Effect of the P-glycoprotein inhibitor tamoxifen on edoxaban plasma levels in women with breast cancer.

Concomitant use of P-glycoprotein inhibitors can reduce clearance of edoxaban and increase its plasma concentration. Caution is advised with simultaneous use of edoxaban and the frequently used P-glycoprotein inhibitor tamoxifen. However, pharmacokinetic data are lacking. This study aimed to assess the effect of tamoxifen on edoxaban clearance. This was a prospective, self-controlled, pharmacokinetic study in breast cancer participants starting tamoxifen. Edoxaban was given at a dose of 60 mg once daily for 4 consecutive days, first without tamoxifen and later with concomitant tamoxifen in steady-state. On day 4 of both edoxaban sequences, serial blood samples were taken. A population pharmacokinetic model was developed using nonlinear mixed effects modelling in which the effect of tamoxifen on edoxaban clearance was assessed. Additionally, mean area under the curves (AUC) were estimated. Geometric least square means (GLM) ratios were calculated and no interaction was concluded if the 90 % CI was within the 80–125 % no-effect boundaries. Twenty-four women with breast cancer scheduled for tamoxifen were included. The median age was 56 years (IQR 51–63). The average edoxaban clearance was 32.0 L/h (95 % CI, 11.1–35.0 L/h). There was no effect of tamoxifen on edoxaban clearance, with a fraction of 100 % (95 % CI 92–108) compared to clearance without tamoxifen. The mean AUCs were 1923 ng*h/ml (SD 695) without tamoxifen and 1947 ng*h/ml (SD 595) with tamoxifen (GLM-ratio 100.4; 90 % CI 98.6–102.2). Concomitant use of the P-glycoprotein inhibitor tamoxifen does not lead to reduced clearance of edoxaban in patients with breast cancer. • Tamoxifen could increase edoxaban plasma levels and bleeding risk in women. • We assessed edoxaban clearance in women with breast cancer on tamoxifen. • No difference in clearance was observed with and without concomitant tamoxifen. • Edoxaban seems safe to combine with tamoxifen in women with breast cancer. [ABSTRACT FROM AUTHOR]