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Rivaroxaban-Induced Hemorrhage Associated with ABCB1 Genetic Defect.

  • Ing Lorenzini K Division of Clinical Pharmacology and Toxicology, University Hospitals of Geneva Geneva, Switzerland.
  • Daali Y Division of Clinical Pharmacology and Toxicology, University Hospitals of Geneva Geneva, Switzerland.
  • Fontana P Division of Angiology and Haemostasis, University Hospitals of Geneva Geneva, Switzerland.
  • Desmeules J Division of Clinical Pharmacology and Toxicology, University Hospitals of Geneva Geneva, Switzerland.
  • Samer C Division of Clinical Pharmacology and Toxicology, University Hospitals of Geneva Geneva, Switzerland.
  • 2017-01-10
Published in:
  • Frontiers in pharmacology. - 2016
ABCB1
CYP3A4/5
adverse drug reaction
direct oral anticoagulants
drug-drug interaction
genetic polymorphism
English 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.
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  • English
Open access status
gold
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https://sonar.ch/global/documents/169611
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