Enzalutamide with Abiraterone Acetate Interaction Details
Brand Names Associated with Enzalutamide
- Enzalutamide
- Xtandi®
Brand Names Associated with Abiraterone Acetate
- Abiraterone
- Zytiga®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 25, 2024
Interaction Effect
Increased enzalutamide exposure and reduced abiraterone exposure
Interaction Summary
Concurrent use of enzalutamide, a CYP2C8 substrate, with a strong CYP2C8 inhibitor (eg, abiraterone) should be avoided, as it may increase enzalutamide exposure[1]. Additionally, concurrent use of abiraterone, a CYP3A4 substrate, with a strong CYP3A4 inducer (eg, enzalutamide) should be avoided if possible, as it may reduce abiraterone exposure [2]. If concurrent use cannot be avoided, increase the abiraterone dosing frequency to twice daily [3][4] and reduce the enzalutamide dose to 80 mg once daily during the period of coadministration. If concurrent abiraterone is discontinued, resume the enzalutamide dose used prior to coadministration [1]; if concurrent enzalutamide is discontinued, reduce the abiraterone to the previous dose and frequency [3][4].
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Coadministration of enzalutamide, a CYP2C8 substrate, with a strong CYP2C8 inhibitor (eg, abiraterone) should be avoided if possible, as it may increase enzalutamide exposure. If concomitant use is necessary, reduce the dose of enzalutamide to 80 mg once daily. If concurrent abiraterone is discontinued, resume the enzalutamide dose used prior to initiation of the strong CYP2C8 inhibitor[1]. Additionally, the concomitant use of abiraterone, a CYP3A4 substrate, with a strong CYP3A4 inducer (eg, enzalutamide) should be avoided if possible, as it may reduce abiraterone exposure [2]. If coadministration cannot be avoided, increase the dosing frequency of abiraterone to twice daily during coadministration. If concurrent enzalutamide is discontinued, reduce the abiraterone dose to the previous dose and frequency [3][4].
Mechanism Of Interaction
Inhibition of CYP2C8-mediated enzalutamide metabolism by abiraterone; induction of CYP3A4-mediated abiraterone metabolism by enzalutamide
Literature Reports
A) Coadministration of multiple oral doses of another strong CYP2C8 inhibitor, gemfibrozil (600 mg twice a day), with a single 160 mg-dose of enzalutamide to healthy volunteers increased the composite AUC of enzalutamide and the major active metabolite, N-desmethyl enzalutamide, by 2.2-fold with minimal effect on Cmax [1].
B) While the concomitant use of abiraterone and enzalutamide has not been studied, administration of another strong CYP3A4 inducer, rifAMPin (600 mg/day for 6 days), followed by a single 1000-mg dose of abiraterone decreased the mean AUC of abiraterone by 55% [3][4].
References
1 ) Product Information: XTANDI(R) oral capsules, enzalutamide oral capsules. Astellas Pharma US, Inc. (per FDA), Northbrook, IL, 2012.
2 ) Product Information: AKEEGA(TM) oral tablets, niraparib, abiraterone acetate oral tablets. Janssen Biotech, Inc. (per FDA), Horsham, PA, 2023.
3 ) Product Information: YONSA(R) oral tablets, abiraterone acetate oral tablets. Sun Pharmaceutical Industries Inc (per FDA), Cranbury, NJ, 2018.
4 ) Product Information: ZYTIGA(R) oral tablets, abiraterone acetate oral tablets. Janssen Biotech Inc (per FDA), Horsham, PA, 2018.
Enzalutamide Overview
-
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.
Abiraterone Acetate Overview
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Abiraterone is used in combination with prednisone to treat a certain type of prostate cancer that has spread to other parts of the body. Abiraterone is in a class of medications called androgen biosynthesis inhibitors. It works by decreasing the amount of certain hormones in the body.
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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.