Effect of enzalutamide on anticoagulant therapy with edoxaban in patients with prostate cancer.

[AIMS] Treatment with enzalutamide in prostate cancer is challenging due to its high potential for drug-drug interactions, particularly in the typically older population of patients with frequent comorbidities treated with multiple drugs, such as anticoagulants. While low molecular weight-heparin can be safely combined with enzalutamide, the safety of combining enzalutamide with more convenient oral anticoagulants remains uncertain. The objective of this study was to assess whether a drug-drug interaction exists between enzalutamide and edoxaban.

[METHODS] A prospective, multicentre, two-arm parallel study was performed in men with prostate cancer who are treated with edoxaban, with and without enzalutamide. Plasma concentrations of edoxaban were measured at steady state. Pharmacokinetic (PK) parameters were calculated using non-compartmental analysis. Geometric mean ratios (GMR) of the area under the plasma concentration time curve over one dosing interval (AUC) were calculated. No clinically relevant interaction was defined if 90% of the confidence interval (CI) of the GMR was within the range of 0.8-1.25.

[RESULTS] Sixteen patients with prostate cancer using edoxaban (eight patients with enzalutamide and eight patients without enzalutamide) were enrolled. The exposure of edoxaban was similar between patients treated with or without enzalutamide, however the 90% CI fell outside of the 0.8-1.25 range (AUC GMR 1.03; 90% CI 0.78-1.35).

[CONCLUSIONS] The average exposure of edoxaban was not affected by enzalutamide. However, bioequivalence could not be established due to the broader than anticipated CI. Despite this, the larger variability in edoxaban exposure is not expected to be clinically relevant, supporting the safe co-administration of both drugs.