Antabuse: A Clinically Proven Deterrent for Alcohol Use Disorder
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Synonyms | |||
Antabuse (disulfiram) is a cornerstone of pharmacological aversion therapy for the maintenance of abstinence in patients with chronic alcohol use disorder. It functions as a powerful psychological and physiological deterrent by modifying the body’s metabolic pathway for ethanol, resulting in a highly unpleasant reaction upon alcohol consumption. This medication is not a cure for alcoholism but is a critical tool within a comprehensive treatment plan that includes counseling and psychosocial support, empowering patients to sustain long-term recovery by creating a tangible consequence for relapse.
Features
- Active Pharmaceutical Ingredient: Disulfiram.
- Mechanism of Action: Irreversible inhibition of the enzyme aldehyde dehydrogenase (ALDH).
- Standard Tablet Strengths: 250 mg and 500 mg.
- Administration: Oral tablet.
- Onset of Action: The disulfiram-ethanol reaction (DER) can occur within 10 minutes of alcohol ingestion and may persist for an hour or more.
- Duration of Effect: The enzymatic inhibition and, therefore, the deterrent effect can persist for up to 14 days following the last dose due to the slow release of disulfiram from its depot in body fat and its irreversible enzyme binding.
Benefits
- Creates a Powerful Psychological Barrier: The known risk of a severe adverse reaction provides a strong psychological deterrent, helping patients resist impulsive drinking.
- Supports Behavioral Conditioning: By associating alcohol consumption with immediate negative physical consequences, it aids in breaking the cycle of addictive behavior.
- Facilitates Engagement in Therapy: The safety net provided by Antabuse allows patients to focus more effectively on the underlying psychological aspects of their addiction during counseling sessions.
- Provides a Structured Framework for Recovery: The daily act of taking the medication reinforces the patient’s daily commitment to sobriety.
- Effective Adjunct Treatment: When used as part of a multimodal treatment plan, it significantly increases the periods of continuous abstinence compared to placebo.
Common use
Antabuse is indicated as an adjunctive agent in the management of selected patients with a confirmed diagnosis of chronic alcohol use disorder who wish to remain in a state of enforced sobriety. It is prescribed for patients who are highly motivated, have undergone a full medical and psychiatric evaluation, and are concurrently participating in a supervised support program or psychotherapy. Its use is predicated on the patient’s full comprehension of the disulfiram-ethanol reaction and their informed consent to the therapy. It is not intended for use as a monotherapy or for the immediate cessation of a current drinking episode.
Dosage and direction
Dosage must be individualized under strict medical supervision. Treatment should not be initiated until the patient has abstained from alcohol for at least 12 hours and a baseline transaminase level has been established.
- Initial Dosage: A maximum of 500 mg daily is administered as a single 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 temptation to drink may be greater later in the day. It can be crushed and mixed with liquid if necessary.
- Duration of Therapy: The duration of treatment is continuous and based on the individual patient’s needs, which may extend for months or even years. The decision to discontinue therapy should be made collaboratively with the prescribing physician.
Precautions
- Hepatotoxicity: Antabuse has been associated with life-threatening hepatitis and hepatic failure. Baseline liver function tests (LFTs) must be performed prior to initiation and at regular intervals (e.g., every 2-4 weeks for the first 6 months, then periodically thereafter) during therapy. Therapy should be discontinued immediately if signs of hepatitis develop (e.g., fatigue, weakness, nausea, vomiting, jaundice, dark urine, right upper quadrant pain).
- Neuropathy: Peripheral neuropathy and polyneuritis have been reported. Patients should be advised to report any numbness, tingling, or muscle weakness in their extremities.
- Psychiatric Effects: Psychotic reactions, including depression, paranoia, and mania, have been observed. Patients with a history of psychosis should be monitored closely.
- Hypersensitivity: Skin eruptions and allergic dermatitis are possible.
- Informed Consent: The patient must be fully aware of the consequences of alcohol consumption while on Antabuse and the pervasiveness of alcohol in certain products (e.g., sauces, vinegars, mouthwashes, tonics, colognes, and other topical preparations).
