Drug Interaction Report

Consumer information for this interaction is not currently available.

ADJUST DOSE: Coadministration with moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of zanubrutinib, which is primarily metabolized by the isoenzyme. When zanubrutinib was coadministered with the moderate CYP450 3A4 inhibitor diltiazem (180 mg once daily), zanubrutinib both peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 62%, in patients with B-cell lymphoma. When zanubrutinib was administered with another moderate CYP450 3A4 inhibitor, fluconazole (400 mg once daily), zanubrutinib Cmax and AUC increased 81% and 88%, respectively. 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: The dosage of zanubrutinib should be reduced to 80 mg twice daily when used concomitantly with moderate CYP450 3A4 inhibitors. Close clinical monitoring for development of zanubrutinib-related toxicities, further dosage adjustment, and/or withholding treatment in accordance with product labeling is advised. Following discontinuation, of the moderate CYP450 3A4 inhibitor, the previous dosage of zanubrutinib may be resumed. 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.