What are the indications, dosing, contraindications, monitoring requirements, and alternative pharmacologic options for using antabuse (disulfiram) in a patient with alcohol use disorder who has been abstinent for at least 12 hours and has normal liver function?

Disulfiram (Antabuse) in Alcohol Use Disorder

Critical Contraindication in Liver Disease

Disulfiram must be avoided entirely in patients with severe alcoholic liver disease due to documented hepatotoxicity risk, including cases of fatal hepatitis. 1, 2

The American Association for the Study of Liver Diseases explicitly excludes disulfiram from their relapse-prevention medication table for patients with alcoholic liver disease, stating it is "not recommended for use in patients with ALD." 1 European hepatology guidelines reinforce this contraindication in hepatic insufficiency. 2

---

Indications

Disulfiram is FDA-approved as an adjunctive treatment for alcohol use disorder in motivated patients who have achieved complete abstinence and require an aversive deterrent to prevent relapse. 3

Patient Selection Criteria

• The patient must be highly motivated and understand the risks of drinking while taking disulfiram 3
• Older, socially stable patients with strong external support systems derive the greatest benefit 3
• The patient must agree to continued clinical supervision and monitoring 3
• Supervised administration (by a family member or healthcare provider) significantly improves compliance and short-term efficacy 3

---

Absolute Contraindications

• Severe alcoholic liver disease or any degree of hepatic dysfunction 1, 2
• Acute hepatitis or elevated liver enzymes 2
• Cardiac disease (due to risk of severe cardiovascular reactions during disulfiram-alcohol interaction) 4
• Active alcohol consumption or ongoing withdrawal symptoms 5
• Psychosis or severe psychiatric illness (disulfiram can precipitate confusional states) 4

---

Timing of Initiation

Disulfiram should never be started at 12 hours after the last drink; the patient must complete alcohol withdrawal first. 5

Correct Timing Protocol

• Alcohol withdrawal symptoms begin 6–24 hours after the last drink and peak at days 3–5 6, 5
• Wait until benzodiazepine-based withdrawal management is complete (typically 7–14 days after the last drink) 5
• Ensure all withdrawal symptoms have fully resolved before initiating disulfiram 5
• The patient must have achieved complete abstinence for at least 12 hours minimum, but ideally 1–2 weeks 5, 3

---

Dosing

Standard Regimen

• Initial dose: 500 mg orally once daily for 1–2 weeks 3
• Maintenance dose: 250 mg orally once daily (range 125–500 mg/day) 3
• Some patients may not experience an aversive reaction at 250 mg/day and may require 500 mg/day 3

Duration

• Short-term efficacy is proven for approximately 6 months in compliant patients 3
• No proven effect on long-term outcome of alcoholism beyond 6 months 3
• Disulfiram should not be prescribed indefinitely without reassessment 3

---

Mechanism of Action

Disulfiram inhibits aldehyde dehydrogenase, causing accumulation of acetaldehyde when alcohol is consumed, producing an intensely unpleasant reaction (flushing, nausea, vomiting, tachycardia, hypotension). 3

However, the psychological deterrent effect—the symbolic act of taking a daily pill representing a commitment not to drink—may be equally or more important than the physiological aversive reaction. 7 The medication removes the need for constant rumination about drinking decisions and provides external structure. 7

---

Monitoring Requirements

Baseline Assessment

• Liver function tests (AST, ALT, bilirubin, alkaline phosphatase) to exclude hepatic dysfunction 2, 4
• Cardiovascular evaluation to exclude cardiac disease 4
• Psychiatric assessment to exclude psychosis or severe mental illness 4

Ongoing Monitoring

• Regular clinical contact (at minimum monthly) to assess compliance, side effects, and drinking status 3, 4
• Liver function tests are probably not necessary if the patient remains in regular contact with a physician and reports no symptoms 4
• However, patients must be instructed to report immediately any fatigue, jaundice, dark urine, or abdominal pain 4, 8

---

Hepatotoxicity Risk

The estimated incidence of disulfiram-induced fatal hepatitis is 1 in 30,000 patients treated per year. 4

• Hepatotoxicity can range from mild transaminase elevation to fulminant hepatitis leading to death 8
• Liver injury typically presents with portal inflammation, eosinophils, and hepatocyte necrosis on biopsy 8
• Most cases resolve with drug withdrawal; some require a brief course of corticosteroids 8
• The risk is higher in patients with pre-existing liver disease, which is why disulfiram is contraindicated in this population 1, 2

---

Other Adverse Effects

Common (Dose-Related)

• Fatigue, headache, drowsiness (most common) 4
• Metallic or garlic-like aftertaste 4

Serious (Rare, Dose-Related)

• Peripheral neuropathy (dose-related; more common at doses >500 mg/day) 4
• Optic neuritis (dose-related) 4
• Psychosis or confusional states (more common in India than Western countries) 4

Drug Interactions

• Disulfiram inhibits cytochrome P450 enzymes, leading to interactions with warfarin, phenytoin, benzodiazepines, and other drugs metabolized by this system 4

---

Disulfiram-Alcohol Reaction

Deaths from the disulfiram-alcohol reaction have not been reported in recent years, likely because current dosing (250–500 mg/day) is lower than historical doses and patients with cardiac disease are now excluded. 4

However, patients must clearly understand that consuming alcohol while taking disulfiram will produce severe symptoms including flushing, nausea, vomiting, chest pain, palpitations, hypotension, and confusion. 3

---

Integration with Psychosocial Treatment

Disulfiram is only an adjunctive therapy; prescribing it without accompanying education, counseling, and concomitant alcoholism therapy is not beneficial. 3

• Cognitive-behavioral therapy, motivational enhancement therapy, or 12-step facilitation must be provided concurrently 1, 3
• Supervised administration by a family member or in a clinic setting significantly improves outcomes 3
• The symbolic act of taking the medication daily reinforces the commitment to abstinence and provides external structure 7

---

Alternative Pharmacologic Options

For Patients with Normal Liver Function

Naltrexone 50 mg daily or acamprosate 666 mg three times daily are first-line alternatives to disulfiram, with superior evidence for efficacy and safety. 2

• Naltrexone (NNT = 20 for preventing any drinking) reduces heavy-drinking episodes but is contraindicated in liver disease 1, 2
• Acamprosate (NNT = 12 for abstinence) has no hepatic metabolism and zero hepatotoxicity risk, making it safe in any degree of liver disease 2
• Both should be initiated 3–7 days after the last drink, once withdrawal has resolved 2

For Patients with Alcoholic Liver Disease or Cirrhosis

Baclofen (30–80 mg/day) is the only medication with validated efficacy and safety in cirrhotic patients and is the preferred first-line agent in this population. 1, 2

• Baclofen is a GABA-B receptor agonist that reduces craving and relapse risk 1
• It should be titrated gradually over 12 weeks, with slower titration in severe liver disease 2
• Gabapentin (1800 mg/day) is a second-line option with no hepatic metabolism 2

---

Common Pitfalls to Avoid

• Never initiate disulfiram during active withdrawal (12 hours is far too early) 5
• Never prescribe disulfiram to patients with any elevation of liver enzymes or hepatic dysfunction 1, 2
• Never prescribe disulfiram without concurrent psychosocial treatment—it is ineffective as monotherapy 3
• Never assume compliance—supervised administration dramatically improves outcomes 3
• Never prescribe disulfiram to patients with cardiac disease due to risk of severe cardiovascular reactions 4