Rivaroxaban-induced hemorrhage associated with ABCB1 genetic defect

• Main Authors: Kuntheavy Ing Lorenzini (Author), Youssef Daali (Author), Pierre Fontana (Author), Jules Desmeules (Author), Caroline Flora Samer (Author)
• Format: Book
• Published: Frontiers Media S.A., 2016-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1663-9812; 10.3389/fphar.2016.00494
• Keywords: Adverse Drug Reaction; Drug-Drug Interaction; Genetic polymorphism; ABCB1; direct oral anticoagulants; CYP3A4/5; Therapeutics. Pharmacology; RM1-950
• Source: Frontiers in Pharmacology, Vol 7 (2016)

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, three 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 to 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.