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英文药名:Epogen(Epoetin Alfa Injection)
中文药名:阿法依泊汀注射剂
生产厂家：安进制药
药品介绍
阿法依泊汀注射剂
别 名:EPO, Epoade, Epogen, Eprex, Erypo, Erythropoietin, Espo, Globuren, KRN-5702 E, Procrit
化学名称: 1-165-Erythropoietin (human clone Iambda HEPOFL 13 protein moiety), glycoform α
开发单位:Amgen
首次上市:1989年，美国
药效类别:抗贫血药
用 途
EPOGEN是一种重组促红细胞生成素，用于依赖透析的慢性肾衰相关的贫血。还用于癌症病人由于化疗引起的贫血。
本品是一种刺激红细胞生成的糖蛋白。它是应用dna重组技术及细胞培养技术而制成的人类红细胞生成素-α，与内源性红细胞生成素有相同的生物活性。
药理作用
红细胞生成素在红细胞系发育的其后各阶段的作用，包括对原始红细胞刺激增加合成血红蛋白，当激素处于高浓度时，加速网织红细胞由骨髓向循环释放。
内源性红细胞生成素主要由肾脏产生，慢性肾衰病人红细胞生成素的产生受到抑制因而不足，是这类病人贫血的原发因素。红细胞生成素对包括需要透析和不需要经常透析的慢性肾衰贫血病人可刺激红细胞生成。
药代动力学
慢性肾衰病人静脉给药循环半衰期大约为4～13h。肝脏是主要的清除途径，肾脏是清除的次要途径。
适应症
慢性肾衰伴有贫血的病人(包括透析和不透析的病人)，也用于多发性骨髓瘤相关的贫血和骨髓增生异常及癌症引起的贫血。
用法与用量
开始剂量：3000u，静注，每周3次，然后根据病情逐渐减少至维持量1500u，静注，每周2～3次：最高维持剂量不得超过3000u/次，每周3次。
不良反应
偶可发生血压升高，心悸、高血压性脑病、头痛、头晕、发热、关节痛、肌肉痛、恶心、呕吐、腹泻、got及gpt升高、瘙痒、皮疹、过敏性休克。
注意事项
①用药期间应定期检查血红蛋白浓度与红细胞比容值(血红蛋白浓度不超过12g/dl或红细胞比容值36%以上)。密切观察血压变化情况，防止高血压性脑病发生，
②使用本品应注意补充铁质。
③本品应慎用于心肌梗塞、肺梗塞、脑梗塞、高血压、孕妇、儿童或有过敏倾向的病人。
Epogen简介
Epogen实际上是一种生物制剂而不是药物，因为它最初是人体中自然产生的一种物质——由肾制造的一种荷尔蒙，用于刺激红血球的再生。
Epogen是1976年芝加哥大学的尤金·哥得沃森（Eugene Goldwasser）发现的，他在若干个研究室中进行了基础研究，认为人体的肾必须能够制造出这样一种物质。哥得沃森和芝加哥大学都没有将这种荷尔蒙申请专利，也没有试图去合成它。而哥伦比亚大学的一项国家卫生研究所资助的研究发明了一种技术用于制造生物制剂，该大学很快将这项技术申请了专利。一家刚设立的小生物技术公司Amgen公司从哥伦比亚大学那里经过授权获得了这项技术，并开始大规模开发商业化合成促红细胞生成素分子的技术。Amgen公司现在已经成为制药业巨人，它每年通过医疗保险向肾衰竭病人销售Epogen能够赚得20亿美元的收入。因此，与紫杉醇（Taxol）的例子一样，公众需要为Epogen两次付费——第一次付费是支持了发现这种药物的研究工作，第二次通过医疗保险为购买药物付费。哥得沃森则没有因为他的基础性研究获得一分钱。
一种分子结构与Epogen亳无二致的药物Procrit由强生公司（Johnson& Johnson）推向了市场，就像它是一种不同的物质一样。这种毫无必要的复制品是Amgen和强生公司之间一笔交易的结果。因为我们知道，贫血症不仅仅出现在肾衰竭的情况下，它还可能出现在其他病状下。特别是，它很可能是癌症治疗中病人衰弱后出现的一种并发症。
在Amgen公司从Epogen上获得巨额利润之前，Amgen出于公司资金流动的需求将它授权给了强生公司。强生公司在美国销售Epogen，只能针对除肾衰竭之外的其它病症（主要是癌症），在欧洲则没有限制用途。强生公司付给Amgen数百万美元，并保证在未来支付专利使用费。强生公司的分部Ortho将这种药物取名为Procrit进行推广。
而Amgen需要将它所有关于Epogen销售收入的1％付给哥伦比亚大学。为了不被强生公司击败，Amgen现在获得了另一种疗效更长的相同药物的批准，名字为Aranesp，它希望能用这种药与Procrit展开竞争，同时又不会违背最初的交易合同。这些药物虽然名字不同，但实际上都是同一种药物。
完整资料附件：https://pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/epogen/epogen_pi_hcp_english.pdf
包装规格[以下产品不同规格和不同价格，采购者以咨询为准]
EPOGEN 10000U/ML 1ML SDV 10/PAC EPOETIN ALFA "AMGEN USA, INC."55513-0144-10
EPOGEN 10000U/ML 2ML MDV 10/PAC EPOETIN ALFA "AMGEN USA, INC." 55513-0283-10
EPOGEN 20000U/ML 1ML MDV 10/PAC EPOETIN ALFA "AMGEN USA, INC." 55513-0478-10
EPOGEN 2000U/ML 1ML SDV 10/PAC EPOETIN ALFA "AMGEN USA, INC." 55513-0126-10
EPOGEN 3000U/ML 1ML SDV 10/PAC EPOETIN ALFA "AMGEN USA, INC." 55513-0267-10
EPOGEN 4000U/ML 1ML SDV 10/PAC EPOETIN ALFA "AMGEN USA, INC." 55513-0148-10
"EPOGEN MDV 20,000U/ML 1ML 10" EPOETIN ALFA AMGEN USA INC 55513-0478-10
EPOGEN MDV 20MU 2ML 10 EPOETIN ALFA AMGEN USA INC 55513-0283-10
EPOGEN SDV 10MU 1ML 10 EPOETIN ALFA AMGEN USA INC 55513-0144-10
