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Kcentra(人凝血酶原复合物)获美国FDA批准用于紧急逆转成人抗凝治疗时出现的大出血症状
Units refer to International Units. Dose is based on body weight up to but not exceeding 100 kg. For patients weighing more than 100 kg, maximum dose should not be exceeded. Example dosing calculation for 80 kg patient For example, an 80 kg patient with a baseline of INR of 5.0, the dose would be 2,800 Factor IX units of Kcentra, calculated as follows based on INR range of 4–6, see Table 1: * For a vial with an actual potency of 30 units/mL Factor IX, 93 mL would be given (2,800 U/30 U per mL = 93 mL). 35 units of Factor IX/kg×80 kg = 2,800 units of Factor IX required* Monitor INR and clinical response during and after treatment. In clinical trials, Kcentra decreased the INR to ≤ 1.3 within 30 minutes in most subjects. The relationship between this or other INR values and clinical hemostasis in patients has not been established [see Clinical Studies (14)]. 2.2 Preparation and Reconstitution Reconstitute using aseptic technique with 20 mL (500 U kit) or 40 mL (1000 U kit) of diluent provided with the kit. Visually inspect parenteral drug products for particulate matter and discoloration prior to administration whenever solution and container permit. Reconstituted Kcentra solution should be colorless, clear to slightly opalescent, and free from visible particles. Do not use solutions that are cloudy or have deposits. Kcentra is for single use only. Contains no preservatives. Discard partially used vials. The procedures provided in Table 2 are general guidelines for the preparation and reconstitution of Kcentra. Reconstitute at room temperature as follows: Table 2: Kcentra Reconstitution Instructions 1. Ensure that the Kcentra vial and diluent vial are at room temperature. Prepare and administer using aseptic technique 2. Place the Kcentra vial, diluent vial, and Mix2Vial ? transfer set on a flat surface. 3. Remove Kcentra and diluent vial flip caps. Wipe the stoppers with the alcohol swab provided and allow to dry prior to opening the Mix2Vial transfer set package. 4. Open the Mix2Vial transfer set package by peeling away the lid. [ Fig. 1] Leave the Mix2Vial transfer set in the clear package.
Includes orthostatic hypotension, hypotension, and hemorrhagic shock Includes anemia, hemoglobin decreased, and hematocrit decreased Serious adverse reactions in subjects receiving Kcentra in both RCTs included ischemic cerebrovascular accident (stroke), DVT, thrombosis, and venous insufficiency. Serious adverse reactions in both RCTs for plasma included myocardial ischemia, myocardial infarction, fluid overload, embolic cerebral infarction, pulmonary edema, respiratory failure, and DVT. There were a total of 10 subjects (9.7%) who died in the Kcentra group (1 additional death occurred on day 46 just after completion of the study reporting period) and 5 (4.6%) who died in the plasma group in the plasma-controlled RCT in acute major bleeding. The 95% confidence interval for the Kcentra minus plasma between-group difference in deaths ranged from -2.7% to 13.5%. From the plasma-controlled RCT in urgent surgery/invasive procedures, there were a total of 3 subjects (3.4%) who died in the Kcentra group (1 additional death occurred on day 48 after completion of the study reporting period) and 8 (9.1%) who died in the Plasma group. The 95% confidence interval for the Kcentra minus plasma between-group difference in deaths in this trial ranged from -14.6% to 2.7%. One death in the Kcentra group in the RCT in Acute Major Bleeding and one death in the plasma group in the RCT in urgent surgery/invasive procedures were considered possibly related to study treatment according to an assessment of masked data by an independent safety adjudication board. No factors common to all deaths were identified, except for the frequent findings of a high comorbidity burden, advanced age, and death after being placed on comfort care. Although, a greater proportion of subjects in the RCT in acute major bleeding than in the RCT in surgery/invasive procedure received the highest two recommended doses of Kcentra because more subjects in the trial in acute major bleeding had a baseline INR in the ranges of 4–6 and > 6.0, an analysis of deaths and factor levels in subjects with major bleeding revealed that subjects who died had similar median factor levels to subjects that did not die. Additionally, outliers