Disulfiram: Uses, Dosage & Side Effects
Alcohol deterrent medication for the treatment of chronic alcohol dependence
Quick facts about Disulfiram
Key takeaways about Disulfiram
- Complete alcohol avoidance is essential: Disulfiram causes severe, potentially dangerous reactions when combined with even small amounts of alcohol – including alcohol in foods, medicines, and cosmetics
- Effects last up to 2 weeks: The disulfiram-alcohol reaction can occur for up to 14 days after the last dose, so alcohol must be avoided for at least 2 weeks after stopping treatment
- Supervised administration improves outcomes: Research shows that having a family member or healthcare professional observe the patient taking the medication significantly improves abstinence rates
- Liver monitoring is important: Disulfiram can cause liver inflammation (hepatitis), which is potentially serious. Liver function tests should be performed before and during treatment
- Must never be given without consent: Due to the severity of the alcohol reaction, it is both unethical and dangerous to administer disulfiram to anyone without their full knowledge and informed consent
What Is Disulfiram and What Is It Used For?
Disulfiram is an alcohol deterrent medication prescribed to support abstinence in people with chronic alcohol dependence. It works by blocking the breakdown of alcohol in the body, causing intensely unpleasant symptoms if alcohol is consumed. Disulfiram is not a cure for alcoholism but serves as a powerful motivational tool within a comprehensive treatment programme.
Disulfiram was the first medication approved by the US Food and Drug Administration (FDA) for the treatment of alcohol dependence, receiving its initial approval in 1951. It has been used clinically for over seven decades and remains an important option in the pharmacological management of alcohol use disorder (AUD). The medication is listed on the WHO Model List of Essential Medicines, reflecting its global importance in addiction medicine.
The mechanism of action of disulfiram is based on its ability to irreversibly inhibit aldehyde dehydrogenase (ALDH), the enzyme responsible for converting acetaldehyde into acetate during the normal metabolism of alcohol (ethanol). Under normal circumstances, when a person drinks alcohol, it is first converted to acetaldehyde by the enzyme alcohol dehydrogenase (ADH), and then rapidly converted to harmless acetate by ALDH. Acetaldehyde is a highly toxic substance, and its rapid conversion to acetate means that it normally accumulates only in very small quantities.
When disulfiram blocks ALDH, acetaldehyde accumulates to concentrations 5 to 10 times higher than normal after alcohol consumption. This triggers the disulfiram-ethanol reaction (DER), which produces a constellation of extremely unpleasant and potentially dangerous symptoms. These symptoms typically appear within 5 to 10 minutes of alcohol ingestion and include severe facial flushing, throbbing headache, rapid heartbeat (tachycardia), nausea, vomiting, and a sensation of breathlessness. The intensity of the reaction is proportional to the amounts of both disulfiram and alcohol consumed.
The primary clinical indication for disulfiram is as an adjunct in the management of alcohol dependence. It is intended for use in patients who have already achieved initial abstinence and are motivated to remain alcohol-free. Disulfiram does not reduce alcohol cravings or withdrawal symptoms; instead, it provides a strong deterrent against drinking by ensuring that any alcohol consumption will result in immediate and severe discomfort. This knowledge helps reinforce the patient’s commitment to sobriety, particularly during moments of temptation.
The therapeutic effect of disulfiram builds gradually over the first 3 days of treatment as the enzyme ALDH is progressively inhibited. Because the inhibition is irreversible, the body must synthesise new ALDH enzyme to restore normal alcohol metabolism. This process takes approximately 1 to 2 weeks after the last dose of disulfiram, meaning that a disulfiram-alcohol reaction can occur for up to 14 days after discontinuing the medication.
Disulfiram is not effective on its own. It works best as part of a comprehensive treatment programme that includes psychological counselling, behavioural therapy, social support groups, and ongoing medical supervision. The medication provides a “safety net” that supports the patient’s own motivation to remain abstinent.
What Should You Know Before Taking Disulfiram?
Disulfiram has important contraindications and precautions. It must not be used in patients with severe heart disease, active liver disease, serious mental illness, or severe brain damage. Complete abstinence from alcohol for at least 24 hours before starting treatment is essential, and liver function should be monitored throughout therapy.
