Which Drug Is Contraindicated with Metronidazole? A Detailed Guide

October 14, 2025 •

4 min read

Adverse drug events are a significant concern, with common side effects like headache and nausea affecting over 10% of metronidazole users [1.8.3]. Understanding which drug is contraindicated with metronidazole is crucial for preventing severe, and sometimes life-threatening, reactions.

Quick Summary

Metronidazole has absolute contraindications with alcohol, disulfiram, and busulfan. It also has significant interactions with warfarin and lithium that require close monitoring.

Key Points

Alcohol Contraindication: Alcohol and metronidazole cause a disulfiram-like reaction; it must be avoided during and for 3 days after therapy [1.2.2].
Disulfiram Danger: Combining metronidazole and disulfiram can trigger psychotic reactions and is absolutely contraindicated within 14 days of each other [1.2.2].
Busulfan Toxicity: Metronidazole significantly increases busulfan levels, leading to a high risk of severe toxicity and should be avoided [1.7.2].
Warfarin Interaction: Metronidazole enhances the anticoagulant effect of warfarin, increasing bleeding risk and requiring frequent INR monitoring [1.5.1].
Lithium Levels: Metronidazole can elevate lithium levels, creating a risk for toxicity; close monitoring of serum lithium is necessary [1.6.2, 1.6.3].
Patient Disclosure: Always inform your healthcare provider of all medications, including over-the-counter drugs and supplements, to screen for interactions [1.3.3].
Pregnancy Considerations: Metronidazole is generally contraindicated in the first trimester of pregnancy for trichomoniasis [1.2.2].

Understanding Metronidazole: An Essential Antibiotic

Metronidazole is a potent antibiotic and antiprotozoal medication belonging to the nitroimidazole class [1.2.2]. It is widely prescribed to treat a variety of infections caused by anaerobic bacteria and certain parasites. Common uses include treating gastrointestinal infections like Clostridioides difficile, vaginal infections such as bacterial vaginosis and trichomoniasis, and skin or mouth infections [1.8.3, 1.10.4]. Its mechanism of action involves entering the microbial cell, where it is reduced and forms toxic free radicals that disrupt the microbe's DNA, leading to cell death. While highly effective, its use must be carefully managed due to a significant potential for drug interactions.

What Does 'Contraindicated' Mean in Pharmacology?

A contraindication is a specific situation in which a drug, procedure, or surgery should not be used because it may be harmful to the person [1.2.2]. There are two main types:

Absolute Contraindication: This means that the drug could cause a life-threatening situation. A drug with an absolute contraindication should never be used in that circumstance. For example, the use of oral metronidazole is absolutely contraindicated in patients who have taken disulfiram within the last two weeks [1.2.2].
Relative Contraindication: This means that caution should be used when two drugs or procedures are used together. It is acceptable to do so if the benefits of treatment outweigh the risks. An example is the co-administration of metronidazole and the blood thinner warfarin, which requires careful monitoring [1.5.1].

Absolute Contraindications with Metronidazole

Certain substances and drugs must be strictly avoided when taking metronidazole due to the risk of severe adverse reactions.

Alcohol and Propylene Glycol

The most well-known contraindication is with alcohol. Consuming alcohol or products containing propylene glycol while taking metronidazole can lead to a 'disulfiram-like reaction' [1.2.2, 1.4.2]. Normally, the body metabolizes alcohol into acetaldehyde, which is then broken down further. Metronidazole is thought to inhibit the enzyme responsible for this second step, leading to a buildup of toxic acetaldehyde [1.4.2, 1.4.3]. Symptoms of this reaction include:

Severe nausea and vomiting [1.2.2]
Flushing (redness and warmth of the skin) [1.2.2]
Headaches [1.2.2]
Abdominal cramps [1.2.2]
Tachycardia (rapid heartbeat)

Patients are advised to avoid alcohol and propylene glycol-containing products during treatment and for at least three days after the final dose [1.2.2, 1.11.2].

Disulfiram

Disulfiram (brand name Antabuse) is a medication used to treat alcohol use disorder. The concurrent use of metronidazole and disulfiram is contraindicated because it can lead to psychotic reactions, including confusion and hallucinations [1.2.2]. To prevent this dangerous interaction, patients should not take metronidazole if they have used disulfiram within the past 14 days [1.2.3, 1.11.3].

Busulfan

Busulfan is a chemotherapy agent used in preparation for stem cell transplantation [1.7.4]. Metronidazole can significantly increase the concentration of busulfan in the blood by inhibiting its metabolism [1.7.2]. This leads to a high risk of severe busulfan toxicity, which can manifest as liver damage (veno-occlusive disease), seizures, and bone marrow suppression [1.7.1, 1.7.4]. Due to this risk, concomitant use should be avoided unless absolutely necessary, and if used, requires intensive monitoring of busulfan plasma levels [1.7.2, 1.7.3].

