Version October 2024
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, moderate to severe (alternative agent):
Note: Suggested for use in patients who want to abstain from alcohol, have sufficient social support, and either prefer disulfiram or are unable to tolerate other preferred therapies (Ref). Do not administer until the patient has abstained from alcohol for at least 12 hours (Ref); some experts suggest waiting 48 hours (Ref). Patients should be advised that reactions with alcohol can occur up to 14 days after taking disulfiram (Ref).
Oral: Initial: 250 to 500 mg once daily for 1 to 2 weeks; afterward, may adjust based on response and tolerability to a maintenance range of 125 to 500 mg once daily; usual maintenance dose: 250 mg once daily; maximum dose: 500 mg/day. Some experts consider alternative therapy if goals are not met within 6 months of treatment (Ref).
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 (Ref).
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.
The following adverse drug reactions are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
Postmarketing:
Dermatologic: Allergic dermatitis (Fusta-Novell 2018), exfoliative dermatitis (Radaschin 2020), macular eruption (Radaschin 2020), pruritus (Radaschin 2020), skin rash
Genitourinary: Impotence (Ranek 1977)
Hepatic: Hepatic failure (Ranek 1977), hepatitis (including cholestatic hepatitis and fulminant hepatitis) (Kahn 1990; Mohanty 2004), hepatotoxicity (Ranek 1977)
Hypersensitivity: Hypersensitivity reaction (including acneiform eruption, erythema of skin, and exfoliation of skin) (Nassberger 1984)
Nervous system: Abnormal behavior (punding) (Fan 2008), bitter taste (garlic) (Kump 1979), catatonia (Reisberg 1978), delusion (Capgras syndrome) (Daniel 1987), drowsiness (Radaschin 2020), encephalopathy (organic brain syndrome) (Kump 1979; Reisberg 1978), fatigue (Radaschin 2020), headache (Radaschin 2020), manic behavior (with psychosis) (Li 2008), metallic taste (Kump 1979; Radaschin 2020), neuropathy (including axonal peripheral polyneuropathy, peripheral neuropathy, polyneuropathy, and sensorimotor neuropathy) (Coronel 2022; Tran 2016; Watson 1980), psychotic reaction (including delirium) (Rossiter 1992), seizure (Daniel 1987)
Ophthalmic: Optic neuritis (Leibold 1971)
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.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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 (manufacturer’s labeling); some experts suggest waiting 48 hours (Holt 2022). 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).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Antabuse: 250 mg [DSC], 500 mg [DSC]
Generic: 250 mg, 500 mg
Yes
Tablets (Disulfiram Oral)
250 mg (per each): $3.40 - $11.60
500 mg (per each): $15.98
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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 (Ref); some experts suggest waiting 48 hours (Ref). 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, moderate to severe: 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
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)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
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
Fezolinetant: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination
Flunitrazepam: Disulfiram may increase the serum concentration of Flunitrazepam. Risk C: Monitor therapy
Fosphenytoin-Phenytoin: Disulfiram may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy
Ilaprazole: May increase the serum concentration of Disulfiram. Risk C: Monitor therapy
Isoniazid: CYP2E1 Inhibitors (Strong) may increase the serum concentration of Isoniazid. Risk C: Monitor therapy
Kombucha: Disulfiram may enhance the adverse/toxic effect of Kombucha. A disulfiram-like reaction may occur. Risk X: Avoid combination
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
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: May enhance the adverse/toxic effect of Disulfiram. 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 (manufacturer’s labeling); some experts suggest waiting 48 hours (Holt 2022). 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 (manufacturer’s labeling); some experts suggest waiting 48 hours (Holt 2022).
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)
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