DESCRIPTION:
Xanax 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-alpha][1,4] benzodiazepine.
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 tablet, for oral administration, contains 0.25, 0.5, 1 or 2 mg of alprazolam.
Inactive Ingredients: Cellulose, corn starch, docusate sodium, lactose, magnesium stearate, silicon dioxide, and sodium benzoate. In addition, the 0.5 mg tablet contains FD&C yellow no. 6 and the 1 mg tablet contains FD&C blue no. 2.
CLINICAL PHARMACOLOGY: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.
Following oral administration, alprazolam is readily absorbed. Peak concentrations in the plasma occur in 1-2 hours following administration. Plasma levels are proportionate to the dose given; over the dose range of 0.5-3.0 mg, peak levels of 8.0-37 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.
The predominant metabolites are alpha-hydroxy-alprazolam and a benzophenone derived from alprazolam. The biological activity of alpha-hydroxy-alprazolam is approximately one-half that of alprazolam. The benzophenone metabolite is essentially inactive. Plasma levels of these metabolites are extremely low, thus precluding precise pharmacokinetic description. However, their half-lives appear to be of the same order of magnitude as that of alprazolam. Alprazolam and its metabolites are excreted primarily in the urine.
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.
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 5-6 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, 37-83% 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, 3.3-5.2), 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.
INDICATIONS AND USAGE:Alprazolam is indicated for the management of anxiety disorder (a condition corresponding most closely to the APA Diagnostic and Statistical Manual [DSM-III-R] diagnosis of generalized anxiety disorder) or the short-term relief of symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.
Generalized anxiety disorder is characterized by unrealistic or excessive anxiety and worry (apprehensive expectation) about two or more life circumstances, for a period of six months or longer, during which the person has been bothered more days than not by these concerns. At least 6 of the following 18 symptoms are often present in these patients: Motor Tension: Trembling, twitching, or feeling shaky; muscle tension, aches, or soreness; restlessness; easy fatigability. Autonomic Hyperactivity: Shortness of breath or smothering sensations; palpitations or accelerated heart rate; sweating, or cold clammy hands; dry mouth; dizziness or lightheadedness; nausea, diarrhea, or other abdominal distress; flushes or chills; frequent urination; trouble swallowing or 'lump in throat'). Vigilance and Scanning: Feeling keyed up or on edge; exaggerated startle response; difficulty concentrating or "mind going blank" because of anxiety; trouble falling or staying asleep; irritability. These symptoms must not be secondary to another psychiatric disorder or caused by some organic factor.
Anxiety associated with depression is responsive to alprazolam.
Alprazolam is also indicated for the treatment of panic disorder, with or without agoraphobia.
Studies supporting this claim were conducted in patients whose diagnoses corresponded closely to the DSM-III-R criteria for panic disorder (see CLINICAL STUDIES).
Panic disorder is an illness characterized by recurrent panic attacks. The panic attacks, at least initially, are unexpected. Later in the course of this disturbance certain situations (e.g., driving a car or being in a crowded place) may become associated with having a panic attack. These panic attacks are not triggered by situations in which the person is the focus of others' attention (as in social phobia). The diagnosis requires 4 such attacks within a 4-week period, or one or more attacks followed by at least a month of persistent fear of having another attack. The panic attacks must be characterized by at least 4 off the following symptoms: dyspnea or smothering sensations; dizziness, unsteady feelings, or faintness; palpitations or tachycardia; trembling or shaking; sweating; choking; nausea or abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest pain or discomfort; fear of dying; fear of going crazy or of doing something uncontrolled. At least some of the panic attack symptoms must develop suddenly, and the panic attack symptoms must not be attributable to some known organic factors. Panic disorder is frequently associated with some symptoms of agoraphobia.