with supraphysiologic factor levels did not have a mortality rate out of proportion to the overall population. Fluid Overload There were 9 subjects (4.7%, all non-related by investigator assessment) in the Kcentra group who experienced fluid overload in the plasma-controlled RCTs in acute major bleeding and urgent surgery/invasive procedures and 25 (12.7%, 13 events related by investigator assessment) who had fluid overload in the plasma group. The 95% confidence interval for the Kcentra minus Plasma between-group difference in fluid overload event incidence ranged from -14.1% to -2.0%. Subgroup analyses of the RCTs in acute major bleeding and urgent surgery/invasive procedures according to whether subjects with fluid overload events had a prior history of congestive heart failure are presented in Table 4. Table 4: Subjects with Fluid Overload Events by Prior History of Congestive Heart Failure in RCTs
In RCTs, there were 13 subjects (6.8%) in the Kcentra group who experienced possible thromboembolic events (TEEs) and 14 (7.1%) who had TEEs in the plasma group. The incidence of thromboembolic (TE) adverse reactions assessed as at least possibly related to study treatment by the Investigator or, in the case of serious thromboembolic events, the blinded safety adjudication board (SAB) was 9 (4.7%) in the Kcentra group and 7 (3.6%) in the plasma group. When also considering the events which began during or within 72 hours of test product infusion, the incidence was 9 (4.7%) in the Kcentra group and 8 (4.1%) in the plasma group. TE events observed in the acute major bleeding and the urgent surgery/invasive procedures RCTs are shown in Table 5. Table 5: Adverse Reactions (TEEs only) Following Kcentra or Plasma Administration in RCTs
Subgroup analyses of the RCTs according to whether subjects with thromboembolic events had a prior history of a thromboembolic event are presented in Table 6. Table 6: Subjects with Thromboembolic Events by Prior History of TE Event in RCTs
? History of prior TE event greater than 3 months from study entry (TE event within 3 months not studied). The European Bleeding and Surgical Study: In a prospective, open label, single-arm, multicenter safety and efficacy trial, 17 subjects who required urgent reversal of VKA due to acute bleeding were enrolled and 26 subjects who required urgent reversal of Vitamin K antagonist due to the need for an urgent surgical/invasive procedure were enrolled, all were treated with Kcentra. Subjects ranged in age from 22 years to 85 years. Serious adverse reactions considered possibly related to Kcentra included a suspected pulmonary embolism which occurred in one subject following a second dose of Kcentra. A single non-fatal TE event occurred in another Kcentra-treated subject in that trial. 6.2 Postmarketing Experience No adverse reactions other than those addressed in Warnings And Precautions (5) and Adverse Reactions (6) have been observed in the postmarketing use of Kcentra outside the US since 1996. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C. Animal reproduction studies have not been conducted with Kcentra. It is also not known whether Kcentra can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Kcentra should be prescribed for a pregnant woman only if clearly needed. 8.2 Labor and Delivery Kcentra has not been studied for use during labor and delivery. Safety and effectiveness in labor and delivery have not been established. 8.3 Nursing Mothers It is not known whether Kcentra is excreted in human milk. Because many drugs are excreted in human milk, use Kcentra only if clearly needed when treating a nursing woman. 8.4 Pediatric Use The safety and efficacy of Kcentra in the pediatric population has not been studied. 8.5 Geriatric Use Of the total number of subjects (431) with acute major bleeding or with the need for an urgent surgery/invasive procedure treated to reverse VKA anticoagulation in three clinical studies, 66% were 65 years old or greater and 39% were 75 years old or greater. There were no clinically significant differences between the safety profile of Kcentra and plasma in any age group. 8.6 Congenital Factor Deficiencies Kcentra has not been studied in patients with congenital factor deficiencies. 11 DESCRIPTION Kcentra is a purified, heat-treated, nanofiltered and lyophilized non-activated four-factor Prothrombin Complex Concentrate (Human) prepared from human U.S. Source Plasma (21 CFR 640.60). It contains the Vitamin K dependent Coagulation Factors II, VII, IX and X, and the antithrombotic Proteins C and S. Factor IX is the lead factor for the potency of the preparation as stated on the vial label. The excipients are human antithrombin III, heparin, human albumin, sodium chloride, and sodium citrate. Kcentra is sterile, pyrogen-free, and does not contain preservatives. The product contents are shown in Table 7 and listed as ranges for the blood coagulation factors. Table 7: Composition per Vial of Kcentra *
