Disulfiram: A Proven Pharmacological Deterrent for Alcohol Use Disorder
| Product dosage: 60mg | |||
|---|---|---|---|
| Package (num) | Per pill | Price | Buy |
| 30 | $1.37 | $41.03 (0%) | 🛒 Add to cart |
| 60 | $1.10 | $82.06 $66.05 (20%) | 🛒 Add to cart |
| 90 | $1.01 | $123.09 $91.07 (26%) | 🛒 Add to cart |
| 120 | $0.98 | $164.12 $117.09 (29%) | 🛒 Add to cart |
| 180 | $0.93 | $246.18 $168.13 (32%) | 🛒 Add to cart |
| 270 | $0.90 | $369.27 $243.18 (34%) | 🛒 Add to cart |
| 360 | $0.88
Best per pill | $492.37 $317.24 (36%) | 🛒 Add to cart |
Synonyms | |||
Disulfiram is an established alcohol-aversion therapy medication indicated for the maintenance of abstinence in patients undergoing comprehensive treatment for chronic alcohol dependence. It functions as an aldehyde dehydrogenase inhibitor, producing a highly unpleasant physiological reaction upon ethanol consumption, thereby creating a powerful psychological and physical deterrent. This agent is intended for use as part of a supervised, integrated treatment plan that includes psychosocial support and counseling. Its efficacy is contingent upon a clear understanding of its mechanism, a commitment to complete abstinence, and consistent daily adherence under medical supervision.
Features
- Pharmacological Class: Aldehyde dehydrogenase inhibitor (ALDH inhibitor).
- Mechanism of Action: Inhibits the conversion of acetaldehyde to acetate, leading to acetaldehyde accumulation upon ethanol ingestion.
- Standard Formulation: Oral tablets, typically 250 mg or 500 mg.
- Bioavailability: Well-absorbed from the gastrointestinal tract, albeit with slow and sometimes incomplete absorption.
- Metabolism: Reduced in the body to diethyldithiocarbamate, with subsequent extensive hepatic metabolism.
- Elimination Half-life: Approximately 60-120 hours, allowing for once-daily dosing and a persistent deterrent effect even after missed doses.
- Onset of Action: The enzymatic inhibition effect begins within 1-2 hours of ingestion and can persist for up to 14 days after the last dose due to irreversible enzyme inactivation.
- Prescription Status: Available only by prescription, necessitating a formal diagnosis and treatment plan.
Benefits
- Creates a powerful physiological deterrent to alcohol consumption, reinforcing the patient’s commitment to sobriety through the threat of an immediate and unpleasant reaction.
- Provides a structured pharmacological component to a multifaceted treatment regimen, offering a tangible tool for patients and clinicians.
- Helps break the cycle of compulsive drinking by introducing a significant negative consequence for relapse, allowing patients to develop new coping mechanisms.
- The long elimination half-life supports adherence, as the protective effect remains for several days, mitigating the impact of occasional missed doses.
- When used appropriately in motivated patients, it can significantly increase the number of continuous abstinence days and improve long-term treatment outcomes.
- Empowers patients by providing a sense of active control over their recovery process within a supervised medical framework.
Common use
Disulfiram is exclusively indicated as an adjunctive agent in the management of selected patients within a supervised, comprehensive treatment program for the maintenance of abstinence from alcohol in individuals diagnosed with Alcohol Use Disorder (AUD). It is not a cure for alcoholism, nor does it diminish the craving for alcohol. Its use is predicated on the patient’s full and informed consent, a clear understanding of the disulfiram-ethanol reaction (DER), and a voluntary desire to remain abstinent. It is most effective in highly motivated, stable patients who are compliant with their medication regimen and are engaged in concurrent psychosocial therapies, such as cognitive-behavioral therapy or participation in support groups like Alcoholics Anonymous. It is sometimes used in structured settings where supervision of ingestion can be ensured.
Dosage and direction
Initialization: Treatment must never be initiated until the patient has abstained from alcohol for at least 12 hours and a baseline transaminase level (ALT/AST) has been established to rule out significant pre-existing hepatic impairment. A test dose is not routinely recommended.
Dosage Regimen:
- Maintenance Therapy: The typical maintenance dosage is 250 mg once daily (range: 125 mg to 500 mg). Dosing may occur in the morning or evening, but consistency is key.
- Initial Titration: A higher initial dose (e.g., 500 mg daily) for one to two weeks may be used in some protocols to rapidly achieve enzyme saturation, before reducing to a standard maintenance dose.
- Administration: The tablet should be swallowed whole, with water. It can be taken with or without food, though taking it with food may minimize potential gastrointestinal upset.
- Supervision: Ingestion should be supervised, especially in the initial stages of treatment, to ensure adherence. This can be done by a family member, a healthcare provider, or within a clinic setting.
Duration of Therapy: The duration of treatment is highly individualized and should continue as long as the patient is deriving therapeutic benefit and remains engaged in a comprehensive treatment plan. This can range from several months to years. Discontinuation should be gradual and medically supervised.
Precautions
- Hepatotoxicity: Disulfiram has been associated with potentially fatal hepatitis and hepatic failure. Baseline liver function tests (LFTs) must be obtained before initiation and monitored regularly (e.g., at 10-14 days, monthly for 6 months, and periodically thereafter).
- Neuropsychiatric Effects: Patients should be monitored for the emergence of depression, suicidal ideation, psychosis, or peripheral neuropathy. Any changes in mood or neurological function should be reported immediately.
- Informed Consent: The patient must be fully educated on the severe consequences of the disulfiram-ethanol reaction and must provide explicit consent. Warnings should extend to hidden sources of ethanol (e.g., sauces, mouthwashes, tonics, solvents, aftershaves).
