Disulfiram adverse drug reaction

The Swedish adverse drug reactions register, SWEDIS, received 149 case reports of 157 adverse reactions associated with disulfiram from 1971 to 1999, of which 63 cited disorders of the liver and biliary tract (26). Of these 63 reports, seven were classified as serious. In three cases of severe liver damage with a fatal outcome, disulfiram was suspected to have caused the reaction. If signs of liver damage appear, it is recommended that disulfiram be withdrawn and liver function tests performed. 

Enghusen Poulsen H, Loft S, Andersen JR, Andersen M. Disulfiram therapy—adverse drug reactions and interactions. Acta Psychiatr Scand Suppl 1992 369 59-66. 

Disulfiram modifies the metabolism of many drugs by inhibiting the cytochrome CYP2E1. Adverse reactions to disulfiram occur with a frequency of 1 in 200 to 1 in 2000 per treatment-year (4). The death rate is about one per 25 000 patients per year, and hepatic failure accounts for most of these (4). Allergic reactions can occur. Tumor-inducing effects have not been described. 

Toxicity Adverse effects include gastrointestinal irritation, headache, and dark coloration of urine. More serious toxicity includes leukopenia, dizziness, and ataxia. Drag interactions with metronidazole include a disulfiram-like reaction with ethanol and potentiation of coumarin anticoagulant effects. Although it is not contraindicated in pregnancy, the drug should be used with caution. 

Not understood. One idea is that some kind of synergy occurs between the two drugs because both can produce similar adverse effects if given in high doses. The authors of one report speculate that isoniazid and disulfiram together inhibit two of three biochemical pathways concerned with the metabolism of dopamine. This leaves a third pathway open, catalysed by COMT (catechol-O-methyl transferase), which produces a number of methylated products of dopamine. These methylated products may possibly have been responsible for the mental and physical reactions... 

This seems to be the only report of an adverse reaction between disulfiram and an MAOI, so it is possible that this is just an idiosyncratic reaction. However, warnings about this drug combination, based on theoretical considerations and studies in animals, have previously been... 

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