndrome: 0.25 mg PO tid.

GERIATRIC PATIENTS OR PATIENTS WITH DEBILITATING DISEASE

Initially, 0.25 mg bid–tid PO; gradually increase if needed and tolerated; ER tablets—0.5 mg PO once each day

Pharmacokinetics

Route	Onset	Peak	Duration
Oral	30 min	1–2 hr	4–6 hr

Metabolism: Hepatic; T_1/2: 6.3–26.9 hr

Distribution: Crosses placenta; enters breast milk

Excretion: Urine

Adverse effects

· CNS: Transient, mild drowsiness initially; sedation, depression, lethargy, apathy, fatigue, light-headedness, disorientation, anger, hostility, episodes of mania and hypomania, restlessness, confusion, crying, delirium, headache, slurred speech, dysarthria, stupor, rigidity, tremor, dystonia, vertigo, euphoria, nervousness, difficulty in concentration, vivid dreams, psychomotor retardation, extrapyramidal symptoms; mild paradoxical excitatory reactions during first 2 weeks of treatment

· CV: Bradycardia, tachycardia, cardiovascular collapse, hypertension, hypotension, palpitations, edema

· Dermatologic: Urticaria, pruritus, rash, dermatitis

· EENT: Visual and auditory disturbances, diplopia, nystagmus, depressed hearing, nasal congestion

· GI: Constipation, diarrhea, dry mouth, salivation, nausea, anorexia, vomiting, difficulty in swallowing, gastric disorders, hepatic dysfunction

· GU: Incontinence, urinary retention, changes in libido, menstrual irregularities

· Hematologic: Elevations of blood enzymes—LDH, alkaline phosphatase, AST, ALT; blood dyscrasias—agranulocytosis, leukopenia

· Other: Hiccups, fever, diaphoresis, paresthesias, muscular disturbances, gynecomastia. Drug dependence with withdrawal syndrome when drug is discontinued; more common with abrupt discontinuation of higher dosage used for longer than 4 mo

Interactions

Drug-drug

· Increased CNS depression with alcohol, other CNS depressants, propoxyphene

· Increased effect with cimetidine, disulfiram, omeprazole, isoniazid, hormonal contraceptives, valproic acid

· Decreased effect with carbamazepine, rifampin, theophylline

· Possible increased risk of digitalis toxicity with digoxin

· Decreased antiparkinson effectiveness of levodopa with benzodiazepines

· Contraindicated with ketoconazole, itraconazole; serious toxicity can occur

Drug-food

· Decreased metabolism and risk of toxic effects if combined with grapefruit juice; avoid this combination.

Drug-alternative therapy

· Risk of coma if combined with kava therapy

· Additive sedative effects with valerian root

Nursing considerations

CLINICAL ALERT!

Name confusion has occurred among Xanax (alprazolam), Celexa (citalopram), and Cerebyx (fosphenytoin), and between alprazolam and lorazepam; use caution.

Assessment

· History: Hypersensitivity to benzodiazepines; psychoses; acute narrow-angle glaucoma; shock; coma; acute alcoholic intoxication with depression of vital signs; labor and delivery; lactation; impaired liver or kidney function; debilitation

· Physical: Skin color, lesions; T; orientation, reflexes, affect, ophthalmologic examination; P, BP; liver evaluation, abdominal examination, bowel sounds, normal output; CBC, liver and renal function tests

Interventions

· Arrange to taper dosage gradually after long-term therapy, especially in epileptic patients.

· Do not administer with grapefruit juice.

Teaching points

· Take this drug exactly as prescribed; take ER form once daily in the AM.

· Do not drink grapefruit juice while on this drug.

· Do not stop taking drug (in long-term therapy) without consulting health care provider.

· Avoid alcohol, sleep-inducing, or OTC drugs.

· You may experience these side effects: Drowsiness, dizziness (these effects will be less pronounced after a few days, avoid driving a car or engaging in other dangerous activities if these occur); GI upset (take drug with food); fatigue; depression; dreams; crying; nervousness.

· Report severe dizziness, weakness, drowsiness that persists, rash or skin lesions, difficulty voiding, palpitations, swelling in the extremities.

Adverse effects in Italic are most common; those in Bold are life-threatening.