J Elbers1, C Hageluken, A Wadham. 1. Global Clinical Development, N.V. Organon, Molenstraat 110, PO Box 20, 5340 BH Oss, The Netherlands. jolanda.elbers@organon.com
Abstract
OBJECTIVE: To investigate the potential drug interaction between tibolone and warfarin in healthy postmenopausal women. METHODS AND RESULTS: The study was designed as a double-blind, randomized, placebo-controlled, two-way crossover study in postmenopausal women. After stabilization of the International Normalized Ratio (INR; a standardized prothrombin time, PT) between 1.4 and 2.0 with warfarin, subjects were randomized to receive either tibolone (2.5mg/day) or placebo for 21 days. After a 7-day wash-out period (during which warfarin treatment was continued) the treatments were crossed over. Primary efficacy parameters were INR and coagulation Factors II, VII, VIIa and X (means of measurements at Days 18 and 20 and Days 46 and 48). Treatment with tibolone induced a statistically significant increase in INR (estimate of mean difference=0.40; P=0.002), and a statistically significant decrease in coagulation factors. Treatments were generally well tolerated and no clinically significant adverse events were observed. CONCLUSIONS:Tibolone enhances warfarin-induced anticoagulation in postmenopausal women, as reflected by increases in INR and decreases in coagulation Factors II, VII, VIIa and X, compared to placebo. It is advisable to monitor for changes in coagulation status during (and after discontinuation of) simultaneous use of tibolone and warfarin.
RCT Entities:
OBJECTIVE: To investigate the potential drug interaction between tibolone and warfarin in healthy postmenopausal women. METHODS AND RESULTS: The study was designed as a double-blind, randomized, placebo-controlled, two-way crossover study in postmenopausal women. After stabilization of the International Normalized Ratio (INR; a standardized prothrombin time, PT) between 1.4 and 2.0 with warfarin, subjects were randomized to receive either tibolone (2.5mg/day) or placebo for 21 days. After a 7-day wash-out period (during which warfarin treatment was continued) the treatments were crossed over. Primary efficacy parameters were INR and coagulation Factors II, VII, VIIa and X (means of measurements at Days 18 and 20 and Days 46 and 48). Treatment with tibolone induced a statistically significant increase in INR (estimate of mean difference=0.40; P=0.002), and a statistically significant decrease in coagulation factors. Treatments were generally well tolerated and no clinically significant adverse events were observed. CONCLUSIONS:Tibolone enhances warfarin-induced anticoagulation in postmenopausal women, as reflected by increases in INR and decreases in coagulation Factors II, VII, VIIa and X, compared to placebo. It is advisable to monitor for changes in coagulation status during (and after discontinuation of) simultaneous use of tibolone and warfarin.