Rivaroxaban-Induced Hemorrhage Associated with ABCB1 Genetic Defect

Kuntheavy Ing Lorenzini, Youssef Daali, Pierre Fontana, Jules Desmeules, Caroline Samer, Kuntheavy Ing Lorenzini, Youssef Daali, Pierre Fontana, Jules Desmeules, Caroline Samer

Abstract

We report a patient who presented a non-ST segment elevation myocardial infarction in the context of severe normocytic hypochromic anemia related to gastrointestinal bleeding, 3 months after switching anticoagulant from the vitamin K antagonist acenocoumarol to the direct oral anticoagulant rivaroxaban. High levels of both anti-Xa activity and rivaroxaban plasma concentrations were measured despite rivaroxaban withdrawal, suggesting reduced elimination/drug clearance. Estimated half-life was 2-3 times longer than usually reported. The patient is a homozygous carrier of ABCB1 variant alleles, which could have participated to reduced elimination of rivaroxaban. Furthermore, CYP3A4/5 phenotyping showed moderately reduced enzyme activity. Drug-drug interaction with simvastatin may have contributed to decreased rivaroxaban elimination. Although in the present case moderate acute renal failure probably played a role, more clinical data are required to elucidate the impact of ABCB1 polymorphism on rivaroxaban pharmacokinetics and bleeding complications.

Keywords: ABCB1; CYP3A4/5; adverse drug reaction; direct oral anticoagulants; drug-drug interaction; genetic polymorphism.

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