disulfiram
Antabuse

Available forms
Available by prescription only
Tablets: 250 mg, 500 mg

Indications and dosages
 Adjunct in management of chronic alcoholism. Adults: Give maximum dose of 500 mg P.O. as a single dose in the morning for 1 to 2 weeks. Can be taken in evening if drowsiness occurs. Maintenance dosage is 125 to 500 mg daily (average dose 250 mg) until permanent self-control is established. Treatment may continue for months or years.

Pharmacodynamics
Antialcoholic action: Disulfiram irreversibly inhibits aldehyde dehydrogenase, which prevents the oxidation of alcohol after the acetaldehyde stage. It interacts with ingested alcohol to produce acetaldehyde levels five to ten times higher than are produced by normal alcohol metabolism. Excess acetaldehyde produces a highly unpleasant reaction (nausea and vomiting) to even a small quantity of alcohol. Tolerance to disulfiram doesn’t occur; rather, sensitivity to alcohol increases with longer duration of therapy.

Pharmacokinetics
Absorption: Absorbed completely after oral administration, but 3 to 12 hours may be required before effects occur.
Distribution: Highly lipid-soluble and initially localized in adipose tissue.
Metabolism: Mostly oxidized in the liver and excreted in urine as free drug and metabolites (for example, diethyldithiocarbamate, diethyl-amine, and carbon disulfide).
Excretion: 5% to 20% is unabsorbed and eliminated in feces. A small amount is eliminated through the lungs, but most is excreted in urine. Several days may be needed to eliminate drug entirely.

Contraindications and precautions
Contraindicated in patients intoxicated by alcohol and within 12 hours of alcohol ingestion; in those with psychoses, myocardial disease, coronary occlusion, or hypersensitivity to disulfiram or to other thiuram derivatives used in pesticides and rubber vulcanization; and in patients receiving metronidazole, paraldehyde, alcohol, or alcohol-containing preparations.
  Use with extreme caution in patients with diabetes mellitus, hypothyroidism, seizure disorder, cerebral damage, or nephritis or hepatic cirrhosis or insufficiency and with concurrent phenytoin therapy. Don’t administer drug during pregnancy.

Interactions
Drug-drug. Bacampicillin: May precipitate disulfiram reaction. Don’t use together.
Barbiturates, chlordiazepoxide, CNS depressants, coumarin anticoagulants, diazepam, midazolam, paraldehyde, phenytoin: Increases blood levels of these drugs. Use together cautiously.
Hydantoins: May increase hydantoin levels. Monitor serum levels and patient for signs of toxicity.
Isoniazid: Increases risk of ataxia, unsteady gait, or marked behavioral changes. Don’t use together.
Metronidazole: Increases risk of psychosis or confusion. Avoid use together.
Tricyclic antidepressants, especially amitriptyline: May cause transient delirium. Monitor patient closely.
Warfarin: May increase anticoagulant effects. Monitor PT and INR, and adjust dose as needed.
Drug-herb. Passion flower, pill-bearing spurge, pokeweed, squaw vine, squill, sundew, sweet flag, tormentil, valerian, yarrow: Causes disulfiram reaction if herbal form contains alcohol. Discourage use together.
Drug-food. Caffeine: May exaggerate or prolong effects of caffeine. Discourage use together.
Drug-lifestyle. Alcohol use (all sources, including cough syrups, liniments, shaving lotions, back-rub preparations): May precipitate disulfiram reaction. Alcohol reaction may occur as long as 2 weeks after single disulfiram dose; the longer patient remains on drug, the more sensitive he becomes to alcohol. Advise patient to be alert for and avoid use of these products.
Marijuana use: Causes synergistic CNS stimulation. Advise patient of this possible interaction.

Adverse reactions
CNS: drowsiness, headache, fatigue, delirium, depression, neuritis, peripheral neuritis, polyneuritis, restlessness, psychotic reactions.
EENT: optic neuritis.
GI: metallic or garlic aftertaste.
GU: impotence.
Hepatic: hepatotoxicity, cholestatic or fulminant hepatitis.
Metabolic: elevated serum cholesterol levels.
Skin: acneiform or allergic dermatitis, occasional eruptions.
Other: disulfiram reaction (precipitated by alcohol use), which may include flushing, throbbing headache, dyspnea, nausea, copious vomiting, diaphoresis, thirst, chest pain, palpitations, hyperventilation, hypotension, syncope, anxiety, weakness, blurred vision, confusion, arthropathy. In severe reactions: respiratory depression, CV collapse, arrhythmias, MI, acute heart failure, seizures, unconsciousness, or death.

Effects on lab test results
• May increase cholesterol level.

Overdose and treatment
Overdose may cause GI upset, vomiting, abnormal EEG findings, drowsiness, altered consciousness, hallucinations, speech impairment, incoordination, and coma.
 Treat overdose by gastric aspiration or lavage along with supportive therapy. Treatment of alcohol-induced disulfiram reaction is supportive and symptomatic. These reactions aren’t usually life-threatening. Emergency equipment and drugs should be available because arrhythmias and severe hypotension may occur. Treat severe reactions like shock by giving plasma or electrolyte solutions, as needed. Large I.V. doses of ascorbic acid, iron, and antihistamines have been used but are of questionable value. Hypokalemia has been reported; treat with careful monitoring and potassium supplements.

Special considerations
 ALERT Caution patient’s family never to give disulfiram to patient without his knowledge; severe reaction or death could result if patient ingests alcohol.
• Don’t give disulfiram for at least 12 hours after alcohol ingestion.
• Drug use requires close medical supervision. Patients should clearly understand consequences of disulfiram therapy and give informed consent before use.
• Use drug only in patients who are cooperative and well motivated, and who are receiving supportive psychiatric therapy.
• Complete physical examination and laboratory studies (CBC, electrolytes, transaminases) should precede therapy and be repeated regularly.
Pregnant patients
• Don’t use drug in pregnant patients.

Patient education
• Explain that, although disulfiram can help discourage use of alcohol, it isn’t a cure for alcoholism.
• Warn patient to avoid all sources of alcohol: sauces or soups made with sherry or other wines or alcohol (even "cooking alcohol"), some herbal preparations, and cough syrups. External applications of after-shave lotion, liniments, or other topical preparations may cause disulfiram reaction (because of the products’ alcohol content).
• Warn patient that drug may cause drowsiness.
• Instruct patient to carry identification card stating that disulfiram is being used and including the telephone number of prescriber or clinic to contact if a reaction occurs.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use