Rivaroxaban for treatment of pediatric venous thromboembolism. An Einstein-Jr phase 3 dose-exposure-response evaluation

Background Recently, the randomized EINSTEIN-Jr study showed similar efficacy and safety for rivaroxaban and standard anticoagulation for treatment of pediatric venous thromboembolism (VTE). The rivaroxaban dosing strategy was established based on phase 1 and 2 data in children and through pharmacokinetic (PK) modeling. Methods Rivaroxaban treatment with tablets or the newly developed granules-for-oral suspension formulation was bodyweight-adjusted and administered once-daily, twice-daily, or thrice-daily for children with bodyweights of >= 30, >= 12 to = 20 kg but only predicted in those Results Of the 335 children (aged 0-17 years) allocated to rivaroxaban, 316 (94.3%) were evaluable for PK analyses. Rivaroxaban exposures were within the adult exposure range. No clustering was observed for any of the PK parameters with efficacy, bleeding, or adverse event outcomes. Results were similar for the tablet and suspension formulation. Acceptability and palatability of the suspension were favorable. Discussion Based on this analysis and the recently documented similar efficacy and safety of rivaroxaban compared with standard anticoagulation, we conclude that bodyweight-adjusted pediatric rivaroxaban regimens with either tablets or suspension are validated and provide for appropriate treatment of children with VTE