antabuse

WARNING:
Disulfiram should never be administered to a patient when he is in a state ofalcohol intoxication, or without his full knowledge antabuse.

The physician should instruct relatives accordingly antabuse.

DESCRIPTION
Disulfiram is an alcohol antagonist drug antabuse.

CHEMICAL NAME:

bis(diethylthiocarbamoyl) disulfide antabuse.

STRUCTURAL FORMULA:

Disulfiram 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 theextent of about 3.8 g in 100 mL antabuse.

Each tablet for oral administration contains 250 mg or 500 mg disulfiram, USP antabuse. Tablets also contain colloidal silicon dioxide, anhydrous lactose, magnesiumstearate, microcrystalline cellulose, sodium starch glycolate, and stearic acid antabuse.

CLINICAL PHARMACOLOGY
Disulfiram produces a sensitivity to alcohol which results in a highly unpleasantreaction when the patient under treatment ingests even small amounts of alcohol antabuse.

Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage antabuse. Duringalcohol metabolism following disulfiram intake, the concentration of acetaldehydeoccurring in the blood may be 5 to 10 times higher than that found during metabolismof the same amount of alcohol alone antabuse.

Accumulation of acetaldehyde in the blood produces a complex of highly unpleasantsymptoms referred to hereinafter as the disulfiram-alcohol reaction antabuse. This reaction,which is proportional to the dosage of both disulfiram and alcohol, will persistas long as alcohol is being metabolized antabuse. Disulfiram does not appear to influencethe rate of alcohol elimination from the body antabuse.

Disulfiram is absorbed slowly from the gastrointestinal tract and is eliminatedslowly from the body antabuse. One (or even two) weeks after a patient has taken hislast dose of disulfiram, ingestion of alcohol may produce unpleasant symptoms antabuse.

Prolonged administration of disulfiram does not produce tolerance; the longera patient remains on therapy, the more exquisitely sensitive he becomes to alcohol antabuse.

INDICATIONS AND USAGE
Disulfiram is an aid in the management of selected chronic alcohol patientswho want to remain in a state of enforced sobriety so that supportive and psychotherapeutictreatment may be applied to best advantage antabuse.

Disulfiram is not a cure for alcoholism antabuse. When used alone, without proper motivationand supportive therapy, it is unlikely that it will have any substantive effecton the drinking pattern of the chronic alcoholic antabuse.

CONTRAINDICATIONS
Patients who are receiving or have recently received metronidazole, paraldehyde,alcohol, or alcohol-containing preparations, e.g., cough syrups, tonics andthe like, should not be given disulfiram antabuse.

Disulfiram is contraindicated in the presence of severe myocardial diseaseor coronary occlusion, psychoses, and hypersensitivity to disulfiram or to otherthiuram derivatives used in pesticides and rubber vulcanization antabuse.

WARNINGS
Disulfiram should never be administered to a patient when he is in a state ofalcohol intoxication, or without his full knowledge antabuse.

The physician should instruct relatives accordingly antabuse.

The patient must be fully informed of the disulfiram-alcohol reaction antabuse. He mustbe strongly cautioned against surreptitious drinking while taking the drug,and he must be fully aware of the possible consequences antabuse. He should be warnedto avoid alcohol in disguised forms, i.e., in sauces, vinegars, cough mixtures,and even in aftershave lotions and back rubs antabuse. He should also be warned thatreactions may occur with alcohol up to 14 days after ingesting disulfiram antabuse.

The Disulfiram-Alcohol Reaction: Disulfiram plus alcohol, even small amounts,produce flushing, throbbing in head and neck, throbbing headache, respiratorydifficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitation,dyspnea, hyperventilation, tachycardia, hypotension, syncope, marked uneasiness,weakness, vertigo, blurred vision, and confusion antabuse. In severe reactions theremay be respiratory depression, cardiovascular collapse, arrhythmias, myocardialinfarction, acute congestive heart failure, unconsciousness, convulsions, anddeath antabuse.

The intensity of the reaction varies with each individual, but is generallyproportional to the amounts of disulfiram and alcohol ingested antabuse. Mild reactionsmay occur in the sensitive individual when the blood alcohol concentration isincreased to as little as 5 to 10 mg per 100 mL antabuse. Symptoms are fully developedat 50 mg per 100 mL, and unconsciousness usually results when the blood alcohollevel reaches 125 to 150 mg antabuse.

The duration of the reaction varies from 30 to 60 minutes, to several hoursin the more severe cases, or as long as there is alcohol in the blood antabuse.

Concomitant Conditions: Because of the possibility of an accidental disulfiram-alcoholreaction, disulfiram should be used with extreme caution in patients with anyof the following conditions: diabetes mellitus, hypothyroidism, epilepsy, cerebraldamage, chronic and acute nephritis, hepatic cirrhosis or insufficiency antabuse.

PRECAUTIONS
Patients with a history of rubber contact dermatitis should be evaluated forhypersensitivity to thiuram derivatives before receiving disulfiram (see CONTRAINDICATIONS) antabuse.

It is suggested that every patient under treatment carry an IdentificationCard stating that he is receiving disulfiram and describing the symptoms mostlikely to occur as a result of the disulfiram-alcohol reaction antabuse. In addition,this card should indicate the physician or institution to be contacted in anemergency antabuse. (Cards may be obtained from ODYSSEY PHARMACEUTICALS upon request.)

Alcoholism may accompany or be followed by dependence on narcotics or sedatives antabuse. Barbiturates and disulfiram have been administered concurrently without untowardeffects; the possibility of initiating a new abuse should be considered antabuse.

Hepatic toxicity including hepatic failure resulting in transplantation ordeath have been reported antabuse. Severe and sometimes fatal hepatitis associated withdisulfiram therapy may develop even after many months of therapy antabuse. Hepatic toxicityhas occurred in patients with or without prior history of abnormal liver function antabuse. Patients should be advised to immediately notify their physician of any earlysymptoms of hepatitis, such as fatigue, weakness, malaise, anorexia, nausea,vomiting, jaundice, or dark urine antabuse.

Baseline and follow-up liver function tests (10-14 days) are suggested to detectany hepatic dysfunction that may result with disulfiram therapy antabuse. In addition,a complete blood count and serum chemistries, including liver function tests,should be monitored antabuse.

Patients taking disulfiram tablets should not be exposed to ethylene dibromideor its vapors antabuse. This precaution is based on preliminary results of animal researchcurrently in progress that suggest a toxic interaction between inhaled ethylenedibromide and ingested disulfiram resulting in a higher incidence of tumorsand mortality in rats antabuse. A correlation between this finding and humans, however,has not been demonstrated antabuse.

Drug Interactions: Disulfiram appears to decrease the rate at which certaindrugs are metabolized and therefore may increase the blood levels and the possibilityof clinical toxicity of drugs given concomitantly antabuse.

DISULFIRAM SHOULD BE USED WITH CAUTION IN THOSE PATIENTS RECEIVING PHENYTOINAND ITS CONGENERS, SINCE THE CONCOMITANT ADMINISTRATION OF THESE TWO DRUGS CANLEAD TO PHENYTOIN INTOXICATION antabuse. PRIOR TO ADMINISTERING DISULFIRAM TO A PATIENTON PHENYTOIN THERAPY, A BASELINE PHENYTOIN SERUM LEVEL SHOULD BE OBTAINED antabuse. SUBSEQUENTTO INITIATION OF DISULFIRAM THERAPY, SERUM LEVELS OF PHENYTOIN SHOULD BE DETERMINEDON DIFFERENT DAYS FOR EVIDENCE OF AN INCREASE OR FOR A CONTINUING RISE IN LEVELS antabuse. INCREASED PHENYTOIN LEVELS SHOULD BE TREATED WITH APPROPRIATE DOSAGE ADJUSTMENT antabuse.

It may be necessary to adjust the dosage of oral anticoagulants upon beginningor stopping disulfiram, since disulfiram may prolong prothrombin time antabuse.

Patients taking isoniazid when disulfiram is given should be observed for theappearance of unsteady gait or marked changes in mental status, the disulfiramshould be discontinued if such signs appear antabuse.

In rats, simultaneous ingestion of disulfiram and nitrite in the diet for 78weeks has been reported to cause tumors, and it has been suggested that disulfirammay react with nitrites in the rat stomach to form a nitrosamine, which is tumorigenic antabuse. Disulfiram alone in the rat's diet did not lead to such tumors antabuse. The relevanceof this finding to humans is not known at this time antabuse.

Usage in Pregnancy: The safe use of this drug in pregnancy has not been established antabuse. Therefore, disulfiram should be used during pregnancy only when, in the judgementof the physician, the probable benefits outweigh the possible risks antabuse.

Pediatric Use: Safety and effectiveness in pediatric patients have not beenestablished antabuse.

Nursing Mothers: It is not known whether this drug is excreted in human milk antabuse. Since many drugs are so excreted, disulfiram should not be given to nursingmothers antabuse.

Geriatric Use: A determination has not been made whether controlled clinicalstudies of disulfiram included sufficient numbers of subjects aged 65 and overto define a difference in response from younger subjects antabuse. Other reported clinicalexperience has not identified differences in responses between the elderly andyounger patients antabuse. In general, dose selection for an elderly patient should becautious, usually starting at the low end of the dosing range, reflecting thegreater frequency of decreased hepatic, renal or cardiac function, and of concomitantdisease or other drug therapy antabuse.

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