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Disulfiram (Monograph)

Brand name: Antabuse
Drug class: Alcohol Deterrents
- Alcohol Deterrents
- Deterrents, Alcohol
- Aldehyde Dehydrogenase Inhibitors

Medically reviewed by Drugs.com on May 10, 2024. Written by ASHP.

Warning

  • Never administer to a patient in a state of alcohol intoxication or without patient's full knowledge; instruct relatives accordingly.

Introduction

Alcohol deterrent; an aldehyde dehydrogenase inhibitor.

Uses for Disulfiram

Alcohol Dependence

Management of alcohol dependence in selected, highly motivated patients; use in conjunction with supportive and psychotherapeutic treatment.

Not a cure for alcohol dependence; unlikely to have substantive effect when used without proper motivation and supportive therapy.

Disulfiram Dosage and Administration

General

Disulfiram-Alcohol Test Reaction

Adherence to Therapy

Administration

Oral Administration

Administer orally once daily, usually in the morning. If sedation occurs, may administer at bedtime.

Do not administer until patient has abstained from alcohol for ≥12 hours. Never administer without the patient’s knowledge. (See Boxed Warning.)

If adherence is a problem, administer under close supervision, preferably as crushed tablets well mixed with liquid.

Dosage

Adults

Alcohol Dependence
Oral

Initially, maximum 500 mg once daily for 1–2 weeks. May reduce dosage if sedation occurs.

Average maintenance dosage: 250 mg daily (range: 125–500 mg daily) until patient is fully recovered socially and a basis for permanent self-control is established. Treatment may be required for months or years.

Prescribing Limits

Adults

Alcohol Dependence
Oral

Maximum 500 mg daily.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time. Use with extreme caution. (See Hepatic Effects and also Concomitant Diseases under Cautions.)

Renal Impairment

No specific dosage recommendations at this time. Use with extreme caution in patients with acute or chronic nephritis. (See Concomitant Diseases under Cautions.)

Geriatric Patients

Select dosage with caution, usually starting at low end of dosing range, because of age-related decreases in hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy.

Cautions for Disulfiram

Contraindications

Warnings/Precautions

Warnings

Disulfiram-Alcohol Reaction

Ingestion of alcohol (even small amounts) produces an adverse disulfiram-alcohol reaction. Symptoms include: flushing, throbbing in the head and neck, throbbing headache, respiratory difficulty, dyspnea, nausea, copious vomiting, sweating, thirst, chest pain, palpitation, hyperventilation, tachycardia, hypotension, syncope, marked uneasiness, anxiety, weakness, vertigo, blurred vision, and confusion. Mild reactions are usually followed by sound sleep and complete recovery. May progress to respiratory depression, cardiovascular collapse, arrhythmias, MI, acute CHF, unconsciousness, seizures, and death.

Reaction may last 30–60 minutes to several hours or as long as alcohol remains in the blood. Intensity and duration of the reaction are subject to individual variation and are proportional to the dosage of both disulfiram and alcohol; a blood alcohol concentration (BAC) of 5–10 mg/dL may precipitate a reaction. Symptoms are fully developed when BAC=50 mg/dL; unconsciousness generally occurs when BAC ≥125–150 mg/dL. Most fatal reactions occur with disulfiram dosages >500 mg daily and >2 alcoholic drinks; however, deaths have occurred with lower disulfiram dosages after a single alcoholic drink (approximately 150 mg/kg of ethanol).

Treatment of disulfiram-alcohol reaction should be performed in facilities with immediate access to emergency equipment and drugs (e.g., emergency rooms) since arrhythmias and severe hypotension occasionally occur. Institute supportive measures to restore BP and treat shock (e.g., oxygen or a mixture of 95% oxygen and 5% carbon dioxide, plasma or electrolyte solutions, ephedrine sulfate). Large IV doses of ascorbic acid (1 g), iron, and antihistamines have been used, but are of questionable value. The therapeutic role of prostaglandin synthetase inhibitors (e.g., indomethacin) and histamine H2-blocking agents (e.g., cimetidine) in decreasing the flushing reaction has not been established. Because hypokalemia has been reported, monitor serum potassium concentrations, particularly in digitalized patients.

Fully inform patients about the disulfiram-alcohol reaction. Warn against surreptitious drinking and/or use of alcohol-containing products and advise of possible consequences. (See Advice to Patients.) Advise patients to carry a disulfiram identification card listing symptoms of the disulfiram-alcohol reaction and clinician contact information. Cards may be obtained from Odyssey Pharmaceuticals at 1-877-427-9068.

Concomitant Diseases

Because of risk of accidental disulfiram-alcohol reaction, use with extreme caution in patients with diabetes mellitus, hypothyroidism, seizure disorders, cerebral damage, chronic or acute nephritis, hepatic cirrhosis or insufficiency, abnormal EEG results, or multiple drug dependence.

