DISULFIRAM
Clinical safety rating
cautionAnimal studies have proved adverse effects but may be safe for humans
Disulfiram irreversibly inhibits aldehyde dehydrogenase, causing accumulation of acetaldehyde after alcohol ingestion, leading to aversive effects such as flushing, nausea, and hypotension.
| Metabolism | Disulfiram is rapidly metabolized in the liver to diethyldithiocarbamate, which is further metabolized; it is primarily excreted in urine and feces. |
| Excretion | Primarily renal as metabolites; approximately 80% of a dose is excreted in urine as glucuronide conjugates and other metabolites, with less than 20% excreted in feces via bile. A small amount is eliminated unchanged in urine. |
| Half-life | Approximately 7–10 hours for parent drug; however, the disulfiram-ethanol reaction can persist up to 14 days due to irreversible inhibition of aldehyde dehydrogenase (ALDH) and slow regeneration of the enzyme. The active metabolite, diethyldithiocarbamate, has a half-life of about 15 hours. |
| Protein binding | Approximately 96% bound primarily to albumin and also to lipoproteins. |
| Volume of Distribution | Approximately 2–4 L/kg, indicating extensive tissue distribution and accumulation, particularly in adipose tissue due to lipophilicity. |
| Bioavailability | Rapidly and almost completely absorbed after oral administration; absolute bioavailability is approximately 70–90% due to first-pass metabolism in the liver. No parenteral forms are approved; only oral route (tablets) is used clinically. |
| Onset of Action | For ethanol sensitization: maximal inhibition of ALDH occurs within 12–24 hours after oral administration, but the full sensitivity to ethanol may take several days to develop. No immediate clinical effect; the drug must be present in the body to react with ethanol. |
| Duration of Action | The sensitizing effect to ethanol lasts at least 7–14 days after the last dose, as ALDH activity recovers slowly. This duration varies with renal and hepatic function; caution with alcohol ingestion for up to 14 days after discontinuation. |
| Molecular Weight | 296.55 |
| Action Class | Alcohol deaddiction |
| Brand Substitutes | Antadict 250mg Tablet, Zanofiram 250mg Tablet, Lifexone 250mg Tablet, D Sulf 250mg Tablet, Desulf 250mg Tablet |
250 mg orally once daily, increased to 500 mg orally once daily if needed; maintenance dose typically 250 mg per day (range 125-500 mg).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment; no specific GFR-based guidelines exist; use with caution in severe renal impairment. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). In mild to moderate impairment (Child-Pugh A or B), no specific dose adjustment, but monitor liver function. Not recommended in active liver disease. |
| Pediatric use | Not recommended for use in patients under 18 years due to lack of established safety and efficacy. |
| Geriatric use | Initiate at lower dose (125 mg/day) due to age-related decreased function; monitor closely for adverse effects. |
| 1st trimester | Contraindicated due to risk of severe fetal malformations (alcohol-disulfiram reaction may cause fetal hypoxia and acidosis). |
| 2nd trimester | Contraindicated due to potential teratogenicity and risk of maternal-fetal alcohol reaction. |
| 3rd trimester | Contraindicated due to risk of withdrawal in neonate and maternal-fetal alcohol reaction. |
Clinical note
Metronidazole and alcohol-containing products can cause a disulfiram-like reaction Can cause hepatotoxicity and psychiatric disturbances.
| Placental transfer | Disulfiram crosses the placenta; animal studies show fetal toxicity. Human data limited but considered high risk. |
| Breastfeeding | Disulfiram is excreted into breast milk in small amounts. Potential for adverse effects in the infant, including disulfiram-ethanol reaction if infant exposed to alcohol. Avoid breastfeeding during therapy. |
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | Pregnancy Category C. First trimester: Limited human data; animal studies show embryotoxic effects at high doses. Avoid unless benefit outweighs risk. Second and third trimesters: No specific malformation patterns reported; however, theoretical risk of disulfiram-ethanol reaction causing fetal hypoxia due to maternal acetaldehyde accumulation. Use only if essential and with strict alcohol avoidance. |
| Fetal Monitoring | Monitor liver function tests (AST, ALT, GGT) at baseline and periodically. Assess ethanol abstinence via patient history and breathalyzer or blood alcohol levels. Monitor for signs of hepatitis, peripheral neuropathy, or optic neuritis. Fetal ultrasound for growth and anatomy if exposed in first trimester. |
| Fertility Effects | No known direct effects on fertility in animal studies. Impairment of spermatogenesis has not been reported. Unlikely to significantly impact male or female fertility, but alcohol abuse itself can impair fertility; disulfiram may improve fertility by promoting abstinence. |
■ FDA Black Box Warning
Disulfiram should never be administered to a patient who is in a state of alcohol intoxication or without the patient's full knowledge and consent. The patient must be fully informed of the disulfiram-alcohol reaction.
| Serious Effects |
Concurrent use of alcohol or alcohol-containing productsConcurrent use of metronidazoleSevere myocardial disease or coronary occlusionPsychosis or severe psychiatric disordersHypersensitivity to disulfiram or thiuram derivatives
| Precautions | Hepatotoxicity including hepatitis and hepatic failure; peripheral neuropathy; optic neuritis; psychotic reactions; hypersensitivity; risk of severe disulfiram-alcohol reaction if alcohol is consumed. |
| Food/Dietary | Avoid foods and products containing alcohol: sauces (e.g., wine sauces, beer batter), vinegar (especially red/white wine vinegar), marinades, ripe fruits (fermentation can produce trace alcohol), some desserts (e.g., tiramisu, fruitcakes), alcohol-infused chocolates, non-alcoholic beer/wine (may contain up to 0.5% alcohol). Also avoid mouthwashes, breath sprays, and hand sanitizers with ethanol. Some medications like paraldehyde, chloral hydrate, and metronidazole may cross-react. Even alcohol in cooking may not fully evaporate and can trigger a reaction. |
| Clinical Pearls | Disulfiram irreversibly inhibits aldehyde dehydrogenase, causing accumulation of acetaldehyde after alcohol ingestion, leading to severe nausea, vomiting, hypotension, and flushing. Avoid use in patients with severe heart disease, psychosis, or cirrhosis. Monitor LFTs and CBC at baseline and periodically. Disulfiram may also inhibit CYP450 enzymes (CYP2E1, CYP1A2, CYP3A4), potentiating warfarin, phenytoin, and theophylline. Onset of aversion therapy requires 12-48 hours after the last alcohol dose; maintain alcohol-free period of 24 hours before starting. Duration of action persists up to 14 days after discontinuation. Inadvertent alcohol exposure in topical products (mouthwash, colognes) can trigger reactions. |
| Patient Advice | Avoid all forms of alcohol, including beverages, mouthwash, cough syrup, cooking wine, vinegar, aftershave, and hand sanitizers. · Reaction to alcohol includes severe flushing, nausea, vomiting, chest pain, difficulty breathing, and blurred vision; seek emergency care if symptoms occur. · The disulfiram-alcohol reaction can be fatal even with small amounts of alcohol. · Inform all healthcare providers (including dentists) that you are taking disulfiram. · Reactions may occur up to 14 days after stopping the medication. · Do not take disulfiram if you have recently consumed alcohol; wait at least 12 hours after the last drink. · Carry a medical alert card or wear a bracelet stating you are on disulfiram. · Report any signs of liver toxicity: yellowing of eyes/skin, dark urine, severe fatigue. |
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