Rivaroxaban-Induced Hemorrhage Associated with ABCB1 Genetic Defect

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

doi:10.3389/fphar.2016.00494

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Title		Rivaroxaban-Induced Hemorrhage Associated with ABCB1 Genetic Defect
Authors		Ing Lorenzini, Kuntheavy Daali, Youssef Fontana, Pierre Desmeules, Jules Alexandre Samer, Caroline Flora
Published in		Frontiers in pharmacology. 2016, vol. 7, 494
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.
Identifiers		DOI: 10.3389/fphar.2016.00494 PMID: 28066243
Full text		Article (Published version) (209 Kb) - Free access
Structures		Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences Faculté des sciences / Section des sciences pharmaceutiques
Research groups		Geneva Platelet Group (13) Groupe Desmeules Jules (pharmacologie/toxicologie) (567) Pharmaco-omiques et médecine de précision (1003)
Citation (ISO format)		ING LORENZINI, Kuntheavy et al. Rivaroxaban-Induced Hemorrhage Associated with ABCB1 Genetic Defect. In: Frontiers in pharmacology, 2016, vol. 7, p. 494. doi: 10.3389/fphar.2016.00494 https://archive-ouverte.unige.ch/unige:93800