Disulfiram: A Proven Pharmacological Deterrent for Alcohol Dependence
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Synonyms | |||
Disulfiram is an established alcohol-aversion therapy medication, prescribed as part of a comprehensive treatment plan for chronic alcohol use disorder. Its unique mechanism of action provides a powerful psychological and physiological deterrent to alcohol consumption. By inhibiting the enzyme acetaldehyde dehydrogenase, it induces an acutely unpleasant reaction if alcohol is ingested, thereby supporting the motivation to maintain abstinence. This medication is intended for use under strict medical supervision within a structured support program that includes counseling and psychosocial interventions.
Features
- Pharmacological Agent: An aldehyde dehydrogenase inhibitor.
- Administration: Oral tablet formulation.
- Mechanism: Causes a buildup of acetaldehyde upon ethanol consumption.
- Onset of Action: The sensitization to alcohol develops within 1-2 hours after ingestion and lasts for a period of up to 14 days after the last dose.
- Bioavailability: Well-absorbed from the gastrointestinal tract, but undergoes significant first-pass metabolism.
- Half-life: The parent drug has a half-life of 60-120 hours, with its metabolites exhibiting activity for an extended period.
Benefits
- Creates a powerful physiological deterrent to alcohol consumption, reinforcing the commitment to sobriety.
- Provides a tangible “safety net” during the vulnerable early stages of recovery, reducing impulsive drinking.
- Empowers patients by giving them an active tool to manage cravings and avoid relapse.
- Supports long-term abstinence goals when integrated into a multifaceted treatment program.
- Allows patients to break the cycle of compulsive drinking by introducing a significant negative consequence.
Common use
Disulfiram is indicated as a pharmacotherapeutic aid in the management of selected patients with chronic and severe alcohol use disorder who wish to remain in a state of enforced sobriety. It is not a cure for alcoholism, nor does it diminish the craving for alcohol. Its use is predicated on the patient’s full knowledge of the consequences of alcohol ingestion and their consent to cooperate. It is most effective for highly motivated individuals in a stable mental condition who are participating in a concurrent supportive and psychotherapeutic program.
Dosage and direction
Initial dosing must be tailored to the individual patient under direct medical supervision. A typical initiation protocol involves a loading dose.
- Initial Dosage: A maximum of 500 mg daily is administered as a single oral dose for one to two weeks.
- Maintenance Dosage: The daily dosage is typically reduced to 250 mg (range 125 mg to 500 mg). The lower end of the dosing range is often sufficient to maintain a deterrent effect and may minimize side effects.
- Administration: The tablet should be taken in the morning, as the sedative effects, if they occur, may be less disruptive. It can be chewed, crushed, or swallowed whole.
- Supervision: To ensure compliance, administration should be supervised by a family member or healthcare professional, especially in the initial phases of treatment.
The patient must be in a state of alcohol abstinence for at least 12 hours before the first dose is administered. A disulfiram-alcohol reaction test is not recommended due to the associated risks.
Precautions
Extreme caution and thorough patient education are paramount.
- Informed Consent: The patient must be fully informed, comprehend, and consent to therapy, explicitly acknowledging the risks of the disulfiram-ethanol reaction (DER).
- Alcohol Avoidance: Patients must be cautioned to avoid all sources of alcohol, including hidden sources like sauces, vinegars, mouthwashes, elixirs, tonics, and even topical applications or inhalants (e.g., aftershave, paint thinner).
- Hepatic Function: Baseline liver function tests (LFTs) are required before initiation and at regular intervals (e.g., every 2-4 weeks for the first 6 months, then periodically thereafter) due to the risk of hepatotoxicity, including potentially fatal hepatitis.
- Neuropathy: Patients should be monitored for the onset of peripheral neuropathy, characterized by numbness or tingling in the extremities.
- Psychiatric Effects: Rare instances of psychotic reactions, confusion, and polyneuritis have been reported and require monitoring.
- Pregnancy/Nursing: Disulfiram is contraindicated in pregnancy (Pregnancy Category C) and should not be used by nursing mothers.
Contraindications
Disulfiram is absolutely contraindicated in the presence of the following conditions:
- Severe myocardial disease or coronary occlusion.
- Psychosis or severe intellectual impairment where the patient cannot comprehend the therapy’s consequences.
