Kcentra

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  • Bleeding disorders
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Kcentra Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Prothrombin complex concentrate (human) 500 units, 1000 units; per vial; lyophilized pwd for IV infusion after reconstitution; contains non-activated coagulation Factors II, VII, IX, X, antithrombotic Proteins C and S; also, heparin, human albumin, antithrombin III; preservative-free; latex-free.

    Pharmacological Class

    Coagulation factor complex.

    How Supplied

    Kit (500 units, 1000 units)—1 (single-use vial + diluent, supplies)

    How Supplied

    Kcentra is supplied in a single-dose vial and contains no preservatives. The actual units of potency of all coagulation factors (Factors II, VII, IX and X), Proteins C and S in units are stated on each Kcentra carton. The excipients are human antithrombin III, heparin, human albumin, sodium chloride, and sodium citrate.

    Each kit consists of the following:

    Nominal potency 500 (range 400-620) units Kcentra in a single-dose vial

    • 20mL vial of Sterile Water for Injection, USP
    • Mix2Vial filter transfer set
    • Alcohol swab

    Nominal potency 1000 (range 800-1240) units Kcentra in a single-dose vial

    • 40mL vial of Sterile Water for Injection, USP
    • Mix2Vial filter transfer set
    • Alcohol swab

    Storage

    Prior to Reconstitution

    • Store Kcentra between 2-25°C (36-77°F), this includes room temperature, not to exceed 25°C (77°F); do not freeze.
    • Kcentra is stable for 36 months from the date of manufacture, up to the expiration date on the carton and vial labels; do not use beyond the expiration date on the vial label and carton.
    • Store vial in the original carton to protect it from light.

    After Reconstitution

    • Must be used within 4 hours after reconstitution.
    • Reconstituted Kcentra can be stored at 2-25°C. 
    • If cooled, the solution should be warmed to 20-25°C prior to administration. 
    • Do not freeze. 
    • Discard partially used vials.

    Manufacturer

    CSL Behring, LLC

    Generic Availability

    NO

    Kcentra Indications

    Indications

    Urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA) therapy in adults with acute major bleeding or need for an urgent surgery/invasive procedure.

    Kcentra Dosage and Administration

    Prior to Treatment Evaluations

    Measure INR prior to treatment and close to the time of dosing because coagulation factors may be unstable in patients with acute major bleeding or an urgent need for surgery and other invasive procedures.

    Adult

    See full labeling. Administer concomitant Vitamin K. Individualize dosing based on patient's baseline INR and weight. Potency (units) is defined by Factor IX content. Give by IV Infusion at a rate of 0.12mL/kg/min (~3 units/kg/min); max rate of 8.4mL/min (~210 units/min). ≤100kg: Pre-treatment INR: (2–<4): 25 units of Factor IX/kg; max 2500 units; (4–6): 35 units of Factor IX/kg; max 3500 units; (>6): 50 units of Factor IX/kg; max 5000 units. >100kg: do not exceed max dose. Repeat dosing: not recommended.

    Children

    Not established.

    Kcentra Contraindications

    Contraindications

    Severe hypersensitivity to heparin, Factors II, VII, IX, X, Proteins C and S, antithrombin III, human albumin. Disseminated intravascular coagulation (DIC). Known heparin-induced thrombocytopenia (HIT).

    Kcentra Boxed Warnings

    Boxed Warning

    Arterial and venous thromboembolic complications.

    Boxed Warning

    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, 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 nonfatal 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.

    Kcentra was not studied in patients who had a thromboembolic event, myocardial infarction, DIC, 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.

    Kcentra Warnings/Precautions

    Warnings/Precautions

    Risk of arterial and venous thromboembolic complications (may be fatal). History of thromboembolic events within the previous 3 months. Monitor for signs/symptoms of thromboembolic events during and after infusion. Discontinue immediately if hypersensitivity reactions occur. Measure INR before, during, and after each treatment. Contains human plasma; monitor for possible infection transmission. Pregnancy (Cat.C). Nursing mothers.

    Warnings/Precautions

    Hypersensitivity Reactions

    Discontinue administration and institute appropriate treatment if severe allergic reaction or anaphylactic type reactions occur with Kcentra. These types of reactions have been observed in clinical trials with Kcentra.

    Thromboembolic Risk/Complications

    In clinical trials and post marketing surveillance, both fatal and nonfatal arterial thromboembolic events (including acute myocardial infarction and arterial thrombosis), and venous thromboembolic events (including pulmonary embolism and venous thrombosis) and DIC have been reported with Kcentra (See Boxed Warning). Closely monitor patients for signs and symptoms of thromboembolism during and after administration of Kcentra.

    Transmissible Infectious Agents

    Kcentra is made from human blood and therefore carries a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The manufacturing of Kcentra includes 2 virus reduction steps; however, there is still a possibility for disease transmission. 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.

