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

Autor: Jamieson MJ; Internal Medicine, Medical affairs, Pfizer, New York, NY, 10017, USA. jamiem@pfizer.com., Byon W; Global Product Development, Clinical Pharmacology, Pfizer, Groton, CT, 06340, USA., Dettloff RW; Internal Medicine, Medical affairs, Pfizer, New York, NY, 10017, USA., Crawford M; Worldwide Research and Development, Computational Sciences, Pfizer, New York, NY, 10017, USA., Gargalovic PS; US Medical Cardiovascular, Bristol Myers Squibb, Princeton, NJ, 08648, USA., Merali SJ; Clinical Pharmacology and Pharmacometrics, Bristol Myers Squibb, Princeton, NJ, 08648, USA., Onorato J; US Medical Cardiovascular, Bristol Myers Squibb, Princeton, NJ, 08648, USA., Quintero AJ; Internal Medicine, Medical Affairs, Medical Innovation and Effectiveness, Pfizer, New York, NY, 10017, USA., Russ C; Internal Medicine, Medical affairs, Pfizer, New York, NY, 10017, USA.
Jazyk: angličtina
Zdroj: American journal of cardiovascular drugs : drugs, devices, and other interventions [Am J Cardiovasc Drugs] 2022 Nov; Vol. 22 (6), pp. 615-631. Date of Electronic Publication: 2022 May 16.
DOI: 10.1007/s40256-022-00524-x
Abstrakt: 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 Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data (MP4 161.22 MB).
(© 2022. © Pfizer.)
Databáze: MEDLINE
Externí odkaz: