Can Metronidazole Cause a Disulfiram-Like Reaction? A Case-Control Study Propensity Matched by Age, Sex, and Ethanol Concentration.

Introduction: There is controversy over the existence of a metronidazole-induced disulfiram-like reaction. Uncontrolled case reports suggest metronidazole can cause a severe disulfiram-like reaction in combination with ethanol. Criticism of these cases suggest the observed effects appear to be as likely caused by ethanol as by a drug interaction. Controlled experimental data refute these reports, demonstrating metronidazole does not increase acetaldehyde and cannot reliably produce disulfiram-like reactions. The purpose of this study is to retrospectively assess the incidence of clinical effects consistent with a disulfiram-like reaction in a population of patients with confirmed ethanol use who received metronidazole. As alcohol may also be responsible for the effects seen, the incidence of effects is assessed against a control group matched for age, sex, and ethanol concentration.

Methods: A retrospective chart review was performed from December 1, 2010, through December 31, 2020 on emergency department patients with ethanol use confirmed via detectable ethanol concentration who received metronidazole while ethanol was predicted to still be present in the serum. A matched comparator group with the same ethanol concentrations, as well as sex and age, was generated for comparison. The incidence of disulfiram-like reaction symptoms documented in the medical record was compared between groups.

Results: Thirty-six patients were included in the study: 18 in the metronidazole group and 18 in the ethanol concentration matched control group. The mean age in both groups was 46 years. The metronidazole group was 50% male, and the mean ethanol concentration was 0.21 g/dL. The control group was 44.4% male. There was significantly less hypertension in the metronidazole group compared to the control group (16.7% vs 61.1%, P $lt;  0.0001). There were no other significant difference in disulfiram-like effects between the two groups. No patients who received metronidazole and had a detectable ethanol concentration had a suspected disulfiram-like reaction documented in the medical record.

Conclusions: This data set further supports the lack of a disulfiram-like reaction when metronidazole is used in patients with recent ethanol use in the acute care setting. Additionally, it highlights that the clinical effects of a disulfiram-like reactions may be present at baseline from ethanol ingestion or underlying disease regardless of metronidazole use. These findings are consistent with well-controlled human and animal data demonstrating no increase in acetaldehyde concentrations or disulfiram-like symptoms when metronidazole is co-administered with ethanol. In patients where metronidazole is indicated as the superior agent, its use should not be avoided due to concern about an interaction with ethanol.