Zanubrutinib with Voriconazole Interaction Details
Brand Names Associated with Zanubrutinib
- Brukinsa®
- Zanubrutinib
Brand Names Associated with Voriconazole
- Vfend®
- Voriconazole
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 22, 2023
Interaction Effect
Increased zanubrutinib exposure and risk of toxicity
Interaction Summary
Zanubrutinib is primarily metabolized by CYP3A, and coadministration with a strong CYP3A inhibitor increases zanubrutinib exposure, which may increase the risk of zanubrutinib toxicities. When zanubrutinib was given with itraconazole 200 mg/day (strong CYP3A inhibitor), zanubrutinin AUC increased 278% and Cmax increased 157%. When zanubrutinib and a strong CYP3A inhibitor are coadministered, reduce zanubrutinib to 80 mg once daily and interrupt dose as required for adverse reactions. After discontinuation of a CYP3A inhibitor, resume previous dose of zanubrutinib.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Concomitant use of zanubrutinib (a CYP3A substrate) and a strong CYP3A inhibitor increases zanubrutinib exposure, which may increase the risk of zanubrutinib toxicities. When coadministered, reduce zanubrutinib to 80 mg once daily and interrupt dose as required for adverse reactions. After discontinuation of a concurrent CYP3A inhibitor, resume previous dose of zanubrutinib.
Mechanism Of Interaction
Inhibition of CYP3A-mediated zanubrutinib metabolism
Literature Reports
A) When zanubrutinib was coadministered with itraconazole 200 mg/day, there was a 157% increase in zanubrutinib Cmax and a 278% increase in AUC .
B) The predicted increase in zanubrutinib exposure when coadministered with clarithromycin 250 mg twice a day, is a 175% increase in zanubrutinib Cmax and a 183% increase in AUC .
Zanubrutinib Overview
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Zanubrutinib is used to treat mantle cell lymphoma (MCL; a fast-growing cancer that begins in the cells of the immune system) in adults who have already been treated with at least one other chemotherapy medication. Zanubrutinib is also used to treat adults with Waldenstrom's macroglobulinemia (WM; a slow-growing cancer that begins in certain white blood cells in your bone marrow), chronic lymphocytic leukemia (CLL; a type of cancer that begins in the white blood cells), and small lymphocytic lymphoma (SLL; a type of cancer that begins mostly in the lymph nodes). It is also used to treat marginal zone lymphoma (MZL; a slow growing cancer that begins in a type of white blood cells that normally fight infection) in adults whose cancer has returned or did not respond to a certain type of medication. Zanubrutinib 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.
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.