Warfarin with Zileuton Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Brand Names Associated with Zileuton
- Zileuton
- Zyflo®
- Zyflo® CR
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 07, 2023
Interaction Effect
Significant increase in prothrombin time
Interaction Summary
Concomitant zileuton and warfarin therapy will result in a clinically significant increase in the prothrombin time (PT). Patients on this drug combination should have their prothrombin times closely monitored and the warfarin dose should be adjusted accordingly.
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Monitoring of prothrombin time and appropriate dose titration of warfarin is recommended for patients under coadministration with zileuton.
Mechanism Of Interaction
Decreased clearance of warfarin
Literature Reports
A) A double-blind parallel randomized study on 24 healthy male volunteers was conducted to assess the effects of zileuton on the steady-state pharmacokinetics and pharmacodynamics of warfarin. Subjects were given warfarin doses to achieve a prothrombin time (PT) of 14 to 18 seconds and then received 24 consecutive doses of zileuton 600 mg every six hours. It was revealed that zileuton had no significant effects on the S-warfarin enantiomer but did significantly alter the pharmacokinetics of the R-warfarin enantiomer. Approximately 20% of a dose of zileuton is metabolized through the cytochrome P450 1A2 pathway. This is the same pathway by which R-warfarin is metabolized, thus resulting in a 15% reduction in R-warfarin clearance. Despite the fact that S-warfarin possesses approximately four times more anticoagulant activity than R-warfarin, the reduced clearance and stereoselective inhibition of R-warfarin by zileuton resulted in a statistically significant prolongation in prothrombin times .
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.
Zileuton Overview
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Zileuton is used to prevent wheezing, shortness of breath, coughing, and chest tightness due to asthma. Zileuton is not used to treat an asthma attack (sudden episode of shortness of breath, wheezing, and coughing) that has already started. Zileuton belongs to a class of medications called leukotriene synthesis inhibitors. It works by stopping the formation of certain natural substances that cause swelling, tightening, and mucus production in the airways.
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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.