Rivaroxaban an Option to Treat Venous Thromboembolism in Pediatric Patients

Omri Cohen, MD

While safe and effective treating adults with venous thromboembolism (VTE), rivaroxaban is understudied in pediatric VTE patients.

A team, led by Omri Cohen, MD, National Hemophilia Center, Institute of Thrombosis and Hemostasis and the Amalia Biron Research Center, Sheba Medical Center, reviewed existing literature regarding how rivaroxaban is used to treat pediatric patients with VTE.

Anticoagulant therapies are commonly used for both prevention and treatment of venous and arterial thromboembolic disorders. However, delivering safe and effective treatments in pediatric patients is challenging because standard therapies with parenteral unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) is troublesome for most pediatric patients, while vitamin K antagonists require frequent internalized normalized ratio (INR) monitoring because of the unpredictable pharmacokinetics and numerous food and drug interactions.

Rivaroxaban—a direct FXa inhibitor—could be an option for pediatric patients as it offers the convenience of oral administration and predictable pharmacokinetics across a wide range of patients. The safety and efficacy of rivaroxaban has also been previously established in several adult indications.

In the study review, the investigators outlined pharmacologic and clinical aspects regarding rivaroxaban in adults and children within the National Center for Biotechnology (NCBI) and EMBASE databases. The investigators also provided a broad appraisal of the EINSTEIN-Jr program, evaluating the safety and efficacy of body-weight adjusted pediatric rivaroxaban regimens for the treatment of VTE in children.

Overall, the drug resulted in a low risk of recurrent VTE and clinically relevant bleeding when compared to standard therapy.

In a pharmacokinetic analysis of bodyweight-adjusted rivaroxaban regimens, the investigators found drug exposure levels within the adult exposure range, with no clustering for any of the pharmacokinetic parameters with efficacy, bleeding, or adverse outcomes.

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

Overall, the results show rivaroxaban should be examined as a potential therapy specifically for pediatric patients suffering from VTE.

“Rivaroxaban represent an appealing therapeutic alternative for VTE in children,” the authors wrote. “Further research should explore additional indications for rivaroxaban in the pediatric population beyond that of VTE.”

While venous thromboembolism is rare in children and typically presents as a secondary complication, it is attributable to central venous catheters in 65.5% of cases.

Earlier this year, the results of an exploratory analysis of the phase 3 MARINER study indicated post-discharge prophylaxis with rivaroxaban could reduce the risk of both fatal and major thromboembolic events in medically ill patients.

Investigators found the composite endpoint occurred in 1.28% of patients receiving rivaroxaban and in 1.77% of those randomized to placebo (HR, 0.72; 95% CI, 0.52-1.00; P=.049). Additionally, incidence of all the components included in the composite endpoint, with the exception of MI, tended to favor rivaroxaban.

Investigators also pointed out symptomatic lower-extremity deep vein thrombosis (HR, 0.20; 95% CI, 0.04-0.91) and symptomatic nonfatal pulmonary embolism (HR, 0.36; 95% CI, 0.12-1.14) showed greater relative risk reduction with rivaroxaban.

The study, “Rivaroxaban for the treatment of venous thromboembolism in pediatric patients,” was published online in the Expert Review of Cardiovascular Therapy.