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Rivaroxaban for treatment of pediatric venous thromboembolism: An Einstein-Jr phase 3 dose-exposure-response evaluation
Rivaroxaban for treatment of pediatric venous thromboembolism: An Einstein-Jr phase 3 dose-exposure-response evaluation
- Source :
- Journal of Thrombosis and Haemostasis, 18(7), 1672-1685. Wiley, Journal of Thrombosis and Haemostasis, 18(7), 1672-1685. Wiley-Blackwell Publishing Ltd, Journal of Thrombosis and Haemostasis, Journal of Thrombosis and Haemostasis, Wiley, 2020, 18 (7), pp.1672-1685. ⟨10.1111/jth.14813⟩
- Publication Year :
- 2020
-
Abstract
- 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 (0-24)ss] and trough [C trough,ss] and maximum [C max,ss] steady-state plasma concentrations were derived using population PK modeling. Exposure-response graphs were generated to evaluate the potential relationship of individual PK parameters with recurrent VTE, repeat imaging outcomes, and bleeding or adverse events. A taste-and-texture questionnaire was collected for suspension-recipients. 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.
- Subjects :
- Adult
Adolescent
ANTITHROMBOTIC THERAPY
Population
venous thromboembolism
Hemorrhage
CHILDREN
030204 cardiovascular system & hematology
03 medical and health sciences
bodyweight-adjusted dosing
0302 clinical medicine
Pharmacokinetics
[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication
medicine
Humans
suspension
Dosing
Child
education
Adverse effect
anticoagulation
Blood Coagulation
rivaroxaban
education.field_of_study
Rivaroxaban
[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics
disease
pediatric patients
business.industry
Infant, Newborn
Anticoagulants
Infant
Atrial fibrillation
[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Hematology
medicine.disease
Thrombosis
3. Good health
atrial-fibrillation
THROMBOSIS
DEFINITION
Child, Preschool
Anesthesia
business
pharmacokinetics
Blood sampling
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 15387933 and 15387836
- Database :
- OpenAIRE
- Journal :
- Journal of Thrombosis and Haemostasis, 18(7), 1672-1685. Wiley, Journal of Thrombosis and Haemostasis, 18(7), 1672-1685. Wiley-Blackwell Publishing Ltd, Journal of Thrombosis and Haemostasis, Journal of Thrombosis and Haemostasis, Wiley, 2020, 18 (7), pp.1672-1685. ⟨10.1111/jth.14813⟩
- Accession number :
- edsair.doi.dedup.....9bb33de5b932faaa8296a766f914b6f7
- Full Text :
- https://doi.org/10.1111/jth.14813⟩