Enzalutamide with Thiotepa Interaction Details
Brand Names Associated with Enzalutamide
- Enzalutamide
- Xtandi®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Increased thiotepa toxicity
Interaction Summary
Concomitant use of thiotepa (a CYP3A4 substrate) and a strong CYP3A4 inducer may increase thiotepa metabolism to its major active metabolite, TEPA, thereby increasing the risk of thiotepa toxicity. In a case report, the concomitant use of thiotepa and phenytoin (a strong CYP3A4 inducer) resulted in a 115% increase in the AUC and 126% increase in the rate of active metabolite formation compared with TEPA exposure prior to coadministration of thiotepa with phenytoin . Avoid coadministration and consider alternative medication with no or minimal CYP3A4 induction. If concomitant use cannot be avoided, monitor the patient closely .
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Concomitant use of thiotepa (CYP3A4 substrate) and a strong CYP3A4 inducer may increase thiotepa metabolism to its major active metabolite, TEPA, thereby increasing the risk of thiotepa toxicity. Avoid coadministration and consider alternative medication with no or minimal CYP3A4 induction. If concomitant use cannot be avoided, monitor the patient closely.
Mechanism Of Interaction
Induction of CYP3A4 mediated thiotepa metabolism to its major active metabolite
Literature Reports
A) The concomitant use of phenytoin (strong CYP3A4 inducer) and thiotepa resulted in a 115% increase in the AUC of tepa, the active metabolite of thiotepa, from 233 to 501 mcmol x hr/L, and a 126% increase in the rate of formation of the active metabolite compared with tepa exposure prior to coadministration with phenytoin, in a case report of a 42-year-old man with relapsing nonseminomatous testis cancer who experienced seizures after a first cycle of cyclophosphamide/thiotepa/carboplatin (CTC regimen). The patient received phenytoin 150 mg orally twice daily 5 days prior to the second cycle of the CTC regimen. The thiotepa dose was subsequently reduced from 230 mg/day during cycle 1 to 140 mg/day in cycle 2, which resulted in tepa plasma levels within the therapeutic margin. The phenytoin dose was increased to 200 mg twice daily, as the phenytoin plasma levels were subtherapeutic before, during, and after the second CTC regimen (4 to 5.5 mg/L). There was no toxicity observed following the thiotepa dose reduction during the second cycle .
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.