Fixed dose rivaroxaban can be used in extremes of bodyweight: A population pharmacokinetic analysis
Victoria Speed, Bruce Green, Lara N. Roberts, Sarah Woolcombe, J. Bartoli-Abdou, Sarah Barsam, Rosalind Byrne, Emma Gee, Julia Czuprynska, Alison Brown, Sinead Duffy, Bipin Vadher, Rachna Patel, Valerie Scott, Anna Gazes, Raj Patel, Roopen Arya, Jignesh P. Patel
Abstract
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.