Prothrombin complex concentrate (PCC) is a parenteral blood coagulation factor product indicated for the urgent reversal of acquired factor deficiency induced by vitamin K antagonist (VKA) therapy in adults with major bleeding or need for an urgent surgery or invasive procedure. PCC is prepared from human plasma and contains factors II, VII, IX and X, and antithrombotic proteins C and S. The potency of PCC is defined by content of factor IX. PCC is preferred over fresh frozen plasma (FFP) for emergent VKA reversal given it lacks the potential for volume overload and has less infection transmission risk compared to FFP. PCC is also recommended for emergent reversal of nonvitamin K oral anticoagulants (NOACs) if the specific NOAC antidote (e.g., idarucizumab for dabigatran, factor Xa for apixaban or rivaroxaban) is not available; effective response may be variable. Guidelines suggest it may be reasonable to consider PCC over FFP for refractory coagulopathy in cardiac surgery in select situations to reduce bleeding. Both fatal and non-fatal arterial and venous thromboembolic events have been reported with PCC in clinical trials and during postmarketing surveillance. PCC may not be suitable for patients with a thromboembolic event in the previous 3 months.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The reconstituted solution should be colorless, clear to slightly opalescent (Kcentra) or colorless to slightly blue, clear (Balfaxar), and free from visible particles. Do not use solutions that are cloudy, discolored, or have deposits.
-Inspect all components for physical integrity prior to use. Do not use products or components that appear damaged or broken.
-The actual potency per vial of Factor IX is stated on the carton. The actual potencies of Factors II, VII, IX, and X, and Proteins C and S are stated on the carton (Kcentra) or indicated as ranges (Balfaxar).
Intravenous Administration
Reconstitution
-Ensure vials of prothrombin complex concentrate (PCC) and diluent (provided) are at room temperature of 20 to 25 degrees C (68 to 77 degrees F) prior to and during reconstitution. Use aseptic technique to reconstitute.
-Open the transfer device package (i.e., Mix2Vial transfer set or Nextaro transfer device), but do not remove from the package or touch the spike.
-Place diluent vial on a flat surface and hold tightly. Grip the transfer device with the clear package and push the spike at the blue end of the transfer device firmly through the center of the stopper of the diluent vial. Do not twist while attaching.
-While holding the diluent vial, carefully remove the clear package from the transfer device by pulling vertically upwards. Leave the transfer device attached firmly to the diluent vial.
-Place the lyophilized PCC vial on flat surface and hold tightly. Invert diluent vial with transfer device attached and push the other end of the transfer device firmly through the center of the stopper of the PCC vial. Do not twist while attaching. The diluent will automatically transfer into the vial.
-Gently swirl (do not shake) the vial until fully dissolved then unscrew the transfer set into 2 pieces. Do not touch the luer lock connector.
-While the reconstituted PCC vial is upright, screw a syringe to the transfer device. Invert the system upside down; draw the concentrate into the syringe.
-Unscrew the syringe from the transfer device.
-To administer, attach the syringe to a suitable intravenous administration set.
-If patient is to receive more than 1 vial, the contents of multiple vials may be pooled together; however, use a separate unused transfer device for each product vial.
-Storage of Kcentra after reconstitution: After reconstitution, administer immediately or within 4 hours. Reconstituted Kcentra can be stored at 2 to 25 degrees C (36 to 77 degrees F). If cooled, warm to 20 to 25 degrees C (68 to 77 degrees F) prior to administration. Do not freeze. Each vial contains no preservatives and is for single use only. Discard partially used vials.
-Storage of Balfaxar after reconstitution: After reconstitution, administer immediately or within 8 hours (provided sterility is maintained). The reconstituted solution can be stored for up to 8 hours at room temperature of 20 to 25 degrees C (68 to 77 degrees F). Each vial contains no preservatives and is for single use only. Discard partially used vials.
Intermittent IV Infusion
-Do not mix with other medicinal products; administer through a separate infusion line. The infusion line may be flushed with normal saline before and after administration.
-Administer at room temperature using aseptic technique.
-Administer by intravenous infusion at a rate of 0.12 mL/kg/minute (approximately 3 units/kg/minute), up to a maximum rate of 8.4 mL/minute (approximately 210 units/minute).
