Background: Edoxaban is an oral factor Xa inhibitor frequently used for treatment of cancer-associated thrombosis. Concomitant treatment with the strong P-glycoprotein inhibitor tamoxifen, a widely used drug for breast cancer, can increase edoxaban plasma levels, which can result in increased bleeding risk. According to guidelines, caution is required in patients who are treated with tamoxifen and edoxaban simultaneously, although there are no pharmacological data available.
Aims: To assess the in-vivo effect of the P-glycoprotein inhibitor tamoxifen on edoxaban plasma levels in patients with breast cancer.
Methods: This was a prospective, open-label, single-sequence crossover study in breast cancer patients with an indication for tamoxifen and no indication for anticoagulation. Edoxaban was given in a dose of 60 mg once daily for 4 days, first without tamoxifen and later with concomitant tamoxifen in steady-state (Figure 1). Edoxaban plasma levels (liquid chromatography-mass spectrometry (LC-MS)) and anti-factor Xa levels were measured on day 4 of edoxaban use just before intake (T=0; trough) and hourly in the 4 hours after intake to identify Cmax and Tmax.
Results: Twenty-four women with breast cancer scheduled for tamoxifen were included. The median age was 56 years (IQR 51-63) and in 18 patients (75%) the tumor was resected. Median edoxaban plasma levels were not different without and with concomitant tamoxifen use at T=0 (14.3 µg/ml vs 12.5 µg/ml, p=0.83) and at Tmax (289.0 µg/ml vs 293.5 µg/ml, p=0.51). Similary, anti-Xa levels were not different at T=0 (12.8 ng/ml vs. 14.0 ng/ml, p=0.98) and Tmax (215.5 ng/ml vs. 214.6 ng/ml, p=0.98) (Figure 2).
Conclusion(s): These data show there is no pharmacological effect of tamoxifen on edoxaban plasma levels and anti-Xa activity in patients with breast cancer and therefore the fear of a clinically important drug-drug interaction is not justified.
To cite this abstract in AMA style:Bosch F, Mulder F, Willemsen A, Rentinck M, van Es N, Mathôt R, Kamphuisen P. No pharmacological effect of the P-glycoprotein inhibitor tamoxifen on edoxaban plasma levels in patients with breast cancer: the PHIX-IT study [abstract]. https://abstracts.isth.org/abstract/no-pharmacological-effect-of-the-p-glycoprotein-inhibitor-tamoxifen-on-edoxaban-plasma-levels-in-patients-with-breast-cancer-the-phix-it-study/. Accessed September 22, 2023.
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