What is the appropriate use and dosing of Disulfiram (Antabuse) tablets for an adult patient with a history of chronic alcoholism?

Disulfiram for Chronic Alcoholism

Disulfiram (250-500 mg daily) is an effective alcohol-aversive medication for alcohol-dependent patients WITHOUT advanced liver disease, but it must be avoided in patients with severe alcoholic liver disease due to hepatotoxicity risk. 1

Patient Selection and Contraindications

Critical exclusion: Disulfiram should be avoided in patients with severe or advanced alcoholic liver disease (ALD) because of potential hepatotoxicity. 1

Ideal candidates for disulfiram include: 2, 3

• Older patients with greater social stability
• Well-motivated individuals committed to abstinence
• Patients who can participate in supervised administration programs
• Those without advanced liver disease or cirrhosis

Alternative medications for patients with advanced ALD: Baclofen (10 mg three times daily) is the only medication proven safe and effective in patients with cirrhosis and should be used instead. 4, 5

Dosing Protocol

Initial phase (weeks 1-2): 6

• Patient must abstain from alcohol for at least 12 hours before first dose
• Start with 500 mg daily as a single dose
• Usually taken in morning; may switch to bedtime if sedation occurs
• Dosage may be adjusted downward to minimize sedative effects

Maintenance phase: 6

• Average dose: 250 mg daily (range 125-500 mg)
• Maximum dose: 500 mg daily
• Continue daily, uninterrupted administration for months to years until social recovery and permanent self-control established

Important caveat: Some patients may report drinking without symptoms while on adequate doses—this typically indicates non-compliance (disposing of tablets) rather than medication failure. Supervised administration with crushed tablets mixed in liquid is recommended to ensure compliance. 6

Evidence Quality and Efficacy

The evidence for disulfiram is mixed (Grade B), with important nuances: 7

What disulfiram DOES accomplish: 3

• Reduces drinking frequency after relapse (49 drinking days vs. 86.5 days in controls over one year)
• Most effective when compliance is supervised
• Works as adjunctive therapy combined with counseling

What disulfiram does NOT accomplish: 2, 3

• Does not substantially enhance continuous abstinence rates
• Does not delay time to first drink
• Has no proven effect on long-term alcoholism outcomes
• Ineffective without accompanying education, counseling, and concomitant alcoholism therapy

Dosing Adequacy Concerns

Common pitfall: The standard 200-250 mg dose is often inadequate. 8

• Only 50% of patients produce significant alcohol-aversive reactions at 200-300 mg daily
• Some patients require up to 1.5 g daily for adequate response
• Significant side effects remain uncommon even at high doses and are reversible

Mandatory Concurrent Treatment

Disulfiram must ALWAYS be combined with: 1, 2

• Brief motivational interventions (Recommendation A1)
• Psychosocial support and counseling
• Regular clinical supervision and monitoring for efficacy and side effects
• Patient education about risks of drinking while taking the medication

Monitoring and Safety

Cardiac, hepatic, and neurologic toxicity can occur at therapeutic doses (250-500 mg/day). 2

Essential monitoring includes: 4, 5

• Regular liver function tests to assess for hepatotoxicity
• Clinical assessment for neurologic and cardiac complications
• Verification of medication compliance

Alcohol-Disulfiram Reaction Management

The test reaction with alcohol is largely abandoned and should NEVER be performed in patients over 50 years old. 6

If severe reaction occurs: 6

• Supportive measures to restore blood pressure and treat shock
• Oxygen or carbogen (95% oxygen/5% carbon dioxide)
• Vitamin C intravenously in massive doses (1 g)
• Ephedrine sulfate
• Antihistamines intravenously
• Monitor potassium levels, particularly in patients on digitalis (hypokalemia reported)

First-Line Alternatives

For patients without advanced liver disease, consider instead: 4, 5

• Naltrexone 50 mg daily (NNT ~20 for preventing heavy drinking relapse)
• Acamprosate 666 mg three times daily (NNT ~12 for preventing return to any drinking)

These medications have stronger evidence (Grade A) and better safety profiles than disulfiram. 4, 7