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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Medication Safety Issues
Sound-alike/look-alike issues:
Disulfiram may be confused with Diflucan®
Antabuse® may be confused with Anturane®
Pronunciation
(dye SUL fi ram)
U.S. Brand Names
Generic Available
No
Pharmacologic Category
Use: Labeled Indications
Management of chronic alcoholism
Pregnancy Risk Factor
C
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
Boxed warnings:
• Ethanol intoxication: See “Other warnings/precautions” below.
Concerns related to adverse effects:
• Hepatotoxicity: Severe (sometimes fatal) hepatitis and/or hepatic failure have been associated with use; may occur in patients with or without prior history of abnormal hepatic function.
Disease-related concerns:
• Diabetes: Use with caution in patients with diabetes mellitus.
• Hepatic impairment: Use with caution in patients with hepatic cirrhosis or impairment.
• Hypothyroidism: Use with caution in patients with hypothyroidism.
• Nephritis: Use with caution in patients with acute or chronic nephritis.
• Seizures: Use with caution in patients with a history of seizure disorder.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions:
• Ethanol intoxication: [U.S. Boxed Warning]: Should never be administered to a patient when he/she is in a state of ethanol intoxication, or without his/her knowledge.
• Patient information: Patients 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).
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
Metabolism/Transport Effects
Substrate (minor) of CYP1A2, 2A6, 2B6, 2D6, 2E1, 3A4; Inhibits CYP1A2 (weak), 2A6 (weak), 2B6 (weak), 2C9 (weak), 2D6 (weak), 2E1 (strong), 3A4 (weak)
Drug Interactions
Alcohol (Ethyl): Disulfiram may enhance the adverse/toxic effect of Alcohol (Ethyl). A disulfiram-like reaction may occur. Risk X: Avoid combination
Amprenavir: Disulfiram may enhance the adverse/toxic effect of Amprenavir. This is specifically related to the propylene glycol contained in amprenavir oral solution, not capsules. Management: Specifically, concurrent amprenavir oral solution and disulfiram is contraindicated due to the large amount of propylene glycol in the oral solution. Risk X: Avoid combination
Benzodiazepines (metabolized by oxidation): Disulfiram may decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Chlorzoxazone: Disulfiram may decrease the metabolism of Chlorzoxazone. Risk C: Monitor therapy
CYP2E1 Substrates: CYP2E1 Inhibitors (Strong) may decrease the metabolism of CYP2E1 Substrates. Risk D: Consider therapy modification
MetroNIDAZOLE: Disulfiram may enhance the adverse/toxic effect of MetroNIDAZOLE. Risk D: Consider therapy modification
MetroNIDAZOLE, Systemic: Disulfiram may enhance the adverse/toxic effect of MetroNIDAZOLE, Systemic. Risk D: Consider therapy modification
MetroNIDAZOLE, Topical: May enhance the adverse/toxic effect of Disulfiram. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Phenytoin: Disulfiram may decrease the metabolism of Phenytoin. Risk D: Consider therapy modification
Ritonavir: Disulfiram may enhance the adverse/toxic effect of Ritonavir. This is specific for the lopinavir/ritonavir (Kaletra) oral solution due to its alcohol content (42%). Management: Concomitant use of Kaletra (lopinavir/ritonavir) oral solution and disulfiram should be avoided. Kaletra contains 42% alcohol. Risk X: Avoid combination
Sertraline: Disulfiram may enhance the adverse/toxic effect of Sertraline. This is specifically related to sertraline oral concentrate due to its alcohol content (12%). Management: Sertraline Oral Concentrate contains 12% alcohol, and its use should be avoided with disulfiram. Risk X: Avoid combination
Theophylline Derivatives: Disulfiram may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy
Tipranavir: Disulfiram may enhance the adverse/toxic effect of Tipranavir. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Disulfiram may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
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: Oral
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
Dietary Considerations
Do not administer disulfiram if ethanol has been consumed within the prior 12 hours.
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 while taking this medication and for at least 3 days (preferably 14 days) after stopping 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
Nursing: Physical Assessment/Monitoring
Assess for adverse drug interactions with other prescription or OTC drugs. Do not administer until the patient has abstained from ethanol for 12 hours. Assess results of laboratory tests and for CNS changes at beginning of therapy and periodically with long-term therapy. Advise patient about disulfiram reaction if alcohol is ingested. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Antabuse®: 250 mg, 500 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Antabuse)
250 mg (30): $117.53
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
Lexi-Comp.com
Last full review/revision January 2010
Content last modified January 2010
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