Disulfiram

Pronunciation: die-SULL-fih-ram
Class: Antialcoholic agent

For Professionals Side Effects Dosage Interactions More...

Trade Names

Antabuse
- Tablets 250 mg

Pharmacology

Produces intolerance to alcohol by blocking oxidation of acetaldehyde by enzyme aldehyde dehydrogenase, resulting in high blood levels of acetaldehyde and unpleasant physical symptoms.

Pharmacokinetics

Absorption

Slowly absorbed from the GI tract.

Metabolism

Ultimately metabolized to carbon disulfide and diethylamine.

Elimination

Slowly eliminated with approximately 20% of the drug remaining in the body after 1 wk.

Peak

12 h.

Duration

1 to 2 wk.

Indications and Usage

Aid in management of alcoholism in selected patients who want to remain in state of enforced sobriety.

Contraindications

Hypersensitivity to thiuram derivatives used in pesticides and rubber vulcanization; severe myocardial disease or coronary occlusion; psychoses; patients receiving or who have recently received metronidazole, paraldehyde, alcohol, or alcohol-containing products.

Dosage and Administration

Adults

PO

Initial dose

500 mg every day (single dose) initially for 1 to 2 wk.

Maintenance dose

125 to 500 mg every day (max, 500 mg/day).

General Advice

May crush or mix tablets with liquid.
May administer at bedtime if sedative effect is experienced.

Storage/Stability

Store tablets at controlled room temperature (59° to 86°F).

Drug Interactions

Alcohol

Causes severe alcohol-intolerance reaction. Symptoms include flushing, throbbing in head and neck, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitations, shortness of breath, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. In severe reactions, there may be respiratory depression, cardiovascular collapse, unconsciousness, convulsions, and death.

Anticoagulants

Disulfiram may increase anticoagulant effect.

Antidepressants, tricyclic

May produce acute organic brain syndrome.

Benzodiazepines

Disulfiram decreases plasma clearance of benzodiazepines metabolized by oxidation, possible increase in CNS side effects.

Chlorzoxazone

CNS side effects of chlorzoxazone may be increased.

Cocaine

CV side effects of cocaine may be increased.

Hydantoins

Disulfiram may increase serum hydantoin levels.

Isoniazid

Acute behavioral and coordination changes.

Metronidazole

May cause patients to exhibit acute toxic psychosis or confusional state. One or both agents may need to be discontinued.

Theophyllines

Disulfiram may inhibit metabolism and increase effect of theophyllines.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Drowsiness; fatigue; headache; psychotic reactions.

Dermatologic

Skin eruptions; allergic dermatitis; acneform eruptions.

EENT

Metallic or garlic-like aftertaste.

Hepatic

Hepatotoxicity; hepatitis (including cholestatic and fulminant).

Miscellaneous

Peripheral neuropathy; polyneuritis; optic or peripheral neuritis; impotence.

Precautions

Warnings

Counseling

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

Monitor

Ensure that serum electrolytes, renal function, and CBC are determined before and every 6 mo during treatment.

Pregnancy

Category C .

Lactation

Undetermined.

Hypersensitivity

Evaluate patients with history of rubber contact dermatitis for hypersensitivity to thiuram derivatives.

Special Risk Patients

Use with caution in patients with diabetes mellitus, hypothyroidism, epilepsy, cerebral damage, chronic and acute nephritis, and hepatic cirrhosis or insufficiency.

Disulfiram-alcohol reaction

Avoid alcohol in all forms, including alcoholic beverages, vinegars, liquid medications such as cough syrups or tonic, some sauces, and aftershave products. Do not give disulfiram within 12 h of drinking alcohol. Reactions can occur up to 2 wk after discontinuing disulfiram.

Ethylene dibromide

Patients receiving disulfiram should not be exposed to ethylene dibromide or its vapors; toxic interaction resulting in tumors and death has occurred in research animals.

Hepatic toxicity

Hepatic toxicity, including hepatic failure resulting in transplantation or death, has been reported. Ensure that transaminases are determined before and 10 to 14 days after starting therapy and then periodically during treatment.

Patient Information

Explain that disulfiram will not cure alcohol dependence and should be used in conjunction with psychotherapy.
Advise patient that even trace amounts of alcohol in some food products or alcohol absorbed through skin (eg, aftershave lotion) can precipitate reaction.
Inform patient of all effects that will occur if alcohol is ingested while taking this medication.
Advise patient and family that some alcohol-disulfiram reactions can have serious effects on heart and respiratory system that may require immediate emergency treatment.
Instruct patients to read all product labels or consult pharmacist about alcohol content of all liquid medications before choosing one.
Instruct patient to carry medical identification (eg, card, bracelet) identification while taking this drug. Information should include health care provider's phone number or name of medical facility that should be contacted in case of reaction.
Caution patient that prolonged disulfiram therapy does not produce tolerance to alcohol but increased sensitivity.
Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.
Explain that alcohol-disulfiram reactions may occur for several weeks after discontinuation of therapy.
Caution patient not to change the dose or stop taking unless advised by health care provider.
Instruct patient to immediately notify health care provider or seek medical care if disulfiram-alcohol reaction occurs.