ALPRAZolam, Xanax, Xanax XR

 Indications

Generalized anxiety disorder (GAD). Panic disorder.

Anxiety associated with depression. Unlabeled Use:

Management of symptoms of premenstrual syndrome

(PMS) and premenstrual dysphoric disorder. Insomnia, irritable bowel syndrome (IBS), and other somatic

symptoms associated with anxiety. Used as an adjunct

with acute mania, acute psychosis.

Action

Acts at many levels in the CNS to produce anxiolytic effect.

May produce CNS depression. Effects may be mediated

by GABA, an inhibitory neurotransmitter. Therapeutic

Effects: Relief of anxiety.

Pharmacokinetics

Absorption: Well absorbed (90%) from the GI tract;

absorption is slower with extended-release tablets.

Distribution: Widely distributed, crosses bloodbrain

barrier. Probably crosses the placenta and enters

breast milk. Accumulation is minimal.

Metabolism and Excretion: Metabolized by the

liver (CYP3A4 enzyme system) to an active compound

that is subsequently rapidly metabolized.

Half-life: 12–15 hr.

TIME/ACTION PROFILE (sedation)

ROUTE ONSET PEAK DURATION

PO 1–2 hr 1–2 hr up to 24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Cross-sensitivity

with other benzodiazepines may exist; Pre-existing

CNS depression; Severe uncontrolled pain; Angle-closure

glaucoma; Obstructive sleep apnea or pulmonary

disease; Concurrent use with itraconazole or ketoconazole;

OB, Lactation: Use in pregnancy or lactation may

cause CNS depression, flaccidity, feeding difficulties,

and seizures in infant.

Use Cautiously in: Renal impairment (pdose required);

Hepatic impairment (pdose required); Concurrent

use with nefazodone, fluvoxamine, cimetidine,

fluoxetine, hormonal contraceptives, diltiazem, isoniazid,

erythromycin, clarithromycin, or grapefruit juice

(pdose may be necessary); History of suicide attempt

or alcohol/drug dependence, debilitated patients (p

dose required); Geri: Appears on Beers list. Elderly patients

haveqsensitivity to benzodiazepines; associated

withqrisk of falls and excessive CNS effects (pdose required);

Pedi: Safety and effectiveness not established.

Adverse Reactions/Side Effects

CNS: dizziness, drowsiness, lethargy, confusion, depression,

hangover, headache, paradoxical excitation.

EENT: blurred vision. GI: constipation, diarrhea,

nausea, vomiting, weight gain. Derm: rash. Misc:

physical dependence, psychological dependence, tolerance.

Interactions

Drug-Drug: Use with opioids or other CNS depressants,

including otherbenzodiazepines, nonbenzodiazepine

sedative/hypnotics, anxiolytics,

general anesthetics, muscle relaxants, antipsychotics,

and alcohol may cause profound sedation, respiratory depression, coma, and death; reserve concurrent

use for when alternative treatment options are

inadequate. Hormonal contraceptives, disulfiram,

fluoxetine, isoniazid, metoprolol, propranolol,

valproic acid, CYP3A4 inhibitors (erythromycin,

ketoconazole, itraconazole, fluvoxamine, cimetidine,

nefazodone)qlevels and effects; dose adjustments

may be necessary; concurrent use with ketoconazole

and itraconazole contraindicated. Maypefficacy

of levodopa. CYP3A4 inducers (rifampin, carbamazepine,

or barbiturates)plevels and effects. Sedative

effects may bepby theophylline. Cigarette

smokingplevels and effects.

Drug-Natural Products: Kava-kava, valerian,

or chamomile canqCNS depression.

Drug-Food: Concurrent ingestion of grapefruit

juiceqlevels and effects.

Route/Dosage

Anxiety

PO (Adults): 0.25–0.5 mg 2–3 times daily (not to exceed

4 mg/day).

PO (Geriatric Patients): Begin with 0.25 mg 2–3

times daily.

Panic Attacks

PO (Adults): 0.5 mg 3 times daily; may beqby 1 mg

or less every 3–4 days as needed (not to exceed 10

mg/day). Extended–release tablets—0.5–1 mg once

daily in the morning, may beqevery 3–4 days by not

more than 1 mg/day; up to 10 mg/day (usual range 3–

6 mg/day).

Availability (generic available)

Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg. Cost: Generic—

0.25 mg $10.59/100, 0.5 mg $5.25/100, 1 mg

$10.41/100, 2 mg $15.13/100. Extended-release

tablets: 0.5mg, 1 mg, 2 mg, 3 mg. Cost: Generic—1

mg $54.05/180, 2 mg $86.76/180, 3 mg $319.38/60.

Orally disintegrating tablets (orange-flavor):

0.25 mg, 0.5 mg, 1 mg, 2 mg. Cost: Generic—0.25

mg $151.73/100, 0.5 mg $189.04/100, 1 mg $252.22/

100, 2 mg $428.86/100. Oral solution (concentrate):

1 mg/mL. Cost: Generic—$81.10/30 mL.