Significant Drug Interactions Requiring Monitoring

Beyond absolute contraindications, metronidazole interacts with several other common medications, necessitating dose adjustments and careful patient monitoring.

Warfarin

Warfarin is an anticoagulant (blood thinner) used to prevent blood clots. Metronidazole can enhance warfarin's effect, increasing the risk of bleeding [1.5.2, 1.5.5]. It does this by inhibiting the CYP2C9 enzyme, which is responsible for metabolizing the more potent S-enantiomer of warfarin [1.5.1]. This slows down the clearance of warfarin from the body, leading to a higher International Normalized Ratio (INR), a measure of blood clotting time. Patients on warfarin who are prescribed metronidazole must have their INR checked frequently, and their warfarin dose may need to be adjusted accordingly [1.5.1].

Lithium

Lithium is a mood stabilizer used primarily for bipolar disorder [1.6.2]. Metronidazole can increase lithium levels in the blood, potentially leading to lithium toxicity [1.6.1, 1.6.2]. The exact mechanism is not fully understood but is believed to involve reduced renal clearance of lithium [1.6.5]. Symptoms of lithium toxicity include severe confusion, vomiting, tremors, and lack of coordination [1.6.2]. Close monitoring of serum lithium levels is recommended if these two drugs must be used together [1.6.3].

Comparison of Key Metronidazole Interactions


Interacting Drug	Type of Interaction	Mechanism	Clinical Management
Alcohol	Absolute Contraindication	Inhibition of aldehyde dehydrogenase, causing acetaldehyde buildup (Disulfiram-like reaction) [1.4.2].	Avoid alcohol during and for at least 3 days after treatment [1.2.2].
Disulfiram	Absolute Contraindication	Combined central nervous system toxicity.	Do not use within 14 days of each other [1.2.2].
Busulfan	Absolute Contraindication	Metronidazole increases plasma concentrations of busulfan, risking severe toxicity [1.7.2].	Avoid co-administration. If necessary, frequent busulfan level monitoring is required [1.7.3].
Warfarin	Significant Interaction	Inhibition of CYP2C9 metabolism of S-warfarin, increasing anticoagulant effect [1.5.1].	Frequent INR monitoring and warfarin dose adjustment [1.5.1].
Lithium	Significant Interaction	May decrease renal clearance of lithium, increasing risk of toxicity [1.6.5].	Monitor serum lithium levels closely [1.6.3].

Conclusion

While metronidazole is a valuable medication for treating specific infections, its use requires a thorough understanding of its pharmacological profile. The absolute contraindications with alcohol, disulfiram, and busulfan are critical to prevent severe, life-threatening reactions. Furthermore, significant interactions with drugs like warfarin and lithium demand vigilant monitoring and management by healthcare professionals. Patient education on these interactions is a cornerstone of safe and effective treatment, ensuring that the benefits of metronidazole therapy are realized without causing unnecessary harm. Always disclose your full medication history to your doctor and pharmacist.

For more detailed information from a primary source, you can review the FDA label for Metronidazole tablets on DailyMed.

Frequently Asked Questions

Drinking alcohol while taking metronidazole can cause a severe disulfiram-like reaction, with symptoms including intense nausea, vomiting, facial flushing, headache, and abdominal cramps [1.2.2, 1.9.2].

It is recommended to wait at least three days (72 hours) after your final dose of metronidazole before consuming any alcohol or products containing propylene glycol [1.2.2].

Disulfiram (Antabuse) is absolutely contraindicated. Using it with metronidazole can cause psychotic episodes. You should not take metronidazole if you have taken disulfiram in the last two weeks [1.2.2, 1.11.3].

You can, but with extreme caution. Metronidazole increases the effect of warfarin, raising your risk of bleeding. Your doctor must monitor your INR closely and will likely need to adjust your warfarin dose [1.5.1].

Yes, it has a significant interaction with lithium, a mood stabilizer. Metronidazole can cause lithium levels to rise to toxic levels. If you take lithium, your doctor will need to monitor your blood levels closely during treatment [1.6.2, 1.6.3].

Metronidazole is contraindicated for treating trichomoniasis during the first trimester of pregnancy [1.2.2]. For other uses or trimesters, a doctor must weigh the risks and benefits [1.2.5].

Metronidazole prevents the body from breaking down busulfan (a chemotherapy drug), which can lead to dangerously high levels of busulfan and cause severe toxicity, including liver damage and bone marrow suppression [1.7.1, 1.7.2].