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ANTABUSE- dis ulfiram tablet Teva Women's Health, Inc.
Antabus e (dis ulfiram tablets USP) IN ALCOHOLISM 523 524 Rx only WARNING Disulfiram should never be administered to a patient when he is in a state of alcohol intoxication, or without his full knowledge. The physician should instruct relatives accordingly. DESCRIPTION Disulfiram, USP is an alcohol antagonist drug. CHEMICAL NAME bis(diethylthiocarbamoyl) disulfide. STRUCTURAL FORMULA C H N S M.W. 296. Disulfiram, USP occurs as a white to off-white, odorless, and almost tasteless powder, soluble in water to the extent of about 20 mg in 100 mL, and in alcohol to the extent of about 3.8 g in 100 mL. Each tablet for oral administration contains 250 mg or 500 mg disulfiram, USP. Tablets also contain colloidal silicon dioxide, lactose anhydrous, magnesium stearate, microcrystalline cellulose, sodium starch glycolate, and stearic acid. CLINICAL PHARMACOLOGY Disulfiram produces a sensitivity to alcohol which results in a highly unpleasant reaction when the patient under treatment ingests even small amounts of alcohol. ® 10 20 2 4
Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage. During alcohol metabolism following disulfiram intake, the concentration of acetaldehyde occurring in the blood may be 5 to 10 times higher than that found during metabolism of the same amount of alcohol alone. Accumulation of acetaldehyde in the blood produces a complex of highly unpleasant symptoms referred to hereinafter as the disulfiram-alcohol reaction. This reaction, which is proportional to the dosage of both disulfiram and alcohol, will persist as long as alcohol is being metabolized. Disulfiram does not appear to influence the rate of alcohol elimination from the body. Disulfiram is absorbed slowly from the gastrointestinal tract and is eliminated slowly from the body. One (or even two) weeks after a patient has taken his last dose of disulfiram, ingestion of alcohol may produce unpleasant symptoms. Prolonged administration of disulfiram does not produce tolerance; the longer a patient remains on therapy, the more exquisitely sensitive he becomes to alcohol. INDICATIONS AND USAGE Disulfiram Tablets USP are an aid in the management of selected chronic alcohol patients who want to remain in a state of enforced sobriety so that supportive and psychotherapeutic treatment may be applied to best advantage. Disulfiram Tablets USP are not a cure for alcoholism. When used alone, without proper motivation and supportive therapy, it is unlikely that it will have any substantive effect on the drinking pattern of the chronic alcoholic. CONTRAINDICATIONS Patients who are receiving or have recently received metronidazole, paraldehyde, alcohol, or alcohol- containing preparations, e.g., cough syrups, tonics and the like, should not be given disulfiram. Disulfiram is contraindicated in the presence of severe myocardial disease or coronary occlusion, psychoses, and hypersensitivity to disulfiram or to other thiuram derivatives used in pesticides and rubber vulcanization. WARNINGS Disulfiram should never be administered to a patient when he is in a state of alcohol intoxication, or without his full knowledge. The physician should instruct relatives accordingly. The patient must be fully informed of the disulfiram-alcohol reaction. He must be strongly cautioned against surreptitious drinking while taking the drug, and he must be fully aware of the possible consequences. He should be warned to avoid alcohol in disguised forms, i.e., in sauces, vinegars, cough mixtures, and even in aftershave lotions and back rubs. He should also be warned that reactions may occur with alcohol up to 14 days after ingesting disulfiram. The Dis ulfiram-Alcohol Reaction Disulfiram plus alcohol, even small amounts, produce flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, marked uneasiness, weakness, vertigo, blurred vision, and confusion. In severe reactions there may be respiratory depression, cardiovascular collapse, arrhythmias, myocardial infarction, acute congestive heart failure, unconsciousness,
Patients taking isoniazid when disulfiram is given should be observed for the appearance of unsteady gait or marked changes in mental status, the disulfiram should be discontinued if such signs appear. In rats, simultaneous ingestion of disulfiram and nitrite in the diet for 78 weeks has been reported to cause tumors, and it has been suggested that disulfiram may react with nitrites in the rat stomach to form a nitrosamine, which is tumorigenic. Disulfiram alone in the rat’s diet did not lead to such tumors. The relevance of this finding to humans is not known at this time. Us age in Pregnancy The safe use of this drug in pregnancy has not been established. Therefore, disulfiram should be used during pregnancy only when, in the judgement of the physician, the probable benefits outweigh the possible risks. Pediatric Us e Safety and effectiveness in pediatric patients have not been established. Nurs ing Mothers It is not known whether this drug is excreted in human milk. Since many drugs are so excreted, disulfiram should not be given to nursing mothers. Geriatric Us e A determination has not been made whether controlled clinical studies of disulfiram included sufficient numbers of subjects aged 65 and over to define a difference in response from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. ADVERSE REACTIONS See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS. OPTIC NEURITIS, PERIPHERAL NEURITIS, POLYNEURITIS, AND PERIPHERAL NEUROPATHY MAY OCCUR FOLLOWING ADMINISTRATION OF DISULFIRAM. Multiple cases of hepatitis, including both cholestatic and fulminant hepatitis, as well as hepatic failure resulting in transplantation or death, have been reported with administration of disulfiram. Occasional skin eruptions are, as a rule, readily controlled by concomitant administration of an antihistaminic drug. In a small number of patients, a transient mild drowsiness, fatigability, impotence, headache, acneform eruptions, allergic dermatitis, or a metallic or garlic-like aftertaste may be experienced during the first two weeks of therapy. These complaints usually disappear spontaneously with the continuation of therapy, or with reduced dosage. Psychotic reactions have been noted, attributable in most cases to high dosage, combined toxicity (with metronidazole or isoniazid), or to the unmasking of underlying psychoses in patients stressed by the withdrawal of alcohol. OVERDOSAGE No specific information is available on the treatment of overdosage with disulfiram. It is recommended that the physician contact the local Poison Control Center.
