A phase 1, open-label, randomized drug–drug interaction study of zanubrutinib with moderate or strong CYP3A inhibitors in patients with B-cell malignancies

Bilal Tariq, Ying C. Ou, Jennifer C. Stern, Vaibhav Mundra, Nicole Wong Doo, Patricia Walker, Katharine L. Lewis, Chester Lin, William Novotny, Srikumar Sahasranaman, Stephen Opat

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1 Citation (Scopus)


BTK inhibitor exposure increases significantly when coadministered with CYP3A inhibitors, which may lead to dose-related toxicities. This study explored the pharmacokinetics, efficacy, and safety of zanubrutinib when coadministered with moderate or strong CYP3A inhibitors in 26 patients with relapsed or refractory B-cell malignancies. Coadministration of zanubrutinib (80 mg BID) with moderate CYP3A inhibitors fluconazole and diltiazem or zanubrutinib (80 mg QD) with strong CYP3A inhibitor voriconazole resulted in comparable exposures to zanubrutinib (320 mg QD) with AUC0-24h geometric least squares mean ratios approaching 1 (0.94, 0.81, and 0.83, for fluconazole, diltiazem, and voriconazole, respectively). The most common treatment-emergent adverse events were contusion (26.9%), back pain (19.2%), constipation and neutropenia (15.4% each), and rash, diarrhea, and fall (11.5% each). This study supports current United States Prescribing Information dose recommendations for the coadministration of reduced-dose zanubrutinib with moderate or strong CYP3A inhibitors and confirms the favorable efficacy and safety profile of zanubrutinib.

Original languageEnglish
Pages (from-to)329–338
Number of pages10
JournalLeukemia and Lymphoma
Issue number2
Publication statusPublished - 2023


  • BTK
  • CYP3A
  • DDI
  • pharmacokinetics
  • Zanubrutinib

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