Nilotinib with Voriconazole Interaction Details
Brand Names Associated with Nilotinib
- Nilotinib
- Tasigna®
Brand Names Associated with Voriconazole
- Vfend®
- Voriconazole
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 19, 2023
Interaction Effect
Increased risk of QT interval prolongation; increased nilotinib and voriconazole exposure
Interaction Summary
Avoid coadministration of nilotinib and voriconazole. Both nilotinib (a moderate CYP3A4 inhibitor and substrate) and voriconazole (a strong CYP3A4 inhibitor and substrate) are known to prolong the QT interval, and concurrent use of these agents may increase the risk of cardiac adverse events. If voriconazole therapy is needed, consider interrupting nilotinib therapy. However, if voriconazole must be coadministered with nilotinib, then consider reducing the nilotinib dose to 200 mg/day in patients with newly diagnosed, Philadelphia chromosome-positive, chronic myeloid leukemia-chronic phase, or to 300 mg/day in patients with resistant or intolerant Philadelphia chromosome-positive, chronic myeloid leukemia. Monitor patients closely for prolongation of the QT interval. Once voriconazole is discontinued, allow a washout period before titrating nilotinib back to the indicated dose .
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Avoid coadministration of nilotinib and voriconazole. Both nilotinib (a moderate CYP3A4 inhibitor and substrate) and voriconazole (a strong CYP3A4 inhibitor and substrate) are known to prolong the QT interval, and concurrent use of these agents may increase the risk of cardiac adverse events. If voriconazole therapy is needed, consider interrupting nilotinib therapy. However, if voriconazole must be coadministered with nilotinib, then consider reducing the nilotinib dose to 200 mg/day in patients with newly diagnosed, Philadelphia chromosome-positive, chronic myeloid leukemia-chronic phase, or to 300 mg/day in patients with resistant or intolerant Philadelphia chromosome-positive, chronic myeloid leukemia. Monitor patients closely for prolongation of the QT interval. Once voriconazole is discontinued, allow a washout period before titrating nilotinib back to the indicated dose .
Mechanism Of Interaction
Additive effects on the QT interval; inhibition of CYP3A4-mediated nilotinib metabolism; inhibition of CYP3A4-mediated voriconazole metabolism
Literature Reports
A) Although not specifically studied with the CYP3A4 substrate voriconazole , multiple doses of nilotinib (a moderate CYP3A4 inhibitor) increased the systemic exposure of midazolam (a CYP3A4 substrate) by 2.6-fold in patients with chronic myeloid leukemia .
B) Although not specifically studied with the strong CYP3A4 inhibitor voriconazole, coadministration of ketoconazole, a strong CYP3A4 inhibitor, at a dose of 400 mg/day for 6 days increased nilotinib AUC by approximately 3-fold in healthy subjects .
Nilotinib Overview
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Nilotinib is used to treat certain types of chronic myeloid leukemia (CML; a type of cancer of the white blood cells) who have recently found to have this condition in adults and children 1 year of age and older. It is also used to treat certain types of CML in adults whose disease could not be treated successfully with imatinib (Gleevec) or adults who cannot take imatinib because of side effects. Nilotinib is also used to treat certain types of CML in children 1 year of age or older whose disease could not be treated successfully with other tyrosine kinase inhibitor therapies or who cannot take these medications because of side effects. Nilotinib 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 to stop or slow the spread of cancer cells.
Voriconazole Overview
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Voriconazole is used in adults and children 2 years of age and older to treat serious fungal infections such as invasive aspergillosis (a fungal infection that begins in the lungs and spreads through the bloodstream to other organs), esophageal candidiasis (a yeast [a type of fungus] infection that may cause white patching in the mouth and throat), and candidemia (a fungal infection in the blood). It is also used to treat certain other fungal infections when other medications will not work for certain patients. Voriconazole is in a class of antifungal medications called triazoles. It works by slowing the growth of the 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.