All plasma used in the manufacture of Kcentra is obtained from US donors and is tested using serological assays for hepatitis B surface antigen and antibodies to HIV-1/2 and HCV. The plasma is tested with Nucleic Acid Testing (NAT) for HCV, HIV-1, HAV, and HBV, and found to be non-reactive (negative), and the plasma is also tested by NAT for human parvovirus B19 (B19V) in order to exclude donations with high titers. The limit for B19V in the fractionation pool is set not to exceed 104 units of B19V DNA per mL. Only plasma that passed virus screening is used for production. The Kcentra manufacturing process includes various steps, which contribute towards the reduction/ inactivation of viruses. Kcentra is manufactured from cryo-depleted plasma that is adsorbed via ion exchange chromatography, heat treated in aqueous solution for 10 hours at 60°C, precipitated, adsorbed to calcium phosphate, virus filtered, and lyophilized. Manufacturing steps were independently validated in a series of in-vitro experiments for their virus inactivation / reduction capacity for both enveloped and non-enveloped viruses. Table 8 shows the virus clearance during the manufacturing process for Kcentra, expressed as the mean log10 reduction factor. Table 8: Mean Virus Reduction Factors [log10] of Kcentra
BVDV Bovine viral diarrhea virus, model for HCV PRV Pseudorabies virus, a model for large enveloped DNA viruses WNV West Nile virus HAV Hepatitis A virus CPV Canine parvovirus, model for B19V n.d. not determined * Reduction factor below 1 log 10 was not considered in calculating the overall virus reduction. Studies using human parvovirus B19, which are considered experimental in nature, have demonstrated a virus reduction factor of 3.5 log 10 by heat treatment. 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Kcentra contains the Vitamin K-dependent coagulation Factors II (FII), VII (FVII), IX (FIX), and X (FX), together known as the Prothrombin Complex, and the antithrombotic Protein C and Protein S. A dose-dependent acquired deficiency of the Vitamin K-dependent coagulation factors occurs during Vitamin K antagonist treatment. Vitamin K antagonists exert anticoagulant effects by blocking carboxylation of glutamic acid residues of the Vitamin K-dependent coagulation factors during hepatic synthesis, lowering both factor synthesis and function. The administration of Kcentra rapidly increases plasma levels of the Vitamin K-dependent coagulation Factors II, VII, IX, and X as well as the antithrombotic Proteins C and S. Coagulation Factor II Factor II (prothrombin) is converted to thrombin by activated FX (FXa) in the presence of Ca2+, FV, and phospholipids. Coagulation Factor VII Factor VII (proconvertin) is converted to the activated form (FVIIa) by splitting of an internal peptide link. The FVIIa-TF complex activates Factor IX and initiates the primary coagulation pathway by activating FX in the presence of phospholipids and calcium ions. Coagulation Factor IX 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. Coagulation Factor X 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 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 Protein S exists in a free form (40%) and in a complex with C4b-binding protein (60%). Protein S (free form) functions as a cofactor for activated Protein C in the inactivation of FVa and FVIIIa, leading to antithrombotic activity. 12.2 Pharmacodynamics International Normalized Ratio (INR) In the plasma-controlled RCT in acute major bleeding, the INR was determined at varying time points after the start or end of infusion, depending upon study design. The median INR was above 3.0 prior to the infusion and dropped to a median value of 1.20 by the 30 minute time point after start of Kcentra infusion. By contrast, the median value for plasma was 2.4 at 30 minutes after the start of infusion. The INR differences between Kcentra and plasma were statistically significant in randomized plasma-controlled trial in bleeding up to 12 hours after start of infusion [see Table 9]. The relationship between these or other INR values and clinical hemostasis in patients has not been established [see Clinical Studies (14)]. Table 9: Median INR (Min-Max) after Start of Infusion in RCTs
