Adult Dosing

Vitamin K antagonist reversal in adult patients with acute major bleeding

• Based on pretreatment INR obtained close to time of dosing (coagulation factor levels may be unstable in patients with acute major bleeding who are receiving Vitamin K)
• Dose in units below is based on factor IX content after reconstitution. See product carton for exact concentration
• INR 2 to <4: 25 units/kg; not to exceed 2500 units
• INR 4-6: 35 units/kg; not to exceed 3500 units
• INR >6: 50 units/kg; not to exceed 5000 units

• Infuse IV at rate of 0.12 mL/kg/min up to maximum rate of 8.4 mL/min

• Not indicated for urgent reversal of vitamin K antagonist anticoagulation in patients WITHOUT acute major bleeding
• Administered in a significantly lower volume than plasma at recommended doses, providing an alternative for volume restricted patients
• Reconstituted solution should be at room temperature before infusing
• Do not mix with other medicinal products
• Administer through a separate infusion line
• No blood should enter the syringe, as there is a possibility of fibrin clot formation
• Record product lot number in patient’s medical record

Pediatric Dosing

• Safety and efficacy in pediatric population has not been studied

[Outline]

• Adult Dosing
• Pediatric Dosing

• 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

• Hypersensitivity to any of the ingredients of the product
• Known anaphylactic or severe systemic reactions to any components including heparin, Factors II, VII, IX, X, proteins C and S, antithrombin III and human albumin
• Disseminated intravascular coagulation
• Known heparin-induced thrombocytopenia

• Patients being treated with vitamin K antagonists (VKA) have underlying disease 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. As soon as the risk of thromboembolic events outweighs the risk of acute bleeding resumption of anticoagulation should be considered carefully
• Both fatal and nonfatal arterial and venous thromboembolic complications reported during clinical trials and postmarketing surveillance; monitor for signs and symptoms of thromboembolic events
• Not studied in individuals 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 before administration. Therapy may not be suitable in such patients

Renal Dose Adjustment

• Renal impairment: Dose adjustments not defined

Hepatic Dosage Adjustment

• Hepatic impairment: Dose adjustments not defined

• Patients being treated with vitamin K antagonists (VKA) have underlying disease 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. As soon as the risk of thromboembolic events outweighs the risk of acute bleeding resumption of anticoagulation should be considered carefully [US black box warning]
• Both fatal and nonfatal arterial and venous thromboembolic complications reported during clinical trials and postmarketing surveillance; monitor for signs and symptoms of thromboembolic events [US black box warning]
• Not studied in individuals 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 before administration. Therapy may not be suitable in such patients[US black box warning]
• Hypersensitivity reactions including flushing, urticaria, tachycardia, anxiety, angioedema, wheezing, nausea, vomiting, hypotension, tachypnea, dyspnea, pulmonary edema, and bronchospasm have been reported
• As the drug is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease agent
• Reports of suspected virus transmission of hepatitis A, B, C, and HIV were generally confounded by concomitant administration of blood/blood components and/or other plasma-derived products

Pregnancy Category:C

Breastfeeding: It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk, use only if clearly needed when treating a nursing woman.

• MISC: headache, nausea/vomiting, arthralgia, hypotension, hypersensitivity reactions
• HEMA: Thromboembolic events including stroke, pulmonary embolism, and deep vein thrombosis

• Contains vitamin-K-dependent coagulation Factors II, VII, IX, and X known as prothrombin complex and the antithrombotic protein C and protein S
• Factor II (prothrombin) is converted to thrombin by activated FX (FXa) in the presence of Ca2+, FV, and phospholipids
• Factor VII (proconvertin) is converted to the activated form (FVIIa) by splitting of an internal peptide link; FVIIa-TF complex activates factor IX and initiates the primary coagulation pathway by activating FX in the presence of phospholipids and calcium ions
• Factor IX (antihemophilic globulin B, or Christmas factor) is activated by the FVIIa-TF complex and by FXIa; factor IXa in the presence of FVIIIa activates FX to FXa
• Factor X (Stuart-Prower factor) activation involves the cleavage of a peptide bond by the FVIIIa-factor IXa complex or the TF-FVIIa complex; factor Xa forms a complex with activated FV (FVa) that converts prothrombin to thrombin in the presence of phospholipids and calcium ions
• Protein C, when activated by thrombin, exerts an antithrombotic effect by inhibiting FVa and FVIIIa leading to a decrease in thrombin formation, and has indirect profibrinolytic activity by inhibiting plasminogen activator inhibitor-1
• Protein S exists in a free form (40%) and in a complex with C4b-binding protein (60%); the free form functions as a cofactor for activated protein C in the inactivation of FVa and FVIIIa, leading to antithrombotic activity
• Half-life:
• Factor IX: 16.7 hrs
• Factor II: 59.7 hrs
• Factor VII: 4.2 hrs
• Factor X: 30.7 hrs
• Protein C: 47.2 hrs
• Protein S: 49.1 hrs

US Trade Name(s)

• Kcentra

US Availability

Kcentra

• PWDR for INJ: 500 units in a single use vial containing coagulation Factors II, VII, IX and X, and antithrombotic Proteins C and S as a lyophilized concentrate

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Hematology/Oncology

Coagulation Factors