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Enzalutamide is an oral androgen receptor antagonist widely used to treat metastatic prostate cancer. Patients who are candidates for enzalutamide therapy are also at risk for the development of venous thromboembolism (VTE) and atrial fibrillation. In the article that accompanies this commentary, offer recommendations for the use of enzalutamide and anticoagulant medications. Enzalutamide is a strong inducer of CYP3A4 and may inhibit P-glycoprotein (P-gp). The authors wisely suggest avoiding concomitant administration of enzalutamide and the direct oral anticoagulants (DOACs) rivaroxaban or apixaban, because both are substrates of CYP3A4 and P-gp; use with enzalutamide would result in clinically relevant decreased plasma concentration and hence less efficacy. The authors instead recommend the use of dabigatran and edoxaban, two DOACs metabolized by P-gp only.

Although edoxaban and dabigatran are less burdensome to use than parenteral agents or vitamin K antagonists, few high-quality clinical data for use in the treatment of malignancy-associated thrombosis are available. No data for the specific drug combination of enzalutamide and these DOACs are available, and so caution and care should be exercised when choosing either one.

Although these DOACs may be effective to treat the VTE, the risk of bleeding may be increased given the effect of enzalutamide on the pharmacokinetics of dabigatran and edoxaban. Robust data are required before they can be used with confidence in all.

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