Alcohol deterrent (aldehyde dehydrogenase inhibitor)
Disulfiram is a medicine that supports the treatment of chronic alcoholism: if the person drinks alcohol during treatment, they experience very uncomfortable reactions (flushing, tachycardia, nausea), which helps maintain abstinence. It should only be used with motivation and psychotherapeutic support.
Also known as: Dissulfiram, Antabuse
Disulfiram + metronidazole: confusion and psychoses have been reported in patients taking disulfiram and metronidazole (mechanism unknown) (QUADRO 2).
The combination of metronidazole with disulfiram has been associated with acute psychotic reactions, confusion and delirium, even at usual doses; the mechanism is not fully understood but probably involves interference with amine metabolism. QUADRO 2 of Annex 7 records this interaction in the disulfiram section. The guidance is to avoid the combination, respecting a minimum interval of about 14 days between stopping one drug and starting the other. If metronidazole is essential in a patient on disulfiram, consider an alternative antibiotic; watch for neuropsychiatric symptoms (confusion, hallucinations, agitation).
Metronidazole + disulfiram: risk of acute psychotic reaction and confusion; avoid — minimum interval of 14 days.
The disulfiram + metronidazole combination has been associated with psychotic/confusional reactions — QUADRO 2 records confusion and psychoses, with unknown mechanism (QUADRO 2, Disulfiram: "Metronidazole: confusion and psychoses have been reported in patients taking disulfiram and metronidazole").
Monitor mental state during concomitant therapy.
Acute confusion, psychosis in a patient taking disulfiram + metronidazole.
Avoid the combination; if metronidazole is required, watch the mental state.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Disulfiram)
FDA label (WARNINGS): alcohol consumption during disulfiram treatment causes the disulfiram-alcohol reaction — flushing, tachycardia, hypotension, nausea and vomiting (acetaldehyde accumulation from aldehyde dehydrogenase inhibition). Severe and potentially fatal reactions are possible; any source of ethanol (incl. beverages, alcohol-containing medicines, perfumes, vinegar) may trigger the reaction.
Instruct the patient to avoid any source of alcohol during treatment (and in the days after discontinuation); explain the symptoms of the reaction and to seek medical help if severe.
DailyMed/FDA (NIH/NLM) — Disulfiram, WARNINGS: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b90f8ff4-4fb3-46ab-8149-cb55f24a4044
FDA label (WARNINGS): multiple cases of hepatitis (cholestatic and fulminant) and hepatic failure resulting in transplantation or death have been reported with disulfiram; watch for prodromal symptoms and monitor liver function.
Watch for hepatitis symptoms (fatigue, anorexia, diarrhoea, nausea) and monitor liver tests; discontinue upon signs of liver injury.
DailyMed/FDA (NIH/NLM) — Disulfiram, WARNINGS: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b90f8ff4-4fb3-46ab-8149-cb55f24a4044
FDA label (WARNINGS): optic neuritis, peripheral neuritis, polyneuritis and peripheral neuropathy may occur following administration of disulfiram.
Watch for signs of neuropathy and visual symptoms; discontinue if they occur.
DailyMed/FDA (NIH/NLM) — Disulfiram, WARNINGS: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b90f8ff4-4fb3-46ab-8149-cb55f24a4044
FDA label (Usage in Pregnancy): safety in pregnancy has not been established — use only if, in the physician's judgement, the probable benefits outweigh the possible risks.
Use only if the probable benefit outweighs the possible risks (safety not established).
It is not known whether it is excreted in human milk; do not give to nursing mothers (Nursing Mothers).
Not applicable (no specific contraception requirements in the label).
DailyMed/FDA (NIH/NLM) — approved Disulfiram label, Usage in Pregnancy/Nursing Mothers sections: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b90f8ff4-4fb3-46ab-8149-cb55f24a4044 ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 2, Drugs and Breastfeeding: Avoid; it is not known whether it is harmful.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Alcohol deterrent: irreversible inhibition of aldehyde dehydrogenase — after alcohol intake, acetaldehyde accumulation causes the disulfiram-alcohol reaction (flushing, tachycardia, hypotension, nausea/vomiting) that discourages consumption (FDA label).
Inhibition of aldehyde dehydrogenase (acetaldehyde accumulation); decreased metabolism rate of certain drugs (increased levels and toxicity risk).
Oral absorption; the effect depends on concomitant alcohol intake (the drug has no effect on sobriety without the alcohol reaction).
Metabolised to diethyldithiocarbamate; excretion is mixed (urine and expired air). The label does not detail percentages.
Half-life not documented in the label; the effect on aldehyde dehydrogenase is prolonged (the reaction may occur up to days after the last dose).
