Alprazolam

Dosage Forms And Strengths

0.25 mg, 0.5 mg, 1.0 mg, and 2.0 mg scored orally disintegrating tablets

Storage And Handling

NIRAVAM (alprazolam orally disintegrating tablets) 0.25 mg are yellow, round, orange-flavored, scored and engraved “SP 321” on the unscored side and “0.25” on the scored side. They are supplied as follows: Bottles of 100 NDC 18860-321-01

NIRAVAM (alprazolam orally disintegrating tablets) 0.5 mg are yellow, round, orange-flavored, scored and engraved “SP 322” on the unscored side and “0.5” on the scored side. They are supplied as follows: Bottles of 100 NDC 18860-322-01

NIRAVAM (alprazolam orally disintegrating tablets) 1 mg are white, round, orange-flavored, scored and engraved “SP 323” on the unscored side and “1” on the scored side. They are supplied as follows: Bottles of 100 NDC 18860-323-01

NIRAVAM (alprazolam orally disintegrating tablets) 2 mg are white, round, orange-flavored, scored and engraved “SP 324” on the unscored side and “2” on the scored side. They are supplied as follows: Bottles of 100 NDC 18860-324-01

Storage

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Protect from moisture.

Dispense in a tight container as defined in the USP/NF.

Manufactured for: Azur Pharma, Inc. Philadelphia, PA 19103, USA. By: CIMA® LABS INC. Eden Prairie, MN 55344, USA

Pharmacodynamics

CNS agents of the 1,4 benzodiazepine class presumably exert their effects by binding at stereo specific receptors at several sites within the central nervous system. Their exact mechanism of action is unknown. Clinically, all benzodiazepines cause a dose-related central nervous system depressant activity varying from mild impairment of task performance to hypnosis.

Pharmacokinetics

Following oral administration, alprazolam is readily absorbed. Peak concentrations in the plasma occur in 1 to 2 hours following administration. Plasma levels are proportionate to the dose given; over the dose range of 0.5 to 3.0 mg, peak levels of 8.0 to 37 ng/mL were observed. Using a specific assay methodology, the mean plasma elimination half-life of alprazolam has been found to be about 11.2 hours (range: 6.3–26.9 hours) in healthy adults.

In vitro, alprazolam is bound (80 percent) to human serum protein. Serum albumin accounts for the majority of the binding.

Alprazolam is extensively metabolized in humans, primarily by cytochrome P450 3A4 (CYP3A4), to two major metabolites in the plasma: 4-hydroxyalprazolam and α-hydroxyalprazolam. A benzophenone derived from alprazolam is also found in humans. Their half-lives appear to be similar to that of alprazolam. The plasma concentrations of 4-hydroxyalprazolam and α-hydroxyalprazolam relative to unchanged alprazolam concentration were always less than 4%. The reported relative potencies in benzodiazepine receptor binding experiments and in animal models of induced seizure inhibition are 0.20 and 0.66, respectively, for 4-hydroxyalprazolam and α-hydroxyalprazolam. Such low concentrations and the lesser potencies of 4-hydroxyalprazolam and α-hydroxyalprazolam suggest that they are unlikely to contribute much to the pharmacological effects of alprazolam. The benzophenone metabolite is essentially inactive.

Alprazolam and its metabolites are excreted primarily in the urine.

Special Populations

Changes in the absorption, distribution, metabolism and excretion of benzodiazepines have been reported in a variety of disease states including alcoholism, impaired hepatic function and impaired renal function. Changes have also been demonstrated in geriatric patients. A mean half-life of alprazolam of 16.3 hours has been observed in healthy elderly subjects (range: 9.0–26.9 hours, n=16) compared to 11.0 hours (range: 6.3–15.8 hours, n=16) in healthy adult subjects. In patients with alcoholic liver disease the half-life of alprazolam ranged between 5.8 and 65.3 hours (mean: 19.7 hours, n=17) as compared to between 6.3 and 26.9 hours (mean=11.4 hours, n=17) in healthy subjects. In an obese group of subjects the half-life of alprazolam ranged between 9.9 and 40.4 hours (mean=21.8 hours, n=12) as compared to between 6.3 and 15.8 hours (mean=10.6 hours, n=12) in healthy subjects.

Because of its similarity to other benzodiazepines, it is assumed that alprazolam undergoes transplacental passage and that it is excreted in human milk.

Maximal concentrations and half-life of alprazolam are approximately 15% and 25% higher in Asians compared to Caucasians.

The pharmacokinetics of alprazolam in pediatric patients have not been studied.

Gender has no effect on the pharmacokinetics of alprazolam.

Alprazolam concentrations may be reduced by up to 50% in smokers compared to non-smokers.

Drug-Drug Interactions

Alprazolam is primarily eliminated by metabolism via cytochrome P450 3A (CYP3A). Most of the interactions that have been documented with alprazolam are with drugs that inhibit or induce CYP3A4.

Compounds that are potent inhibitors of CYP3A would be expected to increase plasma alprazolam concentrations. Drug products that have been studied in vivo, along with their effect on increasing alprazolam AUC, are as follows: ketoconazole, 3.98 fold; itraconazole, 2.70 fold; nefazodone, 1.98 fold; fluvoxamine, 1.96 fold; and erythromycin, 1.61 fold (see CONTRAINDICATIONS, WARNINGS, and DRUG INTERACTIONS).

CYP3A inducers would be expected to decrease alprazolam concentrations and this has been observed in vivo. The oral clearance of alprazolam (given in a 0.8 mg single dose) was increased from 0.90±0.21 mL/min/kg to 2.13±0.54 mL/min/kg and the elimination t was shortened (from 17.1±4.9 to 7.7 ±1.7 h) following administration of 300 mg/day carbamazepine for 10 days (see DRUG INTERACTIONS). However, the carbamazepine dose used in this study was fairly low compared to the recommended doses (1000–1200 mg/day); the effect at usual carbamazepine doses is unknown.

Interactions involving HIV protease inhibitors (eg, ritonavir) and alprazolam are complex and time dependent. Short-term low doses of ritonavir (4 doses of 200 mg) reduced alprazolam clearance to 41% of control values, prolonged its elimination half-life (mean values, 30 versus 13 h) and enhanced clinical effects. However, upon extended exposure to ritonavir (500 mg, twice daily), CYP3A induction offset this inhibition. Alprazolam AUC and Cmax was reduced by 12% and 16%, respectively, in the presence of ritonavir (see WARNINGS).

The ability of alprazolam to induce human hepatic enzyme systems has not yet been determined. However, this is not a property of benzodiazepines in general. Further, alprazolam did not affect the prothrombin or plasma warfarin levels in male volunteers administered sodium warfarin orally.

Clinical Studies

XANAX Tablets were compared to placebo in double blind clinical studies (doses up to 4 mg/day) in patients with a diagnosis of anxiety or anxiety with associated depressive symptomatology. XANAX was significantly better than placebo at each of the evaluation periods of these 4-week studies as judged by the following psychometric instruments: Physician's Global Impressions, Hamilton Anxiety Rating Scale, Target Symptoms, Patient's Global Impressions and Self-Rating Symptom Scale.

Support for the effectiveness of XANAX in the treatment of panic disorder came from three short-term, placebo-controlled studies (up to 10 weeks) in patients with diagnoses closely corresponding to DSMIII- R criteria for panic disorder.

The average dose of XANAX was 5–6 mg/day in two of the studies, and the doses of XANAX were fixed at 2 and 6 mg/day in the third study. In all three studies, XANAX was superior to placebo on a variable defined as "the number of patients with zero panic attacks" (range, 37–83% met this criterion), as well as on a global improvement score. In two of the three studies, XANAX was superior to placebo on a variable defined as "change from baseline on the number of panic attacks per week" (range, 3.3– 5.2), and also on a phobia rating scale. A subgroup of patients who were improved on XANAX during short-term treatment in one of these trials was continued on an open basis up to 8 months, without apparent loss of benefit.