DOSAGE AND ADMINISTRATION
Disulfiram tablets should never be administered until the patient has abstained from alcohol for at least 12 hours. Initial Dos age Schedule In the first phase of treatment, a maximum of 500 mg daily is given in a single dose for one to two weeks. Although usually taken in the morning, disulfiram may be taken on retiring by patients who experience a sedative effect. Alternatively, to minimize, or eliminate, the sedative effect, dosage may be adjusted downward. Maintenance Regimen The average maintenance dose is 250 mg daily (range, 125 to 500 mg), it should not exceed 500 mg daily. Note: Occasionally patients, while seemingly on adequate maintenance doses of disulfiram, report that they are able to drink alcoholic beverages with impunity and without any symptomatology. All appearances to the contrary, such patients must be presumed to be disposing of their tablets in some manner without actually taking them. Until such patients have been observed reliably taking their daily disulfiram tablets (preferably crushed and well mixed with liquid), it cannot be concluded that disulfiram is ineffective. Duration of Therapy The daily, uninterrupted administration of disulfiram must be continued until the patient is fully recovered socially and a basis for permanent self-control is established. Depending on the individual patient, maintenance therapy may be required for months or even years. Trial with Alcohol During early experience with disulfiram, it was thought advisable for each patient to have at least one supervised alcohol-drug reaction. More recently, the test reaction has been largely abandoned. Furthermore, such a test reaction should never be administered to a patient over 50 years of age. A clear, detailed and convincing description of the reaction is felt to be sufficient in most cases. However, where a test reaction is deemed necessary, the suggested procedure is as follows: After the first one to two weeks’ therapy with 500 mg daily, a drink of 15 mL (1/2 oz) of 100 proof whiskey, or equivalent, is taken slowly. This test dose of alcoholic beverage may be repeated once only, so that the total dose does not exceed 30 mL (1 oz) of whiskey. Once a reaction develops, no more alcohol should be consumed. Such tests should be carried out only when the patient is hospitalized, or comparable supervision and facilities, including oxygen, are available. Management of Dis ulfiram-Alcohol Reaction In severe reactions, whether caused by an excessive test dose or by the patient’s unsupervised ingestion of alcohol, supportive measures to restore blood pressure and treat shock should be instituted. Other recommendations include: oxygen, carbogen (95% oxygen and 5% carbon dioxide), vitamin C intravenously in massive doses (1 g) and ephedrine sulfate. Antihistamines have also been used intravenously. Potassium levels should be monitored, particularly in patients on digitalis, since hypokalemia has been reported. HOW SUPPLIED Disulfiram Tablets USP are available as follows: 250 mg - white, round, unscored, biconvex tablets, debossed with OP over 706 on one side and plain on
TEVA
Package/Label Dis play Panel Antabus e® (dis ulfiram tablets USP) 500 mg 100s Label Text NDC 51285- 524 - Antabus e® (disulfiram tablets USP) 500 mg See Side Panel for Warnings Rx only 100 TABLETS TEVA
ANTABUSE
disulfiram tablet Product Information Prod uct T yp e HUMAN PRESCRIPTIO N DRUG^ Ite m Cod e (S ource ) NDC:5128 5- Route of Ad minis tration O RAL Active Ing redient/Active Moiety Ing redient Name Basis o f Streng th Streng th DISULFIRAM (UNII: TR3MLJ1UAI) (DISULFIRAM - UNII:TR3MLJ1UAI) DISULFIRAM 250 mg
Inactive Ing redients Ing redient Name Streng th SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4) ANHYDRO US LACTO SE (UNII: 3SY5LH9 PMK) MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 ) MICRO CRYSTALLINE CELLULO SE (UNII: O P1R32D6 1U) SO DIUM STARCH GLYCO LATE TYPE A PO TATO (UNII: 58 56 J3G2A2) STEARIC ACID (UNII: 4ELV7Z6 5AP) Product Characteristics Color WHITE^ S core no sc o re S hap e RO UND S iz e 10 mm Flavor Imp rint Cod e O P;70 6 **Contains Packag ing
Item Co de Packag e Descriptio n Marketing Start Date Marketing End Date
1** NDC:5128 5-523-0 2 10 0 in 1 BO TTLE; Type 0 : No t a Co mbina tio n Pro duc t 12/0 1/20 0 0
Teva Women's Health, Inc.
Marketing Information
Marke ting Cate gory Ap p lication Numb e r or Monograp h Citation Marke ting S tart Date Marke ting End Date ANDA ANDA0 8 8 48 3 0 2/0 1/20 0 6
Labeler - T eva Women's Health, Inc. (017038951)
Revised: 5/
