Alprazolam

Therapeutic actions

Exact mechanisms of action not understood; main sites of action may be the limbic system and reticular formation; increases the effects of GABA, 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; oral solution—1 mg/mL; rapidly disintegrating tablets—0.25, 0.5, 1, 2 mg

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 theAM once dosage is established (immediate release, intensol solution).
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 (Xanax products, Niravam).

UNLABELED USES

Social phobia: 2–8 mg/day PO.
PMS: 0.25 mg PO tid.

GERIATRIC PATIENTS OR PATIENTS WITH ADVANCED HEPATIC OR 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 wk of treatment
CV: Bradycardia, tachycardia, CV 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 impairment
GU: Incontinence, changes in libido, urinary retention, 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

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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 alprazolamand 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, LFTs, renal function tests

Interventions

Arrange to taper dosage gradually after long-term therapy, especially in epileptic patients.
Do not administer with grapefruit juice.
Taper drug slowly; decrease by no more than 0.5 mg every 3 days.

Teaching points

Take this drug exactly as prescribed; take extended-release form once a day in the morning; place rapidly disintegrating tablet on top of tongue, where it will disintegrate and can be swallowed with saliva.
Do not drink grapefruit juice while on this drug.
Do not stop taking drug (in long-term therapy) without consulting health care provider; drug should not be stopped suddenly.
Avoid alcohol, sleep-inducing, or over-the-counter 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.

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