Revisiting the Disulfiram-Like Reaction Between Alcohol and Oral Metronidazole

Oral metronidazole (MTZ) is a widely used drug in the 5-nitroimidazole class effective against various anaerobic bacteria and protozoa. It has long been thought to cause a disulfiram-like reaction (DLR) when combined with alcohol, believed to result from inhibition of aldehyde dehydrogenase, leading to acetaldehyde accumulation and symptoms such as nausea, flushing, vomiting, and tachycardia. To assess the validity of this association, we reviewed the English-language literature in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from 1/1/1970-11/22/2024, using the broad search term “disulfiram-like reaction.” Eleven studies met inclusion criteria. While all four case reports and one older clinical trial reported a potential link between some oral 5-nitroimidazoles and DLR, 3 clinical trials, one cross-sectional chart review, and 2 experimental animal studies did not. Thus, the available evidence does not strongly support a clinically significant interaction between alcohol and oral MTZ, calling into question the need for strict alcohol abstinence during treatment.