Kcentra is a purified, heat-treated, nanofiltered, lyophilized, non-activated 4-factor prothrombin complex concentrate (4F-PCC) made from pooled human plasma. Kcentra contains all 4 vitamin–K dependent coagulation factors (II, VII, IX and X), and the antithrombotic Proteins C and S.
Kcentra is indicated for the urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (VKA, such as warfarin) therapy in adult patients with:
Kcentra is for intravenous use only
Kcentra is manufactured using the CSL Behring Integrated Safety System, a rigorously controlled manufacturing process that is continuously monitored. All plasma used in the manufacturing of Kcentra is obtained from prescreened US donors, and is carefully tested. A multistep pathogen inactivation and removal process, including heat treatment and virus filtration, is used to reduce the risk of transmission of infectious agents. The risk of virus transmission cannot be completely eliminated.
Patients undergoing VKA treatment experience a dose-dependent acquired deficiency of the vitamin K–dependent coagulation factors. The administration of Kcentra for urgent warfarin reversal increases plasma levels of the vitamin K–dependent coagulation Factors II, VII, IX, and X, as well as the antithrombotic Proteins C and S.
Kcentra is dosed based on units of Factor IX. The dose is determined by the patient’s pretreatment INR and body weight.
Pretreatment INR | 2–<4 | 4–6 | >6 |
---|---|---|---|
Dose* of Kcentra (units† of Factor IX)/kg body weight | 25 | 35 | 50 |
Maximum dose‡ (units of Factor IX) | Not to exceed 2500 | Not to exceed 3500 | Not to exceed 5000 |
*Dosing is based on body weight. Dose based on actual potency is stated on the vial, which will vary from 20–31 Factor IX units/mL after reconstitution. The actual potency for 500 unit vial ranges from 400–620 units/vial. The actual potency for 1000 unit vial ranges from 800–1240 units/vial.
†Units refer to international units.
‡Dose is based on body weight up to but not exceeding 100 kg. For patients weighing more than 100 kg, maximum dose should not be exceeded.
Coagulation factors in Kcentra are ~25 times more concentrated than in plasma, enabling factor levels to be replenished rapidly without delivering a large intravascular volume load.15 Compared with fresh frozen plasma (FFP) administration, Kcentra requires less infusion volume, allowing faster administration with comparable safety.
VKAs like warfarin act by inhibiting the synthesis of fully functional vitamin K–dependent coagulation Factors II, VII, IX, and X. Warfarin also results in a functional deficit of the antithrombotic Proteins C and S, which results in a disruption of normal hemostasis.22 Currently available 3-factor PCCs contain low or variable levels of factor VII and do not include antithrombotic Proteins C and S.11,12 Kcentra contains all 4 Vitamin–K dependent coagulation factors (II, VII, IX and X), and the antithrombotic Proteins C and S.
Unlike 3F-PCCs that are only indicated for hemophilia, Kcentra (as a 4F-PCC) has an FDA indication for urgent warfarin reversal.11,12
Unlike fresh frozen plasma (FFP) administration, Kcentra replaces only those coagulation factors needed for urgent warfarin reversal.
See how Kcentra works to replace the factors that warfarin depletes
In clinical trials, infusion with Kcentra is approximately 7 times faster than with plasma. In the Acute Major Bleeding trial, mean infusion time was 24 minutes for Kcentra and 169 minutes for plasma. In the Urgent Surgery/Invasive Procedure trial, mean infusion time was 21 minutes for Kcentra and 141 minutes for plasma.
Unlike fresh frozen plasma (FFP) administration, Kcentra does not require thawing or ABO typing. Kcentra can be stored at room temperature for up to 36 months.
Explore fast infusion time in 2 head-to-head trials vs plasma
Kcentra demonstrated superiority over plasma in 3 of 4 efficacy endpoints in 2 head-to-head trials.
The relationship between INR values and clinical hemostasis in patients has not been established.
Administer Kcentra by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min) up to a maximum rate of 8.4 mL/min (~210 units/min).
Administer vitamin K concurrently to patients receiving Kcentra. Vitamin K is administered to maintain vitamin K–dependent clotting factor levels once the effects of Kcentra have diminished.
The administration of vitamin K is expected to maintain factor levels once the effects of Kcentra have diminished.
The dose of vitamin K is not specified in the prescribing information. Hospitals may have their own protocols; if not, they can contact 855-4KCENTRA or medinfona@cslbehring.com for information on vitamin K doses used in the clinical trials for Kcentra.