prothrombin complex concentrate, human (Rx)

Brand and Other Names:Kcentra
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

lyophilized concentrate for reconstitution

  • 500 units/vial
  • 1000 units/vial

Composition/vial

  • Exact potency of all coagulation factors and antithrombotic proteins are listed on each carton
  • Total protein: 120-280mg
  • Factor II: 380-800 units
  • Factor VII: 200-500 units
  • Factor IX: 400-620 units
  • Factor X: 500-1020 units
  • Protein C: 420-820 units
  • Protein S: 240-680 units
  • Heparin: 8-40 units
  • Antithrombin III: 4-30 units
  • Human albumin: 40-80mg
  • NaCl: 60-120mg
  • Sodium citrate: 40-80mg
  • Buffering agents (HCl, NaOH): Small amounts

Vitamin K Antagonist Reversal

Indicated for urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonists (VKA, eg, warfarin) therapy in adults with acute major bleeding or need for an urgent surgery/invasive procedure

Individualize dosing based on patient’s current pre-dose INR value and body weight

Administer vitamin K concurrently to maintain vitamin K-dependent clotting factor levels once the effects of prothrombin complex concentrate have diminished

Repeat dosing is not supported by clinical data and is not recommended

Dosing guidelines

  • 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 in product
  • 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

Example dosing calculation

  • For 80 kg patient with INR 5.0: 35 units/kg x 80 kg = 2800 units
  • For vial with actual potency of 30 units/mL Factor IX, 93 mL would be administered (2800 units ÷ 30 units/mL = 93 mL)

Dosing Considerations

Not indicated for urgent reversal of VKA anticoagulation in patients without acute major bleeding

Unlike plasma, does not require blood group typing or thawing, so it can be administered more quickly than frozen plasma

Administered in a significantly lower volume than plasma at recommended doses, providing an alternative for volume restricted patients

Administration

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

Infuse IV at rate of 0.12 mL/kg/min (~3 units/kg/min), up to maximum rate of 8.4 mL/min (~210 units/min)

Record product lot number in patient’s medical record

Safety and efficacy not established

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Interactions

Interaction Checker

and prothrombin complex concentrate, human

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Contraindicated (17)

            • alteplase

              alteplase, prothrombin complex concentrate, human. pharmacodynamic synergism. Contraindicated.

            • anti-inhibitor coagulant complex

              anti-inhibitor coagulant complex increases effects of prothrombin complex concentrate, human by pharmacodynamic synergism. Contraindicated. Coadministration increases risk of thrombosis.

            • apixaban

              apixaban, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.

            • argatroban

              argatroban, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.

            • bivalirudin

              bivalirudin, prothrombin complex concentrate, human. pharmacodynamic synergism. Contraindicated.

            • dabigatran

              dabigatran, prothrombin complex concentrate, human. pharmacodynamic synergism. Contraindicated.

            • dalteparin

              dalteparin, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.

            • enoxaparin

              enoxaparin, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.

            • Factor IX

              Factor IX increases effects of prothrombin complex concentrate, human by pharmacodynamic synergism. Contraindicated. Coadministration increases risk of thrombosis.

            • Factor IX, recombinant

              Factor IX, recombinant increases effects of prothrombin complex concentrate, human by pharmacodynamic synergism. Contraindicated. Coadministration increases risk of thrombosis.

            • Factor VIIa, recombinant

              Factor VIIa, recombinant increases effects of prothrombin complex concentrate, human by pharmacodynamic synergism. Contraindicated. Coadministration increases risk of thrombosis.

            • heparin

              heparin, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.

            • protein C concentrate

              protein C concentrate increases effects of prothrombin complex concentrate, human by pharmacodynamic synergism. Contraindicated. Coadministration increases risk of thrombosis.

            • reteplase

              reteplase, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.

            • rivaroxaban

              rivaroxaban, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.

            • tenecteplase

              tenecteplase, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.

            • tranexamic acid injection

              tranexamic acid injection increases effects of prothrombin complex concentrate, human by pharmacodynamic synergism. Contraindicated. Coadministration increases risk of thrombosis.

            Serious - Use Alternative (0)

              Monitor Closely (3)

              • dichlorphenamide

                dichlorphenamide and prothrombin complex concentrate, human both decrease serum potassium. Use Caution/Monitor.

              • emicizumab

                prothrombin complex concentrate, human, emicizumab. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Thrombotic microangiopathy reported when aPCC was coadministered with emicizumab. Patients presented with thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, without severe deficiencies in ADAMTS13 activity. Thromboembolism was also reported with coadministration.

              • Factor X, human

                Factor X, human, prothrombin complex concentrate, human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Caution is advised in patients who are receiving other plasma products that may contain Factor X, (eg, fresh frozen plasma, prothrombin complex concentrates).

