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

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.