Yes

Benzodiazepine

Treatment of anxiety disorder (GAD); panic disorder, with or without agoraphobia; anxiety associated with depression

C-IV

D

Hypersensitivity to this drug or any component of its formulation (cross-sensitivity with other benzodiazepines may exist); narrow angle glaucoma; concurrent use of ketoconazole and itraconazole; pregnancy

Rebound or withdrawal symptoms, including seizures may occur 18 hours to 3 days following abrupt discontinuation or large decreases in dose (more common in patients receiving >4 mg/day or prolonged treatment). Dose reductions or tapering must be approached with extreme caution. Between dose, anxiety may also occur. Use with caution in patients receiving concurrent CYP3A4 inhibitors, particularly when these agents are added to therapy. Has weak uricosuric properties, use with caution in renal impairment or predisposition to urate nephropathy. Use with caution in elderly or debilitated patients, patients with hepatic disease (including alcoholics), renal impairment, or obese patients.

Use caution in patients with depression, particularly if suicidal risk may be present. Episodes of mania or hypomania have occurred in depressed patients treated with alprazolam. May cause physical or psychological dependence - use with caution in patients with a history of drug dependence. Acute withdrawal, including seizures, may be precipitated in patients after administration of flumazenil to patients receiving long-term benzodiazepine therapy.

Benzodiazepines have been associated with anterograde amnesia. Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients. Does not have analgesic, antidepressant, or antipsychotic properties.

>10%:

Central nervous system: Drowsiness, fatigue, ataxia, lightheadedness, memory impairment, dysarthria, irritability

Dermatologic: Rash

Endocrine & metabolic: Decreased libido, menstrual disorders

Gastrointestinal: Xerostomia, decreased salivation, increased or decreased appetite, weight gain or loss

Genitourinary: Micturition difficulties

1% to 10%:

Cardiovascular: Hypotension

Central nervous system: Confusion, dizziness, disinhibition, akathisia, increased libido

Dermatologic: Dermatitis

Gastrointestinal: Increased salivation

Genitourinary: Sexual dysfunction, incontinence

Neuromuscular & skeletal: Rigidity, tremor, muscle cramps

Otic: Tinnitus

Respiratory: Nasal congestion

Symptoms of overdose include somnolence, confusion, coma, and diminished reflexes

Treatment for benzodiazepine overdose is supportive. Rarely is mechanical ventilation required; flumazenil has been shown to selectively block the binding of benzodiazepines to CNS receptors, resulting in a reversal of benzodiazepine-induced sedation; however, its use may not alter the course of overdose.

CYP3A3/4 enzyme substrate

Cimetidine, ciprofloxacin, clarithromycin, clozapine, CNS depressants, diltiazem, disulfiram, digoxin, erythromycin, ethanol, fluconazole, fluoxetine, fluvoxamine, grapefruit juice, isoniazid, itraconazole, ketoconazole, labetalol, levodopa, loxapine, metoprolol, metronidazole, miconazole, nefazodone, omeprazole, phenytoin, protease inhibitors like amprenavir and ritonavir, rifabutin, rifampin, troleandomycin, valproic acid, verapamil may increase the serum level and/or toxicity of alprazolam; monitor for altered benzodiazepine response

Binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the central nervous system, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to chloride ions. This shift in chloride ions results in hyperpolarization (a less excitable state) and stabilization.

Onset of action: Within 1 hour

Duration: Variable, 8-24 hours

Distribution: V_d: 0.9-1.2 L/kg; distributes into breast milk

Protein binding: 80%

Metabolism: Extensive in the liver; major metabolite is inactive

Half-life: 12-15 hours

Time to peak serum concentration: Within 1-2 hours

Elimination: Excretion of metabolites and parent compound in urine

Oral:

Adults:

Anxiety: Effective doses are 0.5-4 mg/day in divided doses; the manufacturer recommends starting at 0.25-0.5 mg 3 times/day; titrate dose upward; maximum: 4 mg/day

Depression: Average dose required: 2.5-3 mg/day in divided doses

Alcohol withdrawal: Usual dose: 2-2.5 mg/day in divided doses

Panic disorder: Many patients obtain relief at 2 mg/day, as much as 10 mg/day may be required

Dosing adjustment in hepatic impairment: Reduce dose by 50% to 60% or avoid in cirrhosis

Note: Treatment >4 months should be re-evaluated to determine the patient's need for the drug

Alcohol: May have additive CNS effects, avoid use

Can be given sublingually with comparable onset and completeness of absorption

Respiratory and cardiovascular status

alkaline phosphatase

No information available to require special precautions

Significant dry mouth will occur in over 10% of patients; normal salivary flow occurs with cessation of drug therapy

Take exactly as directed (do not increase dose or frequency); may cause physical and/or psychological dependence. Do not use excessive alcohol, or other prescription or OTC medications (especially pain medications, sedatives, antihistamines, or hypnotics) without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience drowsiness, lightheadedness, impaired coordination, dizziness, or blurred vision (use caution when driving or engaging in hazardous tasks until response to drug is known); nausea, vomiting, or dry mouth (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help); altered sexual drive or ability (reversible); photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). Report persistent CNS effects (eg, confusion, depression, increased sedation, excitation, headache, agitation, insomnia or nightmares, dizziness, fatigue, impaired coordination, changes in personality, or changes in cognition); changes in urinary pattern; muscle cramping, weakness, tremors, or rigidity; ringing in ears or visual disturbances; chest pain, palpitations, or rapid heartbeat; excessive perspiration; excessive GI symptoms (cramping, constipation, vomiting, anorexia); or worsening of condition. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures as recommended by your prescriber. Do not breast-feed.

Assist with ambulation during beginning therapy, raise bed rails and keep room partially illuminated at night; monitor for CNS respiratory depression

Solution, oral: 1 mg/mL (30 mL), 0.5 mg/5 mL (500 mL)

Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg

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Freeman EW, Rickels K, Sondheimer SJ, et al, "A Double-Blind Trial of Oral Progesterone, Alprazolam, and Placebo in Treatment of Severe Premenstrual Syndrome," JAMA, 1995, 274(1):51-7.

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Moulin CH, Rolachon A, Cohard M, et al, "Fulminant Hepatitis Secondary to Alprazolam," Therapie, 1994, 49(4):362-3.

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Prischl F, Donner A, Grimm G, et al, "Value of Flumazenil in Benzodiazepine Self-Poisoning," Med Toxicol Adverse Drug Exp, 1988, 3(4):334-9.

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