Metronidazole with Warfarin Interaction Details

Brand Names Associated with Metronidazole

Brand Names Associated with Warfarin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Jan 04, 2024

Interaction Effect

Increased risk of bleeding

Interaction Summary

Concomitant use of warfarin and metroNIDAZOLE may 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. Prolongation of prothrombin time has been demonstrated in small studies and case reports , and bleeding with hemorrhage was reported in another case report . 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 .

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Concomitant use of warfarin and metroNIDAZOLE may 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.

Mechanism Of Interaction

Potentiation of anticoagulation; prolonged prothrombin time

Literature Reports

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 .

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 .

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.

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 .

Metronidazole Overview

• Metronidazole capsules and tablets are used to treat infections of the reproductive system, gastrointestinal (GI) tract, skin, heart, bone, joint, lung, blood, nervous system, and other areas of the body. Metronidazole capsules and tablets are also used to treat sexually transmitted diseases (STDs). Metronidazole extended-release (long-acting) tablets are used to treat bacterial vaginosis (an infection caused by too much of certain types of harmful bacteria in the vagina) in women. Metronidazole is in a class of medications called nitroimidazole antimicrobials. It works by stopping the growth of bacteria.

• Antibiotics will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

Warfarin Overview

• Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart attack. Warfarin is also used to treat or prevent venous thrombosis (swelling and blood clot in a vein) and pulmonary embolism (a blood clot in the lung). Warfarin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.