- Pregnancy and Lactation: Disulfiram is contraindicated in pregnancy. Women of childbearing potential should use effective contraception. It is not recommended during breastfeeding.
- Rubber Reaction: Disulfiram can cause contact dermatitis upon exposure to rubber products (e.g., gloves, condoms) due to the generation of carbon disulfide, a metabolite.
- Polysubstance Use: Use with extreme caution in patients with a history of polydrug use or dependence.
Contraindications
- Hypersensitivity to disulfiram, other thiuram derivatives, or any component of the formulation.
- Severe myocardial disease or coronary occlusion.
- Psychosis or severe intellectual impairment where the patient cannot comprehend the consequences of alcohol ingestion.
- Pregnancy.
- Concurrent use of alcohol or alcohol-containing products (e.g., elixirs, tinctures).
- Concurrent use of metronidazole, paraldehyde, or other drugs that can cause a disulfiram-like reaction.
Possible side effect
Common:
- Drowsiness, fatigue, headache, metallic or garlic-like aftertaste.
- Acneiform eruptions, allergic dermatitis.
- Mild gastrointestinal disturbances (nausea, vomiting).
Less Common / Serious:
- Hepatotoxicity: From transient transaminase elevations to hepatitis, cholestasis, and hepatic failure.
- Neuropsychiatric: Polyneuritis, peripheral neuropathy, optic neuritis, memory impairment, confusion, psychosis, depression, suicidal ideation.
- Other: Impotence, hypersensitivity reactions.
Disulfiram-Ethanol Reaction (DER): This is an expected pharmacologic effect, not a side effect, but occurs upon ethanol ingestion. Symptoms include: flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitations, tachycardia, hypotension, vertigo, blurred vision, and confusion. Severe reactions can involve respiratory depression, cardiovascular collapse, arrhythmias, acute congestive heart failure, myocardial infarction, convulsions, and death.
Drug interaction
Disulfiram inhibits several hepatic microsomal enzymes, notably CYP2E1, and can alter the metabolism of many concomitant medications, leading to increased serum levels and potential toxicity.
- Warfarin: Potentiates anticoagulant effect; prothrombin time must be monitored closely and warfarin dosage reduced.
- Phenytoin: Increases phenytoin levels, risk of phenytoin toxicity (nystagmus, ataxia, lethargy); monitor levels.
- Benzodiazepines (especially those metabolized by oxidation, e.g., diazepam, chlordiazepoxide): May potentiate sedative effects and increase serum levels.
- Tricyclic Antidepressants, Theophylline: Metabolism may be inhibited, increasing their serum concentrations.
- Isoniazid: Increased risk of neurotoxic side effects and dizziness.
- Metronidazole: Concomitant use may provoke psychosis or confusional states; avoid combination.
- Cocaine: Disulfiram is being investigated for the treatment of cocaine dependence, but the combination may increase plasma cocaine levels and cardiovascular effects.
Missed dose
If a dose is missed, it should be taken as soon as remembered on the same day. If it is not remembered until the next day, the missed dose should be skipped, and the regular dosing schedule resumed. The patient should not double the dose to make up for the missed one. Due to the drug’s long half-life, the deterrent effect remains for several days after the last dose. However, adherence is critical for maintaining consistent enzymatic inhibition and psychological deterrence. Any pattern of missed doses should be discussed with the prescribing physician.
Overdose
Symptoms: Overdose can manifest as severe forms of the common side effects, including nausea, vomiting, diarrhea, neurological symptoms (drowsiness, lethargy, extrapyramidal symptoms, seizures, peripheral neuropathy), and cardiovascular instability. Severe overdose can lead to coma and death.
Management: There is no specific antidote for disulfiram overdose. Management is entirely supportive and symptomatic.
- Gastric lavage may be considered if presentation is very early after ingestion.
- Activated charcoal may be administered.
- Supportive care includes maintaining a patent airway, ensuring adequate ventilation, and managing hypotension with intravenous fluids and vasopressors if needed.
- Electrolyte imbalances and metabolic acidosis should be corrected.
- Monitor hepatic and neurological status closely. Hospitalization is required.
Storage
- Store at controlled room temperature, 20°C to 25°C (68°F to 77°F).
- Protect from light and moisture. Keep the bottle tightly closed.
- Keep out of reach of children and pets.
- Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Dispose of unused medication through a medicine take-back program or according to FDA guidelines.
Disclaimer
This information is for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The author and publisher are not responsible for any errors or omissions or for any consequences from the application of this information.
Reviews
- “As an addiction psychiatrist with over 20 years of experience, disulfiram remains a valuable tool in our arsenal for a specific patient population. Its effectiveness is almost entirely dependent on patient motivation and the structure around its administration. In committed patients who understand and fear the reaction, it acts as a powerful ‘circuit breaker’ that provides them with the time and space to engage meaningfully in therapy. The hepatic monitoring is non-negotiable.” – Dr. A., MD, Psychiatry.
- “From a clinical pharmacology perspective, disulfiram is a fascinating drug. Its mechanism is straightforward, but its clinical application is complex. The long half-life is a double-edged sword; it aids adherence but also means the risk of ethanol interaction and drug interactions persists long after discontinuation. It demands respect and meticulous management from the prescriber.” – Clinical Pharmacist Specialist.
- “The reviews from patients are profoundly binary. For those who successfully use it, it’s described as a ’life-saving guardrail.’ They appreciate the concrete consequence that helps them resist impulsive drinking. However, the experience of an accidental disulfiram-ethanol reaction, often from a hidden alcohol source, is universally described as one of the most terrifying experiences of their lives, which ultimately reinforces its deterrent power.” – Addiction Counselor, LCSW.