"The U.S. Food and Drug Administration yesterday approved Rixubis [Coagulation Factor IX (Recombinant)] for use in people with hemophilia B who are 16 years of age and older. Rixubis is indicated for the control and prevention of bleeding episodes"...
Prothrombin Complex Concentrate (Human)
ARTERIAL AND VENOUS THROMBOEMBOLIC COMPLICATIONS
Patients being treated with Vitamin K antagonists (VKA) therapy have underlying disease states that predispose them to thromboembolic events. Potential benefits of reversing VKA should be weighed against the potential risks of thromboembolic events (TE), especially in patients with the history of a thromboembolic event. Resumption of anticoagulation should be carefully considered as soon as the risk of thromboembolic events outweighs the risk of acute bleeding.
Both fatal and non-fatal arterial and venous thromboembolic complications have been reported with Kcentra in clinical trials and post marketing surveillance. Monitor patients receiving Kcentra for signs and symptoms of thromboembolic events. (5.2)
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 may not be suitable in patients with thromboembolic events in the prior 3 months. (5.2)
Kcentra is a purified, heat-treated, nanofiltered and lyophilized non-activated four-factor Prothrombin Complex Concentrate (Human) prepared from human U.S. Source Plasma (21 CFR 640.60). It contains the Vitamin K dependent Coagulation Factors II, VII, IX and X, and the antithrombotic Proteins C and S. Factor IX is the lead factor for the potency of the preparation as stated on the vial label. The excipients are human antithrombin III, heparin, human albumin, sodium chloride, and sodium citrate. Kcentra is sterile, pyrogen-free, and does not contain preservatives.
The product contents are shown in Table 7 and listed as ranges for the blood coagulation factors.
Table 7: Composition per Vial of Kcentra 500 Units*
|Ingredient||Kcentra 500 units|
|Total protein||120 - 280 mg|
|Factor II||380 - 800 units|
|Factor VII||200 - 500 units|
|Factor IX||400 - 620 units|
|Factor X||500 - 1020 units|
|Protein C||420 - 820 units|
|Protein S||240 - 680 units|
|Heparin||8 - 40 units|
|Antithrombin III||4 - 30 units|
|Human albumin||40 - 80 mg|
|Sodium chloride||60 - 120 mg|
|Sodium citrate||40 - 80 mg|
|* 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-½ 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.
Table 8: Virus Reduction Factors [log10] of Kcentra
|Virus Studied||Manufacturing Steps||Overall Virus Reduction [log10]|
|Cryo- precipitation||DE-AE-Adsorption (Ion Exchange Chromatography)||Heat treatment (“Pasteurization”)||Ammonium sulphate precipitation followed by Ca Phosphate adsorption||75/35 nm Filtration||Lyophilization|
|HIV||n.d.||n.d||≥ 6.9||≥ 5.9||≥ 7.3||n.d.||≥ 20.1|
|BVDV||n.d.||n.d||≥ 8.5||2.2||4.2||n.d.||≥ 14.9|
|PRV||n.d.||n.d||4.1||7.2||≥ 6.8||n.d.||≥ 18.1|
|WNV||n.d.||n.d.||≥ 7.4||n.d.||n.d.||n.d.||≥ 4|
|* Reduction factor below 1 log10 was not considered in
calculating the overall virus reduction. Studies using human parvovirus B19,
which are considered experimental in nature, have demonstrated a virus
reduction factor of 3.5 log10 by heat treatment.
HIV Human immunodeficiency virus, a model for HIV-1 and HIV-2
BVDV bovine viral diarrhea virus, model for HCV
PRV Pseudorabies virus, a model for large enveloped DNA viruses
WNV West Nile virus
HAV Hepatitis A virus
CPV canine parvovirus, model for B19V
n.d. not determined
Last reviewed on RxList: 8/12/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Kcentra Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.