Disulfiram


Generic Medicine Info
Indications and Dosage
Oral
Adjunct in chronic alcoholism
Adult: 800 mg as a single dose on the 1st day, reduce by 200 mg daily to a maintenance dose of 100-200 mg daily. Review treatment after, no longer than 6 mth.
Administration
May be taken with or without food.
Contraindications
Cardiac failure, coronary artery disease, history of CVA, HTN, psychosis or severe personality disorders. Patients receiving metronidazole, paraldehyde, alcohol or alcohol-containing preparations (e.g. cough syrups, tonics), alcohol-based topical preparations.
Special Precautions
Patient w/ DM, epilepsy, resp disorders, cerebral damage, hypothyroidism, abnormal EEG results, multiple drug dependence. Renal and hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Drowsiness, fatigue, garlic-like or metallic aftertaste, GI upsets, body odour, halitosis, headache, impotence, acneiform or allergic dermatitis, peripheral and optic neuropathies, psychotic reactions. Disulfiram-alcohol reaction (manifested by flushing of the face, throbbing in the head and neck, pulsating headache, resp difficulties, nausea, copius vomiting, sweating, thirst, chest pain, tachycardia, palpitations, marked hypotension, giddiness, weakness, blurred vision, confusion, and in severe cases, resp depression, CV collapse, cardiac arrhythmias, MI, acute heart failure, unconsciousness, convulsions, and sudden death). Rarely, blood dyscrasias.
Potentially Fatal: Severe hepatitis and/or hepatic failure.
Patient Counseling Information
Do not take alcohol (including alcohol-containing preparations) for up to 14 days after discontinuation. This drug may cause drowsiness or fatigue, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor LFTs (baseline and follow-up every 10-14 days), CBC and serum chemistries.
Overdosage
Symptoms: Nausea, vomiting, abdominal pain, diarrhoea, drowsiness, delirium, hallucinations, lethargy, tachycardia, tachypnoea, hyperthermia, hypotension, hypotonia, hyperglycaemia, leukocytosis, ketosis, methaemoglobinaemia; CV collapse, coma and convulsions in severe cases. Management: Symptomatic and supportive treatment. Gastric lavage and/or activated charcoal may be considered. May admin IV fluids for severe vomiting.
Drug Interactions
Enhances the effects of phenytoin, theophylline and coumarin anticoagulants. Inhibits the metabolism and excretion of rifampicin. Inhibits the metabolism of certain benzodiazepines (e.g. chlordiazepoxide, diazepam). Increased incidence of confusion and behavioural changes w/ isoniazid. May potentiate organic brain syndrome and choreoatphetosis w/ pimozide. Amitryptyline and chlorpromazine may increase the intensity of disulfiram-alcohol reaction.
Potentially Fatal: Disulfiram blocks the metabolism of alcohol leading to disulfiram-alcohol reaction. Increased toxic reactions w/ metronidazole. May increase serum concentration of paraldehyde.
Food Interaction
Avoid alcohol, including alcohol-containing medications and alcohol-based topical preparations as it may cause disulfiram-alcohol reaction.
Lab Interference
May increase urinary concentrations of homovanillic acid. May decrease iodine I 131 uptake or protein bound iodine test results.
Action
Description:
Mechanism of Action: Disulfiram inhibits aldehyde dehydrogenase, the oxidative enzyme of acetaldehyde, a metabolite of alcohol. The latter is accumulated in the blood, thus producing unpleasant symptoms of disulfiram-alcohol reaction when a patient has taken small amounts of alcohol.
Onset: 12 hr.
Duration: Approx 1-2 wk after last dose.
Pharmacokinetics:
Absorption: Absorbed variably from the GI tract.
Distribution: Primarily to the kidney, pancreas, liver, intestines and fat.
Metabolism: Rapidly converted to diethyldithiocarbamate via reduction by the glutathione reductase system in the erythrocytes and further metabolised hepatically to its glucuronide and methyl ester and to diethylamine, carbon disulfide and sulfate ions.
Excretion: Mainly via urine, as metabolites; carbon disulfide is exhaled in the breath.
Chemical Structure

Chemical Structure Image

Source: National Center for Biotechnology Information. PubChem Database. Disulfiram, CID=3117, https://pubchem.ncbi.nlm.nih.gov/compound/Disulfiram (accessed on Jan. 21, 2020)

Storage
Store between 15-30°C. Protect from light.
MIMS Class
Drugs Used in Substance Dependence
ATC Classification
N07BB01 - disulfiram ; Belongs to the class of drugs used in the management of alcohol dependence.
P03AA04 - disulfiram ; Belongs to the class of sulfur-containing agents used as ectoparasiticides.
References
Anon. Disulfiram. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/10/2015.

Buckingham R (ed). Disulfiram. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com . Accessed 06/10/2015.

Disulfiram Tablet (Roxane Laboratories, Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 06/10/2015.

McEvoy GK, Snow EK, Miller J et al (eds). Disulfiram. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 06/10/2015.

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