Drug–Drug Interactions with Direct Oral Anticoagulants

A large body of evidence suggests that not only direct anticoagulant effects but also major bleeding events and stroke prevention depend on plasma concentrations of direct oral anticoagulants (DOACs). Concomitant drugs that cause drug–drug interactions (DDIs) alter DOAC exposure by increasing or dec...

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Autores principales: Foerster, Kathrin I., Hermann, Simon, Mikus, Gerd, Haefeli, Walter E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403169/
https://www.ncbi.nlm.nih.gov/pubmed/32157630
http://dx.doi.org/10.1007/s40262-020-00879-x
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author Foerster, Kathrin I.
Hermann, Simon
Mikus, Gerd
Haefeli, Walter E.
author_facet Foerster, Kathrin I.
Hermann, Simon
Mikus, Gerd
Haefeli, Walter E.
author_sort Foerster, Kathrin I.
collection PubMed
description A large body of evidence suggests that not only direct anticoagulant effects but also major bleeding events and stroke prevention depend on plasma concentrations of direct oral anticoagulants (DOACs). Concomitant drugs that cause drug–drug interactions (DDIs) alter DOAC exposure by increasing or decreasing DOAC bioavailability and/or clearance; hence, they might affect the efficacy and safety of DOAC therapy. Patients with renal impairment already receive smaller DOAC maintenance doses because avoidance of elevated DOAC exposure might prevent serious bleeding events. For other causes of increased exposure such as DDIs, management is often less well-defined. Considering that DOAC patients are often older and have multiple co-morbidities, polypharmacy is highly prevalent. However, the effect of multiple drugs on DOAC exposure, and especially the impact of DDIs when concurring with drug–disease interactions as observed in renal impairment, has not been thoroughly elucidated. In order to provide effective and safe anticoagulation with DOACs, understanding the mechanisms and magnitude of DDIs appears relevant. Instead of avoiding drug combinations with DOACs, more DDI trials should be conducted and new strategies such as dose adjustments based on therapeutic drug monitoring should be investigated. However, dose adjustments based on concentration measurements cannot currently be recommended because evidence-based data are missing.
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spelling pubmed-74031692020-08-13 Drug–Drug Interactions with Direct Oral Anticoagulants Foerster, Kathrin I. Hermann, Simon Mikus, Gerd Haefeli, Walter E. Clin Pharmacokinet Review Article A large body of evidence suggests that not only direct anticoagulant effects but also major bleeding events and stroke prevention depend on plasma concentrations of direct oral anticoagulants (DOACs). Concomitant drugs that cause drug–drug interactions (DDIs) alter DOAC exposure by increasing or decreasing DOAC bioavailability and/or clearance; hence, they might affect the efficacy and safety of DOAC therapy. Patients with renal impairment already receive smaller DOAC maintenance doses because avoidance of elevated DOAC exposure might prevent serious bleeding events. For other causes of increased exposure such as DDIs, management is often less well-defined. Considering that DOAC patients are often older and have multiple co-morbidities, polypharmacy is highly prevalent. However, the effect of multiple drugs on DOAC exposure, and especially the impact of DDIs when concurring with drug–disease interactions as observed in renal impairment, has not been thoroughly elucidated. In order to provide effective and safe anticoagulation with DOACs, understanding the mechanisms and magnitude of DDIs appears relevant. Instead of avoiding drug combinations with DOACs, more DDI trials should be conducted and new strategies such as dose adjustments based on therapeutic drug monitoring should be investigated. However, dose adjustments based on concentration measurements cannot currently be recommended because evidence-based data are missing. Springer International Publishing 2020-03-11 2020 /pmc/articles/PMC7403169/ /pubmed/32157630 http://dx.doi.org/10.1007/s40262-020-00879-x Text en © The Author(s) 2020, Corrected Publication 2020 Open AccessThis article is licensed under a Creative Commons Attribution-Non-commercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Review Article
Foerster, Kathrin I.
Hermann, Simon
Mikus, Gerd
Haefeli, Walter E.
Drug–Drug Interactions with Direct Oral Anticoagulants
title Drug–Drug Interactions with Direct Oral Anticoagulants
title_full Drug–Drug Interactions with Direct Oral Anticoagulants
title_fullStr Drug–Drug Interactions with Direct Oral Anticoagulants
title_full_unstemmed Drug–Drug Interactions with Direct Oral Anticoagulants
title_short Drug–Drug Interactions with Direct Oral Anticoagulants
title_sort drug–drug interactions with direct oral anticoagulants
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403169/
https://www.ncbi.nlm.nih.gov/pubmed/32157630
http://dx.doi.org/10.1007/s40262-020-00879-x
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