Warfarin with Benzbromarone Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 07, 2023
Interaction Effect
An increased risk of bleeding
Interaction Summary
Patients anticoagulated with warfarin and receiving benzbromarone therapy required 36% less of a warfarin dose than patients treated only with warfarin to attain a similar international normalized ratio (INR). Benzbromarone is thought to competitively inhibit the metabolism of (S)-warfarin, the more potent of the two warfarin enantiomers, through cytochrome P450 2C9 enzymes. In support of this theory, no significant differences were observed for (R)-warfarin pharmacokinetics between warfarin recipients who received benzbromarone and those who did not.
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Patients receiving oral anticoagulant therapy with warfarin should be closely monitored using the prothrombin time (PT) ratio or international normalized ratio (INR) during concurrent therapy with benzbromarone. The warfarin dose should be reduced approximately 30% when benzbromarone therapy is present, and further warfarin dose adjustments should be based on INR or PT values.
Mechanism Of Interaction
Competitive inhibition of cytochrome P450 2C9-mediated (S)-warfarin metabolism
Literature Reports
A) Thirty-one Japanese patients with heart disease who were stabilized on warfarin therapy participated in a study to determine the effect of benzbromarone on the pharmacokinetics of warfarin. Eighteen patients served as the control group, receiving only warfarin, while 13 patients were given benzbromarone 50 mg daily in addition to their regular warfarin dose. In patients treated with warfarin monotherapy, the average daily dose of warfarin was 3.9 mg with an INR of 2.2. However, patients who were also treated with benzbromarone had an average daily warfarin dose of 2.5 mg with a corresponding INR of 2.1. In addition, the plasma concentration for (S)-warfarin, the pharmacologically more active enantiomer of warfarin, was approximately 26% greater in the benzbromarone group than in the control group, despite the lower warfarin dose in the benzbromarone group. No significant differences were seen between the two groups with respect to the pharmacokinetics of (R)-warfarin .
Warfarin Overview
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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:
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.