-Do not allow blood to enter the syringe as there is a possibility of fibrin clot formation.
Prothrombin complex concentrate (PCC) has been associated with the development of fatal and non-fatal arterial (including acute myocardial infarction and arterial thrombosis) and venous (including pulmonary embolism and venous thrombosis) thromboembolism and disseminated intravascular coagulation (DIC). In clinical trials of patients with acute major bleeding or needing an urgent surgery/invasive procedure, a possible thromboembolic event (TEE) was reported in 13 patients (6.8%) in the PCC group compared with 14 subjects (7.1%) in the plasma group. Stroke was reported in 2 patients (1.9%) in the acute major bleeding study and in 1 patient (1.1%) in the urgent surgery/invasive procedure study in the PCC groups while no patient in the plasma groups experienced a stroke. In the major bleeding study, 1 patient (1%) in the PCC group experienced deep vein thrombosis (DVT) as compared to none in the plasma group. In the urgent surgery/invasive procedure study, DVT was reported in 1 patient (1.1%) in the PCC group and in 1 patient (1.1%) in the plasma group. A suspected pulmonary embolism was reported in 1 patient after a second dose of PCC in a single-arm clinical trial of patients (n = 43) requiring urgent reversal of vitamin K antagonist due to acute bleeding or the need for an urgent surgical/invasive procedure. Other TEEs reported at an incidence of approximately 1% include calf venous thrombosis, radial vein venous thrombosis, microthrombosis of toes, and fistula clot. Thromboembolic events were also observed in a randomized, controlled, non-inferiority trial comparing PPC brand Kcentra to the biosimilar product Balfaxar. In this trial, 3 Balfaxar recipients (2.9%) experienced 4 TEEs, including cerebral infarction or stroke, pulmonary embolism, unstable angina, and myocardial infarction. One of these events (unstable angina) was assessed as at least possibly related to Balfaxar. There were no TEEs observed in the Kcentra treatment arm. Deaths were reported in 4 patients who received Balfaxar (3.8%) between 22 and 45 days post surgery, with 1 additional death occurring on day 47 just after completion of the study reporting period. In the Kcentra group, 1 death (1%) occurred 10 days after treatment. None of the deaths were considered to be related to the study treatments.
Hypersensitivity reactions including flushing, urticaria, sinus tachycardia (4.7%), anxiety, angioedema, wheezing, nausea (6.3%), vomiting (6.3%), hypotension (7.3%), tachypnea, dyspnea (3.7%), pulmonary edema (1.6%), and bronchospasm have been observed with prothrombin complex concentrate (PCC). During postmarketing use, cases of rash, pruritus, respiratory failure, anaphylactic shock, and anaphylactic or anaphylactoid reactions have been observed. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established. Immediately discontinue PCC and institute appropriate treatment if a severe allergic reaction or anaphylactoid type reactions occur.
Prothrombin complex concentrate (PCC) is made from human blood, and therefore may carry a risk of transmitting infectious agents, including viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease agent. There is also the possibility that unknown infectious agents may be present in such products. Manufacturing processes are designed to reduce the risk of transmitting infection; however, such products may still potentially transmit disease. Reports of suspected virus transmission of hepatitis A, B, C, and HIV were generally confounded by concomitant administration of blood/blood components or other plasma-derived products. No causal relationship to PCC administration was established for any of these reports since introduction of a virus filtration step in 1996. Any infection thought by a physician to have been possibly transmitted by PCC should be reported by the physician or other healthcare provider to the manufacturer or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
In clinical trials comparing prothrombin complex concentrate (PCC) to plasma in patients with acute major bleeding or needing an urgent surgery/invasive procedure, atrial fibrillation was reported more frequently with PCC than with plasma (4.2% vs. 3%). Fluid overload, including congestive heart failure, occurred less frequently with PCC than with plasma (2.6% vs. 8.1%). In another trial comparing PPC brand Kcentra to the biosimilar product Balfaxar, hypertension was noted in 4.9% of patients who received Kcentra and none of the patients in the Balfaxar group. Other cardiovascular adverse events observed during postmarketing use include bradycardia, sinus tachycardia, cardiac arrest, circulatory collapse, and hypotension. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
Headache was reported by 7.3% of patients receiving prothrombin complex concentrate during clinical trials. Other neurologic adverse events reported during postmarketing use of the drug include tremor and paresthesias. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
In clinical trials of patients with acute major bleeding or needing urgent surgery/invasive procedure, insomnia was reported more frequently with prothrombin complex concentrate than with plasma (4.7% vs. 3%).
