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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-...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-9966833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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