Disulfiram

# Disulfiram ## Overview - **Classification**: Aldehyde dehydrogenase inhibitor, Alcohol deterrent - **Mechanism**: Blocks the enzyme aldehyde dehydrogenase, leading to accumulation of acetaldehyde if alcohol is consumed. This causes an unpleasant disulfiram-alcohol reaction. ## Primary Indications 1. **Chronic Alcoholism**: Adjunct to management of chronic alcoholism. 2. **Alcohol Deterrent**: To maintain abstinence in selected patients. ## Adult Dosing ### Standard Dosing **Chronic Alcoholism** - **Dose**: **500 mg** - **Frequency**: Once daily, usually in the morning or at bedtime - **Route**: Oral - **Duration**: 1-2 weeks (initial dose) - **Special Considerations**: Administer after a period of at least 12 hours of alcohol abstinence. **Maintenance Dosing** - **Dose**: **250 mg** (range **125-500 mg**) - **Frequency**: Once daily - **Route**: Oral - **Maximum Dose**: **500 mg** daily - **Duration**: Continued until patient is fully recovered socially and response is stable, typically months to years. ### Dose Adjustments - **Renal Impairment**: No specific dose adjustments provided. Use with caution due to lack of data. - **Hepatic Impairment**: Contraindicated in severe hepatic impairment. Use with extreme caution and reduced doses in mild-moderate impairment due to risk of hepatotoxicity. Baseline LFTs are crucial. - **Elderly Patients**: No specific dose adjustments, but start with lower end of maintenance dose (**125-250 mg**) and titrate slowly due to increased sensitivity and potential for adverse effects. ## Pediatric Dosing *Safety and efficacy of disulfiram have not been established in pediatric patients.* - **General Note**: Disulfiram is not recommended for use in pediatric patients. ### Neonates (0-28 days) - **Dose**: Not recommended. - **Special Notes**: Safety and efficacy not established. ### Infants (1-12 months) - **Dose**: Not recommended. ### Children (1-12 years) - **Dose**: Not recommended. ### Adolescents (13-18 years) - **Dose**: Not recommended. If considered in rare circumstances, adult dosing may be approached with caution after careful risk/benefit assessment, but not typically indicated. - **Maximum**: Not applicable, as generally not recommended. ## Safety Information ### Contraindications - **Absolute**: Recent alcohol ingestion (within 12 hours) or alcohol intoxication. - **Absolute**: Severe myocardial disease or coronary occlusion. - **Absolute**: Psychosis, suicide risk, or other psychiatric conditions where disulfiram may worsen symptoms. - **Absolute**: Concomitant use with metronidazole, alcohol-containing preparations (e.g., cough syrups, mouthwashes). - **Absolute**: Hypersensitivity to disulfiram or other thiuram derivatives used in pesticides or rubber vulcanization. - **Relative**: Severe hepatic impairment, renal insufficiency. ### Common Adverse Effects - **Very Common (>10%)**: Drowsiness, headache, fatigue, metallic or garlic-like aftertaste. - **Common (1-10%)**: Skin rash, acne, erectile dysfunction, mild gastrointestinal upset (nausea, vomiting, diarrhea). - **Serious but Rare**: - **Disulfiram-Alcohol Reaction**: Severe flushing, throbbing head/neck, nausea, vomiting, sweating, thirst, chest pain, palpitations, dyspnea, hyperventilation, hypotension, syncope, vertigo. Can be fatal. - **Hepatotoxicity**: Fulminant hepatitis, hepatic failure (monitor LFTs). - **Neurological**: Peripheral neuropathy, optic neuritis, psychiatric disturbances (depression, psychosis, mania). - **Dermatologic**: Severe allergic dermatitis. ### Key Drug Interactions - **Alcohol (Ethanol)**: **Severe, potentially fatal disulfiram-alcohol reaction** with any form of alcohol (oral, topical, inhaled). Avoid all alcohol for up to 14 days after last disulfiram dose. - **Metronidazole**: Concomitant use **contraindicated** due to risk of toxic psychosis. - **Warfarin**: Disulfiram can inhibit warfarin metabolism, increasing INR and bleeding risk. **Monitor INR closely**, adjust warfarin dose. - **Phenytoin**: Disulfiram can inhibit phenytoin metabolism, increasing phenytoin levels and toxicity. **Monitor phenytoin levels**, adjust dose. - **Isoniazid**: Concomitant use may lead to adverse CNS effects (ataxia, changes in behavior). **Monitor closely**. - **Theophylline**: Disulfiram may increase theophylline levels. **Monitor theophylline levels**. ## Monitoring & Follow-up - **Before Treatment**: - **Complete physical exam**, including neurological and ophthalmic. - **Baseline LFTs** (ALT, AST, alkaline phosphatase, bilirubin). - **CBC with differential**, **renal function tests**. - **Psychiatric evaluation** to rule out contraindications. - **During Treatment**: - **LFTs**: At baseline, at 10-14 days, then periodically (e.g., monthly for 3 months, then quarterly). Discontinue if LFTs rise significantly (>3x ULN). - **Clinical Signs**: Monitor for signs of hepatotoxicity (fatigue, anorexia, dark urine, jaundice), peripheral neuropathy (tingling, numbness), and psychiatric changes. - **Neurological/Ophthalmic exams**: Periodically, especially if symptoms develop. ## Clinical Pearls - 💡 **Strict Alcohol Avoidance**: Patients MUST understand to avoid all forms of alcohol for the duration of treatment and for **up to 14 days** after the last dose. This includes hidden alcohol in foods, mouthwashes, hand sanitizers, cough/cold remedies, vinegars, and aftershaves. - 💡 **Patient Education**: Provide thorough counseling on the severe consequences of consuming alcohol while on disulfiram. A written list of alcohol-containing products is helpful. - 💡 **Timing**: Administering disulfiram at bedtime may help mitigate drowsiness, a common side effect. - 💡 **Discontinuation**: Disulfiram's effects on alcohol metabolism can persist for up to 2 weeks after stopping the drug. - 💡 **Medical Alert**: Patients should carry a medical alert card stating they are taking disulfiram. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.