Abiraterone Acetate with Fosphenytoin Interaction Details
Brand Names Associated with Abiraterone Acetate
- Abiraterone
- Zytiga®
Brand Names Associated with Fosphenytoin
- Cerebyx®
- Fosphenytoin Injection
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 25, 2024
Interaction Effect
Reduced abiraterone exposure and reduced efficacy of abiraterone
Interaction Summary
Concomitant use of abiraterone acetate (a CYP3A4 substrate) and a strong CYP3A4 inducer may result in decreased abiraterone exposure and should be avoided[1]. Coadministration with carBAMazepine decreased exposure of abiraterone by 67% respectively. Monitor abiraterone acetate plasma concentrations to ensure therapeutic exposure during necessary coadministration with a strong CYP3A4 inducer [2]. Coadministration with rifAMPin decreased exposure of abiraterone by 55%. If a strong CYP3A4 inducer must be coadministered, increase the abiraterone acetate dosage frequency to twice a day during coadministration. If the strong CYP3A4 inducer is discontinued, resume the previous abiraterone acetate dose and frequency [3][4].
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Avoid concomitant use of abiraterone acetate (a CYP3A4 substrate) and a strong CYP3A4 inducer[1]. If a strong CYP3A4 inducer must be coadministered, increase the abiraterone acetate dosing frequency to twice a day during coadministration. If the strong CYP3A4 inducer is discontinued, resume the previous abiraterone acetate dose and frequency [3][4]. Monitor abiraterone acetate plasma concentrations to ensure therapeutic exposure during necessary coadministration with a strong CYP3A4 inducer [2].
Mechanism Of Interaction
Induction of CYP3A4-mediated metabolism of abiraterone
Literature Reports
A) A 65-year-old man with metastatic castration-resistant prostate cancer, treated with abiraterone acetate 1000 mg/day and prednisoLONE 10 mg, initiated on carBAMazepine 200 mg twice daily for treatment of facial neuropathy experienced a 67% decrease in abiraterone AUC and a 61% decrease in abiraterone trough concentration. The patient's other medications included paracetamol, leuprorelin, pantoprazole, calcium plus cholecalciferol, denosumab, clemastine, and fentaNYL. The patient had no PSA response, with a maximum PSA decline of 5% at 2 months following carBAMazepine initiation. Following discontinuation of carBAMazepine, the abiraterone exposure normalized. Using the Drug Interaction Probability Score (5 out of 9), this interaction is probable [2].
B) In a pharmacokinetic drug interaction study in healthy subjects receiving rifAMPin 600 mg daily for 6 days, a single dose of abiraterone acetate 1000 mg resulted in a decrease of 55% in the mean plasma AUC(infinity) of abiraterone [3][4][1].
References
1 ) Product Information: AKEEGA(TM) oral tablets, niraparib, abiraterone acetate oral tablets. Janssen Biotech, Inc. (per FDA), Horsham, PA, 2023.
2 ) Benoist GE, van der Doelen MJ, Ter Heine R, et al: A clinically relevant decrease in abiraterone exposure associated with carbamazepine use in a patient with castration-resistant metastatic prostate cancer. Br J Clin Pharmacol 2018; 84(5):1064-1067.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...
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.
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.
Fosphenytoin Overview
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Fosphenytoin injection is used to treat primary generalized tonic-clonic seizures (formerly known as a grand mal seizure; seizure that involves the entire body) and to treat and prevent seizures that may begin during or after surgery to the brain or nervous system. Fosphenytoin injection may also be used to control certain type of seizures in people who cannot take oral phenytoin. Fosphenytoin is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.
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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.