FDA Approves Kcentra to Reverse Warfarin-Induced Anticoagulation

The US Food and Drug Administration (FDA) today approved Kcentra [prothrombin complex concentrate (human)] for the urgent reversal of anticoagulation induced by vitamin K antagonist (VKA) therapies such as warfarin in adult patients with acute major bleeding.

Derived from the pooled plasma of healthy blood donors, CSL Behring’s intravenous Kcentra is processed through “effective and robust pathogen inactivation and removal processes, including heat treatment and virus filtration,” to minimize its risk of transmitting infectious agents and diseases, according to the Pennsylvania-based manufacturer.

Karen Midthun, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in a press release the product’s approval “gives physicians a choice when deciding how to treat patients requiring urgent reversal of VKA anticoagulation,” as she noted the agent is “administered in a significantly lower volume than plasma at recommended doses, providing an alternative for those patients who may not tolerate the volume of plasma required to reverse VKA anticoagulation.”

According to the “Reversal of Warfarin-Induced Hemorrhage in the Emergency Department” study published in the November 2011 issue of the Western Journal of Emergency Medicine, warfarin is administered in approximately 3 to 4 million people in the United States each year to prevent blood clotting in atrial fibrillation, heart valve surgery, or deep vein thrombosis. As a result of acquired coagulation factor deficiency induced by the drug, severe bleeding may occur in those patients, and the study authors of “Bleeding Complications With Warfarin Use: A Prevalent Adverse Effect Resulting in Regulatory Action,” published in the July 2007 edition of Archives of Internal Medicine, estimate U.S. emergency departments see approximately 29,000 VKA-associated bleeding cases each year.

While plasma is currently the most widely administered agent to stop warfarin-associated acute major bleeding when it arises, Ravi Sarode, MD, director of the Transfusion Medicine and Hemostasis Reference Laboratory at the University of Texas Southwestern Medical Center, said in a press release “Kcentra has been shown to restore the decreased vitamin K-dependent clotting factors significantly faster than plasma in patients on warfarin,” and as Kcentra does not require blood group typing or thawing, it can be utilized faster than plasma, as well.

In the product’s open-label, randomized, controlled Phase IIIb clinical trial that formed the basis for today’s FDA approval, VKA-associated bleeding stopped in 72.4 percent of the 103 patients treated with Kcentra — compared to 65.4 percent of the 109 patients receiving plasma — at 24 hours from the start of infusion. At 30 minutes post-treatment, 62.2 percent of the Kcentra subjects achieved International Normalized Ratio reduction, compared to 9.6 percent of plasma subjects, and while the infusion time for plasma was nearly three hours, Kcentra’s infusion time was 24 minutes.

Serious arterial and venous thromboembolic complications such as stroke, pulmonary embolism, and deep vein thrombosis were observed in study subjects, and the most common adverse reactions included hypertension, arthralgia, headache, nausea, and vomiting.