* Statistically significant difference compared to plasma by 2-sided Wilcoxon test 12.3 Pharmacokinetics Fifteen healthy subjects received 50 units/kg of Kcentra. No subjects were receiving VKA therapy or were experiencing acute bleeding. A single intravenous Kcentra infusion produced a rapid and sustained increase in plasma concentration of Factors II, VII, IX and X as well as Proteins C and S. The PK analysis [see Table 10] shows that factor II had the longest half-life (59.7 hours) and factor VII the shortest (4.2 hours) in healthy subjects. PK parameters obtained from data derived from the study of healthy subjects may not be directly applicable to patients with INR elevation due to VKA anticoagulation therapy. Table 10: Vitamin K-Dependent Coagulation Factor Pharmacokinetics after a Single Kcentra Infusion in Healthy Subjects (n=15) Mean (SD)*
MRT: Mean Residence Time Vd ss: Volume of Distribution at steady state The mean in vivo recovery (IVR) of infused factors was calculated in subjects who received Kcentra. The IVR is the increase in measurable factor levels in plasma (units/dL) that may be expected following an infusion of factors (units/kg) administered as a dose of Kcentra. The in vivo recovery ranged from 1.15 (Factor IX) to 2.81 (Protein S) [see Table 11]. Table 11: In vivo Recovery in RCTs*
CI: Confidence Interval 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals to evaluate the carcinogenic potential of Kcentra, or studies to determine the effects of Kcentra on genotoxicity or fertility have not been performed. An assessment of the carcinogenic potential of Kcentra was completed and suggests minimal carcinogenic risk from product use. 14 CLINICAL STUDIES Acute Major Bleeding RCT: The efficacy of Kcentra has been evaluated in a prospective, open-label, (blinded assessor), active-controlled, non-inferiority, multicenter RCT in subjects who had been treated with VKA therapy and who required urgent replacement of their Vitamin K-dependent clotting factors to treat acute major bleeding. A total of 216 subjects with acquired coagulation factor deficiency due to oral Vitamin K antagonist therapy were randomized to a single dose of Kcentra or plasma. Two hundred twelve (212) subjects received Kcentra or plasma for acute major bleeding in the setting of a baseline INR ≥ 2.0 and recent use of a VKA anticoagulant. The doses of Kcentra (25 units/kg, 35 units/kg, or 50 units/kg) based on nominal Factor IX content and plasma (10 mL/kg, 12 mL/kg, or 15 mL/kg) were calculated according to the subject's baseline INR (2–< 4, 4–6, > 6, respectively). The observation period lasted for 90 days after the infusion of Kcentra or plasma. The modified efficacy (ITT-E) population for Kcentra included 98 subjects and for plasma included 104 subjects. Additionally, intravenous Vitamin K was administered. The efficacy endpoint was hemostatic efficacy for the time period from the start of infusion of Kcentra or plasma until 24 hours. Efficacy was adjudicated as "effective" or "not effective" by a blinded, independent Endpoint Adjudication Board for all subjects who received study product. Criteria for effective hemostasis were based upon standard clinical assessments including vital signs, hemoglobin measurements, and CT assessments at pre-defined time points, as relevant to the type of bleeding (i.e., gastrointestinal, intracranial hemorrhage, visible, musculoskeletal, etc.). The proportion of subjects with effective hemostasis was 72.4% in the Kcentra group and 65.4% in the plasma group. The lower limit of the 95% confidence interval (CI) for the difference in proportions of Kcentra minus plasma was -5.8%, which exceeded -10% and thereby demonstrated the non-inferiority of Kcentra versus plasma (the study's primary objective) [see Table 12]. Because the lower limit of the CI was not greater than zero, the prospectively defined criterion for superiority of Kcentra for hemostatic efficacy (a secondary objective) was not met. Table 12: Rating of Hemostatic Efficacy in Subjects with Acute Major Bleeding
