Usage
- Medical Conditions: Disulfiram is prescribed as an adjunctive treatment for chronic alcohol dependence (alcohol use disorder). It’s important to note that disulfiram is not a cure for alcoholism, but it acts as a deterrent to discourage alcohol consumption. It works by causing unpleasant side effects if alcohol is ingested.
- Pharmacological Classification: Alcohol deterrent, enzyme inhibitor (aldehyde dehydrogenase inhibitor).
- Mechanism of Action: Disulfiram inhibits the enzyme aldehyde dehydrogenase, which is involved in the metabolism of alcohol. This inhibition leads to a buildup of acetaldehyde in the body, causing a range of unpleasant effects when alcohol is consumed, thus discouraging further drinking. These effects typically occur within 10-30 minutes of alcohol ingestion.
Alternate Names
- Generic Name: Disulfiram
- Brand Name: Antabuse (Note: Antabuse brand is discontinued in some regions).
How It Works
- Pharmacodynamics: Disulfiram’s primary effect is the inhibition of aldehyde dehydrogenase. This leads to an accumulation of acetaldehyde, a toxic byproduct of alcohol metabolism, when alcohol is consumed. The elevated acetaldehyde levels produce the disulfiram-alcohol reaction (DER), characterized by a range of adverse effects including flushing, throbbing headache, nausea, vomiting, chest pain, difficulty breathing, weakness, blurred vision, mental confusion, sweating, choking, and anxiety. These unpleasant effects are intended to create an aversion to alcohol.
- Pharmacokinetics:
- Absorption: Disulfiram is well-absorbed from the gastrointestinal tract.
- Metabolism: Extensively metabolized in the liver, primarily to diethyldithiocarbamate, which is further metabolized. CYP450 enzymes play a role in disulfiram’s metabolism, leading to potential drug interactions.
- Elimination: Primarily excreted in the urine as metabolites and a small amount in the feces and through the lungs. It can take several days to completely eliminate the drug and its metabolites from the body.
- Mode of Action: Disulfiram irreversibly inhibits aldehyde dehydrogenase.
- Receptor Binding, Enzyme Inhibition, Neurotransmitter Modulation: The primary mechanism is enzyme inhibition of aldehyde dehydrogenase.
- Elimination Pathways: Primarily renal excretion as metabolites. Some elimination also occurs via feces and lungs.
Dosage
Standard Dosage
Adults:
- Initial Dosage: 500 mg orally once daily for 1-2 weeks.
- Maintenance Dosage: 125-500 mg orally once daily (250 mg is the average maintenance dose).
- Maximum Dosage: Do not exceed 500 mg daily.
- Duration: Treatment can continue for months or even years, depending on the patient’s response and the integrated treatment plan.
Children:
- Disulfiram is generally not recommended for use in children. Safety and efficacy have not been established in pediatric patients.
Special Cases:
- Elderly Patients: Start with a lower dose and titrate cautiously, considering age-related decline in hepatic and renal function.
- Patients with Renal Impairment: Use with caution; dose adjustments may be necessary.
- Patients with Hepatic Dysfunction: Use with extreme caution. Disulfiram is extensively metabolized by the liver, and liver disease can increase the risk of adverse effects. Some guidelines recommend avoiding disulfiram in patients with any degree of liver disease.
- Patients with Comorbid Conditions: Disulfiram may be used with caution in patients with certain comorbid conditions, such as diabetes, hypothyroidism, epilepsy, seizures, or cardiovascular disease, under strict medical supervision. However, it is contraindicated in patients with severe myocardial disease, coronary occlusion, or psychosis.
Clinical Use Cases
Disulfiram is specifically indicated for the adjunctive treatment of chronic alcohol dependence as part of a comprehensive treatment program. It’s not typically used in acute medical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dosage adjustments may be needed based on patient response, tolerance, and the presence of hepatic or renal impairment.
Side Effects
Common Side Effects
- Drowsiness
- Fatigue
- Headache
- Metallic or garlic-like taste in mouth
- Skin rash
Rare but Serious Side Effects
- Hepatotoxicity (liver damage)
- Optic neuritis
- Peripheral neuropathy
- Psychotic reactions (hallucinations, delusions)
Long-Term Effects
- Chronic liver disease (with prolonged use)
- Peripheral neuropathy (with prolonged use)
Adverse Drug Reactions (ADR)
- Severe disulfiram-alcohol reaction (DER) (flushing, throbbing headache, nausea, vomiting, chest pain, difficulty breathing, weakness, blurred vision, mental confusion, sweating, choking, and anxiety)
- Hepatotoxicity
- Psychotic reactions
Contraindications
- Absolute: Severe myocardial disease, coronary occlusion, psychosis, hypersensitivity to disulfiram or thiuram derivatives, concomitant or recent use of metronidazole, paraldehyde, or alcohol.
