Key result
Fixed-dose rivaroxaban can be used at extremes of bodyweight provided renal function is satisfactory, as creatinine clearance was the most significant covariate influencing exposure.
Why the study?
Guidance gave no recommendation on the use of DOACs in individuals weighing under 50 kg, prompting investigation into the influence of bodyweight on rivaroxaban exposure.
Does bodyweight significantly influence rivaroxaban exposure in patients receiving anticoagulation therapy in clinical practice?
Observational
No
Does bodyweight significantly influence rivaroxaban exposure in patients receiving anticoagulation therapy in clinical practice?
Population pharmacokinetic modeling demonstrates that fixed-dose rivaroxaban can be used at extremes of bodyweight provided renal function is satisfactory, challenging current ISTH guidance.
Supports rivaroxaban evaluation in extreme bodyweights with adequate renal function; leaves open need for prospective trials before policy changes.
BACKGROUND: and gives no recommendation on the use of DOACs in those <50 kg. OBJECTIVES: To generate a population PK model to understand the influence of bodyweight on rivaroxaban exposure from clinical practice data. METHOD: Rivaroxaban plasma concentrations and patient characteristics were collated between 2013 and 2018 at King's College Hospital anticoagulation clinic. A population PK model was developed using a nonlinear mixed effects approach and then used to simulate rivaroxaban concentrations at the extremes of bodyweight. RESULTS: , and n = 30 <50 kg. A one-compartment model with between-subject variability on clearance and a proportional error model best described the data. Creatinine clearance calculated by Cockcroft-Gault, with lean bodyweight as the weight descriptor in this equation, was the most significant covariate influencing rivaroxaban exposure. CONCLUSIONS: Our work demonstrates rivaroxaban can be used at extremes of bodyweight provided renal function is satisfactory. We recommend that the ISTH SSC revises the current guidance with respect to rivaroxaban at extremes of body size.
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Speed et al. (2020) conducted an observational in Patients requiring anticoagulation. Rivaroxaban was evaluated on Rivaroxaban exposure and plasma concentrations. Fixed-dose rivaroxaban can be used at extremes of bodyweight provided renal function is satisfactory, as creatinine clearance was the most significant covariate influencing exposure.
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