University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Paediatrics (RCH)
  • Paediatrics (RCH) - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Paediatrics (RCH)
  • Paediatrics (RCH) - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    Exploratory evaluation of pharmacodynamics, pharmacokinetics and safety of rivaroxaban in children and adolescents: an EINSTEIN-Jr phase I study

    Thumbnail
    Download
    Published version (1.059Mb)

    Citations
    Scopus
    Web of Science
    Altmetric
    10
    7
    Author
    Kubitza, D; Willmann, S; Becka, M; Thelen, K; Young, G; Brandao, LR; Monagle, P; Male, C; Chan, A; Kennet, G; ...
    Date
    2018-12-04
    Source Title
    Thrombosis Journal
    Publisher
    BMC
    University of Melbourne Author/s
    Monagle, Paul
    Affiliation
    Paediatrics (RCH)
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Kubitza, D., Willmann, S., Becka, M., Thelen, K., Young, G., Brandao, L. R., Monagle, P., Male, C., Chan, A., Kennet, G., Martinelli, I., Saracco, P. & Lensing, A. W. A. (2018). Exploratory evaluation of pharmacodynamics, pharmacokinetics and safety of rivaroxaban in children and adolescents: an EINSTEIN-Jr phase I study. THROMBOSIS JOURNAL, 16 (1), https://doi.org/10.1186/s12959-018-0186-0.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/253321
    DOI
    10.1186/s12959-018-0186-0
    Abstract
    Background: The EINSTEIN-Jr program will evaluate rivaroxaban for the treatment of venous thromboembolism (VTE) in children, targeting exposures similar to the 20 mg once-daily dose for adults. Methods: This was a multinational, single-dose, open-label, phase I study to describe the pharmacodynamics (PD), pharmacokinetics (PK) and safety of a single bodyweight-adjusted rivaroxaban dose in children aged 0.5-18 years. Children who had completed treatment for a venous thromboembolic event were enrolled into four age groups (0.5-2 years, 2-6 years, 6-12 years and 12-18 years) receiving rivaroxaban doses equivalent to 10 mg or 20 mg (either as a tablet or oral suspension). Blood samples for PK and PD analyses were collected within specified time windows. Results: Fifty-nine children were evaluated. In all age groups, PD parameters (prothrombin time, activated partial thromboplastin time and anti-Factor Xa activity) showed a linear relationship versus rivaroxaban plasma concentrations and were in line with previously acquired adult data, as well as in vitro spiking experiments. The rivaroxaban pediatric physiologically based pharmacokinetic model, used to predict the doses for the individual body weight groups, was confirmed. No episodes of bleeding were reported, and treatment-emergent adverse events occurred in four children and all resolved during the study. Conclusions: Bodyweight-adjusted, single-dose rivaroxaban had predictable PK/PD profiles in children across all age groups from 0.5 to 18 years. The PD assessments based on prothrombin time and activated partial thromboplastin time demonstrated that the anticoagulant effect of rivaroxaban was not affected by developmental hemostasis in children. Trial registration: ClinicalTrials.gov number, NCT01145859.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45770]
    • Paediatrics (RCH) - Research Publications [1852]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors