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Alprazolam

Pronunciation

Pronunciation: al-PRAY-zoe-lam
Class: Antianxiety, Benzodiazepine

Trade Names

Alprazolam Intensol
- Oral solution 1 mg/mL

Xanax
- Tablets 0.25 mg
- Tablets 0.5 mg
- Tablets 1 mg
- Tablets 2 mg

Xanax XR
- Tablets, extended-release 0.5 mg
- Tablets, extended-release 1 mg
- Tablets, extended-release 2 mg
- Tablets, extended-release 3 mg

Niravam
- Orally disintegrating tablets 0.25 mg
- Orally disintegrating tablets 0.5 mg
- Orally disintegrating tablets 1 mg
- Orally disintegrating tablets 2 mg

Apo-Alpraz (Canada)
Apo-Alpraz TS (Canada)
Gen-Alprazolam (Canada)
Xanax TS (Canada)

Pharmacology

Potentiates action of GABA, an inhibitory neurotransmitter, resulting in increased neuronal inhibition and CNS depression, especially in limbic system and reticular formation.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Absorption

Readily absorbed; T max is 1 to 2 h; C max is 8 to 37 ng/mL (0.5 to 3 mg doses).

Distribution

80% protein bound. Crosses the placenta and is excreted in breast milk.

Metabolism

Metabolized in the liver to alpha-hydroxy-alprazolam (activity is approximately 50% that of alprazolam) and a benzophenone derivative (inactive).

Elimination

The t ½ is approximately 16.3 h. Excreted in the urine.

Special Populations

Hepatic Function Impairment

The t ½ is approximately 19.7 h in those with alcoholic liver disease.

Elderly

The t ½ is approximately 16.3 h.

Obese

The t ½ is approximately 21.8 h.

Indications and Usage

Treatment of panic disorders with or without agoraphobia ( Niravam , Xanax , Xanax XR ); management of anxiety disorders or for short-term relief of symptoms of anxiety, including anxiety associated with depression ( Niravam , immediate-release tablets and oral solution).

Unlabeled Uses

Treatment of irritable bowel syndrome, depression, PMS.

Contraindications

Hypersensitivity to other benzodiazepines; acute narrow-angle glaucoma; patients receiving itraconazole or ketoconazole.

Dosage and Administration

Panic Disorder
Initial dose

PO Immediate-release tablets: 0.5 mg 3 times daily; if needed, increase by max 1 mg/day every 3 to 4 day. May require more than 4 mg/day. Extended-release tablets: start with 0.5 to 1 mg daily (suggested daily dose ranges between 3 and 6 mg).

Anxiety Disorder (Immediate-Release Tablets and Oral Solution)
Adults

PO Immediate-release tablets and oral solution: 0.25 to 0.5 mg 3 times daily (max, 4 mg/day in divided doses). Extended-release tablets: Start with 0.5 mg daily and gradually increase if needed (suggested total daily dose range 3 to 6 mg/day).

Elderly/Debilitated Patients
Adults

PO Immediate-release tablets: 0.25 mg 2 to 3 times daily; may increase dose gradually. Extended-release tablets: 0.25 mg 2 to 3 times daily. May increase dose gradually.

General Advice

  • Immediate-release and extended-release tablets are interchangeable on a daily mg-to-mg basis.
  • Immediate-release tablets may be administered sublingually to patient who has difficulty swallowing tablets.
  • Administer extended-release tablets once daily, preferably in the morning. Have patient swallow whole. Do not crush, chew, divide, or break tablet.
  • Solution, oral
  • Use calibrated dropper to measure prescribed dose.
  • Add prescribed dose to a liquid (eg, juice, water, soda) or semisolid food (eg, applesauce, pudding), stir for a few seconds then immediately administer entire amount of mixture. Do not prepare and store doses for future use.

Storage/Stability

Store immediate-release tablets below 77°F. Store extended-release tablets, orally disintegrating tablets, and oral solution at controlled room temperature (59° to 86°F). Protect orally disintegrating tablets from moisture.

Drug Interactions

Alcohol and other CNS depressants

Produce additive CNS depressant effects.

Cimetidine, disulfiram, oral contraceptives

May increase effects of alprazolam, producing excessive sedation and impaired psychomotor function.

Desipramine, imipramine

Plasma concentrations of these agents may be increased by alprazolam.

Digoxin

Serum digoxin concentrations may increase.

Drugs that affect salivary flow and stomach pH

May slow dissolution or disintegration, resulting in slowed or decreased Niravam absorption.

Drugs that induce CYP3A4 metabolism (eg, carbamazepine, rifamycins)

May decrease alprazolam plasma levels.

Drugs that inhibit CYP3A4 metabolism (eg, diltiazem, fluoxetine, fluvoxamine, grapefruit juice, isoniazid, macrolide antibiotics [eg, erythromycin], nefazodone, nonnucleoside reverse transcriptase inhibitors [eg, delavirdine, efavirenz], protease inhibitors [eg, indinavir])

May increase alprazolam plasma concentrations.

Itraconazole, ketoconazole

Concurrent use with alprazolam is contraindicated.

Omeprazole

May increase serum levels of alprazolam and enhance alprazolam's effects.

Theophyllines

May antagonize sedative effects of alprazolam.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Tachycardia (15%); hypotension (5%); palpitation (at least 1%).

CNS

Drowsiness (77%); fatigue/tiredness (49%); sedation (45%); irritability, memory impairment (33%); cognitive disorder (29%); somnolence (23%); light-headedness (21%); decreased libido (14%); depression (12%); dysarthria (11%); confusional state (10%); abnormal coordination (9%); ataxia, mental impairment (7%); disturbed attention, impaired balance, disinhibition (3%); disorientation, paresthesia, dyskinesia, talkativeness, derealization, abnormal dreams, lethargy (2%); anxiety, hypesthesia, hypersomnia, fear, warm feeling (1%); malaise, weakness, headache, dizziness, tremor, irritability, insomnia, nervousness, increased libido, restlessness, agitation, depersonalization, nightmare (at least 1%).

Dermatologic

Rash (11%); increased sweating (at least 1%); Stevens-Johnson syndrome (postmarketing).

EENT

Nasal congestion (17%); allergic rhinitis (1%); vertigo, blurred vision (at least 1%).

GI

Constipation (26%); nausea/vomiting (22%); diarrhea (21%); abdominal distress (18%); dry mouth (15%); increased salivation (6%); dyspepsia, abdominal pain (at least 1%).

Genitourinary

Micturition difficulties (12%); menstrual disorders (10%); dysmenorrhea (4%); sexual dysfunction, PMS, incontinence (2%); gynecomastia (postmarketing).

Hepatic

Increased liver enzymes, hepatitis, hepatic failure (postmarketing).

Metabolic-Nutritional

Increased appetite (33%); decreased appetite (28%); weight gain (27%); weight loss (23%); edema (5%); anorexia (2%).

Musculoskeletal

Rigidity (4%); arthralgia, myalgia (2%); limb pain (1%); back pain, muscle cramps, muscle twitching (at least 1%).

Respiratory

Upper respiratory tract infection (4%); dyspnea (2%); hyperventilation (at least 1%).

Miscellaneous

Chest pain (at least 1%); hyperprolactinemia (postmarketing).

Precautions

Monitor

Treatment response

Frequently assess patient for response to treatment. Notify health care provider if condition does not appear to be improving or worsens. Ensure therapy is periodically reviewed to determine if it needs to be continued without change or if a dose change (eg, increase, decrease, discontinuation) is indicated.


Pregnancy

Category D .

Lactation

Excreted in breast milk.

Children

Safety and efficacy in children younger than 18 yr of age not established.

Elderly

Use smallest effective dose to preclude development of ataxia or overdosage.

