Drug interactions with Bruton's tyrosine kinase inhibitors: clinical implications and management

Cancer Chemother Pharmacol. 2020 Oct;86(4):507-515. doi: 10.1007/s00280-020-04137-6. Epub 2020 Sep 17.

Abstract

Bruton's tyrosine kinase (BTK) plays an essential role in B-cell development, differentiation and B-cell receptor (BCR) signaling. The use of Bruton's tyrosine kinase inhibitors (BTKi) in the treatment of lymphoid malignancies has dramatically increased, owing to both impressive efficacy and ease of administration. However, BTKi have a range of drug-drug and drug-food interactions, which may alter drug efficacy and/or increase toxicity. Healthcare professionals should be aware of the probability of drug interactions with BTKi and make recommendations accordingly. In this article, we discuss the relevant drug-drug and drug-food interactions associated with ibrutinib, acalabrutinib, and zanubrutinib, and provide clinical practice recommendations for managing these interactions based on the available literature.

Keywords: Acalabrutinib; Bruton’s tyrosine kinase inhibitor; Drug–Drug interactions; Drug–Food interactions; Ibrutinib; Zanubrutinib.

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives
  • Adenine / pharmacokinetics
  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors*
  • Benzamides / administration & dosage
  • Benzamides / pharmacokinetics
  • Citrus paradisi
  • Citrus sinensis
  • Comorbidity
  • Cytochrome P-450 CYP2D6 / metabolism
  • Cytochrome P-450 CYP2D6 Inducers / administration & dosage
  • Cytochrome P-450 CYP2D6 Inducers / pharmacokinetics
  • Cytochrome P-450 CYP2D6 Inhibitors / administration & dosage
  • Cytochrome P-450 CYP2D6 Inhibitors / pharmacokinetics
  • Cytochrome P-450 CYP3A / metabolism
  • Cytochrome P-450 CYP3A Inducers / administration & dosage
  • Cytochrome P-450 CYP3A Inducers / pharmacokinetics
  • Cytochrome P-450 CYP3A Inhibitors / administration & dosage
  • Cytochrome P-450 CYP3A Inhibitors / pharmacokinetics
  • Drug Interactions
  • Food-Drug Interactions*
  • Fruit and Vegetable Juices
  • Hematologic Neoplasms / drug therapy*
  • Hematologic Neoplasms / epidemiology
  • Humans
  • Lymphoproliferative Disorders / drug therapy*
  • Lymphoproliferative Disorders / epidemiology
  • Piperidines / administration & dosage
  • Piperidines / pharmacokinetics
  • Polypharmacy
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacokinetics*
  • Pyrazines / administration & dosage
  • Pyrazines / pharmacokinetics
  • Pyrazoles / administration & dosage
  • Pyrazoles / pharmacokinetics
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacokinetics
  • Signal Transduction

Substances

  • Benzamides
  • Cytochrome P-450 CYP2D6 Inducers
  • Cytochrome P-450 CYP2D6 Inhibitors
  • Cytochrome P-450 CYP3A Inducers
  • Cytochrome P-450 CYP3A Inhibitors
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazines
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • zanubrutinib
  • CYP3A protein, human
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • acalabrutinib
  • Adenine