What is the shelf life of kcentra?
Prior to Reconstitution Kcentra is for single use only and contains no preservatives Store Kcentra between 2–25°C (36–77°F), not to exceed 25°C (77°F). This allows room-temperature storage. Kcentra is stable for 36 months from the date of manufacture, up to the expiration date on the carton and vial labels.
What is the duration of kcentra infusion?
In the plasma-controlled RCT for patients needing urgent surgery/invasive procedures, the mean duration of Kcentra infusion was 21 minutes (± 14 minutes) and the mean duration of infusion for plasma was 141 minutes (± 113 minutes). The mean infusion volume of Kcentra was 90 mL ± 32 mL and the mean infusion volume of plasma was 819 mL ± 231 mL.
Is kcentra suitable for patients with thromboembolic events?
Kcentra may not be suitable in patients with thromboembolic events in the prior 3 months. 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).
What are the risks of using kcentra?
Kcentra is made from human blood and may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
What is the half-life of Kcentra?
Half-life. Mean terminal half-life of coagulation factors II, VII, IX, and X following single dose of Kcentra in healthy individuals was 60.4, 5, 42.4, and 31.8 hours, respectively.
How long does it take Kcentra to work?
Major bleeding despite INR: Administer vitamin K 5-10 mg IV with Kcentra INR will decrease over ~24- 48 hours (oral) and ~12-14 hours (IV); more frequent INR monitoring and additional vitamin K doses may be necessary.
Can you repeat Kcentra?
If r-time normal Kcentra® is not required. Maximum cumulative dose = 50 units/kg per day. ➢ Use is restricted to a single dose. Repeat doses do not improve efficacy and increases risk for thromboembolic complications.
How long does prothrombin complex concentrate last?
The half-lives of the four clotting factors differ widely. The half-life of FII is much longer (60–72 h) than that of the other factors (6–24 h). FVII has the shortest half-life (approximately 6 h)4.
How quickly does Kcentra reverse INR?
Monitor INR and clinical response during and after treatment. In clinical trials, Kcentra decreased the INR to ≤1.3 within 30 minutes in most subjects. The relationship between this or other INR values and clinical hemostasis in patients has not been established [see Clinical Studies (14)].
Why does Kcentra have to be given with vitamin K?
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.
Can Kcentra reverse apixaban?
There is currently no available reversal agent for apixaban. Prothrombin complex concentrate (PCC) contain clotting factors and can replace factors inhibited by anticoagulants....Condition or diseaseIntervention/treatmentPhaseThrombosisDrug: Kcentra Drug: Apixaban Drug: PlaceboPhase 1Oct 21, 2014
Does PCC reverse Eliquis?
Abstract. Essentials Prothrombin complex concentrates (PCCs) may reverse the effect of factor Xa (FXa) inhibitors. We conducted an open-label, randomized, placebo-controlled, three-period crossover study in 15 subjects. Both PCCs rapidly reversed apixaban-mediated decreases in mean endogenous thrombin potential.
Does Kcentra work in liver failure?
A 4-factor prothrombin complex concentrate (4F-PCC, Kcentra®) was recently approved in the United States for the reversal of vitamin K antagonist-associated major bleeding, but it is often used to reverse coagulopathy in patients with liver disease (LD).
How long is a PT specimen good for?
Storage Instructions Specimens are stable at room temperature for 24 hours. If testing cannot be completed within 24 hours, specimens should be centrifuged for at least 10 minutes at 1500xg.
How long can a PT INR sit out?
Specimen stability: Whole blood: 24 hours at room temperature.
Is Kcentra the same as vitamin K?
Kcentra contains the vitamin K—dependent coagulation factors II, VII, IX, and X—together known as the prothrombin complex—and the antithrombotic proteins C and S.
How fast is Kcentra given?
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).
How quickly does Octaplex work?
*The single dose should not exceed 3000 IU (120 mL Octaplex). The correction of the vitamin K antagonist induced impairment of haemostasis persists for approximately 6-8 hours. However, the effects of vitamin K, if administered simultaneously, are usually achieved within 4-6 hours.
How long does Prothrombinex take to work?
Prothrombinex-VF is able to completely reverse an excessive INR within 15 minutes, but the infused clotting factors have half-lives similar to endogenous clotting factors. Therefore, vitamin K1 5–10 mg should be given intravenously with the PCC to sustain the reversal effect.
How quickly does Beriplex work?
The correction of the vitamin K antagonist-induced impairment of haemostasis is commonly reached approximately 30 minutes after the injection.
How long does it take to infuse Kcentra?
Mean infusion time for Kcentra was under 25 minutes, while mean infusion time for plasma was over 2 hours 7,15. 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.
How long does hemostasis last?
Effective hemostasis measured up to 24 hours for the Acute Major Bleeding trial and until the end of procedure (up to 24 hours) for the Urgent Surgery/Invasive Procedures trial. Rapid INR reduction to ≤1.3 at 0.5 hours after end of infusion.
How long does INR decrease last?
Statistically significant INR reduction sustained for up to 8 hours.
What is Kcentra concentrate?
Kcentra is available as a white or slightly colored lyophilized concentrate in a single use vial containing coagulation Factors II, VII, IX and X, and antithrombotic Proteins C and S.
What are the components of Kcentra?
Patients with known anaphylactic or severe systemic reactions to Kcentra or any components in Kcentra including heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III and human albumin.
What are the vitamins in Kcentra?
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.
How long after Kcentra infusion is INR?
The median INR was above 3.0 prior to the infusion and dropped to a median value of 1.20 by the 30 minute time point after start of Kcentra infusion. By contrast, the median value for plasma was 2.4 at 30 minutes after the start of infusion. The INR differences between Kcentra and plasma were statistically significant in randomized plasma-controlled trial in bleeding up to 12 hours after start of infusion [see Table 9].
How many subjects were randomized to a VKA trial?
In a prospective, randomized, open-label, active-controlled multicenter non-inferiority trial, 212 subjects who required urgent reversal of VKA therapy due to acute major bleeding were enrolled and randomized to treatment; 103 were treated with Kcentra and 109 with plasma. Subjects with a history of a thrombotic event, myocardial infarction, cerebral vascular accident, transient ischemic attack, unstable angina pectoris, severe peripheral vascular disease, or disseminated intravascular coagulation, within the previous 3 months were excluded from participating. Subjects ranged in age from 26 years to 96 years.
How long does factor II infusion last?
A single intravenous Kcentra infusion produced a rapid and sustained increase in plasma concentration of Factors II, VII, IX and X as well as Proteins C and S. The PK analysis [see Table 10] shows that factor II had the longest half-life (59.7 hours ) and factor VII the shortest (4.2 hours) in healthy subjects. PK parameters obtained from data derived from the study of healthy subjects may not be directly applicable to patients with INR elevation due to VKA anticoagulation therapy.
Is Kcentra studied in patients with 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 may not be suitable in patients with thromboembolic events in the prior 3 months. ( 5.2)
What is Kcentra?
Kcentra ( prothrombin complex) is a blood coagulation factor replacement product.
How is Kcentra given?
Kcentra is given as an infusion into a vein. A healthcare provider will give you this injection.
What other drugs will affect Kcentra?
Other drugs may interact with prothrombin complex, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.
What are the symptoms of allergic reactions to Kcentra?
Get emergency medical help if you have signs of an allergic reaction to Kcentra: hives, rash; nausea, vomiting, feeling light-headed; fast heartbeats; chest tightness, wheezing, difficult breathing; swelling of your face, lips, tongue, or throat.
Is Kcentra made from human plasma?
Kcentra is made from donated human plasma and may contain viruses or other infectious agents. Donated plasma is tested and treated to reduce the risk of contamination, but there is still a small possibility it could transmit disease. Ask your doctor about any possible risk.
Can you take Kcentra with warfarin?