- Relative: Liver disease (generally avoid use), diabetes, hypothyroidism, epilepsy, seizures, cardiovascular disease, pregnancy (use only if benefits clearly outweigh risks), breastfeeding (not recommended).
Drug Interactions
- Alcohol: Causes the disulfiram-alcohol reaction. Avoid all sources of alcohol, including medications containing alcohol, foods prepared with alcohol, and even topical products containing alcohol.
- Metronidazole, Paraldehyde: Can potentiate the disulfiram-alcohol reaction even in the absence of alcohol consumption.
- Warfarin and other anticoagulants: Disulfiram may increase the anticoagulant effects of warfarin and other anticoagulants.
- Phenytoin: Disulfiram may increase phenytoin levels.
- Isoniazid: May increase the risk of neurotoxicity.
- Many other drug interactions: Consult a comprehensive drug interaction resource before prescribing or dispensing disulfiram.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.) There are reports of birth defects, but the causal relationship is unclear. Disulfiram is generally avoided during pregnancy, especially in the first trimester. Use only if potential benefits outweigh the risks.
- Breastfeeding: Disulfiram may be excreted in breast milk. Breastfeeding is not recommended while taking disulfiram.
Drug Profile Summary
- Mechanism of Action: Inhibits aldehyde dehydrogenase, leading to acetaldehyde accumulation when alcohol is consumed, causing unpleasant effects.
- Side Effects: Drowsiness, fatigue, headache, metallic taste, skin rash; rarely, hepatotoxicity, optic neuritis, peripheral neuropathy, psychotic reactions.
- Contraindications: Severe heart disease, psychosis, concomitant use of certain drugs (metronidazole, paraldehyde), alcohol intoxication.
- Drug Interactions: Alcohol (severe reaction), metronidazole, paraldehyde, warfarin, phenytoin, isoniazid, many others.
- Pregnancy & Breastfeeding: Avoid during pregnancy unless absolutely necessary; breastfeeding not recommended.
- Dosage: Adults: Initial 500 mg daily for 1-2 weeks, then 125-500 mg daily (average 250 mg); not recommended for children.
- Monitoring Parameters: Liver function tests, neurologic exams.
Popular Combinations
Disulfiram is typically used as monotherapy and is not commonly combined with other drugs for the treatment of alcohol dependence. Its use should be integrated with psychosocial support and counseling.
Precautions
- General Precautions: Detailed patient education about disulfiram-alcohol reaction, careful screening for contraindications and drug interactions, monitoring for adverse events, especially liver function.
- Pregnant Women: Avoid use unless absolutely necessary.
- Breastfeeding Mothers: Do not breastfeed while taking disulfiram.
- Children & Elderly: Not recommended for children; use with caution in elderly patients.
- Lifestyle Considerations: Complete abstinence from alcohol is essential. Avoid alcohol-containing products, including medications, foods, and topical preparations.
FAQs
Q1: What is the recommended dosage for Disulfiram?
A: Adults: Initially 500 mg daily for 1-2 weeks, followed by a maintenance dose of 125-500 mg daily (average 250 mg). Maximum dose 500 mg/day. Not for use in children.
Q2: How does Disulfiram work?
A: It inhibits aldehyde dehydrogenase, leading to a buildup of acetaldehyde if alcohol is consumed, causing unpleasant effects.
Q3: What are the most common side effects of Disulfiram?
A: Drowsiness, fatigue, headache, metallic/garlic taste, and skin rash.
Q4: What are the serious side effects of Disulfiram?
A: Liver damage, optic neuritis, peripheral neuropathy, psychotic reactions, severe disulfiram-alcohol reaction.
Q5: What are the contraindications for Disulfiram?
A: Severe heart disease, psychosis, concurrent use of metronidazole or paraldehyde, alcohol intoxication.
Q6: Can Disulfiram be used during pregnancy or breastfeeding?
A: Generally avoided in pregnancy; not recommended while breastfeeding.
Q7: What are the key drug interactions with Disulfiram?
A: Alcohol (severe reaction), metronidazole, paraldehyde, warfarin, phenytoin, isoniazid. Many other drug interactions are possible, consult a drug interaction resource.
Q8: How long does Disulfiram stay in the system?
A: Several days are needed to completely eliminate disulfiram and its metabolites from the body.
Q9: How should Disulfiram be taken?
A: Orally, once daily. May be taken in the evening if daytime drowsiness occurs. Tablets can be crushed and mixed with liquid if necessary.
Q10: What should patients be instructed about Disulfiram therapy?
A: Patients should be thoroughly educated about the disulfiram-alcohol reaction, including its symptoms and potential severity. They must abstain completely from all forms of alcohol. Patients should also be aware of potential drug interactions and side effects and report any concerns to their healthcare provider. Therapy with disulfiram should be part of a comprehensive treatment program that includes psychosocial support and counseling.