Animal Studies

When rats were treated with alprazolam at 3, 10, and 30 mg/kg/day (15 to 150 times the maximum recommended human dose) orally for 2 years, a tendency for a dose related increase in the number of cataracts was observed in females and a tendency for a dose related increase in corneal vascularization was observed in males. These lesions did not appear until after 11 months of treatment.

XANAX XR Tablets contain alprazolam which is a triazolo analog of the 1,4 benzodiazepine class of central nervous system-active compounds.

The chemical name of alprazolam is 8-chloro-1-methyl-6-phenyl-4H-s-triazolo [4,3-α] [1,4] benzodiazepine. The molecular formula is C17H3ClN4 which corresponds to a molecular weight of 308.76.

The structural formula is represented below:

Alprazolam is a white crystalline powder, which is soluble in methanol or ethanol but which has no appreciable solubility in water at physiological pH.

Each XANAX XR extended-release tablet, for oral administration, contains 0.5 mg, 1 mg, 2 mg, or 3 mg of alprazolam. The inactive ingredients are lactose, magnesium stearate, colloidal silicon dioxide, and hypromellose. In addition, the 1 mg and 3 mg tablets contain D & C yellow No. 10 and the 2 mg and 3 mg tablets contain FD&C blue No. 2.

Alprazolam may be found in some form under the following brand names:

• Niravam

• Xanax

• Xanax XR

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. Talk to your doctor about drinking grapefruit juice while taking this medicine. 

Tell your doctor if you are breastfeeding or plan to breastfeed. Benzodiazepines are known to be excreted in human milk. Because of the possibility for adverse reactions in nursing infants from alprazolam, a choice should be made whether to stop nursing or to stop use of alprazolam. Determining the importance of the drug to the mother should be considered.

Benzodiazepine; anxiolytic.b c

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Anxiety Disorders

Management of anxiety disorders or short-term relief of anxiety or anxiety associated with depressive symptoms.b c

Panic Disorder

Management of panic disorder, with or without agoraphobia.

Cancer Chemotherapy-induced Nausea and Vomiting

Adjunct in the management of nausea and vomiting associated with emetogenic cancer chemotherapy†b (including cisplatin); b currently not recommended as monotherapy.b

May be useful in the management of anticipatory emesis†.c

Anxiety Disorders

Alprazolam tablets were compared to placebo in double blind clinical studies (doses up to 4 mg/day) in patients with a diagnosis of anxiety or anxiety with associated depressive symptomatology. Alprazolam was significantly better than placebo at each of the evaluation periods of these 4-week studies as judged by the following psychometric instruments: Physician’s Global Impressions, Hamilton Anxiety Rating Scale, Target Symptoms, Patient’s Global Impressions and Self-Rating Symptom Scale.

Panic Disorder

Support for the effectiveness of Alprazolam in the treatment of panic disorder came from three short-term, placebo-controlled studies (up to 10 weeks) in patients with diagnoses closely corresponding to DSM-III-R criteria for panic disorder.

The average dose of Alprazolam was 5 mg/day to 6 mg/day in two of the studies, and the doses of Alprazolam were fixed at 2 and 6 mg/day in the third study. In all three studies, Alprazolam was superior to placebo on a variable defined as "the number of patients with zero panic attacks" (range, 37% to 83% met this criterion), as well as on a global improvement score. In two of the three studies, Alprazolam was superior to placebo on a variable defined as "change from baseline on the number of panic attacks per week" (range, 3.3 to 5.2), and also on a phobia rating scale. A subgroup of patients who were improved on Alprazolam during short-term treatment in one of these trials was continued on an open basis up to 8 months, without apparent loss of benefit.

General

Suicide

As with other psychotropic medications, the usual precautions with respect to administration of the drug and size of the prescription are indicated for severely depressed patients or those in whom there is reason to expect concealed suicidal ideation or plans. Panic disorder has been associated with primary and secondary major depressive disorders and increased reports of suicide among untreated patients.

Mania

Episodes of hypomania and mania have been reported in association with the use of Alprazolam in patients with depression.

Uricosuric Effect

Alprazolam has a weak uricosuric effect. Although other medications with weak uricosuric effect have been reported to cause acute renal failure, there have been no reported instances of acute renal failure attributable to therapy with Alprazolam.

Use in Patients with Concomitant Illness

It is recommended that the dosage be limited to the smallest effective dose to preclude the development of ataxia or oversedation which may be a particular problem in elderly or debilitated patients (see DOSAGE AND ADMINISTRATION). The usual precautions in treating patients with impaired renal, hepatic or pulmonary function should be observed. There have been rare reports of death in patients with severe pulmonary disease shortly after the initiation of treatment with Alprazolam. A decreased systemic Alprazolam elimination rate (e.g., increased plasma half-life) has been observed in both alcoholic liver disease patients and obese patients receiving Alprazolam (see CLINICAL PHARMACOLOGY).

Information for Patients

For all users of Alprazolam:

To assure safe and effective use of benzodiazepines, all patients prescribed Alprazolam should be provided with the following guidance.

1. Advise both patients and caregivers about the risks of potentially fatal respiratory depression and sedation when Alprazolam is used with opioids and not to use such drugs concomitantly unless supervised by a health care provider.
2. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined (see Drug Interactions).
3. Inform your physician about any alcohol consumption and medicine you are taking now, including medication you may buy without a prescription. Alcohol should generally not be used during treatment with benzodiazepines.
4. Not recommended for use in pregnancy. Therefore, inform your physician if you are pregnant, if you are planning to have a child, or if you become pregnant while you are taking this medication.
5. Inform your physician if you are nursing.
6. Until you experience how this medication affects you, do not drive a car or operate potentially dangerous machinery, etc.
7. Do not increase the dose even if you think the medication "does not work anymore" without consulting your physician. Benzodiazepines, even when used as recommended, may produce emotional and/or physical dependence.
8. Do not stop taking this medication abruptly or decrease the dose without consulting your physician, since withdrawal symptoms can occur.

Additional advice for panic disorder patients:

The use of Alprazolam at doses greater than 4 mg/day, often necessary to treat panic disorder, is accompanied by risks that you need to carefully consider. When used at doses greater than 4 mg/day, which may or may not be required for your treatment, Alprazolam has the potential to cause severe emotional and physical dependence in some patients and these patients may find it exceedingly difficult to terminate treatment. In two controlled trials of 6 to 8 weeks duration where the ability of patients to discontinue medication was measured, 7 to 29% of patients treated with Alprazolam did not completely taper off therapy. In a controlled postmarketing discontinuation study of panic disorder patients, the patients treated with doses of Alprazolam greater than 4 mg/day had more difficulty tapering to zero dose than patients treated with less than 4 mg/day. In all cases, it is important that your physician help you discontinue this medication in a careful and safe manner to avoid overly extended use of Alprazolam.

In addition, the extended use at doses greater than 4 mg/day appears to increase the incidence and severity of withdrawal reactions when Alprazolam is discontinued. These are generally minor but seizure can occur, especially if you reduce the dose too rapidly or discontinue the medication abruptly. Seizure can be life-threatening.

Laboratory Tests

Laboratory tests are not ordinarily required in otherwise healthy patients. However, when treatment is protracted, periodic blood counts, urinalysis, and blood chemistry analyses are advisable in keeping with good medical practice.

Drug Interactions

Use with Opioids

The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and monitor patients closely for respiratory depression and sedation.

Use with Other CNS Depressants

If Alprazolam tablets are to be combined with other psychotropic agents or anticonvulsant drugs, careful consideration should be given to the pharmacology of the agents to be employed, particularly with compounds which might potentiate the action of benzodiazepines. The benzodiazepines, including Alprazolam, produce additive CNS depressant effects when co-administered with other psychotropic medications, anticonvulsants, antihistaminics, ethanol and other drugs which themselves produce CNS depression.

Use with Imipramine and Desipramine

The steady state plasma concentrations of imipramine and desipramine have been reported to be increased an average of 31% and 20%, respectively, by the concomitant administration of Alprazolam tablets in doses up to 4 mg/day. The clinical significance of these changes is unknown.

