Elevated International Normalized Ratio associated with concurrent use of sorafenib and warfarin

Abstract

The case of a patient who experienced elevated International Normalized Ratio (INR) values and hemorrhage after sorafenib was added to his warfarin regimen is presented. A 70-year-old Caucasian man with a history of hypertension, congestive heart failure, gastroesophageal reflux disease, chronic obstructive pulmonary disease, and chronic hepatitis C was treated with warfarin for anticoagulation subsequent to atrial fibrillation. He began anticoagulation management by a clinical pharmacist in April 2007 and was stabilized on warfarin 36 mg weekly. He was diagnosed with hepatocellular carcinoma in June 2007 and began treatment with sorafenib 200 mg daily in September 2007. The patient arrived at the emergency room one month later with a prothrombin time (PT) of 84.8 and an INR value of 39.5. He was admitted for lower-extremity hemorrhage and diagnosed with warfarin toxicity. Sorafenib was discontinued, and warfarin was held during this hospital stay. The patient was discharged on warfarin 3 mg daily. In November, warfarin was increased to 36 mg weekly, and his INR values stabilized. In late November, he was restarted on sorafenib 200 mg daily presumably due to multiple new hepatic hypodense lesions indicating progression of the metastatic disease. Approximately two weeks later, the patient's INR value increased to 4.7. Sorafenib was discontinued permanently. Both the Naranjo et al. probability scale score and the drug interaction probability scale score suggest that there was a probable interaction between warfarin and sorafenib. A 70-year-old man diagnosed with hepatocellular carcinoma experienced an increase in INR values after the addition of sorafenib to his warfarin regimen.