DESCRIPTION
id: bf3743a0-bcff-40d6-b381-ced52e3a2058
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Alprazolam extended-release tablets contain alprazolam, USP 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-4 H-s-triazolo [4,3-α] [1,4] benzodiazepine. The molecular formula is C17H13ClN4 which corresponds to a molecular weight of 308.76.
The structural formula is:
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 alprazolam extended-release tablet, for oral administration, contains 0.5 mg, 1 mg, 2 mg, or 3 mg of alprazolam, USP. The inactive ingredients are colloidal silicon dioxide, hypromellose, lactose monohydrate, and magnesium stearate. 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.
INDICATIONS AND USAGE
id: b7884454-d50d-4960-bf46-e141deab0106
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
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 STUDIES
).
Panic disorder (DSM-IV) is characterized by recurrent unexpected panic attacks, ie, 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.
CONTRAINDICATIONS
id: 990838d8-bfd6-4457-8d8c-8eb5cb16235e
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Alprazolam extended-release tablets are contraindicated in patients with known sensitivity to this drug or other benzodiazepines. Alprazolam extended-release tablets may be used in patients with open angle glaucoma who are receiving appropriate therapy, but are contraindicated in patients with acute narrow angle glaucoma.
Alprazolam extended-release tablets are 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
).
Information for Patients
id: b52788f8-23df-4416-878e-84a8f63a52a4
displayName: INFORMATION FOR PATIENTS SECTION
FDA Article Code: 34076-0
To assure safe and effective use of alprazolam extended-release tablets, the physician should provide the patient with the following guidance.
- 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.
- 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.
- Inform your physician if you are nursing.
- Until you experience how this medication affects you, do not drive a car or operate potentially dangerous machinery, etc.
- 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.
- Do not stop taking this medication abruptly or decrease the dose without consulting your physician, since withdrawal symptoms can occur.
- Some patients may find it very difficult to discontinue treatment with alprazolam extended-release tablets due to severe emotional and physical dependence. Discontinuation symptoms, including possible seizures, may occur following discontinuation from any dose, but the risk may be increased with extended use at doses greater than 4 mg/day, especially if discontinuation is too abrupt. It is important that you seek advice from your physician to discontinue treatment in a careful and safe manner. Proper discontinuation will help to decrease the possibility of withdrawal reactions that can range from mild reactions to severe reactions such as seizure.
Laboratory Test
id: 895e819a-5be2-4bc7-a745-2df0e5586876
displayName: LABORATORY TESTS SECTION
FDA Article Code: 34075-2
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/Laboratory Test Interactions
id: d76fd95c-e4f0-4f52-9131-71efd1db435d
displayName: DRUG & OR LABORATORY TEST INTERACTIONS SECTION
FDA Article Code: 34074-5
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
id: 6fab95a3-3056-45b2-ba2d-f6c4190eb71a
displayName: CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION
FDA Article Code: 34083-6
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.
Labor and Delivery
id: 67af5f94-ab98-4094-a08e-e0f2728a36d8
displayName: LABOR & DELIVERY SECTION
FDA Article Code: 34079-4
Alprazolam has no established use in labor or delivery.
Nursing Mothers
id: 372548b7-2489-43e5-9d4d-f1a654f783f2
displayName: NURSING MOTHERS SECTION
FDA Article Code: 34080-2
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
id: cbddffc6-b675-4e8f-8226-cf364d572bfc
displayName: PEDIATRIC USE SECTION
FDA Article Code: 34081-0
Safety and effectiveness of alprazolam in individuals below 18 years of age have not been established.
Geriatric Use
id: b78a5a49-fd2a-4aaa-b549-4680e96eb597
displayName: GERIATRIC USE SECTION
FDA Article Code: 34082-8
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
).
ADVERSE REACTIONS
id: dbd9d953-1e5b-4d19-8a51-47662668ee08
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
The information included in the subsection on Adverse Events Observed in Short-Term, Placebo-Controlled Trials with alprazolam extended-release tablets is based on pooled data of five 6- and 8-week placebo-controlled clinical studies in panic disorder.
Adverse event reports were elicited either by general inquiry or by checklist, and were recorded by clinical investigators using terminology of their own choosing. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment emergent if it occurred for the first time or worsened during therapy following baseline evaluation. In the tables and tabulations that follow, standard MedDRA terminology (version 4.0) was used to classify reported adverse events.
DOSAGE AND ADMINISTRATION
id: dc91a583-62c7-444f-97a2-ad39dd111e5a
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
Alprazolam extended-release tablets may be administered once daily, preferably in the morning. The tablets should be taken intact; they should not be chewed, crushed, or broken.
The suggested total daily dose ranges between 3 to 6 mg/day. Dosage should be individualized for maximum beneficial effect. While the suggested total daily dosages given will meet the needs of most patients, there will be some patients who require doses greater than 6 mg/day. In such cases, dosage should be increased cautiously to avoid adverse effects.
HOW SUPPLIED
id: eef38b1a-5273-46c4-a52f-a89042fc815b
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Alprazolam extended-release tablets 0.5 mg are white, round compressed tablets debossed cor over 187 on one side and other side is plain. They are supplied as follows:
Bottles of 60 (NDC 64980-140-06)
Bottles of 100 (NDC 64980-140-01)
Bottles of 1000 (NDC 64980-140-10)
Alprazolam extended-release tablets 1 mg are yellow, round compressed tablets debossed cor over 188 on one side and other side is plain. They are supplied as follows:
Bottles of 60 (NDC 64980-141-06)
Bottles of 100 (NDC 64980-141-01)
Bottles of 1000 (NDC 64980-141-10)
Alprazolam extended-release tablets 2 mg are blue, round compressed tablets debossed cor over 189 on one side and other side is plain. They are supplied as follows:
Bottles of 60 (NDC 64980-142-06)
Bottles of 100 (NDC 64980-142-01)
Bottles of 1000 (NDC 64980-142-10)
Alprazolam extended-release tablets 3 mg are green, round compressed tablets debossed cor over 190 on one side and other side is plain. They are supplied as follows:
Bottles of 60 (NDC 64980-143-06)
Bottles of 100 (NDC 64980-143-01)
Bottles of 1000 (NDC 64980-143-10)
Store at 20° – 25°C (68° – 77°F); excursions permitted to 15° – 30°C (59° – 86°F) [see USP Controlled Room Temperature].
Dispense in a tight light-resistant container as defined in the USP.
Keep container tightly closed.
Keep this and all drugs out of the reach of children.
ANIMAL STUDIES
id: c1b1d639-88da-4cd7-8e7c-68cbb2bed4d7
displayName: ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION
FDA Article Code: 34091-9
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.
Manufactured by:
Corepharma LLC
Middlesex, NJ 08846
Manufactured for:
Rising Pharmaceuticals, Inc.
Allendale, NJ 07401
February 2007
MF # 539-01
Repacked by:
H.J. Harkins Company, Inc.
513 Sandydale Drive
Nipomo, CA 93444
