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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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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
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author Šimičević, Livija
Slišković, Ana Marija
Kirhmajer, Majda Vrkić
Ganoci, Lana
Holik, Hrvoje
Palić, Jozefina
Samardžić, Jure
Božina, Tamara
author_facet Šimičević, Livija
Slišković, Ana Marija
Kirhmajer, Majda Vrkić
Ganoci, Lana
Holik, Hrvoje
Palić, Jozefina
Samardžić, Jure
Božina, Tamara
author_sort Šimičević, Livija
collection PubMed
description 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.
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spelling pubmed-99668332023-02-26 Risk Factors for Rivaroxaban-Related Bleeding Events—Possible Role of Pharmacogenetics: Case Series Šimičević, Livija Slišković, Ana Marija Kirhmajer, Majda Vrkić Ganoci, Lana Holik, Hrvoje Palić, Jozefina Samardžić, Jure Božina, Tamara Pharmacy (Basel) Case Report 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. MDPI 2023-02-05 /pmc/articles/PMC9966833/ /pubmed/36827667 http://dx.doi.org/10.3390/pharmacy11010029 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Šimičević, Livija
Slišković, Ana Marija
Kirhmajer, Majda Vrkić
Ganoci, Lana
Holik, Hrvoje
Palić, Jozefina
Samardžić, Jure
Božina, Tamara
Risk Factors for Rivaroxaban-Related Bleeding Events—Possible Role of Pharmacogenetics: Case Series
title Risk Factors for Rivaroxaban-Related Bleeding Events—Possible Role of Pharmacogenetics: Case Series
title_full Risk Factors for Rivaroxaban-Related Bleeding Events—Possible Role of Pharmacogenetics: Case Series
title_fullStr Risk Factors for Rivaroxaban-Related Bleeding Events—Possible Role of Pharmacogenetics: Case Series
title_full_unstemmed Risk Factors for Rivaroxaban-Related Bleeding Events—Possible Role of Pharmacogenetics: Case Series
title_short Risk Factors for Rivaroxaban-Related Bleeding Events—Possible Role of Pharmacogenetics: Case Series
title_sort risk factors for rivaroxaban-related bleeding events—possible role of pharmacogenetics: case series
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966833/
https://www.ncbi.nlm.nih.gov/pubmed/36827667
http://dx.doi.org/10.3390/pharmacy11010029
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