LACK OF INTERACTION BETWEEN MELOXICAM AND WARFARIN IN HEALTHY-VOLUNTEERS

Objective: The effect of multiple oral doses of meloxicam 15 mg on the pharmacodynamics and pharmacokinetics of warfarin was investigated in healthy male volunteers. Warfarin was administered in an individualiz ed dose to achieve a stable reduction in prothrombin times calculated as International Normalized Ratio (INR) values. Then INR- and a drug c oncentration-time profile was determined. For the interaction phase, m eloxicam was added for 7 days and then INR measurements and the warfar in drug profiles were repeated for comparison. Overall, warfarin treat ment lasted for 30 days. Results: Warfarin and meloxicam were well tol erated by healthy volunteers in this study. Thirteen healthy volunteer s with stable INR values entered the interaction phase. Prothrombin ti mes, expressed as mean INR values, were not significantly altered by c oncomitant meloxicam treatment, being 1.20 for warfarin alone and 1.27 for warfarin with meloxicam cotreatment. R- and S-warfarin pharmacoki netics were similar for both treatments. Geometric mean (% gCV) AUC(SS ) values for the more potent S-enantiomer were 5.07 mg . h . 1(-1) (27 .5%) for warfarin alone and 5.64 mg . h . 1(-1) (28.1%) during the int eraction phase. Respective AUC(SS) values for R-warfarin were 7.31 mg . h . 1(-1) (43.8%) and 7.58 mg . h . 1(-1) (39.1%). Conclusion: The c oncomitant administration of the new non-steroidal anti-inflammatory d rug (NSAID) meloxicam affected neither the pharmacodynamics nor the ph armacokinetics of a titrated warfarin dose. A combination of both drug s should nevertheless be avoided and, if necessary, INR monitoring is considered mandatory.