Disulfiram

Pronunciation

(dye SUL fi ram)

U.S. Brand Names

Antabuse®

Generic Available

Use

Management of chronic alcoholism

Pregnancy Risk Factor

Lactation

Excretion in breast milk unknown

Contraindications

Hypersensitivity to disulfiram and related compounds or any component of the formulation; patients receiving or using ethanol, metronidazole, paraldehyde, or ethanol-containing preparations like cough syrup or tonics; psychosis; severe myocardial disease and coronary occlusion

Warnings/Precautions

Use with caution in patients with diabetes, hypothyroidism, seizure disorders, nephritis (acute or chronic); hepatic cirrhosis or insufficiency; should never be administered to a patient when he/she is in a state of ethanol intoxication, or without his/her knowledge. Patient must receive appropriate counseling, including information on "disguised" forms of ethanol (tonics, mouthwashes, etc) and the duration of the drug's activity (up to 14 days).

Severe (sometimes fatal) hepatitis and/or hepatic failure have been associated with disulfiram. May occur in patients with or without prior history of abnormal hepatic function.

Adverse Reactions

Frequency not defined.

Central nervous system: Drowsiness, headache, fatigue, psychosis

Dermatologic: Rash, acneiform eruptions, allergic dermatitis

Gastrointestinal: Metallic or garlic-like aftertaste

Genitourinary: Impotence

Hepatic: Hepatitis (cholestatic and fulminant), hepatic failure (multiple case reports)

Neuromuscular & skeletal: Peripheral neuritis, polyneuritis, peripheral neuropathy

Ocular: Optic neuritis

Overdosage/Toxicology

Management of disulfiram reaction: Institute support measures to restore blood pressure (vasopressors and fluids). Monitor for hypokalemia.

Drug Interactions

Substrate (minor) of CYP1A2, 2A6, 2B6, 2D6, 2E1, 3A4; Inhibits CYP1A2 (weak), 2A6 (weak), 2B6 (weak), 2C8/9 (weak), 2D6 (weak), 2E1 (strong), 3A4 (weak)

Benzodiazepines: Disulfiram may increase serum concentrations of benzodiazepines; includes only benzodiazepines which undergo oxidative metabolism (all but oxazepam, lorazepam, temazepam)

Cocaine: Disulfiram may increase serum concentrations of cocaine; avoid concurrent use

Co-trimoxazole: Intravenous trimethoprim-sulfamethoxazole contains 10% ethanol as a solubilizing agent and may interact with disulfiram; monitor for disulfiram reaction

CYP2E1 substrates: Disulfiram may increase the levels/effects of CYP2E1 substrates. Example substrates include inhalational anesthetics, theophylline, and trimethadione.

Diphenhydramine: Syrup contains ethanol, avoid use of syrup; monitor for disulfiram reaction

Ethanol: Disulfiram results in severe ethanol intolerance (disulfiram reaction) secondary to disulfiram's ability to inhibit aldehyde dehydrogenase; this combination should be avoided. Pharmaceutical products should be evaluated for possible inclusion of ethanol (eg, elixirs).

Isoniazid: Concurrent use with disulfiram may result in adverse CNS effects; this combination should be avoided

MAO inhibitors: Concurrent use with disulfiram may result in adverse CNS effects; this combination should be avoided

Metronidazole: Concurrent use with disulfiram may result in adverse CNS effects; this combination should be avoided

Omeprazole: May cause CNS adverse effects (limited documentation); monitor

Phenytoin: Disulfiram may increase theophylline serum concentrations; toxicity may occur

Theophylline: Disulfiram may increase theophylline serum concentrations; toxicity may occur

Tricyclic antidepressants: Disulfiram may increase adverse CNS effects; monitor for acute changes in mental status

Warfarin: Disulfiram inhibits the metabolism of warfarin resulting in an increased hypoprothrombinemic response; avoid when possible or monitor INR closely and adjust warfarin dosage

Ethanol/Nutrition/Herb Interactions

Ethanol: Disulfiram inhibits ethanol's usual metabolism. Avoid all ethanol. Patients can have a disulfiram reaction (headache, nausea, vomiting, chest, or abdominal pain) if they drink ethanol concurrently. Avoid cough syrups and elixirs containing ethanol. Avoid vinegars, cider, extracts, and foods containing ethanol.

Mechanism of Action

Disulfiram is a thiuram derivative which interferes with aldehyde dehydrogenase. When taken concomitantly with alcohol, there is an increase in serum acetaldehyde levels. High acetaldehyde causes uncomfortable symptoms including flushing, nausea, thirst, palpitations, chest pain, vertigo, and hypotension. This reaction is the basis for disulfiram use in postwithdrawal long-term care of alcoholism.

Pharmacodynamics/Kinetics

Onset of action: Full effect: 12 hours

Duration: ~1-2 weeks after last dose

Absorption: Rapid

Metabolism: To diethylthiocarbamate

Excretion: Feces and exhaled gases (as metabolites)

Dosage

Adults: Oral: Do not administer until the patient has abstained from ethanol for at least 12 hours

Initial: 500 mg/day as a single dose for 1-2 weeks; maximum daily dose is 500 mg

Average maintenance dose: 250 mg/day; range: 125-500 mg; duration of therapy is to continue until the patient is fully recovered socially and a basis for permanent self control has been established; maintenance therapy may be required for months or even years

Administration

Administration of any medications containing alcohol, including topicals, is contraindicated. Do not administer disulfiram if ethanol has been consumed within the prior 12 hours.

Monitoring Parameters

Hypokalemia; liver function tests at baseline and after 10-14 days of treatment; CBC, serum chemistries, liver function tests should be monitored during therapy

Patient Education

Tablets can be crushed or mixed with water or juice. Metallic aftertaste may occur; this will go away. Do not drink any alcohol, including products containing alcohol (such as cough and cold syrups or some mouthwashes), or use alcohol-containing skin products for at least 3 days and preferably 14 days after stopping this medication or while taking this medication. Drowsiness, tiredness, or visual changes may occur. Use care when driving or engaging in tasks requiring alertness until response to drug is known. Notify prescriber of any respiratory difficulty, weakness, nausea, vomiting, decreased appetite, yellowing of skin or eyes, or dark-colored urine. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Psychotic reactions have been noted

Dosage Forms

Tablet: 250 mg

References

Motte S, Vincent JL, and Gillet JB, "Refractory Hyperdynamic Shock Associated With Alcohol and Disulfiram," Am J Emerg Med , 1986, 4(4):323-5.

Pompidou A, Delsaux MC, Telvi L, et al, "Isoprinosine and Imuthiol, Two Potentially Active Compounds in Patients With AIDS-Related Complex Symptoms," Cancer Res , 1985, 45(9 Suppl):4671-3.

International Brand Names

Abstensyl® (AR); Antabus® (AT, CH, CL, DE, DK, EC, ES, FI, NL, NO, SE, TR); Antabuse® (AU, BE, CY, EG, GB, IE, IT, JO, KW, LB, LU, NZ, TH, ZA); Antaethyl® (HU); Antalcol® (RO); Anticol® (PL); Antietanol® (BR); Difiram® (TH); Disulfiram Implantes® (CL); Disulfiramo L.CH.® (CL); Disulfiram® (PL); Esperal® (FR, HU, IN, PL, RU, YU); Etiltox® (IT); Refusal® (NL); Sarcoton® (BR); Tetradin® (PT); Vandisul® (AR)

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