The Food and Drug Administration (FDA) has approved Xarelto® (rivaroxaban) for 2 new pediatric indications: treatment of venous thromboembolism (VTE) and reduction in the risk of recurrent VTE in patients from birth to less than 18 years after at least 5 days of initial parenteral anticoagulant treatment; and thromboprophylaxis in patients 2 years of age and older with congenital heart disease who have undergone the Fontan procedure.
A new oral suspension formulation of Xarelto has also been approved by the FDA. The oral suspension is administered through a color-coded dosing device designed to minimize dosing errors.
The approvals were based on data from two phase 3 trials in pediatric patients, EINSTEIN-Jr (ClinicalTrials.gov Identifier: NCT02234843) and UNIVERSE (ClinicalTrials.gov Identifier: NCT02846532), along with adequate and well-controlled studies in adults.
In EINSTEIN-Jr, the efficacy and safety of rivaroxaban was assessed in 500 children from birth to 17 years with acute VTE who had received initial parenteral anticoagulant therapy. Patients were randomly assigned 2:1 to receive either a body weight-adjusted dose of rivaroxaban (tablets or oral suspension) or standard of care (eg, unfractionated heparin, low molecular weight heparin, subcutaneous fondaparinux, and/or oral vitamin K antagonist).
Results from EINSTEIN-Jr showed a similar low risk of symptomatic recurrent VTE with rivaroxaban vs standard of care (1.2% vs 3.0%, respectively; hazard ratio [HR] 0.40; 95% CI, 0.11-1.41). Symptomatic recurrent VTE or major bleeding events occurred in 1.2% (n=4/335) of the rivaroxaban arm vs 4.2% (n=7/165) of the comparator arm. Complete resolution of thrombus on repeat imaging without recurrent VTE occurred in 128 of 335 children in the rivaroxaban group and 43 of 165 children in the comparator group.
The UNIVERSE study compared the efficacy and safety of rivaroxaban with aspirin for thromboprophylaxis in children 2 to 8 years of age with congenital heart disease who had the Fontan procedure. In Part A of the study, patients received rivaroxaban for 1 year, while in Part B, patients were randomly assigned to receive rivaroxaban or aspirin for 1 year.
Results from UNIVERSE showed that 8.3% of patients (n=1/12) in Part A experienced a thrombotic event. In Part B of the study, 1.6% of patients (n=1/64) treated with rivaroxaban experienced a thrombotic event compared with 8.8% of patients (n=3/34) treated with aspirin.
The most common adverse reactions reported in pediatric patients were bleeding, cough, vomiting, and gastroenteritis.
Xarelto for oral suspension is supplied in a 150mL bottle containing 1mg/mL of rivaroxaban; it is expected to be available in mid-January 2022.
- FDA approves drug to treat, help prevent types of blood clots in certain pediatric populations. News release. US Food and Drug Administration. Accessed December 21, 2021. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-treat-help-prevent-types-blood-clots-certain-pediatric-populations.
- FDA approves two new indications for Xarelto® (rivaroxaban) to help prevent and treat blood clots in pediatric patients. News release. Janssen Pharmaceutical Companies of Johnson & Johnson. Accessed December 21, 2021. https://www.prnewswire.com/news-releases/fda-approves-two-new-indications-for-xarelto-rivaroxaban-to-help-prevent-and-treat-blood-clots-in-pediatric-patients-301448701.html.
- Xarelto. Package insert. Janssen Pharmaceuticals, Inc.; 2021. Accessed December 21, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215859s000lbl.pdf.