Renal Function

Caution is needed to avoid accumulation of drug.

Hepatic Function

Caution is needed to avoid accumulation of drug.

Dependence

Prolonged use can lead to physical and psychological dependence. Withdrawal syndrome has occurred within 4 to 6 wk of treatment, especially if abruptly discontinued. Cautious use and tapering of dosage are necessary.

Fetal harm

There is a risk of fetal harm (eg, congenital abnormalities) when used during pregnancy.

Impaired pulmonary function

Death has been reported in patients with pulmonary disease shortly after starting alprazolam treatment.

Interdose symptoms

Early morning anxiety and emergence of anxiety symptoms have been reported between doses in patients with panic disorder.

Mania

Hypomania and mania have been reported.

Psychiatric disorders

Not intended for patients with primary depressive disorder, psychoses, or disorders in which anxiety is not prominent.

Seizures

May occur during abrupt drug discontinuation or dose reduction.

Suicide

Use with caution in patients with suicidal tendencies; do not allow access to large quantities of drug.

Withdrawal

If treatment is to be discontinued or the dose reduced, gradually taper the dose (eg, no more than 0.5 mg every 3 days). Monitor patient for withdrawal symptoms (eg, increased anxiety, tremor, muscle or abdominal cramps, sweating). If significant withdrawal symptoms develop, reinstitute previous dosing schedule and attempt a less rapid tapering regimen after patient has stabilized.

Overdosage

Symptoms

Somnolence, confusion, impaired coordination, diminished reflexes, coma, death.

Patient Information

  • Advise patient or caregiver to read the patient information leaflet before starting therapy and with each refill.
  • Advise patient that medication is usually started at a low dose and then gradually increased until max benefit is obtained.
  • Caution patient that medication may be habit forming and to take as prescribed and not to increase the dose or frequency of use unless advised by health care provider.
  • Advise patient to take each dose without regard to meals but to take with food if stomach upset occurs.
  • Advise patient using extended-release tablets to take prescribed dose once daily, preferably in the morning. Caution patient to swallow tablets whole and not to crush, chew, divide, or break the tablet.
  • Advise patient or caregiver using oral solution to measure prescribed dose using calibrated dropper and then add solution to a liquid (eg, juice, water, soda) or semisolid food (eg, applesauce, pudding), stir for a few seconds then immediately take (give) the entire mixture. Caution patient or caregiver not to prepare mixtures ahead of time and store.
  • Advise patient using orally disintegrating tablet to remove tablet from bottle immediately before administration using dry hands and to place the tablet on top of tongue where it will disintegrate and be swallowed with saliva. Advise patient that administration with liquid is not required. Instruct patient to discard any cotton that was included in the bottle and to reseal the bottle tightly after removing tablet(s) to prevent introducing moisture into bottle (which can cause the tablets to disintegrate).
  • Caution patient using ½ of a scored orally disintegrating tablet to discard the unused portion of the tablet and do not save for future use, because the remaining tablet portion may not be stable.
  • Advise patient that if a dose is missed to skip that dose and take the next one at the regularly scheduled time. Caution patient to never take 2 doses at the same time.
  • Advise patient that if medication needs to be discontinued it will be slowly withdrawn for a period of 2 wk or more unless safety concerns (eg, rash) require a more rapid withdrawal. Caution patient not to stop taking the medication abruptly or decrease the dose unless advised by health care provider because of the risk of withdrawal symptoms occurring.
  • Instruct patient to avoid alcoholic beverages and other depressants while taking this medication.
  • Advise patient with anxiety to take as needed and to seek alternative methods for controlling or preventing anxiety (eg, stress reduction, counseling).
  • Instruct patient to contact health care provider if symptoms do not appear to be getting better, worsen, or if bothersome adverse reactions (eg, drowsiness, memory impairment) occur.
  • Advise patient that drug may cause drowsiness or impair judgment, thinking, or reflexes and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.

Copyright © 2009 Wolters Kluwer Health.

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