alprazolam
(al prah' zoe lam)
Apo-Alpraz (CAN), Novo-Alprazol (CAN), Nu-Alpraz (CAN), Xanax, Xanax TS (CAN)

Pregnancy Category D
C-IV controlled substance

Drug classes
Benzodiazepine
Antianxiety drug

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; oral solution--0.5 mg/5 mL; 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.
· 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.
· Social phobia: 2–8 mg/day PO.
· Premenstrual syndrome: 0.25 mg PO tid.
GERIATRIC PATIENTS OR THOSE WITH DEBILITATING DISEASE
Initially 0.25 mg bid–tid PO; gradually increase if needed and tolerated.

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

Metabolism: Hepatic; T1/2: 6.3–26.9 hr
Distribution: Crosses placenta; passes into 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, oral 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

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 exam; P, BP; liver evaluation, abdominal exam, bowel sounds, normal output; CBC, liver and renal function tests

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

Teaching points
· Take this drug exactly as prescribed.
· Do not drink grapefruit juice while on this drug.
· Do not stop taking drug (long-term therapy) without consulting health care provider.
· Avoid alcohol, sleep-inducing, or OTC drugs.
· These side effects may occur: drowsiness, dizziness (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.