* Kcentra non-inferior to plasma if lower limit of 95% CI > –10%; Kcentra superior to plasma if lower limit of 95% CI > 0. Results of a post-hoc analysis of hemostatic efficacy stratified by actual dose of Kcentra or plasma administered in the acute major bleeding RCT are presented in Table 13. Table 13: Rating of Hemostatic Efficacy Stratified by Actual Dose of Kcentra or Plasma (Number and % of Subjects rated "Effective" in Acute Major Bleeding RCT
An additional endpoint was the reduction of INR to ≤ 1.3 at 30 minutes after the end of infusion of Kcentra or plasma for all subjects that received study product. The proportion of subjects with this decrease in INR was 62.2% in the Kcentra group and 9.6% in the plasma group. The 95% confidence interval for the difference in proportions of Kcentra minus plasma was 39.4% to 65.9%. The lower limit of the 95% CI of 39.4% demonstrated superiority of Kcentra versus plasma for this endpoint [see Table 14]. Table 14: Decrease of INR (1.3 or Less at 30 Minutes after End of Infusion) in Acute Major Bleeding RCT
* Kcentra non-inferior to plasma if lower limit of 95% CI > –10%; Kcentra superior to plasma if lower limit of 95% CI > 0. Urgent Surgery/Invasive Procedure RCT: The efficacy of Kcentra has been evaluated in a prospective, open-label, active-controlled, non-inferiority, multicenter RCT in subjects 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. A total of 181 subjects with acquired coagulation factor deficiency due to oral Vitamin K antagonist therapy were randomized to a single dose of Kcentra or plasma. One hundred seventy-six (176) subjects received Kcentra or plasma 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 doses of Kcentra (25 units/kg, 35 units/kg, or 50 units/kg) based on nominal Factor IX content and plasma (10 mL/kg, 12 mL/kg, or 15 mL/kg) were calculated according to the subject's baseline INR (2–< 4, 4–6, > 6, respectively). The observation period lasted for 90 days after the infusion of Kcentra or plasma. The modified efficacy (ITT-E) population for Kcentra included 87 subjects and for plasma included 81 subjects. Additionally, oral or intravenous Vitamin K was administered. The efficacy endpoint was hemostatic efficacy for the time period from the start of infusion of Kcentra or plasma until the end of the urgent surgery/invasive procedure. Criteria for effective hemostasis were based upon the difference between predicted and actual blood losses, subjective hemostasis rating, and the need for additional blood products containing coagulation factors. The proportion of subjects with effective hemostasis was 89.7% in the Kcentra group and 75.3% in the plasma group. The lower limit of the 95% confidence interval (CI) for the difference in proportions of Kcentra minus plasma was 2.8%, which exceeded -10% and thereby demonstrated the non-inferiority of Kcentra versus plasma (the study's primary objective) [see Table 15]. Because the lower limit of the CI was greater than 0, the prospectively defined criterion for superiority of Kcentra for hemostatic efficacy (a secondary objective) was also met. Table 15: Rating of Hemostatic Efficacy in Urgent Surgery/Invasive Procedure RCT
* Kcentra non-inferior to plasma if lower limit of 95% CI > –10%; Kcentra superior to plasma if lower limit of 95% CI > 0. Results of a post-hoc analysis of hemostatic efficacy stratified by actual dose of Kcentra or plasma administered in the urgent surgery/invasive procedure RCT are presented in Table 16. Table 16: Rating of Hemostatic Efficacy Stratified by Actual Dose of Kcentra or Plasma (Number and % of Subjects rated "Effective" in Urgent Surgery/ Invasive Procedure RCT
An additional endpoint was the reduction of INR to ≤ 1.3 at 30 minutes after the end of infusion of Kcentra or plasma for all subjects that received study product. The proportion of subjects with this decrease in INR was 55.2% in the Kcentra group and 9.9% in the plasma group. The 95% confidence interval for the difference in proportions of Kcentra minus plasma was 31.9% to 56.4%. The lower limit of the 95% CI of 31.9% demonstrated superiority of Kcentra versus plasma for this endpoint [see Table 17]. The relationship between a decrease in INR to less than or equal to 1.3 and clinical hemostatic efficacy has not been established. Table 17: Decrease of INR (1.3 or Less at 30 Minutes after End of Infusion) in Urgent Surgery/Invasive Procedure RCT
