| See warnings and precautions below.
Initial U.S. Approval: 2013
The product contents are shown in Table 7 and listed as ranges for the blood coagulation factors.
*Exact potency of coagulant and antithrombotic proteins are listed on the carton
All plasma used in the manufacture of Kcentra is obtained from US donors and is tested using serological assays for hepatitis B surface antigen and antibodies to HIV-1/2 and HCV. The plasma is tested with Nucleic Acid Testing (NAT) for HCV, HIV-1, HAV, and HBV, and found to be non-reactive (negative), and the plasma is also tested by NAT for human parvovirus B19 (B19V) in order to exclude donations with high titers. The limit for B19V in the fractionation pool is set not to exceed 104 units of B19V DNA per mL. Only plasma that passed virus screening is used for production.
The Kcentra manufacturing process includes various steps, which contribute towards the reduction/ inactivation of viruses. Kcentra is manufactured from cryo-depleted plasma that is adsorbed via ion exchange chromatography, heat treated in aqueous solution for 10 hours at 60°C, precipitated, adsorbed to calcium phosphate, virus filtered, and lyophilized.
These manufacturing steps were independently validated in a series of in-vitro experiments for their virus inactivation / reduction capacity for both enveloped and non-enveloped viruses. Table 8 shows the virus clearance during the manufacturing process for Kcentra, expressed as the mean log10 reduction factor.
| Mechanism of Action:
Kcentra contains the Vitamin K-dependent coagulation Factors II (FII), VII (FVII), IX (FIX), and X (FX), together known as the Prothrombin Complex, and the antithrombotic Protein C and Protein S.
A dose-dependent acquired deficiency of the Vitamin K-dependent coagulation factors occurs during Vitamin K antagonist treatment. Vitamin K antagonists exert anticoagulant effects by blocking carboxylation of glutamic acid residues of the Vitamin K-dependent coagulation factors during hepatic synthesis, lowering both factor synthesis and function. The administration of Kcentra rapidly increases plasma levels of the Vitamin K-dependent coagulation Factors II, VII, IX, and X as well as the antithrombotic Proteins C and S.
Coagulation Factor II:
Coagulation Factor VII:
Coagulation Factor IX:
Coagulation Factor X:
Indications and usage
| INDICATIONS AND USAGE:
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, e.g., warfarin) therapy in adult patients with:
Kcentra is contraindicated in:
| WARNINGS AND PRECAUTIONS: [see package insert for more detailed comments]
| ADVERSE REACTIONS:
The most common adverse reactions (ARs) (frequency ≥ 2.8%) observed in subjects receiving Kcentra were headache, nausea/vomiting, hypotension, and anemia.
To report SUSPECTED ADVERSE REACTIONS, contact CSL Behring at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.
Dosage and administration
| DOSAGE AND ADMINISTRATION:
For intravenous use only.
Table 1: Dosage Required for Reversal of VKA Anticoagulation in Patients with acute major bleeding or need for an urgent surgery/invasive procedure
Example dosing calculation for 80 kg patient
35 units of Factor IX/kg × 80 kg = 2,800 units of Factor IX required*
*For a vial with an actual potency of 30 units/mL Factor IX, 93 mL would be given (2,800 U/30 U per mL = 93 mL).
Preparation and Reconstitution:
The procedures provided in Table 2 are general guidelines for the preparation and reconstitution of Kcentra.
Reconstitute at room temperature as follows:
| DOSAGE FORMS AND STRENGTHS:
National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
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