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Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data

ABSTRACT: Relatively little is known about the influence of extreme body weight on the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of drugs used in many disease states. While direct oral anticoagulants (DOACs) have an advantage over warfarin in that they do not require routine...

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Autores principales: Jamieson, Michael J., Byon, Wonkyung, Dettloff, Richard W., Crawford, Matthew, Gargalovic, Peter S., Merali, Samira J., Onorato, Joelle, Quintero, Andres J., Russ, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618533/
https://www.ncbi.nlm.nih.gov/pubmed/35570249
http://dx.doi.org/10.1007/s40256-022-00524-x
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author Jamieson, Michael J.
Byon, Wonkyung
Dettloff, Richard W.
Crawford, Matthew
Gargalovic, Peter S.
Merali, Samira J.
Onorato, Joelle
Quintero, Andres J.
Russ, Cristina
author_facet Jamieson, Michael J.
Byon, Wonkyung
Dettloff, Richard W.
Crawford, Matthew
Gargalovic, Peter S.
Merali, Samira J.
Onorato, Joelle
Quintero, Andres J.
Russ, Cristina
author_sort Jamieson, Michael J.
collection PubMed
description ABSTRACT: Relatively little is known about the influence of extreme body weight on the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of drugs used in many disease states. While direct oral anticoagulants (DOACs) have an advantage over warfarin in that they do not require routine drug monitoring, some may regard this convenience as less compelling in obese patients. Some consensus guidelines discourage using DOACs in patients weighing > 120 kg or with a body mass index > 35–40 kg/m(2), given a sparsity of available data in this population and the concern that fixed dosing in obese patients might lead to decreased drug exposure and lower efficacy. Per the prescribing information, apixaban does not require dose adjustment in patients weighing above a certain threshold (e.g., ≥ 120 kg). Data from healthy volunteers and patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) have shown that increased body weight has a modest effect on apixaban’s PK. However, the paucity of exposure data in individuals > 120 kg and the lack of guideline consensus on DOAC use in obese patients continue to raise concerns about potential decreased drug exposure at extreme weight. This article is the first to comprehensively review the available PK data in obese individuals without NVAF or VTE, and PK, PD, efficacy, effectiveness, and safety data for apixaban in obese patients with either NVAF or VTE, including subgroup analyses across randomized controlled trials and observational (real-world) studies. These data suggest that obesity does not substantially influence the efficacy, effectiveness, or safety of apixaban in these patients. Trial Registration ARISTOTLE: NCT00412984; AVERROES: NCT00496769; AMPLIFY: NCT00643201; AMPLIFY-EXT: NCT00633893; ADVANCE-1: NCT00371683; ADVANCE-2: NCT00452530; ADVANCE-3: NCT00423319 VIDEO ABSTRACT: SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40256-022-00524-x.
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spelling pubmed-96185332022-11-01 Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data Jamieson, Michael J. Byon, Wonkyung Dettloff, Richard W. Crawford, Matthew Gargalovic, Peter S. Merali, Samira J. Onorato, Joelle Quintero, Andres J. Russ, Cristina Am J Cardiovasc Drugs Review Article ABSTRACT: Relatively little is known about the influence of extreme body weight on the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of drugs used in many disease states. While direct oral anticoagulants (DOACs) have an advantage over warfarin in that they do not require routine drug monitoring, some may regard this convenience as less compelling in obese patients. Some consensus guidelines discourage using DOACs in patients weighing > 120 kg or with a body mass index > 35–40 kg/m(2), given a sparsity of available data in this population and the concern that fixed dosing in obese patients might lead to decreased drug exposure and lower efficacy. Per the prescribing information, apixaban does not require dose adjustment in patients weighing above a certain threshold (e.g., ≥ 120 kg). Data from healthy volunteers and patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) have shown that increased body weight has a modest effect on apixaban’s PK. However, the paucity of exposure data in individuals > 120 kg and the lack of guideline consensus on DOAC use in obese patients continue to raise concerns about potential decreased drug exposure at extreme weight. This article is the first to comprehensively review the available PK data in obese individuals without NVAF or VTE, and PK, PD, efficacy, effectiveness, and safety data for apixaban in obese patients with either NVAF or VTE, including subgroup analyses across randomized controlled trials and observational (real-world) studies. These data suggest that obesity does not substantially influence the efficacy, effectiveness, or safety of apixaban in these patients. Trial Registration ARISTOTLE: NCT00412984; AVERROES: NCT00496769; AMPLIFY: NCT00643201; AMPLIFY-EXT: NCT00633893; ADVANCE-1: NCT00371683; ADVANCE-2: NCT00452530; ADVANCE-3: NCT00423319 VIDEO ABSTRACT: SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40256-022-00524-x. Springer International Publishing 2022-05-16 2022 /pmc/articles/PMC9618533/ /pubmed/35570249 http://dx.doi.org/10.1007/s40256-022-00524-x Text en © © Pfizer 2022, Corrected Publication 2022 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 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/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Review Article
Jamieson, Michael J.
Byon, Wonkyung
Dettloff, Richard W.
Crawford, Matthew
Gargalovic, Peter S.
Merali, Samira J.
Onorato, Joelle
Quintero, Andres J.
Russ, Cristina
Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data
title Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data
title_full Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data
title_fullStr Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data
title_full_unstemmed Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data
title_short Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data
title_sort apixaban use in obese patients: a review of the pharmacokinetic, interventional, and observational study data
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618533/
https://www.ncbi.nlm.nih.gov/pubmed/35570249
http://dx.doi.org/10.1007/s40256-022-00524-x
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