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disulfiram 250 mg tablet (generic antabuse)

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Alcohol Dependence

Disulfiram is used as an alcohol deterrent to aid in the management of alcohol dependence. The drug is not a cure for alcohol dependence, and disulfiram therapy should be confined to selected, highly motivated patients in conjunction with supportive psychotherapy. The efficacy of disulfiram therapy has not been established. Without proper motivation and adequate supportive psychotherapy, it is unlikely that disulfiram therapy will have more than a brief effect on the pattern of alcohol consumption in patients with alcohol dependence. Although appreciable, short-term improvement (e.g., abstinence, improved social functioning) has been reported by patients with alcohol dependence during disulfiram therapy, these effects probably result from nonspecific, nonpharmacologic factors (e.g., supportive psychotherapy) rather than from the pharmacologic effects of the drug. A goal of disulfiram therapy is to allow the alcohol-dependent patient to establish the resources and self motivation that are necessary to maintain abstinence once the drug is discontinued. After ingesting as little as 15 mL of 100 proof whiskey or its equivalent, a patient maintained on disulfiram experiences an extremely unpleasant reaction within 5-15 minutes, usually severe enough to require medical attention. (See Cautions: Disulfiram-Alcohol Reaction.)

Disulfiram treatment should be initiated in a hospital or physician's office after a complete physical examination. The patient must be fully aware of therapy and thoroughly understand the disulfiram-alcohol reaction. In addition, the patient should be strongly warned against drinking alcohol while taking disulfiram and cautioned that reactions may occur up to 2 weeks after discontinuance of the drug. For optimum results, disulfiram therapy should be supervised by regular office visits and accompanied by psychotherapy. Although disulfiram can be administered under court order or coercion in some jurisdictions and rehabilitation programs, such mandatory use of the drug has been questioned because of the lack of evidence from well-controlled studies of its efficacy and because of the associated risks of therapy.

Dosage and Administration


Disulfiram is administered orally. If compliance becomes a problem during disulfiram therapy, the patient should take the drug under close supervision, preferably as crushed tablets well mixed with liquid. Disulfiram has also been administered as an implant (not commercially available in the US) subcutaneously into the abdominal wall; however, blood concentrations of disulfiram are lower than those obtained following oral administration and safety and efficacy of this route of administration have not been established.

Disulfiram should not be administered until the patient has abstained from alcohol for at least 12 hours and should never be administered without the patient's knowledge.


The initial dosage of disulfiram is a maximum of 500 mg every morning for 1-2 weeks, then 250 mg daily. The daily dose can be taken in the evening if drowsiness occurs. Maintenance dosage may range from 125-500 mg daily, but the dosage should not exceed 500 mg daily. Daily uninterrupted administration of disulfiram should be continued until a basis for permanent self-control is established. Treatment may be required for months or years.

The practice of inducing an alcohol-disulfiram reaction to demonstrate the reaction to the patient has been largely abandoned; it is considered by most clinicians to be unnecessary, and may, in fact, be associated with increased drug toxicity. An explicit description of the alcohol-disulfiram reaction is usually sufficient to deter the patient from ingesting alcohol during treatment with disulfiram. If an alcohol trial is deemed necessary, it should be performed only under careful medical supervision and with adequate facilities (including oxygen) available for treatment of a severe reaction. Patients older than 50 years of age should not undergo an alcohol test reaction. The procedure for alcohol trial consists of administering 15 mL of 100 proof whiskey (or its equivalent) to the patient after 1-2 weeks of disulfiram therapy. The dose of alcohol may be repeated once, but should not exceed 30 mL of whiskey. Alcohol should be discontinued as soon as symptoms develop.


Disulfiram-Alcohol Reaction

In individuals who ingest alcohol while receiving disulfiram, the drug produces an adverse disulfiram-alcohol reaction that may persist for 30 minutes to several hours, or as long as alcohol remains in the blood. The intensity and duration of the disulfiram-alcohol reaction are subject to individual variation and are proportional to the dosage of both disulfiram and alcohol; a blood alcohol concentration of 5-10 mg/dL may precipitate a reaction. Symptoms are fully developed when blood alcohol concentrations are about 50 mg/dL; unconsciousness generally occurs when the blood alcohol concentration reaches 125-150 mg/dL.

