Drug interactions between warfarin and lenvatinib in a patient with the CYP2C91/3 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. Continuous administration of 4.0 mg/day warfarin on day 10 after co‐administration of 12 mg/day lenvatinib increased the INR value to 3.48 from 1.92. The metabolic pathway of (S)‐warfarin involving CYP2C8 seemed to be inhibited by lenvatinib. Periodic INR assays are necessary after initiating combination therapy with lenvatinib and warfarin.