New Insights into Genetic Polymorphisms Influencing the Therapeutic Efficacy and Toxicity of Rivaroxaban

Thromboembolic diseases, including venous thromboembolism and atrial fibrillation-related stroke, represent a prevalent health concern and a risk for mortality and health care costs. Rivaroxaban is a direct oral factor Xa inhibitor that is used as an anticoagulant to prevent thromboembolism; although it had a predictable pharmacokinetic profile, it had great inter-individual variability, where some experienced inadequate response and recurrent thrombosis, and others were subjected to bleeding risks. Genetic polymorphisms that could impact the pharmacokinetics and/or pharmacodynamics of rivaroxaban should be involved in its dose adjustment. The present work highlighted the current pharmacogenomics evidences influencing rivaroxaban therapy with an analysis of data from previous reports. Using reliable pharmacogenomic profiles can reduce the adverse effects of rivaroxaban and improve patient outcomes in the future. CYP3A4 and CYP3A5 polymorphisms greatly impacted the pharmacokinetics of rivaroxaban; CYP2J2 polymorphisms were not greatly associated with the clinical outcome. Genetic polymorphisms in membrane transporters like ABCB1 and ABCG2 could modulate the distribution and absorption of rivaroxaban, leading to inter-individual variation in response. Furthermore, novel genetic polymorphisms in SUSD3 and APOB were associated with bleeding risk during rivaroxaban therapy. A preliminary effect of polymorphisms in CYP2C19, PRF1, and PRKAG2 on rivaroxaban outcome still needs validation. Both pharmacogenomic analysis (CYP3A4/5, ABCB1, and ABCG2) and drug interactions data could guide dose adjustments of rivaroxaban and significantly decrease the major bleeding risks clinically.