Contraindications
Do not take disulfiram if you have any of the following conditions:
- Allergy to disulfiram or any of the inactive ingredients in the tablet
- Untreated heart disease: Conditions such as severe coronary artery disease, decompensated heart failure, or significant cardiac arrhythmias pose serious risks because the disulfiram-alcohol reaction causes cardiovascular stress including tachycardia and blood pressure changes
- Severe psychiatric disorders: Including active psychosis, severe personality disorders, or suicidal ideation, as disulfiram can worsen psychiatric symptoms and the consequences of an alcohol reaction may be difficult to manage
- Severe brain damage: Including significant organic brain injury, severe cognitive impairment, or advanced dementia, as the patient must be able to understand and consent to the risks of treatment
- Active liver disease: Including acute hepatitis, cirrhosis with decompensation, or significantly elevated liver enzymes. Additionally, patients who have previously developed liver damage during disulfiram treatment must not restart the medication
- Current alcohol intoxication: Disulfiram must never be started while the patient is still intoxicated or has recently consumed alcohol. At least 24 hours of abstinence is required before the first dose
Warnings and Precautions
Tell your doctor before starting disulfiram if you have any of the following conditions, as they may require additional monitoring, dose adjustments, or a decision about whether the benefits outweigh the risks:
- History of liver disease: Even past liver problems require careful monitoring. Liver function tests (LFTs) should be performed before starting treatment and at regular intervals (typically every 2 weeks for the first 2 months, then monthly for 4 months, then every 6 months). If you develop symptoms such as loss of appetite, fatigue, nausea, vomiting, weakness, fever, itching, yellowing of the whites of the eyes or skin, dark urine, or pale stools, contact your doctor immediately as these may indicate liver inflammation (hepatitis)
- Diabetes mellitus: Disulfiram can affect blood glucose levels and may alter the metabolism of certain oral antidiabetic medications. Blood glucose monitoring may need to be more frequent
- Epilepsy: Disulfiram may lower the seizure threshold and can interact with anti-epileptic medications such as phenytoin
- Kidney disease: Impaired renal function may affect the elimination of disulfiram metabolites
- Respiratory disease: The breathlessness experienced during a disulfiram-alcohol reaction may be more severe in patients with underlying lung conditions
- Hypothyroidism: Disulfiram has been associated with thyroid function changes in some patients
Because the disulfiram-alcohol reaction can be severe and potentially life-threatening, disulfiram must never be administered to any person without their full knowledge and voluntary consent. The patient must understand exactly what will happen if they consume alcohol while taking the medication. Covert administration (for example, adding disulfiram to food or drink without the person’s knowledge) is both unethical and medically dangerous.
Pregnancy and Breastfeeding
There is limited clinical experience with disulfiram use during pregnancy. Animal studies have not adequately evaluated reproductive toxicity. Because alcohol dependence itself poses significant risks to pregnancy (fetal alcohol spectrum disorders), the treatment decision must weigh the risks and benefits carefully:
- Pregnancy: Disulfiram should only be used during pregnancy if the potential benefit to the mother (maintaining abstinence from alcohol) clearly outweighs the potential risk to the foetus. The decision should be made on a case-by-case basis by the treating physician
- Breastfeeding: There is a risk that disulfiram or its metabolites may pass into breast milk and affect the nursing infant. Breastfeeding is generally not recommended during disulfiram treatment. Discuss alternatives with your doctor
Driving and operating machinery: Disulfiram can cause drowsiness and sleepiness, particularly during the initial weeks of treatment. You should be aware of this effect before driving or operating heavy machinery. You are responsible for assessing whether you are in a fit condition to drive or perform tasks requiring alertness. Do not drive if you feel drowsy.
Disulfiram effervescent tablets contain less than 1 mmol (23 mg) of sodium per tablet and are therefore considered essentially sodium-free. This is relevant for patients on a sodium-restricted diet.
How Does Disulfiram Interact with Other Drugs?
Disulfiram inhibits several liver enzymes involved in drug metabolism, leading to clinically significant interactions with a number of commonly prescribed medications. It is essential to inform your doctor and pharmacist about all medications you are taking, including over-the-counter medicines and herbal supplements.
Disulfiram is a potent inhibitor of CYP2E1 and also inhibits CYP1A2, CYP3A4, and dopamine beta-hydroxylase. These enzyme interactions mean that the metabolism of several drugs can be significantly slowed, leading to increased blood levels and enhanced effects or toxicity. The following tables summarise the most clinically important interactions.