    Infections thought to have been possibly transmitted by Kcentra should be reported to the CSL Behring Pharmacovigilance Department at 866-915-6958 or FDA at 800-FDA-1088 or www.fda.gov/medwatch.

    Pregnancy Considerations

    It is not known whether Kcentra can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Kcentra should be prescribed for a pregnant woman only if clearly needed.

    Nursing Mother Considerations

    It is unknown whether Kcentra is excreted in human milk. There is also no information available on the effect on the breastfed infant, or the effects on milk production. Kcentra should only be used in nursing mothers if it is clearly needed.

    Pediatric Considerations

    The safety and efficacy of Kcentra in the pediatric population have not been studied.

    Geriatric Considerations

    No clinically significant differences were observed between the safety profile of Kcentra and plasma in any age group. In 3 clinical studies, 66% of patients were aged 65 years or older and 39% were aged 75 years or older.

    Other Considerations for Specific Populations

    Kcentra has not been studied in patients with congenital factor deficiencies.

    Kcentra Pharmacokinetics

    Absorption

    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.

    Elimination

    In healthy subjects, factor II had the longest half-life (59.7 hours) and factor VII the shortest (4.2 hours).

    May not be directly applicable to patients with INR elevation due to VKA anticoagulation therapy.

    Kcentra Interactions

    Not Applicable

    Kcentra Adverse Reactions

    Adverse Reactions

    Headache, nausea, vomiting, hypotension, anemia; hypersensitivity, thromboembolic events (eg, stroke, PE, DVT).

    Kcentra Clinical Trials

    Clinical Trials

    Acute Major Bleeding

    The efficacy of Kcentra has been evaluated in a prospective, open-label, active-controlled, noninferiority, randomized clinical trial in patients who had been treated with VKA therapy and who required urgent replacement of their Vitamin K-dependent clotting factors to treat acute major bleeding.

    Patients were randomly assigned to receive Kcentra (n=98) or plasma (n=104) for acute major bleeding in the setting of a baseline INR ≥ 2.0 and recent use of a VKA anticoagulant. The primary endpoint was hemostatic efficacy for the time period from the start of infusion until 24 hours.

    Effective hemostasis was observed in 72.4% (95% CI, 62.3-82.6) of the Kcentra arm and 65.4% (95% CI, 54.9-75.8) of the plasma arm (difference, 7.1% [95% CI, -5.8, 19.9]). 

    A secondary endpoint included a reduction of INR to ≤1.3 at 30 minutes after the end of infusion. This outcome was demonstrated in 62.2% (95% CI, 52.6-71.8) of patients in the Kcentra group and 9.6% (95% CI, 3.9-15.3) of those in the plasma group (difference, 52.6% [95% CI, 39.4-65.9]).

    Urgent Surgery/Invasive Procedure 

    The efficacy of Kcentra was evaluated in a prospective, open-label, active-controlled, noninferiority study in patients who had been treated with VKA therapy and who required urgent replacement of their Vitamin K-dependent clotting factors because of their need for an urgent surgery/invasive procedure.

    Patients with acquired coagulation factor deficiency due to oral Vitamin K antagonist therapy were randomly assigned to receive Kcentra (n=87) or plasma (n=81) because of their need for an urgent surgery/invasive procedure in the setting of a baseline INR ≥ 2.0 and recent use of a VKA anticoagulant. The primary endpoint was hemostatic efficacy for the time period from the start of infusion until the end of the urgent surgery/invasive procedure.

    Effective hemostasis was observed in 89.7% (95% CI, 83.3-96.1) of the Kcentra group and 75.3% (95% CI, 65.9-84.7) of the plasma group (difference, 14.3% [95% CI, 2.8-25.8]). 

    A secondary endpoint included a reduction of INR to ≤1.3 at 30 minutes after the end of infusion. This outcome was demonstrated in 55.2% (95% CI, 44.7-65.6) of patients in the Kcentra group and 9.9% (CI, 3.4-16.4) of those in the plasma group (difference, 45.3% [95% CI, 31.9-56.4]).

    Kcentra Note

    Notes

    Report all infections suspected to be transmitted by Kcentra to (866) 915-6958.

    Kcentra Patient Counseling

    Patient Counseling

    Alert patients to signs/symptoms of allergic hypersensitivity reactions (eg, urticaria, rash, tightness of the chest, wheezing, hypotension, and/or anaphylaxis) during or after injection of Kcentra.

    Limb or abdomen swelling and/or pain, chest pain or pressure, shortness of breath, loss of sensation or motor power, altered consciousness, vision, or speech could be signs/symptoms of thrombosis.

    There is a risk of transmitting infectious agents as Kcentra is made from human blood.

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