Evaluation of the oral direct factor Xa inhibitor - betrixaban.

Abstract

INTRODUCTION:

For over 60 years vitamin K antagonists have been the mainstay of oral therapy for treatment and prevention of venous and arterial thromboembolic disease. The emergence of two new classes of orally administered anticoagulants, direct thrombin and factor Xa inhibitors have drastically changed the landscape in the management of these disease states. Betrixaban , an orally administered direct factor Xa inhibitor, is entering a Phase III trial and undergoing investigation for similar indications as apixaban, dabigatran and rivaroxaban.

AREAS COVERED:

The chemical development of betrixaban, pharmacokinetic differences between betrixaban and currently available novel anticoagulants and future considerations for clinical use.

EXPERT OPINION:

Betrixaban, the fifth novel oral anticoagulant in line for the Food and Drug Administration (FDA) approval, possesses some unique pharmacokinetic characteristics in comparison with the currently available novel anticoagulants, including limited renal excretion, minimal metabolism through the cytochrome p450 system and a long half-life. This pharmacokinetic profile may allow greater flexibility for use in patients with poor renal function, offer the convenience of once daily dosing, and exhibit less drug interactions. Betrixaban is currently being evaluated for prophylaxis against venous thromboembolic disease (VTED) and the prevention of stroke and systemic embolism associated with nonvalvular atrial fibrillation, its role in the management of acute VTED and acute coronary syndromes is yet to be defined based on clinical data and evaluation. Of interest, a factor Xa decoy, PRT4445, is currently under evaluation in conjunction with betrixaban, and may be a universal reversal agent for all anticoagulants with anti-Xa activity. Currently, there are no specific reversal agents for the novel anticoagulants. The availability of an effective reversal agent would be very attractive for the management of associated bleeding, bleeding due to trauma, or the need for emergent surgery.

• Authors: Michael Palladino, Geno Merli, Lynda Thomson
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 22 Issue 11 Pg. 1465-72 (Nov 2013) ISSN: 1744-7658 [Electronic] England
• PMID: 23964817 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anticoagulants
• Benzamides
• Factor Xa Inhibitors
• Pyridines
• betrixaban

Topics

• Animals
• Anticoagulants (pharmacokinetics, pharmacology, therapeutic use)
• Benzamides (pharmacokinetics, pharmacology, therapeutic use)
• Factor Xa Inhibitors
• Humans
• Pyridines (pharmacokinetics, pharmacology, therapeutic use)
• Treatment Outcome
• Venous Thromboembolism (prevention & control)