Enhancement of Anticoagulant Effect of Warfarin by Benzbromarone, an Uricosuric Drug

Abstract

Recently a rapid decline of thrombotest values in several patients on warfarin therapy with benzbromarone was observed. Since conbination therapy with benzbromarone appeared to give rise to a bleeding tendency, both drugs were investigated for interactions.
The study subjects included 8 patients who had been treated with warfarin for cardiovascular disease and were also given benzbromarone for gout. The doses of warfarin averaged 1.94mg, with a range of 1.0 to 3.0mg/day, and the average dose of benzbromarone was 62.5mg, with a range of 50 to 100mg/day. While keeping the patients on warfarin therapy, benzbromarone was withdrawn for one week only, and changes in the blood coagulation systems were determined before and after withdrawal of benzbromarone.
The mean thrombotest value was increased from 22.3% (PT-INR 2.0) to 43.0% (1.4) after drug withdrawal, coagulation factor II increased from 57.3% to 74.5%, PIVKA-II decreased from 11.5AU/ml to 7.0 AU/ml, and the blood concentration of warfarin decreased from 656.5ng/ml to 563.6ng/ml. All the changes were statistically significant (p<0.05). These results indicate that benzbromarone strongly potentiates warfarin. When both drugs are to be combined clinically, patients should be carefully observed for a bleeding tendency.