Rivaroxaban for the treatment of venous thromboembolism in pediatric patients

ABSTRACT

Introduction

Anticoagulant therapy is in use for both prevention and treatment of venous and arterial thromboembolic disorders. Delivering safe and effective anticoagulation in the pediatric population is challenging, since the available standard therapy with parenteral UFH and LMWH is troublesome for most pediatric patients, and VKAs require frequent INR monitoring due to the unpredictable pharmacokinetics and numerous food and drug interactions. Rivaroxaban, a direct FXa inhibitor, offers the convenience of oral administration and predictable pharmacokinetics across a wide range of patients. Its safety and efficacy have been previously established in various adult indications.

Areas covered

This review outlines pharmacologic and clinical aspects regarding rivaroxaban treatment in adults and children, and provides a broad appraisal of the The EINSTEIN-Jr program which evaluated the safety and efficacy of body-weight adjusted pediatric rivaroxaban regimens for the treatment of VTE in children. A review of the literature using the keywords rivaroxaban and pediatric venous thromboembolism was conducted within the National Center for Biotechnology (NCBI) and EMBASE databases.

Expert opinion

Rivaroxaban represents an appealing therapeutic alternative for VTE in children. Further research should explore additional indications for rivaroxaban in the pediatric population beyond that of VTE.

KEYWORDS:

• Rivaroxaban
• anticoagulation
• venous thromboembolism
• factor Xa
• pediatric

Article highlights

• Venous thromboembolism in children is rare, and typically presents as a secondary complication, attributable to central venous catheters-associated in 65.5% of cases.

• Available standard anticoagulant therapy with parenteral UFH and LMWH is troublesome for most pediatric patients, whereas vitamin K antagonists require frequent INR monitoring.

• Rivaroxaban, a direct FXa inhibitor, offers the convenience of oral administration and predictable pharmacokinetics across a wide range of patients.

• The EINSTEIN-Jr program evaluated the safety and efficacy of body-weight adjusted pediatric rivaroxaban regimens for the treatment of VTE in children, as well as pharmacokinetic parameters.

• Rivaroxaban treatment resulted in a similarly low risk of recurrent VTE and clinically relevant bleeding, compared with standard therapy.

• Pharmacokinetic analyses of bodyweight-adjusted rivaroxaban regimens demonstrated drug exposure levels within the adult exposure range, with no clustering for any of the pharmacokinetic parameters with efficacy, bleeding, or adverse outcomes.

• Rivaroxaban may be indicated for thromboprophylaxis post-Fontan procedure, in children with nephrotic syndromes, congenital protein C, protein S and antithrombin deficiencies and for treatment of heparin-induced thrombocytopenia.

Declaration of interest

W Ageno received honoraria from Boehringer Ingelheim, Bayer Pharmaceuticals, BMS-Pfizer, and Daiichi-Sankyo. W Ageno also received research support from Bayer Pharmaceuticals and Boehringer Ingelheim. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose. 

Additional information

Funding

This paper was not funded.