Drugs that inhibit Alprazolam metabolism via cytochrome P450 3A

The initial step in Alprazolam metabolism is hydroxylation catalyzed by cytochrome P450 3A (CYP3A). Drugs which inhibit this metabolic pathway may have a profound effect on the clearance of Alprazolam (see CONTRAINDICATIONS and WARNINGS for additional drugs of this type).

Drugs demonstrated to be CYP3A inhibitors of possible clinical significance on the basis of clinical studies involving Alprazolam (caution is recommended during coadministration with Alprazolam)

Fluoxetine - Coadministration of fluoxetine with Alprazolam increased the maximum plasma concentration of Alprazolam by 46%, decreased clearance by 21%, increased half-life by 17%, and decreased measured psychomotor performance.

Propoxyphene - Coadministration of propoxyphene decreased the maximum plasma concentration of Alprazolam by 6%, decreased clearance by 38%, and increased half-life by 58%.

Oral Contraceptives - Coadministration of oral contraceptives increased the maximum plasma concentration of Alprazolam by 18%, decreased clearance by 22%, and increased half-life by 29%.

Drugs and other substances demonstrated to be CYP 3A inhibitors on the basis of clinical studies involving benzodiazepines metabolized similarly to Alprazolam or on the basis of in vitro studies with Alprazolam or other benzodiazepines (caution is recommended during coadministration with Alprazolam)

Available data from clinical studies of benzodiazepines other than Alprazolam suggest a possible drug interaction with Alprazolam for the following: diltiazem, isoniazid, macrolide antibiotics such as erythromycin and clarithromycin, and grapefruit juice. Data from in vitro studies of Alprazolam suggest a possible drug interaction with Alprazolam for the following: sertraline and paroxetine. However, data from an in vivo drug interaction study involving a single dose of Alprazolam 1 mg and steady state dose of sertraline (50 to 150 mg/day) did not reveal any clinically significant changes in the pharmacokinetics of Alprazolam. Data from in vitro studies of benzodiazepines other than Alprazolam suggest a possible drug interaction for the following: ergotamine, cyclosporine, amiodarone, nicardipine, and nifedipine. Caution is recommended during the coadministration of any of these with Alprazolam (see WARNINGS).

Drugs demonstrated to be inducers of CYP3A

Carbamazepine can increase Alprazolam metabolism and therefore can decrease plasma levels of Alprazolam.

Drug/Laboratory Test Interactions

Although interactions between benzodiazepines and commonly employed clinical laboratory tests have occasionally been reported, there is no consistent pattern for a specific drug or specific test.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of carcinogenic potential was observed during 2-year bioassay studies of Alprazolam in rats at doses up to 30 mg/kg/day (150 times the maximum recommended daily human dose of 10 mg/day) and in mice at doses up to 10 mg/kg/day (50 times the maximum recommended daily human dose).

Alprazolam was not mutagenic in the rat micronucleus test at doses up to 100 mg/kg, which is 500 times the maximum recommended daily human dose of 10 mg/day. Alprazolam also was not mutagenic in vitro in the DNA Damage/Alkaline Elution Assay or the Ames Assay.

Alprazolam produced no impairment of fertility in rats at doses up to 5 mg/kg/day, which is 25 times the maximum recommended daily human dose of 10 mg/day.

Pregnancy

Teratogenic Effects: Pregnancy Category D: (See WARNINGS section).

Nonteratogenic Effects: It should be considered that the child born of a mother who is receiving benzodiazepines may be at some risk for withdrawal symptoms from the drug during the postnatal period. Also, neonatal flaccidity and respiratory problems have been reported in children born of mothers who have been receiving benzodiazepines.

Labor and Delivery

Alprazolam has no established use in labor or delivery.

Nursing Mothers

Benzodiazepines are known to be excreted in human milk. It should be assumed that Alprazolam is as well. Chronic administration of diazepam to nursing mothers has been reported to cause their infants to become lethargic and to lose weight. As a general rule, nursing should not be undertaken by mothers who must use Alprazolam.

Pediatric Use

Safety and effectiveness of Alprazolam in individuals below 18 years of age have not been established.

