P1-27-6 - Investigation of Drug Interaction Between Warfarin and Gemcitabine -Increase in Anticoagulant Effect of Warfarin-

Abstract

The anticoagulant drug warfarin is used to prevent conditions such as venous thrombosis. Since warfarin has many interactions with other drugs and large inter-individual variability in pharmacodynamics, its dosage must be adjusted according to the prothrombin time/international normalized ratio (PT-INR) in individual patients. Gemcitabine is commonly used to treat malignancies. Potential interactions between gemcitabine and warfarin have been documented in case reports, but remain to be clarified. We investigated drug interactions in patients who were receiving warfarin as well as gemcitabine at the Japanese Red Cross Nagoya Daiichi Hospital from February 1, 2009 to October 31, 2013. The subjects were 4 patients who were receiving stable doses of warfarin before initiation of gemcitabine therapy. Gemcitabine-induced changes in the anticoagulant effect of warfarin were investigated retrospectively. The PT-INR significantly increased (from 1.69±0.37 to 3.02 ± 0.87, P = 0.03) after the initiation of gemcitabine. However, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (SCre), serum albumin (Alb) levels did not change significantly after treatment with gemcitabine. There were no changes in diet or severe episodes of nausea or vomiting in any patient. These results suggest that the anticoagulant effect of warfarin increased after gemcitabine therapy. Therefore, the PT-INR should be closely monitored for several days after the start of gemcitabine therapy, and patients who are receiving warfarin should be informed in advance about the potential risks of concurrent treatment with gemcitabine.