Kcentra is for use in people who use blood thinners such as warfarin. After you are treated with this medicine, do not start using your blood thinner again until your doctor tells you to.
Can you share Kcentra with children?
Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Kcentra only for the indication prescribed.
What are the components of Kcentra?
Patients with known anaphylactic or severe systemic reactions to Kcentra or any components in Kcentra including heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III and human albumin.
How is Kcentra made?
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.
What is Kcentra lyophilized?
Kcentra is available as a single use vial containing coagulation Factors II, VII, IX and X, antithrombotic Proteins C and S as a lyophilized concentrate.
How is Kcentra plasma tested?
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.
Does Kcentra increase coagulation factor?
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: Factor II (prothrombin) is converted to thrombin by activated FX (FXa) in the presence of Ca2+, FV, and phospholipids.
Is Kcentra studied in patients with 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 may not be suitable in patients with thromboembolic events in the prior 3 months.
Is Kcentra fatal?
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.
How long does it take for vitamin K to work?from emcrit.org
FFP or PCC will work only for ~8 hours. Vitamin K will do the job after the FFP/PCC wears off. It takes Vitamin K 6-12 hours to start working, so it must be given up-front, simultaneously with FFP or PCC. Intravenous vitamin K may theoretically cause an anaphylactoid response if infused rapidly.
How many units of cryoprecipitate are needed for a patient?from sciencedirect.com
The usual dose for cryoprecipitate transfusion is 10 units, followed by 6 to 10 units every 8 hours. The goal of transfusion is to elevate fibrinogen levels to 100 mg/dL. Since each cryoprecipitate unit carries the equivalent risk of disease transmission as 1 unit of blood, it is recommended to use recombinant factors in patients who are to be subjected to frequent plasma transfusions.
How much frozen plasma is used for apheresis?from statpearls.com
Each unit of fresh frozen plasma contains approximately 200 to 250 mL. Apheresis-derived units can contain as much as 400 to 600 mL. The administration of one 250 mL unit should raise the fibrinogen level by 5 to 10 mg/dl. The goal of therapy is a cessation of bleeding. The laboratory value goal is to correct the prothrombin time/activated partial thromboplastin time to less than 1.5 times normal. [9] [10] [11]
How much FFP is in plasma?from sciencedirect.com
FFP contains 250 mL of plasma and 500 mg of fibrinogen in a citrate anticoagulant. One unit of FFP has a concentration of coagulation factors similar to that of 4 to 5 units of platelet concentrates, 1 apheresis unit of platelets, and 1 unit of fresh whole blood. FFP, 1 mL/kg, raises most factor levels by approximately 1%. After a dose of 10 to 15 mL/kg of FFP, plasma clotting factors rise approximately 15%, and the fibrinogen rises by 40 mg/dL. However, FFP contains only 0.6% of factor VIII.
What ratio of frozen plasma should be used for transfusion?from statpearls.com
Other situations where the administration of fresh frozen plasma cannot be recommended for or against based on systematic review include fresh frozen plasma transfusion at a plasma-to-RBC ratio of 1 to 3 or more in trauma patients with massive transfusion. Conditions that cause the deficiency of multiple coagulation factors and may require the administration of fresh frozen plasma include liver disease and disseminated intravascular coagulation. Fresh frozen plasma transfusion may not be tolerated in patients with liver disease as patients may not tolerate the infusion volumes necessary to achieve adequate hemostatic levels of coagulation factors. [1] [2] [3]
Why is frozen plasma used for warfarin?from sciencedirect.com
Fresh frozen plasma is used for reversing effect of warfarin because it contains substantial levels of vitamin K dependent clotting factors but requires a relatively large amount of FFP to correct INR. Presence of hemorrhage is a solid indication of using FFP. However, transfusion-related acute lung injury (TRALI), transfusion-related circulatory overload, allergic reactions from mild to anaphylactoid, acute hemolysis and transfusion-related infections are risks of FFP transfusion. Therefore, FFP is best used in high-risk patients in appropriate dosage after considering potential transfusion reactions [3].
What is frozen plasma?from statpearls.com
Fresh frozen plasma is indicated for the deficiency of coagulation factors with abnormal coagulation tests in the presence of active bleeding . Fresh frozen plasma is also indicated for a planned surgery or invasive procedure in the presence of abnormal coagulation tests, the reversal of warfarin in the presence of active bleeding or planned procedure when vitamin K is inadequate to reverse the warfarin effect, thrombotic thrombocytopenic purpura, and congenital or acquired factor deficiency with no alternative therapy. This activity reviews the indications for fresh frozen plasma and highlights the role of the interprofessional team in managing patients with coagulopathy that requires the use of fresh frozen plasma.
How long has Kcentra been in the US?
Kcentra has over 20 years of clinical experience as Beriplex®outside the US.
What is a kcentra?
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.
How long does it take for Kcentra to decrease INR?
Monitor INR and clinical response during and after treatment. In clinical trials, Kcentra decreased the INR to 1.3 within 30 minutes in ≤ most subjects. The relationship between this or other INR values and clinical hemostasis in patients has not been established [see Clinical Studies (14)].
What are the adverse reactions to Kcentra?
Serious adverse reactions in subjects receiving Kcentra in both RCTs included ischemic cerebrovascular accident (stroke), DVT, thrombosis, and venous insufficiency. Serious adverse reactions in both RCTs for plasma included myocardial ischemia, myocardial infarction, fluid overload, embolic cerebral infarction, pulmonary edema, respiratory failure, and DVT. There were a total of 10 subjects (9.7%) who died in the Kcentra group (1additional death occurred on day 46 just after completion of the study reporting period) and 5 (4.6%) who died in the plasma group in the plasma-controlled RCT in acute major bleeding. The 95% confidence interval for the Kcentra minus plasma between-group difference in deaths ranged from -2.7% to 13.5%. From the plasma-controlled RCT in urgent surgery/ invasive procedures, there were a total of 3 subjects (3.4%) who died in the Kcentra group (1 additional death occurred on day 48 after completion of the study reporting period) and 8 (9.1%) who died in the Plasma group. The 95% confidence interval for the Kcentra minus plasma between-group difference in deaths in this trial ranged from -14.6% to 2.7%. One death in the Kcentra group in the RCT in Acute Major Bleeding and one death in the plasma group in the RCT in urgent surgery/invasive procedures were considered possibly related to study treatment according to an assessment of masked data by an independent safety adjudication board. No factors common to all deaths were identified, except for the frequent findings of a high comorbidity burden, advanced age, and death after being placed on comfort care. Although, a greater proportion of subjects in the RCT in acute major bleeding than in the RCT in surgery/invasive procedure received the highest two recommended doses of Kcentra because more subjects in the trial in acute major bleeding had a baseline INR in the ranges of 4‒6 and > 6.0, an analysis of deaths and factor levels in subjects with major bleeding revealed that subjects who died had similar median factor levels to subjects that did not die. Additionally, outliers with supraphysiologic factor levels did not have a mortality rate out of proportion to the overall population. Fluid Overload There were 9 subjects (4.7%, all non-related by investigator assessment) in the Kcentra group who experienced fluid overload in the plasma-controlled RCTs in acute major bleeding and urgent surgery/invasive procedures and 25 (12.7%, 13 events related by investigator assessment) who had fluid overload in the plasma group. The 95% confidence interval for the Kcentra minus Plasma between-group difference in fluid overload event incidence ranged from -14.1% to -2.0%. Subgroup analyses of the RCTs in acute major bleeding and urgent surgery/invasive procedures according to whether subjects with fluid overload events had a prior history of congestive heart failure are presented in Table 4.
What is Kcentra concentrate?
Kcentra is available as a white or slightly colored lyophilized concentrate in a single-use vial containing coagulation Factors II, VII, IX and X, and antithrombotic Proteins C and S. (3)
What is kcentra vk antagonist?