Geriatric Use

The elderly may be more sensitive to the effects of benzodiazepines. They exhibit higher plasma Alprazolam concentrations due to reduced clearance of the drug as compared with a younger population receiving the same doses. The smallest effective dose of Alprazolam should be used in the elderly to preclude the development of ataxia and oversedation (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

NDC 0228-2027-10

Alprazolam Tablets, USP  CIV

0.25 mg

PHARMACIST: Dispense the Medication Guide provided separately to each patient.

Actavis

100 Tablets

Rx Only

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Concentrate, Oral:

ALPRAZolam Intensol: 1 mg/mL (30 mL) [unflavored flavor]

Tablet, Oral:

Xanax: 0.25 mg [scored]

Xanax: 0.5 mg [scored; contains fd&c yellow #6 (sunset yellow)]

Xanax: 1 mg [scored; contains fd&c blue #2 (indigotine)]

Xanax: 2 mg [scored]

Generic: 0.25 mg, 0.5 mg, 1 mg, 2 mg

Tablet Disintegrating, Oral:

Niravam: 0.25 mg [DSC] [scored; orange flavor]

Niravam: 0.5 mg [DSC], 1 mg [DSC], 2 mg [DSC]

Generic: 0.25 mg, 0.5 mg, 1 mg, 2 mg

Tablet Extended Release 24 Hour, Oral:

ALPRAZolam XR: 0.5 mg

ALPRAZolam XR: 1 mg [contains fd&c yellow #10 (quinoline yellow)]

ALPRAZolam XR: 2 mg [contains fd&c blue #2 (indigotine)]

ALPRAZolam XR: 3 mg [contains fd&c blue #2 (indigotine), fd&c yellow #10 (quinoline yellow)]

Xanax XR: 0.5 mg

Xanax XR: 1 mg [contains fd&c yellow #10 (quinoline yellow)]

Xanax XR: 2 mg [contains fd&c blue #2 (indigotine)]

Xanax XR: 3 mg [contains fd&c blue #2 (indigotine), fd&c yellow #10 (quinoline yellow)]

Generic: 0.5 mg, 1 mg, 2 mg, 3 mg

Note: Titrate dose gradually as needed and tolerated. Periodic reassessment and consideration of dosage reduction is recommended.

Anxiety disorders: Oral: Immediate release tablet, oral concentrate, orally-disintegrating tablet: Initial: 0.25 to 0.5 mg 3 times daily; titrate dose every 3 to 4 days; usual maximum: 4 mg/day. Patients requiring doses >4 mg/day should be increased cautiously.

Panic disorder: Oral:

Immediate release tablet, oral concentrate, orally-disintegrating tablet: Initial: 0.5 mg 3 times daily; titrate dose every 3 to 4 days in increments ≤1 mg/day. Mean effective dosage: 5 to 6 mg/day, in 3 or 4 divided doses; some patients may require as much as 10 mg/day.

Extended release: 0.5 to 1 mg once daily; titrate dose every 3 to 4 days in increments ≤1 mg/day (range: 3 to 6 mg/day).

Switching from immediate release to extended release: Patients may be switched to extended release tablets by taking the total daily dose of the immediate release tablets and giving it once daily using the extended release preparation.

Preoperative anxiety (off-label use): Oral: 0.5 mg 60-90 minutes before procedure (De Witte, 2002)

Dose reduction: Abrupt discontinuation should be avoided. Daily dose may be decreased by 0.5 mg every 3 days; however, some patients may require a slower reduction. If withdrawal symptoms occur, resume previous dose and discontinue on a less rapid schedule.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, dry mouth, increased hunger, lack of appetite, nausea, constipation, sexual dysfunction, decreased libido, or weight change. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), shortness of breath, burning or numbness feeling, angina, tachycardia, abnormal heartbeat, severe dizziness, passing out, change in balance, confusion, hallucinations, memory impairment, difficulty speaking, severe loss of strength and energy, twitching, tremors, dark urine, jaundice, blurred vision, or difficult urination (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Mechanism of Action

