Axitinib with Itraconazole Interaction Details
Brand Names Associated with Axitinib
- Axitinib
- Inlyta®
Brand Names Associated with Itraconazole
- Itraconazole
- Onmel®
- Sporanox®
- Tolsura®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Mar 04, 2024
Interaction Effect
Increased axitinib exposure
Interaction Summary
The concomitant use of axitinib (a CYP3A4/5 substrate) with itraconazole (a strong CYP3A4 inhibitor) should be avoided during and for 2 weeks after itraconazole therapy[1][2] due to a risk of increased axitinib plasma concentrations. Although no formal drug interaction studies have been performed with axitinib and itraconazole, in a drug interaction study of axitinib and ketoconazole (also a strong CYP3A4 inhibitor), concomitant use in healthy subjects increased axitinib plasma exposure by at least 2-fold. When possible, an alternate concomitant medication with little or no CYP3A4/5 inhibitory effect should be substituted for itraconazole. If concomitant use is required, reduce the dose of axitinib by approximately one-half and increase or decrease subsequent doses based on patient tolerability and safety. If itraconazole is discontinued, wait 3 to 5 half-lives of itraconazole and then return the axitinib dose to that used prior to itraconazole initiation [3].
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
The concomitant use of axitinib with a strong CYP3A4 inhibitor, such as itraconazole, may cause increased axitinib plasma concentrations. Therefore, administration of axitinib should be avoided during and for 2 weeks after itraconazole therapy[1][2]. When possible, substitute an alternate concomitant medication with little or no CYP3A4/5 inhibition. If concomitant use is required, reduce the dose of axitinib by approximately one-half and increase or decrease subsequent doses based on patient tolerability and safety. If itraconazole is discontinued, wait 3 to 5 half-lives of itraconazole and then return the axitinib dose to that used prior to itraconazole initiation [3].
Mechanism Of Interaction
Inhibition of CYP3A-mediated axitinib metabolism by itraconazole
References
1 ) Product Information: SPORANOX(R) oral capsules, itraconazole oral capsules. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2022.
2 ) Product Information: Sporanox oral solution, itraconazole oral solution. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2017.
3 ) Product Information: INLYTA(R) oral tablets, axitinib oral tablets. Pfizer Inc. (per FDA), New York, NY, 2012.
Axitinib Overview
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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.
Itraconazole Overview
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Itraconazole capsules (Sporanox, Tolsura) are used to treat fungal infections in the lungs that can spread throughout the body. Itraconazole capsules (Sporanox) are also used to treat fungal infections of the fingernails and toenails. Itraconazole oral solution (liquid) is used to treat yeast infections of the mouth and throat or of the esophagus (tube that connects the throat to the stomach). Itraconazole is in a class of antifungals called triazoles. It works by slowing the growth of fungi that cause infection.
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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.