Hypokalemia was reported in 4.7% of prothrombin complex concentrate-treated patients compared to 7.1% of plasma-treated patients in clinical trials of patients with acute major bleeding or needing urgent surgery/invasive procedure.
In clinical trials of patients with acute major bleeding or needing an urgent surgery or invasive procedure, anemia was reported less frequently with prothrombin complex concentrate than with plasma (5.7% to 5.8% vs. 8.1%).
In clinical trials of patients with acute major bleeding or needing urgent surgery/invasive procedures, pleural effusion (4.2% vs. 1.5%) was reported more frequently with prothrombin complex concentrate (PCC) than with plasma. Respiratory distress/dyspnea/hypoxia (3.7% vs. 5.1%) and pulmonary edema (1.6% vs. 5.1%) were reported less frequently with PCC than with plasma.
The safety of prothrombin complex concentrate (PPC) brand Kcentra was compared to the biosimilar product Balfaxar in a randomized, controlled, non-inferiority trial. In this trial, the following adverse reactions were reported in more than 3% of patients receiving either Kcentra or Balfaxar: abdominal pain (4.9% Kcentra vs. 2.9% Balfaxar), asthenia (17.5% vs. 12.4%), catheter site related reactions (1.9% vs. 3.8%), increased body temperature (3.9% vs. 0%), and dysuria (1.9% vs. 4.8%). Additionally, the following procedural complications were noted: postoperative wound complications (14.6% vs. 14.3%), procedural pain (48.5% vs. 47.6%), procedural vomiting (0% vs. 3.8%), and suture related complications (3.9% vs. 1.9%).
Fever and chills have been reported during postmarketing use of prothrombin complex concentrate (PPC). Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
Prothrombin complex concentrate is contraindicated in patients with known anaphylactic or severe systemic reactions to prothrombin complex concentrate, heparin hypersensitivity, plasma protein hypersensitivity (i.e., proteins C and S, antithrombin III), hypersensitivity to coagulation factors II, VII, IX, and X, and human albumin hypersensitivity.
Prothrombin complex concentrate (PCC) is contraindicated in patients with a history of disseminated intravascular coagulation (DIC). Reversing vitamin K antagonist (VKA) therapy with PCC exposes patients to the thromboembolic risk of their underlying disease. Weigh the benefits of reversing VKA therapy against the potential risks of thromboembolism, especially in patients with a history of thromboembolic disease. Because of the increased risk of thromboembolic events, PCC may not be suitable for use in patients with a thromboembolic disease event in the previous 3 months. Patients with a thromboembolic event, myocardial infarction, DIC, stroke, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within the previous 3 months were excluded from clinical trials of PCC. Monitor for signs and symptoms of thromboembolism during and after administration of PCC in patients with a history of coronary artery disease, hepatic disease, or patients at risk of thromboembolic events or DIC. Carefully consider resuming anticoagulation after administration of PCC once the risk of thromboembolic events outweighs the risk of acute bleeding.
Prothrombin complex concentrate contains heparin and is therefore contraindicated in patients with known heparin-induced thrombocytopenia (HIT).
There are no data regarding the use of prothrombin complex concentrate (PCC) during pregnancy. It is not known whether PCC can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Administer PCC to a pregnant woman only if clearly needed.
There are no data regarding the excretion of prothrombin complex concentrate (PCC) in human milk, the effect on the breast-fed infant, or the effects on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated maternal condition.
As with other products prepared from human blood or plasma, the possibility of transmission of viral or bacterial infections exists in patients receiving prothrombin complex concentrate. Screening plasma donors for prior exposure to certain viruses, testing for the presence of viruses, and inactivating or removing viruses has reduced the risk of transmission of infectious agents. Additionally, the manufacturing processes are designed to reduce the risk of transmitting viral infection; however, none of the processes are completely effective. There is also the possibility that unknown infectious agents may be present.
The prothrombin complex concentrate biosimilar product, Balfaxar, is contraindicated for use in patients with IgA deficiency with known antibodies against IgA. Administration of blood products that contain IgA to these patients could result in severe hypersensitivity reactions.
For vitamin K antagonist reversal in persons with acute major bleeding or need for urgent surgery or invasive procedure:
NOTE: Prothrombin complex concentrate has been designated an orphan drug by the FDA for this indication.
-for vitamin K antagonist reversal in persons with an INR of 2 or more and need for urgent surgery or invasive procedure:
Intravenous dosage:
Adults: 25 units factor IX/kg (Max: 2,500 units factor IX) IV for pre-treatment INR 2 to 3.9; 35 units factor IX/kg (Max: 3,500 units factor IX) IV for pre-treatment INR 4 to 6; and 50 units factor IX/kg (Max: 5,000 units factor IX) IV for pre-treatment INR more than 6. Because coagulation factor concentrations may be unstable in patients with urgent need for surgery or other invasive procedure, measure INR prior to treatment and close to the time of dosing. Administer vitamin K concurrently to maintain vitamin K-dependent clotting factor concentrations once the effects of prothrombin complex concentrate have diminished. Repeat dosing is not recommended.
-for vitamin K antagonist reversal in persons with an INR of 2 or more and acute non-intracranial major bleeding:
Intravenous dosage (Kcentra):
Adults: 25 units factor IX/kg (Max: 2,500 units factor IX) IV for pre-treatment INR 2 to 3.9; 35 units factor IX/kg (Max: 3,500 units factor IX) IV for pre-treatment INR 4 to 6; and 50 units factor IX/kg (Max: 5,000 units factor IX) IV for pre-treatment INR more than 6. Because coagulation factor concentrations may be unstable in patients with acute major bleeding, measure INR prior to treatment and close to the time of dosing. Administer vitamin K concurrently to maintain vitamin K-dependent clotting factor concentrations once the effects of prothrombin complex concentrate have diminished. Repeat dosing is not recommended.
Intravenous dosage (Kcentra fixed dose*):
Adults: 1,000 units factor IX IV for pre-treatment INR of 2 or more. Because coagulation factor concentrations may be unstable in patients with acute major bleeding, measure INR prior to treatment and close to the time of dosing. Administer vitamin K concurrently to maintain vitamin K-dependent clotting factor concentrations once the effects of prothrombin complex concentrate have diminished. Repeat dosing is not recommended.
-for vitamin K antagonist reversal in persons with an INR of 2 or more and acute intracranial major bleeding:
Intravenous dosage (Kcentra):
Adults: 25 units factor IX/kg (Max: 2,500 units factor IX) IV for pre-treatment INR 2 to 3.9; 35 units factor IX/kg (Max: 3,500 units factor IX) IV for pre-treatment INR 4 to 6; and 50 units factor IX/kg (Max: 5,000 units factor IX) IV for pre-treatment INR more than 6. Because coagulation factor concentrations may be unstable in patients with acute major bleeding, measure INR prior to treatment and close to the time of dosing. Administer vitamin K concurrently to maintain vitamin K-dependent clotting factor concentrations once the effects of prothrombin complex concentrate have diminished. Repeat dosing is not recommended.
Intravenous dosage (Kcentra fixed dose*):
Adults: 1,500 units factor IX IV for pre-treatment INR of 2 or more. Because coagulation factor concentrations may be unstable in patients with acute major bleeding, measure INR prior to treatment and close to the time of dosing. Administer vitamin K concurrently to maintain vitamin K-dependent clotting factor concentrations once the effects of prothrombin complex concentrate have diminished. Repeat dosing is not recommended.
-for vitamin K antagonist reversal in persons with an INR 1.4 to 1.9 and acute intracranial major bleeding*:
Intravenous dosage (Kcentra):
Adults: 25 units factor IX/kg (Max: 2,500 units factor IX) IV for pre-treatment INR 1.4 to 1.9. Because coagulation factor concentrations may be unstable in patients with acute major bleeding, measure INR prior to treatment and close to the time of dosing. Administer vitamin K concurrently to maintain vitamin K-dependent clotting factor concentrations once the effects of prothrombin complex concentrate have diminished. Repeat dosing is not recommended.
