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Basic Drug Info
Drug Name:Alprazolam Extended-release
Manufacturer:Mylan Pharmaceuticals Inc.
Other Info:Mylan Pharmaceuticals Inc.Morgantown, WV 26505REV AUGUST 2005ALPER:R1



Clinical Trials:


Indications and Usage

Alprazolam extended-release tablets are indicated for the treatment of panic disorder, with or without agoraphobia.This claim is supported on the basis of two positive studies with alprazolam extended-release tablets conducted in patients whose diagnoses corresponded closely to the DSM-III-R/IV criteria for panic disorder (see CLINICAL EFFICACY TRIALS).Panic disorder (DSM-IV) is characterized by recurrent unexpected panic attacks, i.e., a discrete period of intense fear or discomfort in which four (or more) of the following symptoms develop abruptly and reach a peak within 10 minutes: (1) palpitations, pounding heart, or accelerated heart rate; (2) sweating; (3) trembling or shaking; (4) sensations of shortness of breath or smothering; (5) feeling of choking; (6) chest pain or discomfort; (7) nausea or abdominal distress; (8) feeling dizzy, unsteady, lightheaded, or faint; (9) derealization (feelings of unreality) or depersonalization (being detached from oneself); (10) fear of losing control; (11) fear of dying; (12) paresthesias (numbness or tingling sensations); (13) chills or hot flushes.The longer-term efficacy of alprazolam extended-release tablets has not been systematically evaluated.

Thus, the physician who elects to use this drug for periods longer than 8 weeks should periodically reassess the usefulness of the drug for the individual patient.
PANIC DISORDER 1 --

Sensory Discomfort -- A feeling of mental or physical uneasiness, pain, or distress.

Symptoms -- An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.

Trembling --

Chest Pain -- Pressure, burning, or numbness in the chest.

Nausea -- An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.

Lightheadedness --

Numbness --

Chills -- The sudden sensation of being cold. It may be accompanied by SHIVERING.

Hot flushes -- A sudden, temporary onset of body warmth, flushing, and sweating (often associated with menopause).

Menopausal hot flushes -- A sudden, temporary sensation of heat predominantly experienced by some women during MENOPAUSE. (Random House Unabridged Dictionary, 2d ed)

Contraindications

Alprazolam extended-release tablets are contraindicated in patients with known sensitivity to this drug or other benzodiazepines.

Alprazolam extended-release may be used in patients with open angle glaucoma who are receiving appropriate therapy, but is contraindicated in patients with acute narrow angle glaucoma.Alprazolam extended-release is contraindicated with ketoconazole and itraconazole, since these medications significantly impair the oxidative metabolism mediated by cytochrome P450 3A (CYP3A) (see CLINICAL PHARMACOLOGY, WARNINGS and PRECAUTIONS: Drug Interactions).
Open Angle Glaucoma -- Glaucoma in which the angle of the anterior chamber is open and the trabecular meshwork does not encroach on the base of the iris.

Angle Closure Glaucoma -- A form of glaucoma in which the intraocular pressure increases because the angle of the anterior chamber is blocked and the aqueous humor cannot drain from the anterior chamber.

Warnings

Certain adverse clinical events, some life-threatening, are a direct consequence of physical dependence to alprazolam.

These include a spectrum of withdrawal symptoms; the most important is seizure (see DRUG ABUSE AND DEPENDENCE).

Even after relatively short-term use at doses of ? 4 mg/day, there is some risk of dependence.

Spontaneous reporting system data suggest that the risk of dependence and its severity appear to be greater in patients treated with doses greater than 4 mg/day and for long periods (more than 12 weeks).

However, in a controlled postmarketing discontinuation study of panic disorder patients who received alprazolam tablets, the duration of treatment (3 months compared to 6 months) had no effect on the ability of patients to taper to zero dose.

In contrast, patients treated with doses of alprazolam tablets greater than 4 mg/day had more difficulty tapering to zero dose than those treated with less than 4 mg/day.Relapse or return of illness was defined as a return of symptoms characteristic of panic disorder (primarily panic attacks) to levels approximately equal to those seen at baseline before active treatment was initiated.

Rebound refers to a return of symptoms of panic disorder to a level substantially greater in frequency, or more severe in intensity than seen at baseline.

Withdrawal symptoms were identified as those which were generally not characteristic of panic disorder and which occurred for the first time more frequently during discontinuation than at baseline.The rate of relapse, rebound, and withdrawal in patients with panic disorder who received alprazolam extended-release tablets has not been systematically studied.

Experience in randomized placebo-controlled discontinuation studies of patients with panic disorder who received alprazolam tablets showed a high rate of rebound and withdrawal symptoms compared to placebo treated patients.In a controlled clinical trial in which 63 patients were randomized to alprazolam tablets and where withdrawal symptoms were specifically sought, the following were identified as symptoms of withdrawal: heightened sensory perception, impaired concentration, dysosmia, clouded sensorium, paresthesias, muscle cramps, muscle twitch, diarrhea, blurred vision, appetite decrease, and weight loss.

Other symptoms, such as anxiety and insomnia, were frequently seen during discontinuation, but it could not be determined if they were due to return of illness, rebound, or withdrawal.In two controlled trials of 6 to 8 weeks duration where the ability of patients to discontinue medication was measured, 71% to 93% of patients treated with alprazolam tablets tapered completely off therapy compared to 89% to 96% of placebo treated patients.

In a controlled postmarketing discontinuation study of panic disorder patients treated with alprazolam tablets, the duration of treatment (3 months compared to 6 months) had no effect on the ability of patients to taper to zero dose.Seizures were reported for three patients in panic disorder clinical trials with alprazolam extended-release.

In two cases, the patients had completed 6 weeks of treatment with alprazolam extended-release tablets 6 mg/day before experiencing a single seizure.

In one case, the patient abruptly discontinued alprazolam extended-release, and in both cases, alcohol intake was implicated.

The third case involved multiple seizures after the patient completed treatment with alprazolam extended-release tablets 4 mg/day and missed taking the medication on the first day of taper.

All three patients recovered without sequelae.Seizures have also been observed in association with dose reduction or discontinuation of alprazolam tablets, the immediate release form of alprazolam.

Seizures attributable to alprazolam were seen after drug discontinuance or dose reduction in 8 of 1980 patients with panic disorder or in patients participating in clinical trials where doses of alprazolam greater than 4 mg/day for over 3 months were permitted.

Five of these cases clearly occurred during abrupt dose reduction, or discontinuation from daily doses of 2 to 10 mg.

Three cases occurred in situations where there was not a clear relationship to abrupt dose reduction or discontinuation.

In one instance, seizure occurred after discontinuation from a single dose of 1 mg after tapering at a rate of 1 mg every three days from 6 mg daily.

In two other instances, the relationship to taper is indeterminate; in both of these cases the patients had been receiving doses of 3 mg daily prior to seizure.

The duration of use in the above 8 cases ranged from 4 to 22 weeks.

There have been occasional voluntary reports of patients developing seizures while apparently tapering gradually from alprazolam.

The risk of seizure seems to be greatest 24 to 72 hours after discontinuation (see DOSAGE AND ADMINISTRATION for recommended tapering and discontinuation schedule).

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