Kcentra (human prothrombin complex concentrate 4-factor)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Prothrombin complex concentrate (human), a preparation of nonactivated blood coagulation factors II, VII, IX, and X derived from pooled human plasma, is a hemostatic agent. The drug is a 4-factor prothrombin complex concentrate (PCC).
Prothrombin complex concentrate (human) (Kcentra(R)) is a lyophilized concentrate of nonactivated blood coagulation factors II, VII, IX, and X derived from pooled human plasma. The drug is a 4-factor PCC. Kcentra(R) also contains the antithrombotic proteins C and S, human antithrombin III, and heparin.
All plasma used in the manufacture of Kcentra(R) is obtained from US donors and is tested using serologic assays for hepatitis B surface antigen and antibodies to human immunodeficiency virus-1 (HIV-1), HIV-2, and hepatitis C virus (HCV). The plasma also undergoes nucleic acid testing for HCV, HIV-1, hepatitis A virus (HAV), hepatitis B virus (HBV), and human parvovirus B19. Only plasma that passes these virus screening methods is used for production.
Additional viral reduction/inactivation processes employed in the manufacture of Kcentra(R) include cryoprecipitation, ion exchange chromatography, pasteurization, solvent/detergent treatment, and nanofiltration.
During treatment with vitamin K antagonists (e.g., warfarin), patients develop an acquired deficiency of the vitamin K-dependent coagulation factors II (prothrombin), VII (proconvertin), IX (antihemophilic globulin B or Christmas factor), and X (Stuart-Prower factor). These clotting factors play key roles in the coagulation cascade and are essential for the ultimate conversion of factor II (prothrombin) to thrombin and formation of a fibrin clot; thus, deficiencies in one or more of these coagulation factors can cause bleeding. Administration of prothrombin complex concentrate (human) temporarily corrects the acquired coagulation deficiency induced by vitamin K antagonists by rapidly increasing plasma levels of the vitamin K-dependent clotting factors.
In healthy individuals, administration of a single IV infusion of Kcentra(R) 50 units/kg produced a rapid and sustained increase in plasma concentrations of factors II, VII, IX, and X and the anticoagulant proteins C and S within 5 minutes; median terminal half-life of the clotting factors ranged from 4.2 to 59.7 hours. In patients with acute major bleeding due to an acquired deficiency of vitamin K-dependent coagulation factors, mean in vivo recovery of factor II, factor VII, factor IX, factor X, protein C, and protein S following a single IV dose of Kcentra(R) was 2, 2.15, 1.29, 1.96, 2.04, and 2.17% per unit/kg administered, respectively. In patients with an acquired deficiency of vitamin K-dependent coagulation factors requiring reversal for urgent surgery or invasive procedures, mean in vivo recovery of factor II, factor VII, factor IX, factor X, protein C, and protein S following a single IV dose of Kcentra(R) was 2.14, 1.9, 1.15, 1.94, 1.88, and 2.81% per unit/kg administered, respectively.
Generic name: human prothrombin complex concentrate 4-factor
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Kcentra
Indications
The following indications are listed for Kcentra:
- Anticoagulant-Induced Prothrombin Deficiency
Also known as: Anticoagulant-Induced Serum Factor Ii Deficiency, Anticoagulant-Induced Serum Prothrombin Deficiency, Anticoagulant-Related Prothrombin Deficiency.
Dosing
The dose of prothrombin complex concentrate (human) (Kcentra(R)) is expressed in international units (IU, units) and is based on units of factor IX activity. The actual amount of factor IX contained in each vial of Kcentra(R) labeled with 500 units ranges from 400 to 620 units, and the actual amount of factor IX contained in each vial labeled with 1000 units ranges from 800 to 1240 units. The actual potency of each vial is indicated on the carton and vial label.
Prothrombin complex concentrate (human) (Kcentra(R)) is administered by IV infusion. The drug is given as a single dose for the urgent reversal of warfarin anticoagulation; repeat dosing of the drug currently is not recommended due to the lack of supporting clinical data.
Kcentra(R) is commercially available as a kit that contains a single-use vial of lyophilized drug (with nominal potency of 500 or 1000 units), a 20- or 40-mL vial of sterile water for injection diluent, and a filter transfer set. Prior to use, the lyophilized powder for injection should be stored at 2-25degreesC in the original container and protected from light and freezing. When stored under recommended conditions, unopened vials of Kcentra(R) are stable for 36 months from the date of manufacture up to the expiration date.
Kcentra(R) should be reconstituted as directed by the manufacturer. Prior to reconstitution, the lyophilized powder for injection and sterile water for injection diluent provided by the manufacturer should be warmed to room temperature. Each vial of Kcentra(R) should be reconstituted with 20 mL (for the vial labeled with nominal potency of 500 units) or 40 mL (for the vial labeled with nominal potency of 1000 units) of sterile water for injection using the filter transfer set provided by the manufacturer; the resultant solution will contain 20-31 units of factor IX per mL depending on the actual amount of factor IX contained in the vial, which is listed on the carton and vial label. Following addition of diluent, the vial should be gently swirled (not shaken) until the powder is completely dissolved. The reconstituted solution should be colorless and clear to slightly opalescent, and free from visible particles. If more than one vial is required for a dose, the reconstituted contents of multiple vials may be pooled; however, a separate transfer filter set should be used to reconstitute each vial.
Kcentra(R) must be administered within 4 hours after reconstitution. If not used immediately, the solution may be stored at 2-25degreesC but should not be frozen; if stored under refrigeration, the solution should be warmed to room temperature (20-25degreesC) prior to administration. Vials of Kcentra(R) contain no preservatives and are for single use only; partially used vials should be discarded.
Kcentra(R) should not be mixed with other drugs and should be administered through a separate infusion line. During administration, care should be taken to prevent blood from entering the syringe to minimize the risk of fibrin clot formation.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known anaphylactic or severe systemic reactions to any component in the formulation (i.e., factors II, VII, IX, or X; proteins C or S; heparin; antithrombin III; human albumin)
*Disseminated intravascular coagulation (DIC)
*Known heparin-induced thrombocytopenia (HIT).
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse reactions (frequency >=2.8%) reported with prothrombin complex concentrate (human) in clinical trials include headache, nausea, vomiting, anemia, and hypotension. The most serious adverse effects observed in these trials were thromboembolic events, including stroke, pulmonary embolism, and deep-vein thrombosis.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of prothrombin complex concentrate (human) (Kcentra(R)) have not been established in pediatric patients.
There are no data on the use of prothrombin complex concentrate (human) (Kcentra(R)) during pregnancy. Animal reproduction studies have not been conducted. It is not known whether prothrombin complex concentrate (human) can cause fetal harm when administered to pregnant women or affect reproduction capacity. Prothrombin complex concentrate (human) should be used during pregnancy only when clearly needed.
It is not known whether prothrombin complex concentrate (human) is distributed into human milk. Because many drugs are distributed into milk, the manufacturer states that prothrombin complex concentrate (human) should be used in breast-feeding women only if clearly needed.
Among 431 patients in clinical studies who received prothrombin complex concentrate (human) (Kcentra(R)) for reversal of warfarin anticoagulation, 66% were 65 years of age or older and 39% were 75 years of age or older. No clinically important age-related differences in safety were observed.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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