Bleeding disorders:
Indications for: KCENTRA
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.
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]).
Adult Dosage:
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 Dosage:
Not established.
KCENTRA 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).
Boxed Warning:
Arterial and venous thromboembolic complications.
KCENTRA 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.
KCENTRA Classification:
Coagulation factor complex.
Adverse Reactions:
Headache, nausea, vomiting, hypotension, anemia; hypersensitivity, thromboembolic events (eg, stroke, PE, DVT).
Note:
Report all infections suspected to be transmitted by Kcentra to (866) 915-6958.
Drug 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.
Generic Drug Availability:
NO
How Supplied:
Kit (500 units, 1000 units)—1 (single-use vial + diluent, supplies)
