Adult: 800 mg as a single dose on Day 1,600 mg on Day 2,400 mg on Day 3, then 200 mg on Days 4-5. Maintenance dose: 100-200 mg daily for up to 6 months. Alternatively, an initial dose of 500 mg daily for 1-2 weeks, followed by a maintenance dose of 250 mg daily or within the range of 125 mg up to Max of 500 mg daily. Treatment duration may range from months to years and is dependent on the patient's ability to abstain from alcohol ingestion. Reevaluate treatment after 6 months. Dosage recommendations may vary between countries (refer to local product guidelines). Elderly: Initiate at the lower end of the dosing range.
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Psychosis, suicidal risk, severe personality disorder, CV disease (e.g. coronary occlusion), history of CVA, hypertension. Patient receiving or using alcohol or alcohol-containing preparations (e.g. cough syrups, tonics), alcohol-based topical preparations; or if patient is in a state of alcoholic intoxication. Concomitant use with metronidazole or paraldehyde.
Special Precautions
Patient with respiratory disease, diabetes mellitus, hypothyroidism, abnormal EEGs, cerebral damage, epilepsy or history of seizure disorder; history of rubber contact dermatitis for hypersensitivity to thiuram derivatives. Not intended as cure for alcoholism. Do not administer to the patient without their full knowledge. Do not administer until the patient has abstained from alcohol for at least 12 hours. Renal and hepatic impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Gastrointestinal disorders: Halitosis. General disorders and administration site conditions: Fatigue. Hepatobiliary disorders: Hepatic cell damage. Nervous system disorders: Drowsiness, optic neuritis, peripheral neuritis, encephalopathy. Psychiatric disorders: Psychotic reactions, depression, paranoia, schizophrenia, mania, reduced libido. Skin and subcutaneous tissue disorders: Allergic dermatitis, rash. Potentially Fatal: Hepatotoxicity (e.g. severe hepatitis, hepatic failure); disulfiram-alcohol reaction (e.g. flushing, throbbing in the head and neck, throbbing headache, respiratory difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitation, dyspnoea, hyperventilation, tachycardia, weakness, marked uneasiness, vertigo, confusion, hypotension, syncope; severe reactions may include respiratory depression, CV collapse, arrhythmias, MI, acute CHF, unconsciousness, convulsions).
Patient Counseling Information
This drug may cause drowsiness and fatigue, if affected, do not drive or operate machinery. Do not consume alcohol during treatment and for up to 14 days after treatment discontinuation.
Monitoring Parameters
Monitor LFTs before initiation of treatment ant periodically thereafter; CBC, serum chemistries, and cardiac function at baseline. Monitor for CNS changes (e.g. restlessness, sedation, peripheral neuropathy) before treatment and periodically thereafter.
Overdosage
Symptoms: Nausea, vomiting, diarrhoea, abdominal pain, lethargy, delirium, hallucination, drowsiness, tachycardia, hyperthermia, tachypnoea, hypotension, hypotonia, hyperglycaemia, ketosis, leucocytosis, methaemoglobinaemia; CV collapse, convulsion and coma (severe cases). Rarely, sensorimotor neuropathy, ECG abnormalities, psychosis, catatonia, encephalopathy, dysarthria, dystonia, akinesia, myoclonus, and ataxia. Management: Symptomatic and supportive treatment. May perform gastric lavage or administer activated charcoal if needed. May give IV fluids in case of severe vomiting.
Drug Interactions
May inhibit the metabolism of chlordiazepoxide and diazepam leading to enhanced adverse effects. May inhibit the metabolism and enhance the effect of phenytoin, theophylline, and warfarin. Rarely, may potentiate organic brain syndrome and choreoathetosis with pimozide. May inhibit the oxidation and renal excretion of rifampicin. May cause behavioural changes, incoordination, and unsteady gait when used concurrently with isoniazid. May increase the overall intensity of disulfiram-alcohol reaction with chlorpromazine and amitriptyline. Potentially Fatal: May increase the toxic effect of metronidazole (e.g. acute psychotic reaction and confusion). May increase the serum concentration of paraldehyde.
Lab Interference
May increase urinary levels of homovanillic acid. Rarely, may reduce iodine-131 uptake or protein-bound iodine test results.
Action
Description: Mechanism of Action: Disulfiram is a thiuram derivative. It irreversibly inhibits aldehyde dehydrogenase, an enzyme responsible for the oxidation of acetaldehyde (metabolite of alcohol) to acetate, thereby leading to an increased level of acetaldehyde in the blood. The accumulation of acetaldehyde in the blood leads to highly unpleasant symptoms, known as the disulfiram-alcohol reaction, which can occur after alcohol ingestion even in small quantities. Synonym(s): Tetraethylthiuram disulfide. Onset: 12 hours (full effect). Duration: Approx 1-2 weeks after last dose. Pharmacokinetics: Absorption: Variably absorbed from the gastrointestinal tract. Metabolism: Rapidly reduced to diethyldithiocarbamate mainly by glutathione reductase system in the erythrocytes; diethyldithiocarbamate is further metabolised in the liver to glucuronide and methyl ester and to diethylamine, carbon disulfide, and sulfate ions. Excretion: Via faeces (20% as unchanged drug); urine (50% as metabolites); exhaled gas (as carbon disulfide).
Chemical Structure
Disulfiram Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3117, Disulfiram. https://pubchem.ncbi.nlm.nih.gov/compound/Disulfiram. Accessed July 26, 2024.
N07BB01 - disulfiram ; Belongs to the class of drugs used in the management of alcohol dependence.
References
Anon. Disulfiram. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 03/06/2024.Antabuse Tablets 200 mg (Teva UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 03/06/2024.Brayfield A, Cadart C (eds). Disulfiram. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/06/2024.Disulfiram Tablet (Chartwell RX, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 03/06/2024.Disulfiram. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 17/07/2024.Disulfiram. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 03/06/2024.Joint Formulary Committee. Disulfiram. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/06/2024.Teva Pharma (New Zealand) Limited. Antabuse Effervescent Tablet 200 mg data sheet 29 June 2018. Medsafe. http://www.medsafe.govt.nz. Accessed 03/06/2024.
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