Drug Interaction Report

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of zanubrutinib, which is primarily metabolized by the isoenzyme. When zanubrutinib was coadministered with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily), zanubrutinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased 157% and 278%, respectively, in healthy volunteers. Data evaluating coadministration of zanubrutinib, in patients with B-cell lymphoma, and several other known CYP450 3A4 inhibitors have been reported. For example, the CYP450 3A4 inhibitor, clarithromycin (250 mg twice daily), increased zanubrutinib Cmax and AUC 101% and 92%, respectively. The moderate CYP450 3A4 inhibitor diltiazem (180 mg once daily) increased both zanubrutinib Cmax and AUC by 62%. Another moderate CYP450 3A4 inhibitor, fluconazole (400 mg once daily), increased zanubrutinib Cmax and AUC 81% and 88%, respectively. Clinical data for less potent inhibitors are not available. Increased zanubrutinib exposure may potentiate the risk of toxicities such as hemorrhage, infection, cytopenias, malignancies, and serious cardiac arrhythmias, primarily atrial fibrillation and atrial flutter.

MANAGEMENT: Caution is advised when zanubrutinib is used with CYP450 3A4 inhibitors. Patients should be monitored for increased adverse effects such as rash, diarrhea, constipation, cough, hemorrhage, infection, cytopenias, and atrial fibrillation or flutter, and the zanubrutinib dosage adjusted as necessary. Additional consultation with individual package labeling, as well as relevant institutional protocols, may be advisable for further guidance.

Grapefruit juice and Seville orange juice can increase the blood levels of zanubrutinib. This may increase side effects such as rash, diarrhea, constipation, cough, hemorrhage, development of other cancers, abnormal heart rhythm, and impaired bone marrow function resulting in low numbers of different types of blood cells. You may also be more likely to develop anemia, bleeding problems, or infections due to low blood cell counts. You should avoid the consumption of Seville oranges, Seville orange juice, grapefruit and grapefruit juice during treatment with zanubrutinib. Be sure to take the medication at approximately the same time(s) everyday to maintain consistent blood levels and effects. Talk to your doctor or pharmacist if you have questions on how to take this or other medications you are prescribed. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.