Contraindications
Antabuse is absolutely contraindicated in the presence of:
- Severe myocardial disease or coronary occlusion.
- Psychosis.
- Hypersensitivity to disulfiram or other thiuram derivatives used in pesticides and rubber vulcanization.
- Concurrent use of alcohol or alcohol-containing products.
- Concurrent use of metronidazole, paraldehyde, or any drug that may produce a disulfiram-like reaction.
- Pregnancy.
Possible side effect
The most significant side effect is the intentional or accidental disulfiram-ethanol reaction (DER), characterized by:
- Flushing of the face and upper chest
- Throbbing headache
- Respiratory difficulty, hyperventilation
- Tachycardia, hypotension, syncope
- Nausea, copious vomiting
- Sweating, thirst, blurred vision
- Chest pain, palpitations
- Vertigo, marked uneasiness, weakness
- In severe cases: respiratory depression, cardiovascular collapse, arrhythmias, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death.
Non-DER related side effects may include:
- Drowsiness, fatigue, headache, metallic or garlic-like aftertaste
- Acneiform eruptions, allergic dermatitis
- Impotence
- Peripheral neuropathy
- Hepatitis (idiosyncratic)
Drug interaction
Antabuse inhibits several hepatic microsomal enzymes, including CYP450 2E1, and can alter the metabolism of concurrently administered drugs.
- Warfarin: Potentiates anticoagulant effect by inhibiting its metabolism; prothrombin time must be monitored closely and warfarin dosage reduced.
- Phenytoin: Increases phenytoin plasma levels and risk of toxicity; monitor phenytoin levels.
- Benzodiazepines: May increase the levels and sedative effects of certain benzodiazepines (e.g., chlordiazepoxide, diazepam).
- Tricyclic Antidepressants: Metabolism may be inhibited.
- Theophylline: Metabolism may be inhibited, increasing the risk of toxicity.
- Isoniazid: May increase the risk of unsteady gait or significant behavioral changes.
- Metronidazole: Concomitant use is contraindicated due to the risk of psychosis or confusional states.
Missed dose
If a dose is missed, it should be taken as soon as remembered that 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. The protective deterrent effect remains for a considerable time after the last dose; however, consistency is key to maintaining the psychological routine of treatment.
Overdose
Overdose in the absence of alcohol may present as extreme drowsiness, impaired coordination, confusion, nausea, vomiting, and neurological symptoms including seizures. In severe cases, it can progress to coma, respiratory depression, and cardiovascular collapse. Management is supportive and symptomatic. There is no specific antidote for disulfiram. Gastric lavage may be considered if performed soon after ingestion. Support of respiration and circulation is paramount. In cases of concomitant ethanol ingestion, the resulting DER will complicate the clinical picture and must be managed aggressively.
Storage
Store at controlled room temperature, 20°C to 25°C (68°F to 77°F). Dispense in a tight, light-resistant container as defined in the USP. Keep out of reach of children and pets. Do not use after the expiration date printed on the bottle.
Disclaimer
This information is for educational 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 before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The patient must be fully informed of the risks and benefits of Antabuse therapy by a qualified healthcare professional before initiation.
Reviews
- Clinical Evidence: “Numerous controlled studies have demonstrated the efficacy of disulfiram as an aversion therapy. Its effectiveness is highly dependent on patient motivation and supervised administration. It remains a valuable, though underutilized, tool in the addiction specialist’s armamentarium when integrated into a comprehensive treatment model.” - Journal of Addiction Medicine
- Patient Experience (Compiled): Patient testimonials frequently highlight the “safety net” effect of Antabuse, noting that the knowledge of the inevitable reaction provided the necessary barrier to break habitual drinking patterns. Many report that it gave them the initial stability required to engage meaningfully in therapy. Common criticisms relate to its side effect profile, particularly the initial drowsiness and the constant vigilance required to avoid hidden alcohol in products.