Peak plasma rivaroxaban levels in patients weighing 120 kg or greater

Abdulrehman, Jameel; Selby, Rita; Joundi, Raed A.; Yeo, Erik

doi:10.1016/j.thromres.2021.02.013

Cited by 4 publications

(16 citation statements)

References 10 publications

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Section: Discussionsupporting

confidence: 90%

“…Subgroup analysis of plasma concentration based on patient weight did not show any significant differences in DOAC concentrations between patients with high and low body weight, which is in agreement with previous reports on rivaroxaban. 31 However, it has also been reported that weight can be an important determinant of plasma DOAC concentration in some patient groups, especially in younger cohorts. 32 Ensuring appropriate plasma drug concentrations is especially important for patients at high risk of thromboembolic or bleeding events, as evidenced by for example, high CHA 2 DS 2 -VASc and HAS-BLED or ORBIT bleeding scores respectively, 33 as there are reports of associations not only between high plasma DOAC concentrations and increased bleeding risk, 34 but also between lower plasma DOAC concentrations and greater thrombotic risk.…”

Section: Discussionmentioning

confidence: 99%

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Assessment of exposure to direct oral anticoagulants in elderly hospitalised patients

et al. 2021

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Summary It is unclear whether elderly patients established on direct oral anticoagulants (DOACs) have greater exposure to these drugs, which could subsequently increase their risk of bleeding. We assessed DOAC exposure and factors affecting it in a real‐world elderly cohort of patients. For this, 151 medically stable hospital inpatients (76 established on apixaban, 61 on rivaroxaban, 14 on dabigatran) with a median [interquartile range (IQR)] age of 84 (78–89) years were recruited. Patients provided blood samples for measurement of peak and trough plasma DOAC concentrations. There was up to 48‐fold and 13‐fold variation in trough and peak plasma drug concentrations respectively. A significantly greater proportion of patients on apixaban had peak plasma drug concentrations within the reported ranges compared to those on either rivaroxaban or dabigatran (82·9% vs. 44·3% vs. 64·3% respectively; P < 0·001). A third of the variability in DOAC plasma concentrations was attributed to the influences of DOAC dosage, renal function and gender. To what extent the observed increases in DOAC exposure in the older patients is the cause of their increased risk of bleeding, which could potentially be ameliorated by dosing titration, requires further investigation.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Assessment of exposure to direct oral anticoagulants in elderly hospitalised patients

et al. 2021

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“…A full-text reading of the remaining 46 potentially eligible studies was performed, of which 35 studies were excluded for different reasons, including study type and study outcomes. Finally, 11 studies were included in the review [30,31,[69][70][71][72][73][74][75][76][77]. The detailed PRISMA flow diagram that summarizes the search results and the study selection process is shown in Fig.…”

Section: Literature Search Findingsmentioning

confidence: 99%

“…Four of the studies were retrospective cohort studies [69,72,75,77], one was an RCT [31], two were observational prospective studies [74,76], and the remaining four were PK modelling studies [30,70,71,73], one of which was pooled from seven RCTs [70]. Two studies were multinational and multicentre [70,71], while the remaining nine studies were conducted in the UK (three studies), Canada (two studies), Germany, France, Italy, and the Netherlands (one each) [30,31,69,[72][73][74][75][76][77]. In the 11 studies included, over 7140 healthy and diseased subjects received rivaroxaban therapy (sample size ranged from 12 to 4918).…”

Section: Characteristics and Key Pharmacokinetic-related Findings Of ...mentioning

confidence: 99%

“…The CCAT total scores for the studies ranged from 31 to 39 out of 40, with an average of 35.4 out of 40. Average percentage scores of the studies were 88.4% (range 78-98%), with individual study CCAT scores of 78% [76], 80% [74], 83% [71], 85% [69,72], 90% [31,75], Values were visually extracted from study graphs 93% [73], 95% [30,77], and 98% [70]. For example, one included study lacked the explanatory diagrams, secondary questions among its objective, and did not account for interindividual variability or potential bias [69].…”

Section: Characteristics and Key Pharmacokinetic-related Findings Of ...mentioning

confidence: 99%

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Rivaroxaban Pharmacokinetics in Obese Subjects: A Systematic Review