Major Interactions (Avoid or Use with Extreme Caution)
| Drug / Class | Effect | Clinical Significance |
|---|---|---|
| Metronidazole | Risk of acute psychosis and confusion | Combination should be avoided. Both drugs inhibit ALDH, and the combination can cause severe neuropsychiatric reactions including confusion, psychosis, and catatonia |
| Warfarin | Increased anticoagulant effect | Disulfiram inhibits the metabolism of warfarin, leading to increased INR and bleeding risk. Warfarin dose reduction and more frequent INR monitoring required |
| Phenytoin | Increased phenytoin levels | Disulfiram inhibits phenytoin metabolism (CYP2C9), potentially leading to phenytoin toxicity with symptoms such as nystagmus, ataxia, and drowsiness. Monitor phenytoin levels closely |
| Isoniazid | Increased risk of CNS toxicity | Combination may cause coordination difficulties, behavioural changes, and psychotic episodes. Avoid if possible; if necessary, monitor closely for neurological symptoms |
| Alcohol-containing products | Disulfiram-ethanol reaction | All forms of alcohol must be avoided, including alcohol in liquid medicines, mouthwashes, cough syrups, vinegar-based foods, and alcohol-containing cosmetics applied near the face |
Moderate Interactions (Use with Caution)
| Drug / Substance | Effect | Recommendation |
|---|---|---|
| Diazepam (and other benzodiazepines) | Increased sedation and reduced clearance | Disulfiram inhibits the oxidative metabolism of diazepam and chlordiazepoxide. Consider using lorazepam or oxazepam instead, as these are metabolised by glucuronidation and are not affected |
| Imipramine (and tricyclic antidepressants) | Increased TCA levels and toxicity risk | Monitor for signs of TCA toxicity including dry mouth, constipation, urinary retention, and cardiac conduction abnormalities. Dose adjustment may be needed |
| Theophylline | Increased theophylline levels | Disulfiram reduces the clearance of theophylline by approximately 50%. Monitor theophylline blood levels and reduce dose accordingly |
| Caffeine | Reduced caffeine metabolism | Disulfiram inhibits CYP1A2, slowing caffeine clearance. Patients may experience increased caffeine effects (insomnia, nervousness, palpitations). Consider reducing caffeine intake |
| Amitriptyline | Increased amitriptyline levels | Monitor for increased sedation and anticholinergic side effects. Consider dose reduction of amitriptyline |
While taking disulfiram, be aware that alcohol can be found in unexpected products: certain liquid cough and cold medicines, vitamin and herbal supplements in liquid form, some chocolate liqueurs and pralines, vinegar, fermented foods, hand sanitisers, aftershave and perfume (if applied near the mouth), and some cooking extracts (vanilla extract). Always read labels carefully and ask your pharmacist if you are unsure whether a product contains alcohol.
What Is the Correct Dosage of Disulfiram?
The dosage of disulfiram is individualised by the prescribing physician. A typical starting dose is 200–400 mg taken 2–3 times per week, with a maintenance dose of 100–200 mg daily or 600–800 mg twice weekly. The effervescent tablet should be dissolved in half a glass of water immediately before taking.
Disulfiram should always be taken exactly as prescribed by your doctor. Do not change the dose or stop taking the medication without consulting your physician. Treatment should only be started after a minimum of 24 hours of complete alcohol abstinence, and ideally after a longer period of sobriety has been established.
Adults
Standard Dosing Regimen
Starting dose: 200–400 mg, taken 2–3 times per week during the initial phase of treatment. Some clinicians prefer to start with a daily dose to ensure consistent enzyme inhibition during the early, most vulnerable period.
Maintenance dose: 600–800 mg twice weekly, or alternatively 100–200 mg daily. The choice between intermittent and daily dosing depends on patient preference, supervision arrangements, and clinical response.
Timing: The dose is typically taken in the morning. If disulfiram causes drowsiness, the dose may be moved to the evening. When dosing is intermittent (e.g., twice weekly), doses are often given on specific, regular days to establish a routine.
Supervised Administration
Research consistently demonstrates that supervised disulfiram administration produces significantly better outcomes than unsupervised use. Supervision may be provided by a healthcare professional at a clinic, a pharmacist, a family member, or another trusted person. The supervisor observes the patient dissolving and drinking the tablet, ensuring adherence. This approach transforms disulfiram from a medication that relies on patient willpower alone into a structured, accountable treatment.
