BETHESDA, MD 30 April 2013—CSL Behring today announced the approval of prothrombin complex concentrate, or Kcentra, for the urgent reversal of acquired coagulation factor deficiency caused by warfarin or another vitamin K antagonist in adults with acute major bleeding.
The human-plasma-derived product is expected to be available in the third quarter of this year, a company spokesperson said.
Kcentra contains the vitamin K-dependent coagulation factors II, VII, IX, and X and the antithrombotic proteins C and S. According to CSL Behring, the product is the first four-factor prothrombin complex concentrate approved for the urgent reversal of vitamin K antagonist-related major bleeding.
FDA stated that Kcentra is the only product other than fresh human plasma that is licensed for that indication.
Kcentra is not intended for use in the absence of acute major bleeding, according to the product's labeling (PDF).
A boxed warning in the product's labeling explains that the use of Kcentra does not affect the underlying condition that is the reason for anticoagulant therapy with a vitamin K antagonist. The warning urges clinicians to carefully weigh the risk of thromboembolic events related to the underlying condition against the need for urgent reversal of bleeding. Patients must be closely monitored for thromboembolic events during Kcentra therapy.
Kcentra has not been studied in patients with a recent history of thrombosis. The labeling states that the product may not be suitable in patients who have had a thrombotic event within the past three months.
The safety and efficacy of Kcentra were evaluated in 212 clinical trial participants with acquired coagulation factor deficiency who received that product or fresh plasma.
In this study, both treatments were about equally effective at stopping major bleeding within 24 hours after the start of infusion. Kcentra therapy was associated with a rapid decrease in International Normalized Ratio (INR) values and a rapid and sustained increase in serum levels of the product's four clotting factors.
According to CSL Behring, infusion times for Kcentra averaged 24 minutes, compared with about 3 hours for plasma.
The most frequently reported adverse events in clinical trial participants treated with Kcentra were headache, nausea or vomiting, arthralgia, and hypotension. Rare but serious adverse events included stroke, pulmonary embolism, and deep vein thrombosis.
The recommended dosage of Kcentra is 25–50 units/kg of body weight, depending on the patient's pretreatment INR value.
Detailed instructions for calculating the correct dosage and reconstituting and administering the product are included in the labeling. Only one course of treatment should be given to stop the bleeding episode.
Kcentra will be available in kits that include one 500-unit, single-use glass vial of the plasma product, a vial of Sterile Water for Injection, USP, a filter transfer set, and an alcohol swab. Kcentra should be stored at 2–25 °C and never frozen.