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.
|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.
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.
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 firstname.lastname@example.org for information on vitamin K doses used in the clinical trials for Kcentra.
Important Safety Information
WARNING: ARTERIAL AND VENOUS THROMBOEMBOLIC COMPLICATIONS
Patients being treated with Vitamin K antagonist therapy have underlying disease states that predispose them to thromboembolic events. Potential benefits of reversing VKA should be weighed against the risk of thromboembolic events, especially in patients with history of such events. Resumption of anticoagulation therapy should be carefully considered once the risk of thromboembolic events outweighs the risk of acute bleeding. Both fatal and nonfatal arterial and venous thromboembolic complications have been reported in clinical trials and postmarketing surveillance. Monitor patients receiving KCENTRA, and inform them of signs and symptoms of thromboembolic events. KCENTRA was not studied in subjects who had a thromboembolic event, myocardial infarction, disseminated intravascular coagulation, cerebral vascular accident, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within the prior 3 months. KCENTRA might not be suitable for patients with thromboembolic events in the prior 3 months.
KCENTRA is contraindicated in patients with known anaphylactic or severe systemic reactions to KCENTRA or any of its components (including heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III and human albumin). KCENTRA is also contraindicated in patients with disseminated intravascular coagulation. Because KCENTRA contains heparin, it is contraindicated in patients with heparin-induced thrombocytopenia (HIT).
Hypersensitivity reactions to KCENTRA may occur. If patient experiences severe allergic or anaphylactic type reactions, discontinue administration and institute appropriate treatment.
In clinical trials, the most frequent (≥2.8%) adverse reactions observed in subjects receiving KCENTRA were headache, nausea/vomiting, hypotension, and anemia. The most serious adverse reactions were thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis.
KCENTRA is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent and its variant (vCJD), cannot be completely eliminated.
KCENTRA®, Prothrombin Complex Concentrate (Human), is a blood coagulation factor replacement product indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA—eg, warfarin) therapy in adult patients with acute major bleeding or the need for urgent surgery or other invasive procedure. KCENTRA is for intravenous use only.
Please see full prescribing information for KCENTRA.
To report SUSPECTED ADVERSE REACTIONS, contact the CSL Behring Pharmacovigilance Department at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.