Pharmacokinetic Interactions Between Abiraterone, Apalutamide, Darolutamide or Enzalutamide and Antithrombotic Drugs: Prediction of Clinical Events and Review of Pharmacological Information.

purposeAbiraterone, apalutamide, darolutamide and enzalutamide are second-generation hormone therapies used for advanced prostate cancer; the majority of patients receiving these treatments are elderly, poly-medicated patients. Since their first market authorizations, their pharmacokinetic (PK) characteristics are increasingly well known. A potential risk of drug-drug interaction (DDI), especially with cardiovascular drugs, needs to be considered. In the case of antithrombotics, treatment imbalance can lead to severe consequences.

objectivesTo describe PK profiles of hormone therapies and antithrombotics and to predict DDIs and potentially related clinical events.

methodsPK profiles (CYP450 and P-gp substrate, inducer or inhibitor) are described by cross-referencing data sources (summary of product characteristics, European public assessment reports, PubMed database, Micromedex

resultsAntithrombotics are mainly metabolized by CYP 2C9, 2C19 or 3A4. For abiraterone (CYP 2C8, 2D6 inhibitor) and darolutamide (CYP 3A4 inducer), no interaction was identified with antithrombotics. For apalutamide (CYP 2C9, 2C19, 3A4 and P-gp inducer) and enzalutamide (CYP 2C9, 2C19, 3A4 inducer and P-gp inhibitor), several PK interactions were identified with antithrombotics, which could lead to various clinical events (haemorrhage or thromboembolism).

conclusionNumerous interactions are expected between enzalutamide or apalutamide and antithrombotics, for which management should be deployed on a case-by-case basis. PK and pharmaco-epidemiological studies could shed light on whether or not there are clinically significant events related to DDIs with antithrombotics.