Binds receptors at several sites within the CNS, including the limbic system and reticular formation; effects may be mediated through GABA receptor system; increase in neuronal membrane permeability to chloride ions enhances the inhibitory effects of GABA; the shift in chloride ions causes hyperpolarization (less excitability) and stabilization of the neuronal membrane

Absorption

Bioavailability: 90%

Peak serum time: 1-2 hr (immediate release); 9 hr (extended release); 1.5-2 hr (disintegrating tablet)

Peak plasma concentration: 8-37 ng/mL (dose dependent)

Distribution

Protein bound: 80%

Vd: 0.9-1.2 L/kg

Metabolism

Metabolized by hepatic P-450 enzyme CYP3A4

Elimination

Half-life: 11 hr average for immediate release, 13 hr average for extended release, and 13 hr average for disintegrating tablets (adults); 16.3 hr (elderly); 21.8 hr (obesity)

Excretion: Urine

Do not drink alcohol while taking alprazolam. This medication can increase the effects of alcohol.

Alprazolam may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Grapefruit and grapefruit juice may interact with alprazolam and lead to unwanted side effects. Discuss the use of grapefruit products with your doctor.

Your pharmacist can provide more information about alprazolam.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 9.01. Revision date: 10/22/2012.

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Do not drink alcohol while taking alprazolam. This medication can increase the effects of alcohol.

Alprazolam may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Grapefruit and grapefruit juice may interact with alprazolam and lead to unwanted side effects. Discuss the use of grapefruit products with your doctor.

It is dangerous to purchase alprazolam on the Internet or from vendors outside the United States. Medications distributed from Internet sales may contain dangerous ingredients, or may not be distributed by a licensed pharmacy. The sale and distribution of alprazolam outside the U.S. does not comply with the regulations of the Food and Drug Administration (FDA) for the safe use of this medication.

You should not take alprazolam if you have:

• narrow-angle glaucoma;

• if you are also taking itraconazole or ketoconazole; or

• if you are allergic to alprazolam or to other benzodiazepines, such as chlordiazepoxide (Librium), clorazepate (Tranxene), diazepam (Valium), lorazepam (Ativan), or oxazepam (Serax).

To make sure this medicine is safe for you, tell your doctor if you have:

• seizures or epilepsy;

• kidney or liver disease (especially alcoholic liver disease);

• asthma or other breathing disorder;

• open-angle glaucoma;

• a history of depression or suicidal thoughts or behavior;

• a history of drug or alcohol addiction; or

• if you also use a narcotic (opioid) medication.

Do not use alprazolam if you are pregnant. This medicine can cause birth defects. Your baby could also become dependent on the drug. This can cause life-threatening withdrawal symptoms in the baby after it is born. Babies born dependent on habit-forming medicine may need medical treatment for several weeks. Tell your doctor if you are pregnant or plan to become pregnant. Use effective birth control to prevent pregnancy while you are taking this medicine.

Alprazolam can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using this medicine.

The sedative effects of alprazolam may last longer in older adults. Accidental falls are common in elderly patients who take benzodiazepines. Use caution to avoid falling or accidental injury while you are taking alprazolam.

Alprazolam is not approved for use by anyone younger than 18 years old.

Elderly or debilitated patients:
Immediate-release tablets/ disintegrating tablets:
0.25 mg orally administered 2 or 3 times a day

Comments:
-If side effects develop, the dose may be lowered.
-The lowest possible effective dose should be administered and the need for continued treatment reassessed frequently.
-Dosage should be reduced gradually when discontinuing therapy or when decreasing the daily dosage.

Uses:
-Management of anxiety disorder
-Short-term relief of symptoms of anxiety

Data not available

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Low blood pressure, dizziness on standing (may increase the risk of falls), and heart palpitations.
• Stomach upset including constipation and nausea. Dry mouth, headache and a decrease in libido (sexual drive) are also common.
• Known to cause emotional and physical dependence (addiction).
• May impair reaction skills and affect a person's ability to drive or operate machinery. Avoid alcohol.
• Smokers may have less of a response.

Notes: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. For a complete list of all side effects, click here.