* Kcentra non-inferior to plasma if lower limit of 95% CI > -10%; Kcentra superior to plasma if lower limit of 95% CI > 0. The European Bleeding and Surgical Study was an open-label, single-arm, multicenter study.1 Forty-three (43) subjects who were receiving VKA were treated with Kcentra, because they either (1) required a surgical or an invasive diagnostic intervention (26 subjects), or (2) experienced an acute bleeding event (17 subjects). The dose of Kcentra (25 units/kg, 35 units/kg, or 50 units/kg) based on nominal Factor IX content was calculated according to the subject's baseline INR value (2–< 4, 4–6, > 6). The endpoint was the decrease of the INR to ≤ 1.3 within 30 minutes after end of Kcentra infusion in subjects who received any portion of study product. Of the 17 evaluable subjects receiving Kcentra for acute bleeding, 16 subjects (94%) experienced a decrease in INR to ≤ 1.3 within 30 minutes after the end of the Kcentra infusion. In RCTs, levels of Coagulation Factors II, VII, IX, X, and Antithrombotic Proteins C and S were measured after the infusion of Kcentra or plasma and the results were similar for subjects with acute major bleeding or subjects requiring an urgent surgery or invasive procedure. In the plasma-controlled RCT in acute major bleeding, the mean duration of Kcentra infusion was 24 minutes (± 32 minutes) and the mean duration of infusion for plasma was 169 minutes (± 143 minutes). The mean infusion volume of Kcentra was 105 mL ± 37 mL and the mean infusion volume of plasma was 865 mL ± 269 mL. In the plasma-controlled RCT for patients needing urgent surgery/invasive procedures, the mean duration of Kcentra infusion was 21 minutes (± 14 minutes) and the mean duration of infusion for plasma was 141 minutes (± 113 minutes). The mean infusion volume of Kcentra was 90 mL ± 32 mL and the mean infusion volume of plasma was 819 mL ± 231 mL. The increase in mean factor levels over time following Kcentra and plasma administration in the plasma-controlled RCT in acute major bleeding is shown in Figure 9 below (the mean factor levels over time following Kcentra and plasma administration in the plasma-controlled RCT for patients needing urgent surgery/invasive procedures are not shown, but showed similar profiles). Levels of some factors continued to increase at later time points, consistent with the effect of concomitant Vitamin K treatment. Formal pharmacokinetic parameters were not derived because of the effect of Vitamin K on factor levels at time points required for pharmacokinetic profiling. Figure 9: Mean Factor Levels (Factors II, VII, IX, X, Proteins C & S) over 24 hours in Acute Major Bleeding RCT
Time axis is scheduled measuring time: hours after start of infusion (P=pre-infusion)
Prior to Reconstitution Kcentra is for single use only. Contains no preservatives. Store Kcentra between 2–25°C (36–77°F), this includes room temperature, not to exceed 25°C (77°F). Do not freeze. Kcentra is stable for 36 months from the date of manufacture, up to the expiration date on the carton and vial labels. Do not use Kcentra beyond the expiration date on the vial label and carton. Store the vial in the original carton to protect it from light. After Reconstitution The product must be used within 4 hours following reconstitution. Reconstituted product can be stored at 2–25°C. If cooled, the solution should be warmed to 20–25°C prior to administration. Do not freeze the reconstituted product. Discard partially used vials. 17 PATIENT COUNSELING INFORMATION Inform patients of the signs and symptoms of allergic hypersensitivity reactions, such as urticaria, rash, tightness of the chest, wheezing, hypotension and/or anaphylaxis experienced during or after injection of Kcentra [see Warnings and Precautions (5.1)]. Inform patients of signs and symptoms of thrombosis, such as limb or abdomen swelling and/or pain, chest pain or pressure, shortness of breath, loss of sensation or motor power, altered consciousness, vision, or speech [see Warnings and Precautions (5.2)]. Inform patients that, because Kcentra 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 (CJD) agent [see Warnings and Precautions (5.3) and Description (11)]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Kcentra(人凝血酶原复合浓缩物/冻干粉)简介：
Kcentra(人凝血酶原复合物)获美国FDA批准用于紧急逆转成人抗凝治疗时出现的大出血症状4月29日，美国食品药品管理局FDA批准Kcentra（人凝血酶原复合物）用于紧急逆转成人患者急性大出血时的维生素K拮抗剂 ... 责任编辑：admin |
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