For direct thrombin inhibitor reversal*, including dabigatran reversal*, in persons with acute major bleeding or need for urgent surgery or invasive procedure:
Intravenous dosage:
Adults: 50 units factor IX/kg (Max: 4,000 units) IV as a single dose as an alternative.
For direct oral anticoagulant reversal*, including apixaban reversal*, edoxaban reversal*, and rivaroxaban reversal*, in persons with acute major bleeding or need for urgent surgery or invasive procedure:
Intravenous dosage (weight-based dose):
Adults: 50 units factor IX/kg IV as a single dose as an alternative.
Maximum Dosage Limits:
-Adults
Individualize dosage based on pre-treatment INR and body weight. In patients with pre-treatment INR 2 to 3.9, do not exceed 2,500 units of factor IX; pre-treatment INR 4 to 6, do not exceed 3,500 units factor IX; pre-treatment INR greater than 6, do not exceed 5,000 units factor IX. For patients weighing more than 100 kg, do not exceed maximum dose.
-Geriatric
Individualize dosage based on pre-treatment INR and body weight. In patients with pre-treatment INR 2 to 3.9, do not exceed 2,500 units of factor IX; pre-treatment INR 4 to 6, do not exceed 3,500 units factor IX; pre-treatment INR greater than 6, do not exceed 5,000 units factor IX. For patients weighing more than 100 kg, do not exceed maximum dose.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Alteplase: (Major) The concomitant use of protein C concentrate and alteplase, tPA may further increase the risk of bleeding from tPA. In clinical trials, several episodes of bleeding were reported. Concurrent anticoagulant medication may have been responsible for these bleeding episodes.
Aminocaproic Acid: (Major) In general, aminocaproic acid should not be administered simultaneously with factor IX complex, factor IX concentrates, factor IX Fc fusion protein, recombinant, and factor IX albumin fusion protein, recombinant due to the increased risk of thrombosis. Some hematologists recommend separating administration of aminocaproic acid from these clotting factor complexes by 8 hours. Aminocaproic acid has been used concurrently with human factor IX complexes or anti-inhibitor coagulant complex perioperatively in hemophiliac patients. The risk of developing thrombosis, however, is increased. In rare instances, thrombosis leading to acute myocardial infarction or gangrene has been reported in patients with hemophilia receiving combination therapy with factor IX concentrate and aminocaproic acid. Concomitant administration of aminocaproic acid with purer formulations of factor IX may also result in an increased risk of thrombosis.
Apixaban: (Contraindicated) The actions of factor X are likely to be counteracted by direct and indirect factor Xa inhibitors such as apixaban, edoxaban, rivaroxaban, and fondaparinux.
Betrixaban: (Major) The actions of factor X are likely to be counteracted by factor Xa inhibitors such as betrixaban.
Edoxaban: (Major) The actions of factor X are likely to be counteracted by direct and indirect factor Xa inhibitors such as apixaban, edoxaban, rivaroxaban, and fondaparinux.
Fondaparinux: (Major) The actions of factor X are likely to be counteracted by direct and indirect factor Xa inhibitors such as apixaban, edoxaban, rivaroxaban, and fondaparinux.
Protein C Concentrate, Human: (Major) Use factor X cautiously with other plasma products that may contain factor X (e.g., fresh frozen plasma, prothrombin complex concentrate, human).
Rivaroxaban: (Major) The actions of factor X are likely to be counteracted by factor Xa inhibitors such as rivaroxaban.
Tranexamic Acid: (Major) Tranexamic acid should not be administered concomitantly with factor IX complex, Factor IX Fc fusion protein, recombinant, or Factor IX concentrates, due to the increased risk of thrombosis.
