ANTABUSE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ANTABUSE (ANTABUSE).
Irreversibly inhibits aldehyde dehydrogenase (ALDH), causing accumulation of acetaldehyde after alcohol ingestion, leading to aversive reaction.
| Metabolism | Metabolized primarily in the liver to diethyldithiocarbamate, which is further metabolized and excreted renally; minor CYP involvement. |
| Excretion | Primarily renal: 80-90% as metabolites (mainly diethyldithiocarbamate and its glucuronide, plus sulfate esters) within 24 hours; <20% fecal (unabsorbed disulfiram and biliary metabolites). |
| Half-life | 10.8 ± 3.5 hours (range 6-16 hours) for disulfiram; metabolites (e.g., 2-mercapto-2-methyl-4-butyl-γ-thiobutyrolactone) have prolonged half-lives up to 120-200 hours, contributing to sustained sensitivity to ethanol. |
| Protein binding | 96% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 1.8 L/kg (range 1.3-2.4 L/kg); indicates extensive tissue distribution, with accumulation in adipose tissue and slow release. |
| Bioavailability | Oral: ~80-90% (extensive first-pass metabolism to diethyldithiocarbamate; parent drug bioavailability is low due to rapid hepatic reduction). |
| Onset of Action | Oral: Maximal inhibition of aldehyde dehydrogenase occurs within 12 hours after a single dose, but peak effect develops over 4-5 days with daily dosing; topical/intramuscular: not applicable. |
| Duration of Action | Clinically significant ethanol sensitivity persists for 2-14 days after last disulfiram dose due to irreversible inhibition of aldehyde dehydrogenase and slow enzyme resynthesis; duration depends on dose and individual metabolic factors. |
250 mg orally once daily, initiated after 12 hours of no alcohol intake; maintenance dose may be reduced to 125 mg daily based on tolerance.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment required for renal impairment; however, caution is advised in severe renal impairment due to potential accumulation of metabolites. |
| Liver impairment | Contraindicated in severe hepatic impairment or Child-Pugh class C cirrhosis. In mild to moderate impairment (Child-Pugh A or B), use with caution and consider reduced dosing; no specific dose recommendations exist. |
| Pediatric use | Not approved for use in children; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; monitor for increased sensitivity and adverse effects, particularly hepatotoxicity, and start at lower end of dosing range (125 mg daily) if warranted. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ANTABUSE (ANTABUSE).
| Breastfeeding | Not recommended. M/P ratio unknown; disulfiram and its metabolite may pass into breast milk; potential for toxicity in breastfed infant. |
| Teratogenic Risk | First trimester: limited data, but not associated with major malformations. Second trimester: potential for disulfiram-ethanol reaction causing maternal hypotension and fetal hypoxia. Third trimester: risk of disulfiram-ethanol reaction; avoid use near term due to neonatal withdrawal risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
Never administer to a patient in a state of alcohol intoxication or without their full knowledge. Do not use in patients with severe myocardial disease or coronary occlusion.
| Common Effects | Dryness in mouth Constipation Blurred vision Nausea Upset stomach Urinary tract infection |
| Serious Effects |
["Recent or concurrent ingestion of alcohol or alcohol-containing products","Severe myocardial disease or coronary occlusion","Hypersensitivity to disulfiram or other thiuram derivatives","Psychosis"]
| Precautions | ["Hepatotoxicity including hepatitis and hepatic failure","Peripheral neuropathy","Psychotic reactions","Hypersensitivity reactions","Must abstain from alcohol for at least 12 hours before starting therapy"] |
| Food/Dietary |
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| Monitor liver function tests (LFTs) periodically. Educate patient to avoid all ethanol exposure; monitor for signs of disulfiram-ethanol reaction (flushing, hypotension, nausea, vomiting). |
| Fertility Effects | No known direct effects on fertility. However, its use in alcohol use disorder may improve overall health and indirectly benefit fertility. |
| Avoid all foods and beverages containing alcohol including cooking wines, vinegar, certain sauces (e.g., Worcestershire), some desserts (e.g., rum cake), and overripe fruit. Alcohol used in cooking does not always fully evaporate; avoid any food prepared with alcohol. Also avoid products like alcohol-free beer or wine that may contain trace amounts. |
| Clinical Pearls | Initiate only after patient has abstained from alcohol for at least 12 hours. Monitor liver function tests baseline and periodically. Avoid alcohol in all forms including mouthwash, cough syrups, and topical preparations. Disulfiram reaction can be severe and potentially fatal. Use extreme caution in patients with liver disease, diabetes, or seizure disorders. |
| Patient Advice | Do not consume any alcohol while taking this medication, including beer, wine, liquor, and alcohol-containing products like mouthwash, cough syrup, and cooking extracts. · Avoid hidden sources of alcohol such as vinegar, certain sauces, and fermentation products. · Symptoms of alcohol reaction include flushing, nausea, vomiting, headache, chest pain, and difficulty breathing; seek immediate medical attention if these occur. · Take the medication exactly as prescribed, usually once daily in the morning. · Inform all healthcare providers (doctors, dentists, pharmacists) that you are taking Antabuse. · Do not stop taking the medication without consulting your doctor, as alcohol sensitivity may persist for up to 14 days after the last dose. · Carry an identification card stating you are taking Antabuse in case of emergency. · Report any signs of liver problems such as jaundice, dark urine, or abdominal pain to your doctor immediately. |