Preparation and Administration
Disulfiram effervescent tablets must be dispersed in approximately half a glass (100–150 ml) of water immediately before taking or at most 1 hour beforehand. The tablet will fizz and dissolve. Stir the solution before drinking to ensure uniform distribution of the medication. Do not swallow the tablet whole. Do not crush or chew the tablet.
Children and Adolescents
Disulfiram is not approved for use in children and adolescents under 18 years of age. There are no clinical studies supporting its safety or efficacy in this age group. Alcohol use disorder in adolescents requires specialised assessment and treatment approaches that do not typically include aversion therapy.
Elderly Patients
Elderly patients may be more susceptible to the side effects of disulfiram, including drowsiness, confusion, and peripheral neuropathy. Lower starting doses may be appropriate. Liver and kidney function should be assessed before treatment and monitored regularly. The cardiovascular consequences of a disulfiram-alcohol reaction may be more severe in elderly patients with underlying heart disease.
Missed Dose
If you miss a dose of disulfiram, take it as soon as you remember on the same day. If you do not remember until the next day, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. The protective effect of disulfiram may be reduced if several doses are missed in succession, so contact your doctor if you are having difficulty maintaining your dosing schedule.
Overdose
If you or someone else has taken too much disulfiram, seek medical attention immediately. Contact your local poison control centre or emergency services.
Signs and symptoms of disulfiram overdose include:
- Nausea and vomiting
- Severe headache
- Drowsiness and extreme fatigue
- Impaired coordination and unsteady gait
- Restlessness and irritability
- Hallucinations and confusion
In severe overdose, more serious complications can develop including loss of consciousness, seizures, dangerously low body temperature (hypothermia), severe hypotension (low blood pressure), and rapid or irregular heart rhythm. Treatment is supportive and symptomatic, as there is no specific antidote for disulfiram overdose.
What Are the Side Effects of Disulfiram?
Like all medicines, disulfiram can cause side effects, although not everybody gets them. The most important distinction is between side effects of the medication itself and the symptoms of the disulfiram-alcohol reaction, which occur only when alcohol is consumed. Many side effects are most noticeable during the first weeks of treatment and can be difficult to distinguish from symptoms of alcohol withdrawal.
It is important to understand that many symptoms experienced during the early phase of disulfiram treatment may be related to alcohol withdrawal rather than to the medication itself. These symptoms typically improve as the body adjusts both to the medication and to sustained abstinence from alcohol. If you are concerned about any symptoms, discuss them with your doctor.
Common
- Drowsiness and fatigue, particularly in the first weeks of treatment
- Gastrointestinal disturbances (stomach discomfort, nausea)
- Diarrhoea
- Halitosis (bad breath) with a characteristic garlic-like odour
- Metallic taste in the mouth
- Headache
- Mania (elevated mood, increased energy)
- Low mood or depression
Uncommon
- Acne-like skin rash
- Allergic skin reactions with itching and/or redness
- Sexual dysfunction (reduced libido, erectile dysfunction)
Rare
- Peripheral neuropathy (tingling, numbness, and muscle weakness, particularly in the arms and legs)
- Optic neuritis (reduced vision, eye pain, and pain around the eyes)
- Changes in blood cell counts
- Liver function disturbances, sometimes with jaundice (yellowing of skin and eyes)
- Psychiatric disturbances including personality changes, psychosis, or paranoia
The following symptoms occur only when alcohol is consumed while taking disulfiram. They are not side effects of the medication itself but are the intended deterrent effect. Symptoms include: intense facial flushing and redness, throbbing headache, rapid heartbeat (palpitations), nausea and severe vomiting, sensation of breathlessness, chest tightness, dizziness, sweating, and anxiety. In severe cases (large amounts of alcohol), the reaction can include severe hypotension, respiratory depression, cardiac arrhythmias, loss of consciousness, and cardiovascular collapse. If you experience a severe reaction, seek emergency medical attention immediately.
Hepatotoxicity (liver damage) is the most clinically serious adverse effect of disulfiram itself. It can range from mild, asymptomatic elevations in liver enzymes to fulminant hepatic failure, which can be fatal. The incidence is estimated at 1 in 10,000 to 1 in 30,000 treated patients per year. Risk factors include pre-existing liver disease, heavy prior alcohol use, and concurrent hepatotoxic medications. Liver function should be monitored regularly during treatment, and disulfiram should be stopped immediately if clinically significant hepatotoxicity is suspected.
If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed above. You can also report side effects directly to your national medicines regulatory authority to help ensure the ongoing monitoring of the benefit-risk balance of this medicine.
How Should You Store Disulfiram?
Store disulfiram at room temperature in its original container, away from moisture. Keep the container tightly closed and out of the sight and reach of children. Do not use after the expiry date printed on the label.
Disulfiram effervescent tablets should be stored in their original high-density polyethylene (HDPE) plastic container with the lid tightly secured. The container includes a desiccant capsule (silica gel) to protect the tablets from moisture – do not remove or swallow the desiccant. Store at room temperature, below 25°C (77°F), and protect from excessive heat and humidity.
Do not use this medicine after the expiry date (EXP) stated on the container label. The expiry date refers to the last day of the stated month. Once opened, the tablets should be used within the period recommended by your pharmacist, keeping the container tightly closed between uses.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures help to protect the environment and ensure that unused medication does not pose a risk to others.
What Does Disulfiram Contain?
Each disulfiram effervescent tablet contains 200 mg of the active substance disulfiram. The tablets also contain several inactive ingredients (excipients) that help with tablet formation, stability, and the effervescent dissolution in water.
Active Ingredient
Each effervescent tablet contains 200 mg disulfiram as the active pharmaceutical ingredient. Disulfiram (chemical name: tetraethylthiuram disulphide) is a white to off-white crystalline powder with a faint odour.
Inactive Ingredients (Excipients)
The tablets also contain the following inactive ingredients:
- Maize starch (corn starch) – binder
- Microcrystalline cellulose – filler and disintegrant
- Povidone – binder
- Tartaric acid – effervescent agent (provides the fizzing action)
- Colloidal anhydrous silica – glidant (improves powder flow)
- Magnesium stearate – lubricant
- Talc – lubricant and glidant
- Sodium hydrogen carbonate – effervescent agent (reacts with tartaric acid to produce CO2 bubbles)
- Polysorbate 20 – wetting agent
The 200 mg effervescent tablet is white, round, with a score line, and has a diameter of 11 mm. The tablets are supplied in HDPE plastic containers with HDPE plastic lids. Each container includes a silica gel desiccant capsule to protect against moisture.
Frequently Asked Questions About Disulfiram
References & Medical Sources
This article is based on the following authoritative international medical sources. All medical claims adhere to Level 1A evidence standards based on systematic reviews, meta-analyses, and international clinical guidelines.
- Skinner MD, Lahmek P, Pham H, Aubin HJ. Disulfiram efficacy in the treatment of alcohol dependence: a meta-analysis. PLoS One. 2014;9(2):e87366. DOI: 10.1371/journal.pone.0087366
- Jorgensen CH, Pedersen B, Tonnesen H. The efficacy of disulfiram for the treatment of alcohol use disorder. Alcohol Clin Exp Res. 2011;35(10):1749–1758. DOI: 10.1111/j.1530-0277.2011.01523.x
- National Institute for Health and Care Excellence (NICE). Alcohol-use disorders: diagnosis, assessment and management of harmful drinking (high-risk) and alcohol dependence. Clinical guideline CG115. 2011 (updated 2023). Available at: nice.org.uk/guidance/cg115
- American Psychiatric Association. Practice Guideline for the Pharmacological Treatment of Patients with Alcohol Use Disorder. APA Practice Guidelines. 2018. DOI: 10.1176/appi.ajp.2017.1750101
- World Health Organization. WHO Model List of Essential Medicines – 23rd List. Geneva: WHO; 2023. Available at: who.int
- European Medicines Agency. Disulfiram – Summary of Product Characteristics. EMA SmPC. Updated 2024.
- US Food and Drug Administration. Antabuse (disulfiram) – Prescribing Information. FDA Label. Reference ID: 4889685.
- British National Formulary (BNF). Disulfiram. NICE Evidence Services. Available at: bnf.nice.org.uk
- De Sousa A, De Sousa A. A one-year pragmatic trial of naltrexone vs disulfiram in the treatment of alcohol dependence. Alcohol Alcohol. 2004;39(6):528–531. DOI: 10.1093/alcalc/agh104
- Substance Abuse and Mental Health Services Administration (SAMHSA). Medications for Substance Use Disorders. Treatment Improvement Protocol (TIP) Series 63. 2020.
Editorial Team
iMedic Medical Editorial Team – Specialists in addiction medicine and clinical pharmacology. Our team includes board-certified physicians with extensive experience in the pharmacological treatment of substance use disorders.
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