Axitinib with Enasidenib Interaction Details
Brand Names Associated with Axitinib
- Axitinib
- Inlyta®
Brand Names Associated with Enasidenib
- Enasidenib
- Idhifa®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Mar 04, 2024
Interaction Effect
Altered (increased/reduced) axitinib exposure and an increased risk of axitinib-related adverse effects or reduced efficacy of axitinib
Interaction Summary
Avoid coadministration of enasidenib and axitinib. Enasidenib is an OATP1B1 inhibitor and a CYP3A inducer. Coadministration of enasidenib and axitinib (OATP1B1 and CYP3A substrate with NTI) may either increase the exposure of axitinib or decrease the exposure of axitinib, for which minimal concentration changes may lead to serious toxicities or may lead to reduced efficacy of axitinib. If coadministration cannot be avoided, modify the dosage of axitinib as recommended and as clinically indicated[1].
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Avoid coadministration of enasidenib and axitinib. Enasidenib is an OATP1B1 inhibitor and a CYP3A inducer. Coadministration of enasidenib and axitinib (OATP1B1 and CYP3A substrate with NTI) may either increase the exposure of axitinib or decrease the exposure of axitinib, for which minimal concentration changes may lead to serious toxicities or may lead to reduced efficacy of axitinib. If coadministration cannot be avoided, modify the dosage of axitinib as recommended and as clinically indicated[1].
Mechanism Of Interaction
Inhibition of OATP1B1-efflux transport by enasidenib; induction of CYP3A-substrate metabolism by enasidenib
Literature Reports
A) Coadministration of rosuvastatin 10 mg (OATP1B1, OATP1B3, and BCRP substrate) after multiple doses of enasidenib 100 mg (OATP1B1, OATP1B3, and BCRP inhibitor) increased rosuvastatin Cmax by 366% and AUC(0 to infinity) by 244% [1].
B) In the drug interaction studies, midazolam (a sensitive CYP3A substrate) AUC (0 to inf) and Cmax decreased by 43% and 23%, respectively, following concomitant use of multiple doses of enasidenib 100 mg with a single intravenous dose of midazolam 0.03 mg/kg. The decrease in midazolam exposure following oral administration of midazolam is expected to be larger than that following intravenous administration of midazolam. This is due to induction of CYP3A4 first pass metabolism by enasidenib and the reduced bioavailability of the midazolam oral formulation compared to the midazolam intravenous formulation [1].
References
1 ) Product Information: IDHIFA(R) oral tablets, enasidenib oral tablets. Bristol-Myers Squibb (per FDA), Princeton, NJ, 2023.
Axitinib Overview
-
Axitinib is used alone to treat advanced renal cell carcinoma (RCC, a type of cancer that begins in the cells of the kidneys) in people who have not been treated successfully with another medication. Axitinib is used in combination with avelumab (Bavencio) or pembrolizumab (Keytruda) to treat advanced renal cell carcinoma. Axitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells.
Enasidenib Overview
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Enasidenib is used to treat a certain type of acute myeloid leukemia (AML; a type of cancer that begins in the white blood cells) that has worsened or come back after treatment with other chemotherapy medications. Enasidenib is in a class of medications called an isocitrate dehydrongenase-2 (IDH2) inhibitor. It works by slowing or stopping the growth 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.