Interaction Between Fenofibrate and Warfarin Experienced Hematuria: Case Report and Review of the Literature

OBJECTIVE To explore the interaction between fenofibrate and warfarin as well as the mechanism of action. METHODS The case of 78-year-old man received stable warfarin therapy before initiation of fenofibrate. After 1 week, the patient experienced hemoptysis and hematuria. On admission to the emergency department, the INR was 5.9, so warfarin was discontinued and using vitamin K1 administered intramuscularly. Adjusted the dosage of warfarin based on the INR after discharge and warfarin dose was reduced by 40%. Half month later he discontinued fenofibrate because of myalgia and INR declined for two consecutive weeks. The dosage of warfarin was adjusted and the patient’s INR remained stable. RESULTS The addition of fenofibrate on stable and therapeutic doses of warfarin increased the anticoagulant response to warfarin. Fenofibrate was highly protein bound, with the potential to displace warfarin from its binding protein, leading to an enhanced anticoagulant effect. Fenofibrate was also a mild to moderate inhibitor of CYP2C9, the enzyme was responsible for S-warfarin metabolism. The combination of the two effects may increase the anticoagulant response to warfarin. CONCLUSION It is suggested that serial monitoring of INR and consider an empiric 20% reduction in warfarin dosage when fenofibrate is initiated when patient on stable and therapeutic dose of warfarin.