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Risk Factors for Rivaroxaban-Related Bleeding Events—Possible Role of Pharmacogenetics: Case Series

Non-vitamin K antagonist oral anticoagulants’ interindividual trough concentration variability affects efficacy and safety, especially in bleeding events. Rivaroxaban is metabolised via CYP3A4/5-, CYP2J2-, and CYP-independent mechanisms and is a substrate of two transporter proteins: ABCB1 (MDR1, P-...

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Detalles Bibliográficos
Autores principales: Šimičević, Livija, Slišković, Ana Marija, Kirhmajer, Majda Vrkić, Ganoci, Lana, Holik, Hrvoje, Palić, Jozefina, Samardžić, Jure, Božina, Tamara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966833/
https://www.ncbi.nlm.nih.gov/pubmed/36827667
http://dx.doi.org/10.3390/pharmacy11010029
Descripción
Sumario:Non-vitamin K antagonist oral anticoagulants’ interindividual trough concentration variability affects efficacy and safety, especially in bleeding events. Rivaroxaban is metabolised via CYP3A4/5-, CYP2J2-, and CYP-independent mechanisms and is a substrate of two transporter proteins: ABCB1 (MDR1, P-glycoprotein) and ABCG2 (BCRP; breast-cancer-resistance protein). The polymorphisms of these genes may possibly affect the pharmacokinetics of rivaroxaban and, consequently, its safety profile. Rivaroxaban variability may be associated with age, liver and kidney function, concomitant illness and therapy, and pharmacogenetic predisposition. This case series is the first, to our knowledge, that presents multiple risk factors for rivaroxaban-related bleeding (RRB) including age, renal function, concomitant diseases, concomitant treatment, and pharmacogenetic data. It presents patients with RRB, along with their complete clinical and pharmacogenetic data, as well as an evaluation of possible risk factors for RRB. Thirteen patients were carriers of ABCB1, ABCG2, CYP2J2, and/or CYP3A4/5 gene polymorphisms. Possible drug–drug interactions with increased bleeding risk were identified in nine patients. Six patients had eGFR <60 mL/min/1.73 m(2). Our data suggest a possible role of multiple factors and their interactions in predicting RRB; however, they also indicate the need for further comprehensive multidisciplinary research to enable safer use of this product based on a personalised approach.