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: • acute major bleeding or • need for an urgent surgery/invasive procedure. (1)
Is Kcentra contraindicated for thromboembolic events?
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).
Indications and Usage For Kcentra
Dosage Forms and Strengths
- Kcentra is available as a white or slightly colored lyophilized concentrate in a single-dose vial containing coagulation Factors II, VII, IX and X, and antithrombotic Proteins C and S.
- Kcentra potency (units) is defined by Factor IX content. The actual potency for 500 unit vial ranges from 400-620 Factor IX units/vial. The actual potency for 1000 unit vial ranges from 800-1240 Fa...
- Kcentra is available as a white or slightly colored lyophilized concentrate in a single-dose vial containing coagulation Factors II, VII, IX and X, and antithrombotic Proteins C and S.
- Kcentra potency (units) is defined by Factor IX content. The actual potency for 500 unit vial ranges from 400-620 Factor IX units/vial. The actual potency for 1000 unit vial ranges from 800-1240 Fa...
- The actual units of potency for each coagulation factor (Factors II, VII, IX and X), and Proteins C and S are stated on the carton.
Contraindications
- Kcentra is contraindicated in: 1. Patients with known anaphylactic or severe systemic reactions to Kcentra or any components in Kcentra including heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III and human albumin. 2. Patients with disseminated intravascular coagulation (DIC). 3. Patients with known heparin-induced thrombocytopenia (HIT). Kcentra contains hepari…
Warnings and Precautions
- Hypersensitivity Reactions
Hypersensitivity reactions including flushing, urticaria, tachycardia, anxiety, angioedema, wheezing, nausea, vomiting, hypotension, tachypnea, dyspnea, pulmonary edema, and bronchospasm have been observed with Kcentra. If severe allergic reaction or anaphylactic typ… - Thromboembolic Risk/Complications
Both fatal and non-fatal arterial thromboembolic events (including acute myocardial infarction and arterial thrombosis), and venous thromboembolic events (including pulmonary embolism and venous thrombosis) and disseminated intravascular coagulation have been reported with Kcentr…
Adverse Reactions
- The most common adverse reactions (ARs) (frequency ≥2.8%) observed in subjects receiving Kcentra were headache, nausea/vomiting, hypotension, and anemia. The most serious ARs were thromboembolic events including stroke, pulmonary embolism, and deep vein thrombosis. The following serious adverse reactions are described below and/or elsewhere in the labeling: 1. Hyp…
Use in Specific Populations
- Pregnancy
Risk Summary There are no data with Kcentra use in pregnancy to inform on drug-associated risk. Animal reproduction studies have not been conducted with Kcentra. It is not known whether Kcentra can cause fetal harm when administered to a pregnant woman or can affect reproductio… - Lactation
Risk Summary There is no information regarding the excretion of Kcentra in human milk, the effect on the breastfed infant, or the effects on milk production. Because many drugs are excreted in human milk, use Kcentra only if clearly needed when treating a nursing woman.
Kcentra Description
- 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 a…
Kcentra - Clinical Pharmacology
- 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 occur… - Pharmacodynamics
International Normalized Ratio (INR) In the plasma-controlled RCT in acute major bleeding, the INR was determined at varying time points after the start or end of infusion, depending upon study design. The median INR was above 3.0 prior to the infusion and dropped to a median value of 1.…
Nonclinical Toxicology
- Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals to evaluate the carcinogenic potential of Kcentra, or studies to determine the effects of Kcentra on genotoxicity or fertility have not been performed. An assessment of the carcinogenic potential of Kcentra was completed and suggests minimal carci…
Clinical Studies
- Acute Major Bleeding RCT The efficacy of Kcentra has been evaluated in a prospective, open-label, (blinded assessor), active-controlled, non-inferiority, multicenter RCT in subjects who had been treated with VKA therapy and who required urgent replacement of their Vitamin K-dependent clotting factors to treat acute major bleeding. A total of 216 subjects with acquired coagulation fa…