2022

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Introduction Venous thromboembolism (VTE) is a leading cause of morbidity and mortality globally. The direct oral anticoagulants, including rivaroxaban, are relatively novel therapeutic options in the treatment and prevention of VTE. There is a conflicting and inconclusive evidence surrounding the pharmacokinetics (PK) of rivaroxaban in patients with VTE who are obese. Objectives We conducted a systematic review to provide an overview, and to synthesize the available evidence in the current literature pertaining to rivaroxaban PK in obese subjects who are healthy or diseased. Methods The PubMed, Embase, ScienceDirect, Rayyan, and Cochrane Library databases were systematically searched from 1 May 2021 through 28 February 2022. Studies investigating rivaroxaban PK in adult obese subjects were included in the review. Pertinent data, including anthropometric parameters, rivaroxaban dosage regimen, PK parameters, PK model, and outcome measures were extracted. Reference values of rivaroxaban PK parameters in the general population were used for comparison purposes. The review protocol was registered in the PROSPERO database (CRD42020177770). Results In the 11 studies included in this systematic review, over 7140 healthy or diseased subjects received rivaroxaban therapy, with varying clinical indications in the diseased population. The reported PK parameters of rivaroxaban in obese subjects compared with reference values in the general population were variable. The reported values of the volume of distribution (V d ) among obese subjects (73.4-82.8 L) fell within the range of values reported/calculated for the general population (59.4-104 L), assuming complete bioavailability. However, some of the reported values of clearance (CL) in obese subjects (7.86-16.8 L.h −1 ) do not fall within the range of values reported/calculated for the general population (5.57-11.3 L.h −1 ). The reported maximum plasma concentrations in obese subjects versus the general population following a 10 mg dose were 149 vs. 143-180 µg.L −1 , and following a 20 mg dose were 214-305 vs. 299-360 µg.L −1 , respectively. The area under the plasma concentration versus time curves (AUC) over different intervals in obese subjects versus the general population following a 10 mg dose were 1155 (AUC from time zero to infinity [AUC ∞ ]) vs. 1029 (AUC ∞ ) µg.h.L −1 ; and 1204-2800 (AUC from time zero to 24 h [AUC 24 ]) vs. 3200 (AUC 24 ) µg.h.L −1 , respectively, following a 20 mg dose. The reported values of half-life and time to reach the maximum plasma concentration in obese subjects versus the general population were not consistent across studies. Conclusion Variable changes and inconsistencies in different rivaroxaban PK parameters were reported in obese subjects. Further well-designed studies are warranted to better characterize the PK and clinical outcomes of rivaroxaban in subjects with obesity.

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Pharmacokinetics of single‐dose rivaroxaban under fed state in obese vs. non‐obese subjects: An open‐label controlled clinical trial (RIVOBESE‐PK)

Alalawneh,

Awaisu,

Abdallah

et al. 2024

Clinical Translational Sci

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The evidence of rivaroxaban's pharmacokinetics in obese compared with non‐obese populations remains inconclusive. We aimed to compare the pharmacokinetic profile of rivaroxaban between obese and non‐obese populations under fed state. Participants who met the study's eligibility criteria were assigned into one of two groups: obese (body mass index ≥35 kg/m2) or non‐obese (body mass index 18.5–24.9 kg/m2). A single dose of rivaroxaban 20 mg was orally administered to each participant. Nine blood samples over 48 h, and multiple urine samples over 18 h were collected and analyzed for rivaroxaban concentration using ultra‐performance liquid chromatography coupled with tandem mass detector. Pharmacokinetic parameters were determined using WinNonlin software. Thirty‐six participants were recruited into the study. No significant changes were observed between obese and non‐obese participants in peak plasma concentration, time to reach peak plasma concentration, area under the plasma concentration–time curve over 48 h or to infinity, elimination rate constant, half‐life, apparent volume of distribution, apparent clearance, and fraction of drug excreted unchanged in urine over 18 h. Rivaroxaban's exposure was similar between the obese and non‐obese subjects, and there were no significant differences in other pharmacokinetic parameters between the two groups. These results suggest that dose adjustment for rivaroxaban is probably unwarranted in the obese population.

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Peak plasma rivaroxaban levels in patients weighing 120 kg or greater

Cited by 4 publications

References 10 publications

Assessment of exposure to direct oral anticoagulants in elderly hospitalised patients

Assessment of exposure to direct oral anticoagulants in elderly hospitalised patients

Rivaroxaban Pharmacokinetics in Obese Subjects: A Systematic Review

Pharmacokinetics of single‐dose rivaroxaban under fed state in obese vs. non‐obese subjects: An open‐label controlled clinical trial (RIVOBESE‐PK)

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