Imatinib with Enzalutamide Interaction Details
Brand Names Associated with Imatinib
- Gleevec®
- Imatinib
Brand Names Associated with Enzalutamide
- Enzalutamide
- Xtandi®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Decreased imatinib exposure
Interaction Summary
Avoid concomitant use of imatinib and strong CYP3A4 inducers, as coadministration may reduce total imatinib exposure. In a drug interaction study of the strong CYP3A4 inducer, rifampin used concomitantly with oral imatinib, mean imatinib Cmax and AUC decreased significantly. Consider alternative agents with less enzyme induction potential for patients receiving concomitant imatinib; however, if coadministration is required, increase imatinib dosage by at least 50% and carefully monitor clinical response.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Avoid concomitant use of imatinib and strong CYP3A4 inducers, as coadministration may reduce total imatinib exposure. Consider alternative agents with less enzyme induction potential for patients receiving concomitant imatinib; however, if coadministration is required, increase imatinib dosage by at least 50% and carefully monitor clinical response.
Mechanism Of Interaction
Induction of CYP3A4-mediated metabolism of imatinib
Literature Reports
A) An 80-year-old man with chronic myeloid leukemia experienced an inadequate response to imatinib due to concurrent use of phenytoin (strong CYP3A4 inducer). His medications included phenytoin, bronchodilators and triptorelin. Imatinib was initiated at 400 mg/day resulting in a quick initial hematologic response. However, 3 months later there was a decrease in molecular response and the imatinib dose was increased to 600 mg resulting in a plasma trough level of 458 nanograms (ng/mL), which was still below the level for optimal response (greater than 1000 to 1165 ng/mL). Phenytoin was maintained for the entire duration of therapy without changes in dosage. Imatinib was increased further to 800 mg and plasma trough levels were increased to 699 ng/mL but lower than the anticipated median of 2690 ng/mL. The dose was reduced to 600 mg due to cytopenias, and 1 year later to 400 mg without any deterioration on the molecular response. Eight years after imatinib initiation, he is currently receiving imatinib 400 mg and is still in deep molecular response .
B) In a systematic review of studies of pharmacokinetic interactions involving St John's Wort, concomitant use with imatinib in 2 studies (N=12; N=10) resulted in a decrease in imatinib AUC of 30% and 32% with St John's Wort products containing hyperforin dosage of 15 mg/day .
C) In a drug interaction study in healthy volunteers receiving multiple doses of the strong CYP3A4 inducer rifampin followed by a single dose of oral imatinib, imatinib clearance increased by 3.8-fold, which significantly decreased mean Cmax and AUC .
Imatinib Overview
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Imatinib is used to treat certain types of leukemia (cancer that begins in the white blood cells) and other cancers and disorders of the blood cells. Imatinib is also used to treat certain types of gastrointestinal stromal tumors (GIST; a type of tumor that grows in the walls of the digestive passages and may spread to other parts of the body). Imatinib is also used to treat dermatofibrosarcoma protuberans (a tumor that forms under the top layer of skin) when the tumor cannot be removed surgically, has spread to other parts of the body, or has come back after surgery. Imatinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells.
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.