Warfarin 복용 환자에서 Regorafenib 병용 시 INR 변화 사례 보고
A Case Report of International Normalized Ratio Changes in Patients Taking Warfarin with Regorafenib
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Background : Regorafenib is an oral multi-kinase inhibitor warfarin is an anticoagulant used for the prevention and treatment of venous thrombosis, atrial fibrillation, and pulmonary embolism. Since warfarin is metabolized by CYP2C9 and regorafenib inhibits CYP2C9, concurrent use of regorafenib and warfarin increases the serum concentration of warfarin, which leads to elevation of international normalized ratio (INR). We report two cases of increased INR from concurrent use of warfarin and regorafenib by reviewing electric medical records respectively. Case 1. An age 66 man with pulmonary embolism received warfarin 23 mg/week, and his target INR was 2.0-3.0. He started regorafenib for rectal cancer with pulmonary and brain metastasis, and then INR increased from 1.74 to 5.71 at day 29 of the regorafenib 1st cycle. After four days of warfarin withdrawal, warfarin was restarted and maintained with approximately 15 mg/week. INR increased from 1.26 to 2.77 at day 15 of the regorafenib 2nd cycle, and 1.37 to 2.8 at day 29 of regorafenib 3rd cycle. Case 2. An age 65 man with atrial fibrillation received warfarin 59.5 mg/week, and his target INR was 1.6-2.0. He started regorafenib for hepatocellular carcinoma with bone and pulmonary metastasis, and then INR increased from 1.48 to 8.22 at day 18 of the regorafenib 1st cycle. Thus, warfarin was withdrawn while vitamin K and fresh frozen plasma were administered, and INR decreased to 1.75. Conclusion : Since concurrent use of warfarin and regorafenib can increase INR, close monitoring of INR is recommended for patients receiving warfarin and regorafenib. INR should be monitored at least weekly, and warfarin dose should be adjusted if necessary.
Abstract
Background : Regorafenib is an oral multi-kinase inhibitor warfarin is an anticoagulant used for the prevention and treatment of venous thrombosis, atrial fibrillation, and pulmonary embolism. Since warfarin is metabolized by CYP2C9 and regorafenib inhibits CYP2C9, concurrent use of regorafenib and warfarin increases the serum concentration of warfarin, which leads to elevation of international normalized ratio (INR). We report two cases of increased INR from concurrent use of warfarin and regorafenib by reviewing electric medical records respectively. Case 1. An age 66 man with pulmonary embolism received warfarin 23 mg/week, and his target INR was 2.0-3.0. He started regorafenib for rectal cancer with pulmonary and brain metastasis, and then INR increased from 1.74 to 5.71 at day 29 of the regorafenib 1st cycle. After four days of warfarin withdrawal, warfarin was restarted and maintained with approximately 15 mg/week. INR increased from 1.26 to 2.77 at day 15 of the regorafenib 2nd cycle, and 1.37 to 2.8 at day 29 of regorafenib 3rd cycle. Case 2. An age 65 man with atrial fibrillation received warfarin 59.5 mg/week, and his target INR was 1.6-2.0. He started regorafenib for hepatocellular carcinoma with bone and pulmonary metastasis, and then INR increased from 1.48 to 8.22 at day 18 of the regorafenib 1st cycle. Thus, warfarin was withdrawn while vitamin K and fresh frozen plasma were administered, and INR decreased to 1.75. Conclusion : Since concurrent use of warfarin and regorafenib can increase INR, close monitoring of INR is recommended for patients receiving warfarin and regorafenib. INR should be monitored at least weekly, and warfarin dose should be adjusted if necessary.
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