Effects of lasofoxifene on the pharmacokinetics and pharmacodynamics of single‐dose warfarin

Aim To investigate the effect of steady‐state lasofoxifene on the pharmacokinetics and pharmacodynamics of warfarin. Methods Twelve healthy postmenopausal women received warfarin (single 20‐mg dose) alone and during lasofoxifene. R‐ and S‐warfarin concentrations, prothrombin time (PT) and international normalized ratio (INR) were determined with each treatment. Results Lasofoxifene had no clinically meaningful effect on R‐ or S‐warfarin pharmacokinetics. The S‐warfarin area under the plasma concentration–time curve (AUC) was 23% and 67% larger in subjects with *1/*2 and *1/*3 heterozygous mutations, relative to *1/*1, respectively. The mean PT AUC and Cmax ratio (90% confidence interval) was 91.9 (89.6, 94.2) and 84.2 (80.6, 87.8), respectively. INR results were similar. Conclusions Lasofoxifene has no clinically meaningful effect on the pharmacokinetics of warfarin. Although the decrease in PT/INR may not be clinically meaningful, more frequent INR monitoring may be considered during lasofoxifene introduction and discontinuation, consistent with warfarin’s label.