Symptoms of the disulfiram-alcohol reaction include flushing, throbbing in the head and neck, throbbing headache, dyspnea, nausea, copious vomiting, sweating, thirst, chest pain, palpitation, hyperventilation, tachycardia, hypotension, syncope, anxiety, weakness, vertigo, blurred vision, and confusion. Mild reactions are usually followed by sound sleep and complete recovery. However, symptoms may progress to respiratory depression, cardiovascular collapse, arrhythmias, myocardial infarction, acute congestive heart failure, unconsciousness, seizures, and death. Although most fatal disulfiram-alcohol reactions have occurred with disulfiram dosages greater than 500 mg daily followed by ingestion of more than 2 alcoholic drinks, deaths have occurred with lower disulfiram dosages after a single alcoholic drink (approximately 150 mg of ethanol per kg).

Treatment of reactions following ingestion of alcohol by patients receiving disulfiram therapy is largely supportive and symptomatic. Although most disulfiram-alcohol reactions are self-limited and do not present a life-threatening risk to the patient, these reactions should be managed in facilities with immediate access to emergency equipment and drugs (e.g., emergency rooms) since arrhythmias and severe hypotension occasionally occur. Respiration may be assisted with oxygen or a mixture of 95% oxygen and 5% carbon dioxide. Severe reactions should be treated like shock. Plasma or electrolyte solutions can be given to maintain adequate circulation. One manufacturer states that ephedrine sulfate may be administered for hypotension. Large IV doses of ascorbic acid, iron, and antihistamines have been used, but are of questionable value. Although it has been suggested that inhibitors of prostaglandin synthetase (e.g., indomethacin) and histamine2-blocking agents (e.g., cimetidine) may decrease the flushing reaction, a therapeutic role for the use of these drugs in the treatment of a disulfiram-alcohol reaction has not been established. Hypokalemia has been reported; therefore, serum potassium concentrations should be monitored, particularly in digitalized patients.

Hepatic Effects

Numerous cases of hepatitis, including both cholestatic and fulminant hepatitis, as well as hepatic failure resulting in transplantation or death, have been reported in patients receiving disulfiram. Because severe and sometimes fatal hepatitis associated with disulfiram therapy may develop even after many months of therapy in patients with or without a prior history of abnormal liver function, the manufacturer recommends performing baseline and follow-up liver function tests in patients receiving the drug.(See Cautions: Precautions and Contraindications.)

Nervous System Effects

Vertigo, irritability, insomnia, abnormal gait, slurred speech, disorientation, confusion, and personality changes also have been reported during disulfiram therapy. Tonic-clonic (grand mal) seizures, peripheral neuropathy, polyneuritis, optic neuritis, delirium, bizarre behavior, drowsiness, and psychoses also have occurred. Although these adverse nervous system effects have been produced by low doses of disulfiram in patients with no previous history of neurologic illness, sudden withdrawal from alcohol itself may disclose a preexisting neurologic disorder.

Disulfiram may aggravate preexisting EEG abnormalities.

Other Adverse Effects

Disulfiram itself may produce adverse effects in the absence of alcohol, especially during the first 2 weeks of therapy. Fatigue, impotence, headache, acneiform or allergic dermatitis, and a metallic or garlic-like aftertaste may occur, but usually disappear with continued therapy or temporary dosage reduction. Skin eruptions that occur during disulfiram therapy may be controlled by concomitant antihistamine therapy.

The drug rarely has caused blood dyscrasias.

Precautions and Contraindications

Patients receiving disulfiram should be warned to avoid cough syrups, sauces, vinegars, elixirs, and other preparations that contain alcohol. External application of alcoholic liniments or lotions, including aftershave or back rub, may be sufficient to produce a disulfiram-alcohol reaction. Patients should be cautioned that disulfiram-alcohol reactions may occur for several weeks after discontinuance of disulfiram. Patients undergoing treatment with disulfiram should be fully advised of the risks (e.g., the disulfiram-alcohol reaction) associated with disulfiram therapy and should be instructed to carry identification cards describing the symptoms of a disulfiram-alcohol reaction and indicating the clinician who should be contacted in case of emergency. Close contacts (e.g., relatives) of the patient should also be advised of the risks of disulfiram-alcohol reactions; they should also be advised that disulfiram should not be used to treat acute alcohol intoxication in the patient.

Because hepatic toxicity, including hepatic failure resulting in transplantation or death, and blood dyscrasias have been reported with disulfiram, the manufacturer recommends baseline and follow-up liver function tests every 10-14 days, and monitoring of complete blood cell counts and blood chemistries in patients receiving the drug. In addition, patients should be advised to immediately notify their clinician of any early signs or symptoms of hepatitis, such as fatigue, weakness, malaise, anorexia, nausea, vomiting, jaundice, or dark urine. (See Cautions: Hepatic Effects.)

