Enhancement of anticoagulant action by warfarin-benzbromarone interaction

To investigate the interaction between warfarin potassium and benzbromarone, administration of benzbromarone to patients receiving long-term treatment with both drugs was discontinued for 1 week and then resumed, and the resulting changes in the coagulation system were examined. Thrombotest value, activity of coagulation factors II and VIII, concentration of protein induced by vitamin K absence or antagonist-II (PIVKA-II), total plasma concentration of warfarin, and free warfarin concentration were measured during the period of concurrent administration of the two drugs, 1 week after discontinuation of benzbromarone, and after resumption of benzbromarone administration. After administration of benzbromarone had been discontinued for 1 week, the thrombotest value and factor II activity rose significantly whereas PIVKA-II activity dropped significantly compared with corresponding levels before discontinuation, but these parameters tended to revert to the previously maintained levels after resumption of benzbromarone treatment. Activity of the vitamin K-independent factor VIII displayed almost no changes, however. Total plasma warfarin concentration also decreased significantly, and free warfarin concentration was nearly unchanged. These results verified that the anticoagulant action of warfarin is enhanced by concurrent administration of benzbromarone. Accordingly, adequate consideration must be devoted to the prevention of grave hemorrhagic tendencies when these two drugs are administered concurrently.