Drug interactions between warfarin and lenvatinib in a patient with the CYP2C9*1/*3 and VKORC1-1639G/A genotype

J Clin Pharm Ther. 2019 Dec;44(6):977-980. doi: 10.1111/jcpt.13030. Epub 2019 Aug 30.

Abstract

What is known and objective: Lenvatinib inhibits CYP2C8. (S)-Warfarin is metabolized to (S)-7-hydroxywarfarin by CYP2C9 and (S)-4'-hydroxywarfarin by CYP2C8. Here, we report drug interactions between warfarin and lenvatinib in a patient with CYP2C9*1/*3.

Case summary: The patient was administered warfarin. His international normalized ratio (INR) was 1.92 before lenvatinib administration. On day 8 after beginning 12 mg/day lenvatinib, plasma trough concentrations of lenvatinib and (S)-warfarin were 33.3 ng/mL and 0.67 μg/mL, respectively. On day 10, his INR increased to 3.48.

What is new and conclusion: Lenvatinib-dependent (S)-warfarin inhibition could involve CYP2C9 and CYP2C8. After initiating warfarin plus lenvatinib, INR assays are necessary.

Keywords: CYP2C9; interaction; lenvatinib; vitamin K epoxide reductase complex subunit 1; warfarin.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Cytochrome P-450 CYP2C8 / genetics
  • Cytochrome P-450 CYP2C9 / genetics*
  • Drug Interactions / genetics*
  • Genotype
  • Humans
  • Male
  • Phenylurea Compounds / therapeutic use*
  • Quinolines / therapeutic use*
  • Vitamin K Epoxide Reductases / genetics*
  • Warfarin / therapeutic use*

Substances

  • Phenylurea Compounds
  • Quinolines
  • Warfarin
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP2C8
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases
  • lenvatinib