Froedtert & the Medical College of Wisconsin, Department of Pharmacy, Milwaukee, Wisconsin,
Medical College of Wisconsin, School of Pharmacy, Milwaukee, Wisconsin.
WMJ. 2023 Jul;122(3):171-177.
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.
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.
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%, $lt; 0.0001). There were no other significant difference in disulfiram-like effects between the two groups. No patients who received metronidazole and had a detectable ethanol concentration had a suspected disulfiram-like reaction documented in the medical record.
This data set further supports the lack of a disulfiram-like reaction when metronidazole is used in patients with recent ethanol use in the acute care setting. Additionally, it highlights that the clinical effects of a disulfiram-like reactions may be present at baseline from ethanol ingestion or underlying disease regardless of metronidazole use. These findings are consistent with well-controlled human and animal data demonstrating no increase in acetaldehyde concentrations or disulfiram-like symptoms when metronidazole is co-administered with ethanol. In patients where metronidazole is indicated as the superior agent, its use should not be avoided due to concern about an interaction with ethanol.
关于甲硝唑诱导的戒酒硫样反应是否存在存在争议。未经控制的病例报告表明，甲硝唑与乙醇联合使用可能会导致严重的戒酒硫样反应。对这些病例的批评表明，观察到的效应似乎更可能是由乙醇引起的，而不是由药物相互作用引起的。对照实验数据反驳了这些报告，证明甲硝唑不会增加乙醛，也不能可靠地产生戒酒硫样反应。本研究的目的是回顾性评估在一组已确认使用乙醇且血清中仍预测存在乙醇的患者中，使用甲硝唑后出现与戒酒硫样反应一致的临床效应的发生率。由于酒精也可能导致观察到的效应，因此根据年龄、性别和乙醇浓度匹配的对照组来评估效应的发生率。
对 2010 年 12 月 1 日至 2020 年 12 月 31 日期间因确认有乙醇使用而接受急诊治疗的患者进行了回顾性图表审查，这些患者的乙醇浓度可通过检测到的乙醇浓度来确定，且在接受甲硝唑治疗时，预计血清中仍存在乙醇。为了进行比较，生成了一个具有相同乙醇浓度以及性别和年龄的匹配对照组。比较了两组记录在病历中的戒酒硫样反应症状的发生率。
本研究共纳入 36 例患者：甲硝唑组 18 例，乙醇浓度匹配对照组 18 例。两组患者的平均年龄均为 46 岁。甲硝唑组中 50%为男性，平均乙醇浓度为 0.21 g/dL。对照组中 44.4%为男性。与对照组相比，甲硝唑组的高血压发生率显著降低（16.7% vs 61.1%，$lt; 0.0001）。两组之间在戒酒硫样效应方面没有其他显著差异。在接受甲硝唑治疗且检测到乙醇浓度的患者中，没有记录到疑似戒酒硫样反应。
本数据集进一步支持在急性护理环境中，当近期使用乙醇的患者使用甲硝唑时，不会出现戒酒硫样反应。此外，这也强调了无论是否使用甲硝唑，戒酒硫样反应的临床效应可能由于乙醇摄入或基础疾病而存在于基线。这些发现与精心控制的人体和动物数据一致，这些数据表明，当甲硝唑与乙醇联合使用时，不会增加乙醛浓度或出现戒酒硫样症状。在需要使用甲硝唑的患者中，不应因担心与乙醇相互作用而避免使用该药物。
