Disulfiram should never be administered to a patient when they are in a state of alcohol intoxication, or without their full knowledge. The physician should instruct relatives accordingly.
Alcohol use disorder:
Note: Suggested for use in patients with alcohol use disorder (moderate to severe) who want to abstain from alcohol and either prefer disulfiram or are unable to tolerate other oral therapies (APA [Reus 2018]). Do not administer until the patient has abstained from alcohol for at least 12 hours.
Oral: Initial: 250 mg once daily; may adjust based on response and tolerability up to 500 mg once daily (maximum: 500 mg/day) (Carroll 1998; manufacturer's labeling). Maintenance: 250 mg once daily (range: 125 to 500 mg/day; maximum: 500 mg/day).
Cocaine use disorder (adjunctive therapy) (off-label use):
Note: Used concomitantly with other substance use disorder treatments, including psychotherapy or methadone.
Oral: 250 mg once daily (Carroll 2004; Carroll 2012).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. Use with extreme caution in chronic and acute nephritis.
There are no dosage adjustments provided in the manufacturer's labeling. Use with extreme caution in hepatic cirrhosis or insufficiency.
Refer to adult dosing; use with caution, starting at low end of dosing range.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Antabuse: 250 mg [DSC]
Antabuse: 500 mg [DSC] [scored]
Generic: 250 mg, 500 mg
Yes
Oral: Administration of any medications containing alcohol (eg, elixirs), including topicals, is contraindicated. Do not administer disulfiram if alcohol has been consumed within the prior 12 hours. Morning administration is preferred but may be given at bedtime if sedation is experienced. Tablets may be crushed and mixed with liquids.
Alcohol use disorder: Management of chronic alcohol use disorder.
Limitations of use: Generally not first-line for alcohol use disorder due to tolerability issues; suggested for use in patients with alcohol use disorder (moderate to severe) who want to abstain from alcohol and either prefer disulfiram or are unable to tolerate or are unresponsive to naltrexone and acamprosate (APA [Reus 2018]).
Cocaine use disorder
Disulfiram may be confused with Diflucan
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Central nervous system: Bitter taste (garlic), drowsiness, fatigue, headache, metallic taste, peripheral neuritis, peripheral neuropathy, polyneuropathy, psychosis
Dermatologic: Acneiform eruption, allergic dermatitis, skin rash
Genitourinary: Impotence
Hepatic: Cholestatic hepatitis, fulminant hepatitis, hepatic failure (multiple case reports)
Ophthalmic: Optic neuritis
Hypersensitivity to disulfiram or any component of the formulation or to other thiuram derivatives used in pesticides and rubber vulcanization; patients receiving or using alcohol, metronidazole, paraldehyde, or alcohol-containing preparations (eg, cough syrup, tonics); psychosis; severe myocardial disease or coronary occlusion.
Concerns related to adverse effects:
• Disulfiram reaction: Ingesting alcohol, even in small amounts, during treatment with disulfiram may result in flushing, throbbing in head and neck, nausea, copious vomiting, respiratory difficulty, diaphoresis, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, marked uneasiness, weakness, vertigo, blurred vision and confusion. Severe reactions may involve respiratory depression, cardiovascular collapse, arrhythmias, myocardial infarction, acute congestive heart failure, unconsciousness, seizure and death. The intensity of the reaction is generally proportional to the amounts of disulfiram and alcohol ingested. The reaction can last from 30 minutes to several hours in more severe cases, or as long as it takes the alcohol to be metabolized. Patients should avoid alcohol consumption for >12 hours prior to administration; disulfiram reactions can occur up to 14 days after taking disulfiram if alcohol is consumed (APA [Reus 2018]).
• Hepatotoxicity: Severe (sometimes fatal) hepatitis and/or hepatic failure resulting in transplantation have been associated with use; may occur in patients with or without prior history of abnormal hepatic function. Monitor for hepatotoxicity and educate patients about signs and symptoms.
Disease-related concerns:
• Cerebral damage: Use with extreme caution in patients with cerebral damage.
• Contact dermatitis: Evaluate patients with a history of rubber contact dermatitis for hypersensitivity to thiuram derivatives before administering disulfiram.
• Diabetes: Use with extreme caution in patients with diabetes mellitus.
• Hepatic impairment: Use with extreme caution in patients with hepatic cirrhosis or impairment.
• Hypothyroidism: Use with extreme caution in patients with hypothyroidism.
• Nephritis: Use with extreme caution in patients with acute or chronic nephritis.
• Seizures: Use with extreme caution in patients with a history of seizure disorder.
Other warnings/precautions:
• Alcohol intoxication: [US Boxed Warning]: Should never be administered to a patient when they are in a state of alcohol intoxication, or without their full knowledge. The physician should instruct relatives accordingly.
• Patient information: Patients must receive appropriate counseling, including information on the disulfiram reaction, “disguised” forms of alcohol (eg, tonics, mouthwashes, cough mixtures, sauces, vinegars, aftershave lotions, back rubs) and the duration of drug activity (up to 14 days).
