Pronunciation
al-PRAY-zoe-lam [Pronunciation]

Trade Name(s)

• Niravam

• Xanax

• Xanax XR

Controlled Substance Schedule
IV

Pregnancy Category
Category D

Ther. class.
antianxiety agents

Pharm. class.
benzodiazepines

• Generalized anxiety disorder (GAD).

• Panic disorder.

• Anxiety associated with depression.

Unlabelled Use(s):

• Management of symptoms of premenstrual syndrome (PMS).

• Insomnia, irritable bowel syndrome (IBS) and other somatic symptoms associated with anxiety.

• Used as an adjunct with acute mania, acute psychosis.

• 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 Effect(s):
Relief of anxiety.

Absorption: Well absorbed (90%) from the GI tract; absorption is slower with extended-release tablets.

Distribution: Widely distributed, crosses blood-brain 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

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(↓ dose required);

• Hepatic impairment (↓ dose required);

• Concurrent use with nefazodone, fluvoxamine, cimetidine, fluoxetine, hormonal contraceptives, diltiazem, isoniazid, erythromycin, clarithromycin, or grapefruit juice (↓ dose may be necessary);

• History of suicide attempt or alcohol/drug dependence, debilitated patients (↓ dose required);

• Pedi: Safety and efficacy not established; ↓ dosage and frequent monitoring required;

• Geri: Appears on Beers list. Elderly patients have ↑ sensitivity to benzodiazepines; associated with ↑ risk of falls and excessive CNS effects (↓ dose required).

CNS: dizziness, drowsiness, lethargy, confusion, hangover, headache, mental depression, paradoxical excitation.

EENT: blurred vision.

GI: constipation, diarrhea, nausea, vomiting, weight gain.

Derm: rash.

Misc: physical dependence, psychological dependence, tolerance.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Drug-Drug

• Alcohol , antidepressants , other benzodiazepines , antihistamines , and opioid analgesics —concurrent use results in ↑ CNS depression.

• Hormonal contraceptives , disulfiram , fluoxetine , isoniazid , metoprolol , propranolol , valproic acid , CYP3A4 inhibitors ( erythromycin , ketoconazole , itraconazole , fluvoxamine , cimetidine , nefazodone ) ↑ levels and effects; dose adjustments may be necessary; concurrent use with ketoconazole and itraconazole contraindicated.

• May ↓ efficacy of levodopa .

• CYP3A4 inducers ( rifampin , carbamazepine , or barbiturates ) ↓ levels and effects.

• Sedative effects may be ↓ by theophylline .

• Cigarette smoking ↓ levels and effects.

Drug-Natural Products
Kava-kava , valerian , or chamomile can ↑ CNS depression.

Drug-Food
Concurrent ingestion of grapefruit juice ↑ levels and effects.

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 be ↑ by 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 be ↑ every 3–4 days by not more than 1 mg/day; up to 10 mg/day (usual range 3–6 mg/day)..

• Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg

» Cost:
Generic: 0.25 mg $17.74/100, 0.5 mg $19.94/100, 1 mg $18.86/100, 2 mg $25.51/100.

• Extended-release tablets: 0.5 mg, 1 mg, 2 mg, 3 mg

» Cost:
Generic: 0.5 mg $71.98/90, 1 mg $196.96/90, 2 mg $219.97/90, 3 mg $309.97/90.

• Orally disintegrating tablets (orange-flavor): 0.25 mg, 0.5 mg, 1 mg, 2 mg

» Cost:
Generic: 0.25 mg $119.97/90, 1 mg $195.97/90.

• Oral solution (concentrate): 1 mg/mL

• Assess degree and manifestations of anxiety and mental status (orientation, mood, behavior) prior to and periodically during therapy.

• Assess patient for drowsiness, light-headedness, and dizziness. These symptoms usually disappear as therapy progresses. Dose should be reduced if these symptoms persist.

• Geri: Assess CNS effects and risk of falls. Institute falls prevention strategies.

• Prolonged high-dose therapy may lead to psychological or physical dependence. Risk is greater in patients taking >4 mg/day. Restrict the amount of drug available to patient. Assess regularly for continued need for treatment.

Lab Test Considerations

• Monitor CBC and liver and renal function periodically during long-term therapy. May cause ↓ hematocrit and neutropenia.

Toxicity and Overdose

• Flumazenil is the antidote for alprazolam toxicity or overdose. (Flumazenil may induce seizures in patients with a history of seizures disorder or who are on tricyclic antidepressants").

• Anxiety (Indications)

• Risk for injury (Side Effects)

• Risk for falls (Side Effects)

• Do not confuse Xanax (alprazolam) with Zantac (ranitidine) or Fanapt (iloperidone).

» Do not confuse alprazolam with lorazepam.

» If early morning anxiety or anxiety between doses occurs, the same total daily dose should be divided into more frequent intervals.

• PO: May be administered with food if GI upset occurs. Administer greatest dose at bedtime to avoid daytime sedation.

» Tablets may be crushed and taken with food or fluids if patient has difficulty swallowing. Do not crush, break, or chew extended-release tablets.

» Taper by 0.5 mg q 3 days to prevent withdrawal. Some patients may require longer tapering period (months).

» For orally disintegrating tablets: Remove tablet from bottle with dry hands just prior to taking medication. Place tablet on tongue. Tablet will dissolve with saliva; may also be taken with water. Remove cotton from bottle and reseal tightly to prevent moisture from entering bottle. If only 1/2 tablet taken, discard unused portion immediately; may not remain stable.

• Instruct patient to take medication as directed; do not skip or double up on missed doses. If a dose is missed, take within 1 hr; otherwise, skip the dose and return to regular schedule. If medication is less effective after a few weeks, check with health care professional; do not increase dose. Abrupt withdrawal may cause sweating, vomiting, muscle cramps, tremors, and seizures.

• May cause drowsiness or dizziness. Caution patient to avoid driving and other activities requiring alertness until response to the medication is known. Geri: Instruct patient and family how to reduce falls risk at home.

• Advise patient to avoid drinking grapefruit juice during therapy.

• Advise patient to avoid the use of alcohol or other CNS depressants concurrently with alprazolam. Instruct patient to consult health care professional before taking Rx, OTC, or herbal products concurrently with this medication.

• Inform patient that benzodiazepines are usually prescribed for short-term use and do not cure underlying problems.

• Teach other methods to decrease anxiety (exercise, support group, relaxation techniques).

• Advise patient to not share medication with anyone.

• Decreased sense of anxiety without CNS side effects.

• Decreased frequency and severity of panic attacks.

• Decreased symptoms of premenstrual syndrome.