title: Rivaroxaban-Induced Hemorrhage Associated withABCB1Genetic Defect.
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 ofABCB1variant 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 ofABCB1polymorphism on rivaroxaban pharmacokinetics and bleeding complications.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, University Hospitals of Geneva Geneva, Switzerland.
authors.forename: Kuntheavy
authors.initials: K
authors.lastname: Ing Lorenzini
authors.affiliation: Division of Clinical Pharmacology and Toxicology, University Hospitals of Geneva Geneva, Switzerland.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Daali
authors.affiliation: Division of Angiology and Haemostasis, University Hospitals of Geneva Geneva, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fontana
authors.affiliation: Division of Clinical Pharmacology and Toxicology, University Hospitals of Geneva Geneva, Switzerland.
authors.forename: Jules
authors.initials: J
authors.lastname: Desmeules
authors.affiliation: Division of Clinical Pharmacology and Toxicology, University Hospitals of Geneva Geneva, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Samer
keywords: ABCB1; CYP3A4/5; adverse drug reaction; direct oral anticoagulants; drug-drug interaction; genetic polymorphism