prothrombin complex concentrate, human (Rx)

Brand and Other Names:Kcentra
  • Print

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
more...

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

Next:

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

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            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

            Previous
            Next:

            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)

            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)

            Previous
            Next:

            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.

            more...
            Previous
            Next:

            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
            Previous
            Next:

            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
            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • 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.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous