Warfarin and Metronidazole Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Warfarin
Metronidazole Topical
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased warfarin exposure and INR, and an increased risk of bleeding
Interaction Deep Dive
Concomitant use of warfarin and metroNIDAZOLE may increase warfarin exposure and increase INR3. Hence result in an increased risk of bleeding due to potentiation of the anticoagulant effect of warfarin and prolongation of prothrombin time. In patients receiving concomitant oral anticoagulant therapy with warfarin and metroNIDAZOLE, closely monitor the prothrombin time, INR, or other suitable anticoagulation tests, and monitor patients for signs or symptoms of bleeding 42. Consider the CYP2C9 inhibition potential when starting, stopping, or changing dose of concomitant medications 3. Prolongation of prothrombin time has been demonstrated in small studies and case reports 7, and bleeding with hemorrhage was reported in another case report 6. A decrease in warfarin dosage by 33% with close monitoring may be appropriate with coadministration of metronidazole 5.
Why it happens (mechanism)
Potentiation of anticoagulation; prolonged prothrombin time; inhibition of CYP2C9-mediated metabolism of warfarin
Literature reports
4 reports — tap to read
a) A case was reported of a 78-year old white woman who developed a profuse nosebleed with an international normalized ratio (INR) of 8 and an intraparenchymal hemorrhage of the left occipital lobe after concomitant administration of warfarin and metroNIDAZOLE. The patient was on a stable warfarin dose of 7 mg daily, with her most recent INR being 2.5, when metroNIDAZOLE 250 mg every 8 hours for 5 days and levoFLOXacin 500 mg daily for 6 days was initiated for an upper respiratory tract infection. Nine days later, the patient was admitted to the hospital with a profuse nosebleed with an INR of 8 and intraparenchymal hemorrhage of the left occipital lobe. Based on the Naranjo adverse drug reaction probability scale, the association with metroNIDAZOLE was probable and the association with levoFLOXacin was possible (scores of 7 and 4, respectively). The patient was discharged after a 1-week hospital stay without extension of the hemorrhage. The postulated mechanism of action was inhibition of S-warfarin metabolism by metroNIDAZOLE 6.
b) Eight healthy subjects who were concomitantly treated with oral metroNIDAZOLE 250 mg three times daily for eight days and a single dose of warfarin 1.5 mg/kg were studied. It was found that the combination of racemic warfarin with metroNIDAZOLE resulted in an increase in the one stage prothrombin time expressed as a percent increase of area under the curve from 100 to 142 with a concomitant increase in mean plasma warfarin half-life of 35 hours to 46 hours. Subsequent studies indicate that the S (-) isomer of warfarin was the specific enantiomer most effected by metroNIDAZOLE with an increase in prothrombin time from 100 to 196 and a concomitant increase in half-life from 32 hours to 50 hours 7.
c) After two weeks of watery stools, a 52-year-old female was hospitalized with possible Giardia lamblia and started on metroNIDAZOLE 500 mg three times a day. Her other medications included digoxin 0.125 mg daily, furosemide 40 mg every eight hours, and potassium 40 mEq daily for CHF; quiNIDine 200 mg every six hours for atrial fibrillation; and warfarin 5 mg daily for prevention of clotting on a Bjork-Shiley mitral valve prosthesis. She had been on this regimen for over two years, with two bleeding episodes during that time. During the four months prior to her admission, her anticoagulation was well-controlled (prothrombin time (PT) 21 to 27 seconds/control 11 to 12 seconds). Four days after discharge, she experienced back pain, fever, headache, and diarrhea. The next day she was readmitted with multiple bruises and painful, hard masses in her right calf, dizziness, weakness, pallor, and continuous headache. Her lab tests showed a PT of 75 seconds (control 12 sec), activated partial thromboplastin time (APTT) greater than 120 seconds (control 29 sec), hemoglobin 8.5 g/100mL, hematocrit 27.6%, and blood pressure 104/56 mmHg. A drug interaction was suspected, and her warfarin and metroNIDAZOLE were discontinued. She was given packed red blood cells and frozen plasma. Within 24 hours her PT was 34.9 and APTT 93.5. It was concluded that the interaction of warfarin and metroNIDAZOLE was the cause of her exaggerated anticoagulation. The postulated mechanism was inhibition of S-warfarin metabolism by metroNIDAZOLE 8.
d) Because the maximum concentration (Cmax) of topically administered metroNIDAZOLE is approximately 1% of values seen with oral administration, this interaction with warfarin is less likely to occur with topical metroNIDAZOLE administration 1.
Common questions
Can I take Warfarin and Metronidazole Topical together?
Increased warfarin exposure and INR, and an increased risk of bleeding Always confirm with your pharmacist or prescriber before making any change.
How serious is the Warfarin and Metronidazole Topical interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Warfarin or Metronidazole Topical need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (8)
- Product Information: Noritate(R) topical cream, metronidazole topical cream. Bausch Health US, LLC (per DailyMed), Bridgewater, NJ, 2020. DailyMed
- Product Information: LIKMEZ(TM) oral suspension, metronidazole oral suspension. Saptalis Pharmaceuticals LLC (per FDA), Hauppauge, NY, 2024. DailyMed
- Product Information: WARFARIN SODIUM oral tablets, warfarin sodium oral tablets. Teva Pharmaceuticals (per Dailymed), Parsippany, NJ, 2023. DailyMed
- Product Information: PYLERA(R) oral capsules, bismuth subcitrate potassium, metronidazole, tetracycline HCl oral capsules. H2-Pharma, LLC (per FDA), Montgomery, AL, 2024. DailyMed
- Mar PL, Gopinathannair R, Gengler BE, et al: Drug interactions affecting oral anticoagulant use. Circ Arrhythm Electrophysiol 2022; 15(6):e007956. PubMed
- Howard-Thompson A, Hurdle AC, Arnold LB, et al: Intracerebral hemorrhage secondary to a warfarin-metronidazole interaction. Am J Geriatr Pharmacother 2008; 6(1):33-36. PubMed
- O'Reilly RA: The stereoselective interaction of warfarin and metronidazole in man. N Engl J Med 1976; 295:354. DOI
- Dean RP & Talbert RL: Bleeding associated with concurrent warfarin and metronidazole therapy. Drug Intell Clin Pharm 1980; 14:864-866. DOI
Keep reading about Warfarin
Keep reading about Metronidazole Topical
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