Challenges and possible solutions to Direct-Acting Oral Anticoagulants (DOACs) dosing in patients with extreme bodyweight and renal impairment
Challenges and possible solutions to Direct-Acting Oral Anticoagulants (DOACs) dosing in patients with extreme bodyweight and renal impairment
This article aims to highlight the dosing issues of direct oral anticoagulants (DOACs) in patients with renal impairment and/or obesity in an attempt to develop solutions employing advanced data-driven techniques. DOACs have become widely accepted by clinicians worldwide because of their superior clinical profiles, more predictable pharmacokinetics, and hence more convenient dosing relative to other anticoagulants. However, the optimal dosing of DOACs in extreme bodyweight patients and patients with renal impairment is difficult to achieve using the conventional dosing approach. The standard dosing approach (fixed-dose) is based on limited data from clinical studies. The existing formulae (models) for determining the appropriate doses for these patient groups leads to suboptimal dosing. This problem of mis-dosing is worsened by the lack of standardized laboratory parameters for monitoring the exposure to DOACs in renal failure and extreme bodyweight patients. Model-informed precision dosing (MIPD) encompasses a range of techniques like machine learning and pharmacometrics modelling, which could uncover key variables and relationships as well as shed more light on the pharmacokinetics and pharmacodynamics of DOACs in patients with extreme bodyweight or renal impairment. Ultimately, this individualized approach-if implemented in clinical practice-could optimise dosing for the DOACs for better safety and efficacy.
Administration, Oral, Anticoagulants/adverse effects, Body Weight, Factor Xa Inhibitors/therapeutic use, Humans, Obesity/drug therapy, Renal Insufficiency/complications
9-17
Nwanosike, Ezekwesiri Michael
cfa7e99a-976a-43c3-8c46-00669d8e5da4
Sunter, Wendy
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Merchant, Hamid A
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Conway, Barbara R
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Ansari, Muhammad Ayub
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Hasan, Syed Shahzad
e402cff7-ef4d-431e-8b82-905d3c8cfb89
1 January 2023
Nwanosike, Ezekwesiri Michael
cfa7e99a-976a-43c3-8c46-00669d8e5da4
Sunter, Wendy
c667654f-5551-4aba-8d32-a24b96eebbe1
Merchant, Hamid A
16e7d300-a50c-480f-99f5-86e30e9274ec
Conway, Barbara R
2c87aa00-8c01-480c-befb-6092900011c9
Ansari, Muhammad Ayub
7852fd5f-d9a8-4113-911a-533476958966
Hasan, Syed Shahzad
e402cff7-ef4d-431e-8b82-905d3c8cfb89
Nwanosike, Ezekwesiri Michael, Sunter, Wendy, Merchant, Hamid A, Conway, Barbara R, Ansari, Muhammad Ayub and Hasan, Syed Shahzad
(2023)
Challenges and possible solutions to Direct-Acting Oral Anticoagulants (DOACs) dosing in patients with extreme bodyweight and renal impairment.
American Journal of Cardiovascular Drugs, 23 (1), .
(doi:10.1007/s40256-022-00560-7).
Abstract
This article aims to highlight the dosing issues of direct oral anticoagulants (DOACs) in patients with renal impairment and/or obesity in an attempt to develop solutions employing advanced data-driven techniques. DOACs have become widely accepted by clinicians worldwide because of their superior clinical profiles, more predictable pharmacokinetics, and hence more convenient dosing relative to other anticoagulants. However, the optimal dosing of DOACs in extreme bodyweight patients and patients with renal impairment is difficult to achieve using the conventional dosing approach. The standard dosing approach (fixed-dose) is based on limited data from clinical studies. The existing formulae (models) for determining the appropriate doses for these patient groups leads to suboptimal dosing. This problem of mis-dosing is worsened by the lack of standardized laboratory parameters for monitoring the exposure to DOACs in renal failure and extreme bodyweight patients. Model-informed precision dosing (MIPD) encompasses a range of techniques like machine learning and pharmacometrics modelling, which could uncover key variables and relationships as well as shed more light on the pharmacokinetics and pharmacodynamics of DOACs in patients with extreme bodyweight or renal impairment. Ultimately, this individualized approach-if implemented in clinical practice-could optimise dosing for the DOACs for better safety and efficacy.
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More information
Accepted/In Press date: 4 November 2022
e-pub ahead of print date: 14 December 2022
Published date: 1 January 2023
Additional Information:
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Keywords:
Administration, Oral, Anticoagulants/adverse effects, Body Weight, Factor Xa Inhibitors/therapeutic use, Humans, Obesity/drug therapy, Renal Insufficiency/complications
Identifiers
Local EPrints ID: 485159
URI: http://eprints.soton.ac.uk/id/eprint/485159
ISSN: 1175-3277
PURE UUID: c274f8b5-5fe7-421a-9ba3-1cebb980a349
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Date deposited: 30 Nov 2023 17:40
Last modified: 18 Mar 2024 04:17
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Contributors
Author:
Ezekwesiri Michael Nwanosike
Author:
Wendy Sunter
Author:
Hamid A Merchant
Author:
Barbara R Conway
Author:
Muhammad Ayub Ansari
Author:
Syed Shahzad Hasan
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