Article date: June 2006
By: Daniele Ouellet, Candace Bramson, Santos Carvajal‐Gonzalez, Doina Roman, Edward Randinitis, Ann Remmers, Mark J. Gardner, in Volume 61, Issue 6, pages 741-745
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.
DOI: 10.1111/j.1365-2125.2006.02589.x
View this article