Disulfiram should be given with caution, if at all, to patients with diabetes mellitus, hypothyroidism, seizure disorders, cerebral damage, chronic or acute nephritis, hepatic cirrhosis or insufficiency, abnormal EEG results, or multiple drug dependence.

Disulfiram is contraindicated in patients with alcohol intoxication, cardiovascular disease, or psychoses.

Disulfiram is also contraindicated in individuals hypersensitive to the drug or other thiuram derivatives such as those used in pesticides or rubber vulcanization. Patients with a history of rubber contact dermatitis should be evaluated for hypersensitivity to thiuram derivatives prior to administration of disulfiram.


Preliminary studies in rats indicate that a toxic reaction may occur between inhaled ethylene dibromide and ingested disulfiram resulting in a higher incidence of tumors and mortality. Although this effect has not been reported in humans, patients receiving disulfiram should not be exposed to ethylene dibromide or its vapors.

In rats, simultaneous ingestion of disulfiram and nitrite in the diet for 78 weeks has caused tumors; however, disulfiram alone in the diet of rats did not cause such tumors. It has been suggested that disulfiram reacts with nitrites in the rat stomach to form a nitrosamine which is tumorigenic. The relevance of this reaction to humans has not been established.



Safe use of disulfiram during pregnancy has not been established. The drug should be administered during pregnancy only when the potential benefits justify the possible risks to the fetus.

Drug Interactions

Disulfiram interferes with the hepatic metabolism of alcohol, barbiturates, coumarin anticoagulants, paraldehyde (no longer commercially available in the US), terfenadine (no longer commercially available in the US), and phenytoin and its congeners, and therefore may increase blood concentrations and toxicity of these drugs.


Disulfiram should be used with caution in patients receiving phenytoin and its congeners, since the concomitant use of disulfiram and the anticonvulsant can lead to phenytoin intoxication. Plasma concentrations of phenytoin should be determined prior to and during concomitant disulfiram therapy and dosage of phenytoin adjusted as needed.


Because disulfiram may prolong the prothrombin time in patients receiving anticoagulant therapy by increasing the plasma concentrations of oral anticoagulants, it may be necessary to reduce the dosage of coumarin anticoagulants when disulfiram is given concomitantly.


Because disulfiram produces a sensitivity to alcohol that results in a highly unpleasant reaction, the drug should never be used concomitantly with alcohol or alcohol-containing preparations.(See Cautions: Disulfiram-Alcohol Reaction and also Precautions and Contraindications.)


Disulfiram should not be administered concomitantly with paraldehyde (no longer commercially available in the US) because paraldehyde, like alcohol, is metabolized to acetaldehyde in the liver.


When disulfiram and caffeine are administered concomitantly in healthy individuals or recovering alcohol-dependent patients, the total blood clearance of caffeine is substantially decreased and its elimination half-life is increased. The exact mechanism of the interaction is not known, but disulfiram may inhibit hepatic metabolism of caffeine. The clinical importance of the interaction has not been established, but the possibility that exaggerated or prolonged effects of caffeine might occur in patients receiving disulfiram who also ingest substantial quantities of coffee, tea, or other caffeine-containing beverages should be considered. Further studies are needed.


Patients receiving isoniazid during treatment with disulfiram may experience behavioral changes, incoordination, and unsteady gait; concurrent administration of these drugs should be avoided.


Disulfiram is contraindicated in patients receiving metronidazole because concomitant administration has produced acute psychoses and confusion in some patients.


Concurrent administration of disulfiram and amitriptyline has been reported to enhance the reaction between alcohol and disulfiram.



Disulfiram is rapidly absorbed from the GI tract; however, 3-12 hours may be required before effects occur. Toxic reactions to alcohol may occur as long as 1-2 weeks following the last dose of disulfiram. During maintenance therapy, a 500-mg dose of disulfiram produces average blood concentrations of 2.4 mcg/mL (range 0-6 mcg/mL) within 4 hours.


Disulfiram is slowly metabolized in the liver to diethyldithiocarbamate, diethylamine, and carbon disulfide. Six hours after oral administration of the drug, one-third of plasma disulfiram is in the form of diethyldithiocarbamate. From 5-20% of an ingested dose of disulfiram is not absorbed and is excreted unchanged in feces; most of the remainder is excreted in urine, mainly as free and esterified sulfates. Some disulfiram may be excreted from the lungs in expired air as carbon disulfide. Radioisotope studies have shown that up to 20% of absorbed disulfiram remains in the body 6 days after a single 2-g dose of the drug; therefore, the possibility of cumulative effects should be considered.

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