Usage
Sulfiram is prescribed for the treatment of chronic alcoholism. It belongs to the pharmacological classification of enzyme inhibitors, specifically acetaldehyde dehydrogenase inhibitors. It works by blocking the enzyme acetaldehyde dehydrogenase, which is responsible for breaking down acetaldehyde, a byproduct of alcohol metabolism. This leads to a buildup of acetaldehyde in the body, causing unpleasant effects when alcohol is consumed, thus discouraging further drinking.
Alternate Names
Sulfiram is also known as disulfiram. Brand names include Antabuse.
How It Works
Pharmacodynamics: Sulfiram inhibits acetaldehyde dehydrogenase, leading to accumulation of acetaldehyde when alcohol is ingested. This results in a disulfiram-alcohol reaction (DER) characterized by unpleasant symptoms, including flushing, throbbing headache, nausea, vomiting, chest pain, difficulty breathing, weakness, blurred vision, confusion, and sweating.
Pharmacokinetics: Sulfiram is well-absorbed orally. It is metabolized in the liver to diethyldithiocarbamate, which is further metabolized and excreted in the urine and feces. Sulfiram’s metabolites are also excreted in the breath, sweat, and bile. Sulfiram and its metabolites inhibit several hepatic cytochrome P450 enzymes, including CYP2E1.
Mode of Action: Sulfiram irreversibly inhibits acetaldehyde dehydrogenase, preventing the conversion of acetaldehyde to acetic acid.
Elimination Pathways: Sulfiram and its metabolites are primarily eliminated through hepatic metabolism and excretion in the urine and feces.
Dosage
Standard Dosage
Adults:
Initial dosage: A maximum of 500 mg orally once daily for 1-2 weeks. Some protocols recommend starting with 800mg on day 1, then tapering down over the next few days before arriving at the maintenance dose.
Maintenance dosage: 125-500 mg (usually 250 mg) orally once daily. The maximum dose is 500 mg/day.
Duration of Therapy: Treatment may continue for months or even years, depending on the individual patient’s response and ability to maintain abstinence.
Children:
Sulfiram use is not recommended for children. The safety and efficacy have not been established in this population.
Special Cases:
-
Elderly Patients: Initiate at the lower end of the dosing range (125 mg/day) due to potential age-related decline in hepatic and renal function.
-
Patients with Renal Impairment: Use with caution. Dosage adjustment guidelines are not available for renal impairment.
-
Patients with Hepatic Dysfunction: Use with extreme caution. Dose reduction may be necessary.
-
Patients with Comorbid Conditions: Close monitoring is essential in patients with cardiovascular disease, diabetes, hypothyroidism, epilepsy, seizure disorders, cerebral damage, or mental illness.
Clinical Use Cases
Sulfiram is not typically used in medical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary use is in the outpatient setting as part of a comprehensive alcoholism treatment program.
Dosage Adjustments
Dose adjustments may be needed in patients with hepatic or renal dysfunction. Individualized dosing is essential based on patient response and tolerance.
Side Effects
Common Side Effects:
Drowsiness, fatigue, headache, acne, flushing, sweating, increased thirst, metallic or garlic-like taste in the mouth.
Rare but Serious Side Effects:
Hepatotoxicity (liver damage), peripheral neuropathy, optic neuritis, psychotic reactions, depression.
Long-Term Effects:
Chronic complications from prolonged use are rare, but hepatotoxicity and peripheral neuropathy are potential concerns.
Adverse Drug Reactions (ADR):
Severe DER, hepatotoxicity, psychosis, peripheral neuropathy, optic neuritis.
Contraindications
Absolute contraindications include hypersensitivity to sulfiram or thiuram derivatives, severe myocardial disease, coronary occlusion, psychosis, concurrent or recent use of metronidazole or paraldehyde, and alcohol intoxication. Relative contraindications include severe hepatic or renal disease, diabetes, hypothyroidism, epilepsy, seizure disorder, cerebral damage.
Drug Interactions
Sulfiram interacts with numerous medications, including:
-
Alcohol: Concurrent alcohol ingestion can cause a severe and potentially life-threatening reaction.
-
Metronidazole, Paraldehyde: Concurrent use is contraindicated due to the potential for serious adverse effects.
-
Warfarin: Sulfiram can inhibit warfarin metabolism, increasing the risk of bleeding.
-
Phenytoin: Sulfiram can increase phenytoin levels, requiring dose adjustment.
-
Theophylline: Sulfiram can increase theophylline levels, requiring dose adjustment.
-
Tricyclic antidepressants: Concurrent use can increase the risk of delirium or altered antidepressant levels.
-
Benzodiazepines (certain types): Dosage adjustments may be necessary.
-
Isoniazid: Concurrent use can lead to unsteady gait or mental status changes.
Pregnancy and Breastfeeding
Pregnancy Safety Category: C. Sulfiram is not recommended during pregnancy, especially the first trimester, due to potential fetal risks. It is not known if sulfiram passes into breast milk. Breastfeeding while taking sulfiram is not recommended.
Drug Profile Summary
- Mechanism of Action: Inhibits acetaldehyde dehydrogenase, leading to acetaldehyde accumulation when alcohol is consumed.
- Side Effects: Common: Drowsiness, fatigue, headache. Serious: Hepatotoxicity, peripheral neuropathy, psychotic reactions.
- Contraindications: Hypersensitivity to sulfiram, alcohol intoxication, concurrent use of metronidazole or paraldehyde.
- Drug Interactions: Alcohol, metronidazole, paraldehyde, warfarin, phenytoin, theophylline, tricyclic antidepressants.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Initial: 250-500 mg/day. Maintenance: 125-500 mg/day (max 500 mg/day).
- Monitoring Parameters: Liver function tests, complete blood count, renal function tests.
Popular Combinations
Sulfiram is typically used as monotherapy in the treatment of alcoholism.
Precautions
General precautions: Alcohol avoidance is paramount. Monitor liver function. Screen for pre-existing medical conditions, especially cardiovascular disease, diabetes, and mental health disorders.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sulfiram?
A: Initial: 250-500 mg/day for 1-2 weeks. Maintenance: 125-500 mg/day (max 500 mg/day).
Q2: What is the mechanism of action of Sulfiram?
A: Sulfiram irreversibly inhibits acetaldehyde dehydrogenase.
Q3: What are the most common side effects?
A: Drowsiness, fatigue, headache, metallic or garlic-like taste.
Q4: What are the serious side effects of Sulfiram?
A: Hepatotoxicity, peripheral neuropathy, optic neuritis, psychotic reactions.
Q5: Can Sulfiram be used during pregnancy?
A: No, it is generally contraindicated during pregnancy.
Q6: Can Sulfiram be used with alcohol?
A: No, concurrent alcohol use is contraindicated and can cause a severe reaction.
Q7: What are the drug interactions with Sulfiram?
A: Sulfiram interacts with numerous medications, including metronidazole, paraldehyde, warfarin, phenytoin, and theophylline. Consult a comprehensive drug interaction resource for a complete list.
Q8: Can patients with liver disease take Sulfiram?
A: Sulfiram should be used with extreme caution in patients with liver disease, and dose adjustments might be necessary.
Q9: How long does the disulfiram-alcohol reaction (DER) last?
A: The DER can last from 30 minutes to several hours.
Q10: Can Sulfiram cure alcoholism?
A: No, Sulfiram is not a cure for alcoholism but an aid in maintaining abstinence as part of a comprehensive treatment program.
