Disulfiram

• disulfiram blocks the oxidation of alcohol causing an accumulation of acetaldehyde after drinking - disulfiram is an inhibitor of hepatic aldehyde dehydrogenase (ALDH). This results in symptoms such as abdominal colic, flushing, anxiety, dizziness, tachycardia, vomiting and headache. Symptoms start 5-15 minutes after drinking alcohol and last for several hours. Note that the intensity of the reaction is dependent on the individual, the disulfiram dose and the alcohol intake (1)
  
  
  
  
• if large doses of alcohol are consumed whilst receiving disulfiram treatment, collapse, cardiac arrhythmias and even death can occur
  
  
• disulfiram has been given to break the drinking habit in alcoholics and it may deter relapse in abstinent patients
  
  
• before prescribing disulfiram, patients should be warned that the severity of the reaction is unpredictable. Occasionally a reaction may be triggered by the small amount of alcohol in preparations such as cough linctuses
  
  
• hepatoxicity and psychotic reactions are rare adverse effects to disulfiram treatment
  • elevated liver function tests - hepatotoxicity is a rare adverse effect to disulfiram treatment; liver function tests should be checked before commencement of and at regular intervals throughout treatment - disulfiram treatment should be witheld if liver enzymes are elevated ten or more times than normal (2)
    
    
• disulfiram is contraindicated during pregnancy and in patients with a psychosis; also contraindicated if there is an established hypersensitivity
  • disulfiram should be used with caution in patients with diabetes, epilepsy and hypercholesterolaemia (1)
  • disulfiram is also contraindicated in patients with seriously impaired cardiac, respiratory, hepatic or cerebral function.

NICE state that (5):

• Disulfiram Make sure that service users taking disulfiram: Warn service users taking disulfiram, and their families and carers, about:
  • if using disulfiram, start treatment at least 24 hours after the last alcoholic drink consumed. Usually prescribe at a dose of 200 mg per day. For service users who continue to drink, if a dose of 200 mg (taken regularly for at least 1 week) does not cause a sufficiently unpleasant reaction to deter drinking, consider increasing the dose in consultation with the service user
  • before starting treatment with disulfiram, test liver function, urea and electrolytes to assess for liver or renal impairment. Check the SPC for warnings and contraindications in pregnancy and in the following conditions: a history of severe mental illness, stroke, heart disease or hypertension
  • stay under supervision, at least every 2 weeks for the first 2 months, then monthly for the following 4 months
  • if possible, have a family member or carer, who is properly informed about the use of disulfiram, oversee the administration of the drug
  • are medically monitored at least every 6 months after the initial 6 months of treatment and monitoring
    
    
  • the interaction between disulfiram and alcohol (which may also be found in food, perfume, aerosol sprays and so on), the symptoms of which may include flushing, nausea, palpitations and, more seriously, arrhythmias, hypotension and collapse
  • the rapid and unpredictable onset of the rare complication of hepatotoxicity; advise service users that if they feel unwell or develop a fever or jaundice that they should stop taking disulfiram and seek urgent medical attention.

The summary of product characteristics must be consulted before prescribing this drug.

Reference:

1. Prescriber 2004; 15(9): 16-25.
2. Drug and Therapeutics Bulletin (2000); 38 (8):60-64.
3. Drug and Therapeutics Bulletin (1996), Drugs and alcohol: harmful cocktails?; 34 (5): 36-8.
4. Kwentus J, Major LF (1979), Disulfiram in the treatment of alcoholism, J Stud Alcohol, 40, 428-46.
5. NICE (February 2011). Alcohol-use disorders - Diagnosis, assessment and management of harmful drinking and alcohol dependence