Sensitivity Reactions

Evaluate patients with a history of rubber contact dermatitis for hypersensitivity to thiuram derivatives before beginning disulfiram. (See Contraindications under Cautions.)

Major Toxicities

Hepatic Effects

Hepatic toxicity (e.g., cholestatic or fulminant hepatitis, hepatic failure resulting in transplantation or death) reported in patients with or without prior history of abnormal liver function. Severe or fatal hepatitis may develop even after many months of therapy.

Perform baseline and follow-up liver function tests every 10–14 days; monitor CBC and blood chemistries. Advise patients to immediately report early signs or symptoms of hepatitis. (See Advice to Patients.)

Nervous System Effects

Vertigo, irritability, insomnia, abnormal gait, slurred speech, disorientation, confusion, and personality changes reported. Tonic-clonic (grand mal) seizures, peripheral neuropathy, polyneuritis, optic neuritis, delirium, bizarre behavior, drowsiness, and psychoses also reported.

Possible exacerbation of preexisting EEG abnormalities.

General Precautions

Precipitation of New Abuse

Alcoholism may accompany or be followed by dependence on narcotics or sedatives; consider possibility of precipitating a new abuse.

Ethylene Dibromide Exposure

Do not expose patients on disulfiram to ethylene dibromide or its vapors; higher incidence of tumors and mortality observed in rats.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether disulfiram is distributed into milk; however, expected to distribute into milk because of relatively low molecular weight. Use not recommended.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Response in patients ≥65 years of age does not appear to differ from that in younger adults. However, select dosage with caution because of greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly. (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with extreme caution. (See Hepatic Effects and also Concomitant Diseases under Cautions.)

Renal Impairment

Use with extreme caution in patients with chronic or acute nephritis. (See Concomitant Diseases under Cautions.)

Common Adverse Effects

Cholestatic or fulminant hepatitis, hepatic failure, skin eruptions (e.g., acneiform eruptions, allergic dermatitis), drowsiness, fatigue, impotence, headache, metallic or garlic-like aftertaste, psychotic reactions. Optic or peripheral neuritis, polyneuritis, or peripheral neuropathy also may occur.

Drug Interactions

Nonspecific inhibitor of microsomal drug metabolism.

Specific Drugs

Drug

Interaction

Comments

Alcohol or alcohol-containing preparations (e.g., cough syrups, elixirs, tonics)

Increased sensitivity to alcohol, resulting in disulfiram-alcohol reaction

Concomitant use contraindicated

Amitriptyline

Enhanced alcohol-disulfiram reaction

Anticoagulants, oral (e.g., warfarin)

Possible increased plasma concentrations of anticoagulant, resulting in prolonged PT

Adjust anticoagulant dosage as needed upon initiation or discontinuance of disulfiram

Barbiturates

Interference with hepatic metabolism of barbiturate, possibly resulting in increased blood concentrations and toxicity of barbiturate

Caffeine

Decreased total blood clearance and increased half-life of caffeine, possibly resulting from inhibition of hepatic metabolism of caffeine

Clinical importance not established, but consider possibility of exaggerated or prolonged caffeine effects in patients who ingest substantial quantities of coffee, tea, or other caffeine-containing beverages

Isoniazid

Possible behavioral changes, marked changes in mental status, psychotic reactions, incoordination, or unsteady gait

Avoid concomitant use. However, if used concomitantly, discontinue disulfiram if such signs appear

Metronidazole

Acute psychoses and confusion reported

Concomitant use contraindicated

Phenytoin (and congeners)

Inhibition of hepatic metabolism of phenytoin, possibly resulting in phenytoin intoxication

Use concomitantly with caution. Determine phenytoin concentrations prior to and during disulfiram therapy; adjust phenytoin dosage as needed

Disulfiram Pharmacokinetics

Absorption

Bioavailability

Slowly absorbed from the GI tract.

Onset

3–12 hours following administration.

Duration

Effects may persist up to 14 days after last dose.

Distribution

Extent

Not known whether disulfiram crosses the placenta or is distributed into milk; however, expected to cross the placenta and distribute into milk because of relatively low molecular weight.

Elimination

Metabolism

Slowly metabolized in the liver to diethyldithiocarbamate, diethylamine, and carbon disulfide.

Elimination Route

Slowly eliminated from the body. Excreted principally in urine as metabolites; unabsorbed disulfiram (5–20%) is excreted unchanged in feces. Some excreted from the lungs as carbon disulfide.

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 20–25°C.

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Disulfiram

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

250 mg

Antabuse

Odyssey

500 mg

Antabuse (scored)

Odyssey

AHFS DI Essentials™. © Copyright 2024, Selected Revisions May 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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