- Hypersensitivity to disulfiram or other thiuram derivatives used in pesticides or rubber vulcanization.
- Concurrent use of alcohol or alcohol-containing products.
- Pregnancy and lactation.
- Severe hepatic impairment or previous history of disulfiram-induced hepatitis.
Possible side effects
In the absence of alcohol, disulfiram is generally well-tolerated, but side effects can occur.
- Common: Drowsiness, fatigue, headache, metallic or garlic-like aftertaste, and acneiform eruptions.
- Less Common: Hepatotoxicity (elevated transaminases, hepatitis, jaundice), peripheral neuropathy, optic neuritis, and psychotic reactions.
- Rare: Allergic dermatitis, impotence, and a metallic aftertaste.
The most significant adverse effect is the intentional or accidental disulfiram-ethanol reaction (DER), which is not a side effect but a direct pharmacodynamic consequence.
Drug interaction
Disulfiram inhibits several hepatic microsomal enzymes, notably aldehyde dehydrogenase and dopamine β-hydroxylase, and can affect the metabolism of numerous concomitant medications.
- Warfarin: Disulfiram potentiates the anticoagulant effect by inhibiting its metabolism, increasing the risk of bleeding. Prothrombin time must be monitored closely, and warfarin dosage will likely need reduction.
- Phenytoin: Disulfiram inhibits the metabolism of phenytoin, increasing the risk of phenytoin toxicity (ataxia, nystagmus, lethargy). Serum phenytoin levels must be monitored.
- Benzodiazepines: Metabolism of certain benzodiazepines (e.g., chlordiazepoxide, diazepam) may be inhibited, potentiating their sedative effects.
- Tricyclic Antidepressants: Metabolism may be inhibited.
- Isoniazid & Other CYP2E6 Substrates: Increased risk of neurotoxicity and adverse effects.
- Theophylline: Disulfiram may decrease theophylline clearance, increasing the risk of toxicity.
- Metronidazole: Concurrent use is not recommended due to the potential for psychotic reactions.
A comprehensive review of the patient’s medication list is essential prior to initiation.
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 patient should skip the missed dose and resume the normal schedule the following day. The patient must never double the dose to make up for a missed one. The long half-life of disulfiram means a single missed dose is unlikely to immediately compromise the deterrent effect, but consistent compliance is critical for maintained efficacy.
Overdose
Overdose can be severe, manifesting as neurological, cardiovascular, and gastrointestinal symptoms.
- Symptoms: Nausea, vomiting, dizziness, lethargy, incoordination, seizures, electrocardiogram changes, and cardiovascular collapse. Neurological symptoms may progress from agitation to stupor and coma.
- Management: There is no specific antidote for disulfiram overdose. Treatment is entirely supportive and symptomatic. Gastric lavage may be considered if presentation is immediate. Management focuses on maintaining respiration, treating hypotension with pressors, and controlling seizures with benzodiazepines. Electrolyte imbalance and shock must be aggressively managed. The patient must be hospitalized for close monitoring for at least one week due to the drug’s prolonged half-life.
Storage
Store at controlled room temperature (20°-25°C or 68°-77°F) in a tight, light-resistant container. Keep out of reach of children and pets. Do not flush medications down the toilet or pour them into a drain. Dispose of unused medication via a official medicine take-back program.
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 application of the information in this document.
Reviews
- Clinical Efficacy (4/5): “Disulfiram remains a cornerstone of pharmacological aversion therapy for a specific patient demographic. Its efficacy is almost entirely dependent on supervised administration and patient motivation. In compliant patients within a structured program, it is a powerfully effective deterrent.” – Addiction Psychiatrist, 15 years experience.
- Safety Profile (3/5): “The hepatotoxicity risk requires vigilant and lifelong monitoring. We see its use declining with the advent of safer alternatives like naltrexone and acamprosate, but for the right, highly motivated patient who understands and accepts the risks, it has a definitive role.” – Clinical Pharmacologist.
- Patient Experience (Variable): “It gave me the fear I needed to stop. Knowing what would happen if I drank made saying ’no’ easier. The side effects were manageable for me—some drowsiness at first and the taste.” – Anonymous patient, 3 years sober.
- “The metallic taste was unbearable for me, and I experienced significant fatigue. I switched to a different medication after 4 months, but it did help me through the first critical 90 days of my recovery.” – Anonymous patient.