Disulfiram is an irreversible inhibitor of aldehyde dehydrogenase (ALDH), used as an aversive agent in the management of chronic alcoholism. It produces an acute sensitivity to ethanol, leading to an unpleasant reaction (disulfiram-ethanol reaction) upon alcohol ingestion, which serves as a deterrent. It is a second-line pharmacotherapy for alcohol use disorder (AUD) in India, used as part of a comprehensive treatment program including counseling and psychosocial support.
Adult: Initial (loading): 500 mg daily for 1-2 weeks. Maintenance: 125 mg to 500 mg daily (commonly 250 mg/day). Maximum recommended maintenance dose is 500 mg/day. Therapy should be initiated only after the patient has abstained from alcohol for at least 12 hours.
Note: Administer orally, once daily, preferably in the morning. Can be taken with or without food. Tablet should be swallowed whole with a glass of water. For patients on maintenance therapy, a family member should supervise administration to ensure compliance.
Disulfiram irreversibly inhibits the mitochondrial isoform of aldehyde dehydrogenase (ALDH2). Normally, ethanol is metabolized to acetaldehyde by alcohol dehydrogenase (ADH). Acetaldehyde is then rapidly converted to acetate by ALDH. By inhibiting ALDH, disulfiram causes a rapid and marked accumulation of acetaldehyde in the blood upon ethanol ingestion. Acetaldehyde is a toxic metabolite responsible for the highly unpleasant 'disulfiram-ethanol reaction' (DER).
Pregnancy: Category C (US FDA). Contraindicated. Animal studies have shown teratogenicity. There is no adequate and well-controlled data in pregnant women. Risk of DER poses a threat to both mother and fetus.
Driving: May cause drowsiness, dizziness, or blurred vision. Patients should be cautioned against driving or operating heavy machinery until their response to the drug is known.
| Ethanol (in any form: beverages, tonics, elixirs, sauces, vinegars) | Precipitates the disulfiram-ethanol reaction (DER). | Contraindicated |
| Metronidazole, Tinidazole, Secnidazole | May cause psychotic reactions; confusional state; additive disulfiram-like reaction with alcohol. | Major |
| Phenytoin | Disulfiram inhibits its metabolism, leading to phenytoin toxicity (nystagmus, ataxia, drowsiness). | Major |
| Warfarin and other Coumarin anticoagulants | Disulfiram potentiates anticoagulant effect, increasing risk of bleeding. Requires frequent INR monitoring. | Major |
| Theophylline | Disulfiram decreases its clearance, leading to potential theophylline toxicity. | Moderate |
| Tricyclic Antidepressants (e.g., Amitriptyline) | Increased levels of TCA due to metabolic inhibition. | Moderate |
| Benzodiazepines (e.g., Diazepam, Chlordiazepoxide) | Disulfiram may reduce clearance, potentiating sedative effects. | Moderate |
| Isoniazid | Increased risk of CNS effects like dizziness, incoordination. | Moderate |
| Paraldehyde | Contraindicated due to metabolic interaction. | Contraindicated |