General Information

Kcentra is a 4-factor prothrombin complex concentrate containing four vitamin K-dependent factors: Factor II (prothrombin), Factor VII, Factor IX and Factor X, as well as antithrombotic Proteins C and S.

Kcentra is specifically indicated for for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients with acute major bleeding.

Kcentra is supplied as a solution for intravenous administration. Kcentra dosing is based on the patient’s current pre-dose International Normalized Ratio (INR) value, and body weight. Administer Vitamin K concurrently to patients receiving Kcentra.

Clinical Results

FDA Approval
The FDA approval of Kcentra was based on a randomized, controlled Phase IIIb study in 212 evaluable subjects. The study compared Kcentra (4-factor PCC) and vitamin K with plasma and vitamin K for urgent warfarin reversal in patients with acute major bleeding. Kcentra achieved the endpoints of hemostatic efficacy with respect to the adequacy of stopping a major bleed assessed at 24 hours from the start of infusion (72.4% of patients receiving Kcentra versus 65.4% receiving plasma) and INR reduction (1.3) at 30 minutes post treatment (62.2% of patients receiving Kcentra versus 9.6% receiving plasma). The secondary endpoints included plasma levels of major clotting factors (Factors II, VII, IX, X, proteins C and S); time to INR correction; and safety and tolerability (including all-cause mortality). A single Kcentra infusion produced a rapid and sustained increase in plasma levelsof clotting factors II, VII, IX, and X within 30 minutes post-treatment (p values<0.0001) with 87 percent less volume (105 mL +/-37 mL versus 865 mL +/- 269 mL) than plasma. Additionally, infusion time with Kcentra was seven times faster than with plasma (24 minutes versus nearly 3 hours for plasma). The most common adverse reactions (frequency 2.8%) observed in subjects receiving Kcentra were headache, nausea/vomiting, arthralgia, and hypotension. The most serious adverse reactions were thromboembolic events including stroke, pulmonary embolism and deep vein thrombosis.

Side Effects

Adverse effects associated with the use of Kcentra may include, but are not limited to, the following:

• headache
• nausea/vomiting
• arthralgia
• hypotension