              Minor (0)

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                Adverse Effects

                1-10%

                Thromboembolic events (8.7%)

                Headache (7.8%)

                Hypotension (4.9%)

                Nausea/vomiting (3.9%)

                Arthralgia (3.9%)

                Hemorrhage intracranial (2.9%)

                Mental status changes (2.9%)

                Increased BP/hypertension (2.9%)

                Skin laceration/contusion/ hematoma (2.9%)

                Respiratory distress/dyspnea/hypoxia (1.9%)

                Constipation (1.9%)

                Fluid overload (1%)

                Breath sounds, abnormal rates (1%)

                Chest pain (1%)

                Insomnia (1%)

                Postmarketing Reports

                Hypersensitivity or allergic reactions: Flushing, urticaria, tachycardia, anxiety, angioedema, wheezing, nausea, vomiting, hypotension, tachypnea, dyspnea, pulmonary edema, and bronchospasm

                Thromboembolic complications: Arterial thromboembolic events (including acute MI and arterial thrombosis), venous thromboembolic events (including PE and venous thrombosis), and DIC

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                Warnings

                Black Box Warnings

                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

                Both fatal and nonfatal arterial and venous thromboembolic complications reported during clinical trials and postmarketing surveillance; monitor for signs and symptoms

                Not studied in individuals who had a thromboembolic event, MI, DIC, CVA, TIA, unstable angina, or severe PVD within the prior 3 months before administration

                Contraindications

                Anaphylaxis or severe systemic reactions to any component

                Disseminated intravascular coagulation (DIC) Known heparin-induced thrombocytopenia (HIT)

                Cautions

                Fatal and nonfatal arterial and venous thromboembolic complications reported (see Black Box Warnings)

                Reversing VKA therapy, due to thromboembolic complications, exposes patients to thromboembolic risk of their underlying disease; once the risk of thromboembolic events outweighs the risk of acute bleeding, resumption of anticoagulation should be carefully considered following administration of Kcentra and Vitamin K

                Because of risk of thromboembolism associated with reversal of VKA, closely monitor patients for signs and symptoms of thromboembolism during and after therapy administration

                Hypersensitivity reactions reported, including flushing, urticaria, tachycardia, anxiety, angioedema, wheezing, nausea, vomiting, hypotension, tachypnea, dyspnea, pulmonary edema, and bronchospasm

                Made from human blood; risk of transmitting infectious agents (eg, viruses including hepatitis and HIV, Creutzfeldt-Jakob variant or disease)

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                Pregnancy & Lactation

                Pregnancy Category: C

                Lactation: Unknown whether distributed in human breast milk; breast feeding not advised

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

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                Pharmacology

                Mechanism of Action

                Contains vitamin-K-dependent coagulation Factors II, VII, IX, and X, together known as prothrombin complex and the antithrombotic protein C and protein S

                A dose-dependent acquired deficiency of vitamin K-dependent coagulation factors occurs during vitamin K antagonist treatment; vitamin K antagonists exert anticoagulant effects by blocking carboxylation of glutamic acid of vitamin K-dependent coagulation factors during hepatic synthesis, lowering both factor synthesis and function

                Administration of prothrombin complex rapidly increases plasma levels of coagulation factors and the anti-thrombotic proteins

                Median INR before treatment (3.0) dropped to median value of 1.2 at 30 minutes after starting infusion (in contrast to plasma which dropped to 2.4 after 30 minutes)

                Coagulation factors MOA

                • 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

                Pharmacokinetics

                AUC (IU/dL x hr)

                • Factor IX: 1490
                • Factor II: 6577
                • Factor VII: 424
                • Factor X: 6707
                • Protein C: 5276
                • Protein S: 3667

                Vd (mL/kg)

                • Factor IX: 92.4
                • Factor II: 71.0
                • Factor VII: 41.8
                • Factor X: 56.1
                • Protein C: 62.9
                • Protein S: 76.6

                Half-life, terminal (hr)

                • Factor IX: 16.7
                • Factor II: 59.7
                • Factor VII: 4.2
                • Factor X: 30.7
                • Protein C: 47.2
                • Protein S: 49.1
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                Administration

                IV Preparation

                Reconstitute vial with 20 mL of diluent provided in kit using Mix2Vial transfer set provided (see package instructions)

                Visually inspect reconstituted vial for particulate matter and discoloration; it should be colorless, clear to slightly opalescent, and free from visible particles

                Do not use solutions that are cloudy or have deposits

                For single use only, contains no preservatives

                Discard partially used vials

                When reconstituted, final concentration of drug product in Factor IX units will range between 20-31 units/mL (depending on actual potency listed on the carton)

                IV Administration

                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

                Infuse IV at rate of 0.12 mL/kg/min (~3 units/kg/min), up to maximum rate of 8.4 mL/min (~210 units/min)

                Record product lot number in patient’s medical record

                Storage

                Unopened vials

                • Stable until date indicated on package (36 months from manufacture date)
                • Store between 2-25°C [36-77°F]) in original carton and protect from light
                • Do not freeze

                Reconstituted vials

                • Use within 4 hr following reconstitution
                • Store between 2-25°C (36-36-77°F)
                • If cooled, the solution should be warmed to 20-25°C before administration
                • Do not freeze
                • Discard partially used vials
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                Images

                BRAND FORM. UNIT PRICE PILL IMAGE
                Kcentra intravenous
                -
                500 unit (400-620 unit) vial

                Copyright © 2010 First DataBank, Inc.

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                Patient Handout

                Patient Education
                human prothrombin complex (PCC) 4-factor intravenous

                NO MONOGRAPH AVAILABLE AT THIS TIME

                USES: Consult your pharmacist.

                HOW TO USE: Consult your pharmacist.

                SIDE EFFECTS: Consult your pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

                PRECAUTIONS: Consult your pharmacist.

                DRUG INTERACTIONS: Consult your pharmacist.Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

                OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

                NOTES: No monograph available at this time.

                MISSED DOSE: Consult your pharmacist.

                STORAGE: Consult your pharmacist.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

                Information last revised July 2016. Copyright(c) 2021 First Databank, Inc.

                IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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                Formulary

                FormularyPatient Discounts

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                • Access your plan list on any device – mobile or desktop.

                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                QL Quantity Limits
                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                ST Step Therapy
                Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                OR Other Restrictions
                Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.