Substrate of CYP1A2 (minor), CYP2A6 (minor), CYP2B6 (minor), CYP2D6 (minor), CYP2E1 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (weak), CYP2E1 (strong)
Alcohol (Ethyl): Disulfiram may enhance the adverse/toxic effect of Alcohol (Ethyl). A disulfiram-like reaction may occur. Risk X: Avoid combination
Atazanavir: May diminish the therapeutic effect of Disulfiram. Risk C: Monitor therapy
Bacampicillin: May enhance the adverse/toxic effect of Disulfiram. Risk X: Avoid combination
Benznidazole: May enhance the adverse/toxic effect of Disulfiram. In particular, the risk for CNS toxicities such as psychosis may be increased. Risk X: Avoid combination
ChlordiazePOXIDE: Disulfiram may increase the serum concentration of ChlordiazePOXIDE. Risk C: Monitor therapy
Chlorzoxazone: CYP2E1 Inhibitors (Strong) may increase the serum concentration of Chlorzoxazone. Risk C: Monitor therapy
CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Cocaine (Topical): Disulfiram may increase the serum concentration of Cocaine (Topical). Risk X: Avoid combination
Dronabinol: Disulfiram may enhance the adverse/toxic effect of Dronabinol. Specifically, disulfiram may produce severe intolerance to the alcohol contained in the dronabinol oral solution. Risk X: Avoid combination
Fexinidazole: May enhance the adverse/toxic effect of Disulfiram. Risk X: Avoid combination
Flunitrazepam: Disulfiram may increase the serum concentration of Flunitrazepam. Risk C: Monitor therapy
Fosphenytoin: Disulfiram may increase the serum concentration of Fosphenytoin. Management: Avoid concomitant use of disulfiram and phenytoin when possible. Phenytoin dose adjustment will likely be necessary when starting and/or stopping concurrent disulfiram. Monitor phenytoin response and concentrations closely. Risk D: Consider therapy modification
Isoniazid: CYP2E1 Inhibitors (Strong) may increase the serum concentration of Isoniazid. Risk C: Monitor therapy
MetroNIDAZOLE (Systemic): Disulfiram may enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). In particular, the risk for CNS toxicities such as psychosis may be increased. Risk X: Avoid combination
MetroNIDAZOLE (Topical): May enhance the adverse/toxic effect of Disulfiram. In particular, the risk for CNS toxicities such as psychosis may be increased. Management: Warn patients and monitor for the development of serious CNS toxicity if topical metronidazole is used in a patient taking disulfiram. Some manufacturers of vaginal metronidazole products list disulfiram use within 2 weeks as a contraindication. Risk D: Consider therapy modification
Paraldehyde: Disulfiram may increase the serum concentration of Paraldehyde. Risk X: Avoid combination
Phenytoin: Disulfiram may increase the serum concentration of Phenytoin. Management: Avoid concomitant use of disulfiram and phenytoin when possible. Phenytoin dose adjustment will likely be necessary when starting and/or stopping concurrent disulfiram. Monitor phenytoin response and concentrations closely. Risk D: Consider therapy modification
Products Containing Ethanol: Disulfiram may enhance the adverse/toxic effect of Products Containing Ethanol. Management: Do not use disulfiram with dosage forms that contain ethanol. Risk X: Avoid combination
Theophylline: Disulfiram may increase the serum concentration of Theophylline. Risk C: Monitor therapy
Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Tinidazole: May enhance the adverse/toxic effect of Disulfiram. Risk X: Avoid combination
Tipranavir: Disulfiram may enhance the adverse/toxic effect of Tipranavir. Risk X: Avoid combination
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Disulfiram may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Disulfiram inhibits the usual metabolism of alcohol. Patients can have a disulfiram reaction (headache, nausea, vomiting, chest, or abdominal pain) if they drink alcohol concurrently. Management: Avoid all alcohol for at least 12 hours before taking a dose; disulfiram reactions can occur up to 14 days after taking disulfiram if alcohol is consumed (APA [Reus 2018]). Avoid cough syrups and elixirs containing alcohol. Avoid vinegars, cider, extracts, and foods containing alcohol.
Safety in pregnancy has not been established; there is limited data on maternal use during pregnancy (Reitnauer 1997).
Pharmacological agents should not be used for the treatment of alcohol use disorder in pregnant women unless needed for the treatment of acute alcohol withdrawal or a coexisting disorder; agents other than disulfiram are recommended for acute alcohol withdrawal.
It is not known if disulfiram is present in breast milk. Breastfeeding is not recommended by the manufacturer. Pharmacological agents should not be used for the treatment of alcohol use disorder in breastfeeding women unless needed for the treatment of acute alcohol withdrawal or a coexisting disorder; agents other than disulfiram are recommended for acute alcohol withdrawal (APA [Reus 2018]).
Do not administer disulfiram if alcohol has been consumed within the prior 12 hours.
Liver function tests (baseline and after 10 to 14 days of treatment), CBC, serum chemistries; cardiac function at baseline if clinically appropriate (APA [Reus 2018])
Disulfiram is a thiuram derivative which blocks the oxidation of alcohol at the acetaldehyde stage. When taken concomitantly with alcohol, there is an increase in serum acetaldehyde levels. High acetaldehyde causes uncomfortable symptoms including flushing, throbbing in head and neck, nausea, vomiting, diaphoresis, thirst, palpitations, chest pain, dyspnea, hyperventilation, tachycardia, syncope, weakness, blurred vision, confusion, vertigo, and hypotension. This reaction is the basis for disulfiram use in post-withdrawal long-term care of alcohol use disorder.
Onset of action: Full effect: 12 hours
Duration: ~1 to 2 weeks after last dose
Absorption: Slow
Metabolism: Reduction of disulfide linkage to diethyldithiocarbamic acid, then further metabolized via glucuronidation, non-enzymatic degradation, methylation and oxidation (Eneanya 1981)
Excretion: Feces (20% unchanged) and exhaled gases (as metabolites), urine (50% metabolites) (Eneanya 1981)
Tablets (Disulfiram Oral)
250 mg (per each): $3.40 - $11.60
500 mg (per each): $6.46 - $15.98
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