Warfarin with Enzalutamide Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Brand Names Associated with Enzalutamide
- Enzalutamide
- Xtandi®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Decreased exposure to warfarin
Interaction Summary
Coadministration of enzalutamide (a strong CYP3A4 and moderate CYP2C9 inducer) may decrease warfarin exposure (a CYP3A4 and CYP2C9 substrate) . Avoid concurrent use of enzalutamide with drugs metabolized by CYP3A4 and CYP2C9, which have a narrow therapeutic index, such as warfarin . If coadministration is unavoidable, monitor INR closely . If initiating enzalutamide during chronic use of warfarin, consider increasing the warfarin dosage. If initiating warfarin during enzalutamide treatment, administer a higher warfarin starting dose (greater than 5 mg/day) .
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Concomitant administration of enzalutamide and warfarin may result in decreased warfarin exposure. Due to the potential for reduced efficacy of warfarin (a drug with a narrow therapeutic index), avoid coadministration with enzalutamide. If concurrent use is unavoidable, monitor INR closely . If initiating enzalutamide during chronic use of warfarin, consider increasing the warfarin dosage. If initiating warfarin during enzalutamide treatment, administer a higher warfarin starting dose (greater than 5 mg/day) .
Mechanism Of Interaction
Induction of CYP3A4-, and CYP2C9-mediated metabolism of warfarin by enzalutamide
Literature Reports
A) A 77-year-old Caucasian male with a past medical history of metastatic prostrate cancer, bilateral hydronephrosis, and history of DVTs on chronic warfarin therapy required warfarin dose adjustment following therapy initiation of enzalutamide 160 mg/day. The patient had been relatively stable on a weekly warfarin dose of 42 to 45 mg. Despite a single supratherapeutic INR of 3.5 following initiation of enzalutamide 160 mg daily, a weekly warfarin dose increase ranging from 36% to 50% was necessary to maintain warfarin within the therapeutic range. The patient continued enzalutamide and a weekly warfarin dose of 57 mg .
B) When a single dose of S-warfarin 10 mg was administered to patients with castration-resisitant prostate cancer concomitantly receiving enzalutamide 160 mg once daily for at least 55 days, there was a significant decrease in the AUC of 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.
Enzalutamide Overview
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Enzalutamide is used to treat prostate cancer that has spread to other parts of the body in men and who have been helped by certain medical and surgical treatments that decrease testosterone levels. It is also used to treat prostate cancer in men who have not been helped by certain medical and surgical treatments that decrease testosterone levels. Enzalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of cancer cells.
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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.