Warfarin: (Major) Concomitant administration of vitamin K antagonists (coumarin anticoagulants such as warfarin) and protein C concentrate should be done with close monitoring. Upon initiation of vitamin K antagonists, patients may experience a transient hypercoagulable state before the desired anticoagulant effect becomes apparent. This transient effect may occur because protein C also is a vitamin K-dependent plasma protein with a much shorter half-life than other vitamin K-dependent proteins such as Factor II, IX and X. Upon initiation of treatment, the activity of protein C is more rapidly suppressed than that of the procoagulant factors. Therefore, if a patient is switched to oral anticoagulants, protein C replacement must be continued until stable anticoagulation is established. In addition, patients with severe congenital protein C deficiency are at a higher risk of developing warfarin-induced skin necrosis. Monitor patients closely during treatment.
The coagulation cascade is a series of procoagulant and antithrombotic reactions involving the activation of zymogens. The vascular endothelium provides a protective barrier separating blood cells and plasma factors from subendothelial vessel wall reactive adhesive proteins and tissue factor; the proteins trigger blood coagulation. During vitamin K antagonist therapy, a dose-dependent acquired deficiency of the vitamin K-dependent coagulation factors occurs. Administration of prothrombin complex concentrate rapidly increases plasma concentrations of vitamin K-dependent coagulation factors II, VII, IX, and X and the antithrombotic proteins C and S.
-Factor II: Factor II is converted to thrombin by factor Xa in the presence of calcium, factor V, and phospholipids. Thrombin converts fibrinogen to fibrin for clot formation.
-Factor VII: Factor VII is converted to factor VIIa by splitting of an internal peptide link. The factor VIIa-tissue factor complex activates factor IX and initiates the primary coagulation pathway by activating factor X in the presence of phospholipids and calcium ions.
-Factor IX: Factor IX may be activated by factor VIIa-tissue factor complex and by factor XIa. In the presence of factor VIIIa, factor IXa activates factor X to factor Xa.
-Factor X: Factor X activation involves the cleavage of a peptide bond by the factor VIIIa-factor IXa complex or the tissue factor-factor VIIa complex. Factor Xa forms a complex with factor Va that converts prothrombin to thrombin in the presence of phospholipids and calcium ions.
-Protein C: Protein C is activated by thrombin then exerts an antithrombotic effect by inhibiting factor Va and factor VIIIa leading to a decrease in thrombin formation and has indirect profibrinolytic activity by inhibiting plasminogen activator inhibitor-1.
-Protein S: Protein S exists in a free form (40%) and in a complex with C4b-binding protein (60%). The free form of protein S functions as a cofactor for activated protein C in the inactivation of factor Va and factor VIIIa, leading to antithrombotic activity.
Prothrombin complex concentrate (PCC) is administered intravenously. PCC is distributed, metabolized, and excreted in the same manner as the endogenous proteins; however, the following pharmacokinetic parameters of PCC were obtained in healthy subjects and may not be applicable to patients with acute major bleeding and elevated INR due to vitamin K antagonist therapy. Factor II had the longest elimination half-life (60.4 hours) and factor VII had the shortest (5 hours) in healthy subjects. The elimination half-life for factors IX, X, and proteins C and S are as follows: factor IX: 42.4 hours, factor X: 31.8 hours, protein C: 49.6 hours, and protein S: 50.4 hours. In a trial of 98 anticoagulated patients with acute major bleeding, the median INR was 3.9 prior to PCC, and 30 minutes after the start of PCC infusion, the median INR was 1.2. In contrast, patients who received plasma instead of PCC (n=104), the median INR decreased from 3.6 to 2.4 after 30 minutes from start of plasma infusion. In a trial of 105 patients requiring urgent surgery, administration of PCC dropped the median baseline INR from 3.05 (range: 2 to 21.1) to 1.3 (range: 1 to 3.1) at 30 minutes after end of the infusion. After 24 hours, the median INR was 1.25 (range 0.8 to 3.4). The relationship between these INR values and clinical hemostasis in patients has not been established.
Affected cytochrome P450 isoenzymes: none
-Route-Specific Pharmacokinetics
Intravenous Route
In healthy subjects, a single intravenous infusion of prothrombin complex concentrate resulted in a rapid and sustained increase in the plasma concentrations of factors II, VII, IX, and X as well as proteins C and S. Bioavailability is proportional to the dose administered.