EPOGEN SDV 2MU 1ML 10 EPOETIN ALFA AMGEN USA INC 55513-0126-10
EPOGEN SDV 3MU 1ML 10 EPOETIN ALFA AMGEN USA INC 55513-0267-10
EPOGEN SDV 4MU 1ML 10 EPOETIN ALFA AMGEN USA INC 55513-0148-10
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Epogen(Epoetin Alfa)Indications
INDICATIONS AND USAGE
Treatment of Anemia of Chronic Renal Failure Patients
EPOGEN® is indicated for the treatment of anemia associated with CRF, including patients on dialysis and patients not on dialysis. EPOGEN® is indicated to elevate or maintain the red blood cell level (as manifested by the hematocrit or hemoglobin determinations) and to decrease the need for transfusions in these patients.
Non-dialysis patients with symptomatic anemia considered for therapy should have a hemoglobin less than 10 g/dL.
EPOGEN® is not intended for patients who require immediate correction of severe anemia. EPOGEN® may obviate the need for maintenance transfusions but is not a substitute for emergency transfusion.
Prior to initiation of therapy, the patient’s iron stores should be evaluated. Transferrin saturation should be at least 20% and ferritin at least 100 ng/mL. Blood pressure should be adequately controlled prior to initiation of EPOGEN® therapy, and must be closely monitored and controlled during therapy.
Treatment of Anemia in Zidovudine-treated HIV-infected Patients
EPOGEN® is indicated for the treatment of anemia related to therapy with zidovudine in HIV-infected patients. EPOGEN® is indicated to elevate or maintain the red blood cell level (as manifested by the hematocrit or hemoglobin determinations) and to decrease the need for transfusions in these patients. EPOGEN® is not indicated for the treatment of anemia in HIV-infected patients due to other factors such as iron or folate deficiencies, hemolysis, or gastrointestinal bleeding, which should be managed appropriately. EPOGEN® use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being.
EPOGEN®, at a dose of 100 Units/kg TIW, is effective in decreasing the transfusion requirement and increasing the red blood cell level of anemic, HIV-infected patients treated with zidovudine, when the endogenous serum erythropoietin level is≤500 mUnits/mL and when patients are receiving a dose of zidovudine≤ 4200 mg/week.
Treatment of Anemia in Cancer Patients on Chemotherapy
EPOGEN® is indicated for the treatment of anemia due to the effect of concomitantly administered chemotherapy based on studies that have shown a reduction in the need for RBC transfusions in patients with metastatic, non-myeloid malignancies receiving chemotherapy for a minimum of 2 months. Studies to determine whether EPOGEN® increases mortality or decreases progression-free/recurrence-free survival are ongoing.
EPOGEN® is not indicated for use in patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy.
EPOGEN® is not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure due to the absence of studies that adequately characterize the impact of EPOGEN® on progression-free and overall survival (see WARNINGS: Increased Mortality and/or Increased Risk of Tumor Progression or Recurrence).
EPOGEN® is not indicated for the treatment of anemia in cancer patients due to other factors such as iron or folate deficiencies, hemolysis, or gastrointestinal bleeding (see PRECAUTIONS: Lack or Loss of Response).
EPOGEN® use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being.
Reduction of Allogeneic Blood Transfusion in Surgery Patients
EPOGEN® is indicated for the treatment of anemic patients (hemoglobin > 10 to ≤ 13 g/dL) who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery to reduce the need for allogeneic blood transfusions.17-19 EPOGEN® is not indicated for anemic patients who are willing to donate autologous blood (see BOXED WARNINGS and DOSAGE AND ADMINISTRATION).
DOSAGE AND ADMINISTRATION
IMPORTANT: See BOXED WARNINGS and WARNINGS: Increased Mortality, Serious Cardiovascular and Thromboembolic Events.
Chronic Renal Failure Patients
The recommended range for the starting dose of EPOGEN® is 50 to 100 Units/kg TIW for adult patients. The recommended starting dose for pediatric CRF patients on dialysis is 50 Units/kg TIW. Individualize dosing to achieve and maintain hemoglobin levels between 10-12 g/dL. The dose of EPOGEN® should be reduced as the hemoglobin approaches 12 g/dL or increases by more than 1 g/dL in any 2-week period. If hemoglobin excursions outside the recommended range occur, the EPOGEN® dose should be adjusted as described below.
EPOGEN® may be given either as an IV or SC injection. In patients on hemodialysis, the IV route is recommended (see WARNINGS: Pure Red Cell Aplasia). While the administration of EPOGEN® is independent of the dialysis procedure, EPOGEN® may be administered into the venous line at the end of the dialysis procedure to obviate the need for additional venous access. In adult patients with CRF not on dialysis, EPOGEN® may be given either as an IV or SC injection.
Patients who have been judged competent by their physicians to self-administer EPOGEN® without medical or other supervision may give themselves either an IV or SC injection. The table below provides general therapeutic guidelines for patients with CRF:
Individually titrate to achieve and maintain hemoglobin levels between 10 to 12 g/dL.
During therapy, hematological parameters should be monitored regularly. Doses must be individualized to ensure that hemoglobin is maintained at an appropriate level for each patient.
For patients whose hemoglobin does not attain a level within the range of 10 to 12 g/dL despite the use of appropriate EPOGEN® dose titrations over a 12-week period:
do not administer higher EPOGEN® doses and use the lowest dose that will maintain a hemoglobin level sufficient to avoid the need for recurrent RBC transfusions,
evaluate and treat for other causes of anemia (see PRECAUTIONS: Lack or Loss of Response), and
thereafter, hemoglobin should continue to be monitored and if responsiveness improves, EPOGEN® dose adjustments should be made as described above; discontinue EPOGEN® if responsiveness does not improve and the patient needs recurrent RBC transfusions.
Pretherapy Iron Evaluation: Prior to and during EPOGEN® therapy, the patient’s iron stores, including transferrin saturation (serum iron divided by iron binding capacity) and serum ferritin, should be evaluated. Transferrin saturation should be at least 20%, and ferritin should be at least 100 ng/mL. Virtually all patients will eventually require supplemental iron to increase or maintain transferrin saturation to levels that will adequately support erythropoiesis stimulated by EPOGEN®.
Dose Adjustment: The dose should be adjusted for each patient to achieve and maintain hemoglobin levels between 10 to 12 g/dL.
Increases in dose should not be made more frequently than once a month. If the hemoglobin is increasing and approaching 12 g/dL, the dose should be reduced by approximately 25%. If the hemoglobin continues to increase, dose should be temporarily withheld until the hemoglobin begins to decrease, at which point therapy should be reinitiated at a dose approximately 25% below the previous dose. If the hemoglobin increases by more than 1 g/dL in a 2-week period, the dose should be decreased by approximately 25%.
If the increase in the hemoglobin is less than 1 g/dL over 4 weeks and iron stores are adequate (see PRECAUTIONS: Laboratory Monitoring), the dose of EPOGEN® may be increased by approximately 25% of the previous dose. Further increases may be made at 4-week intervals until the specified hemoglobin is obtained.
Maintenance Dose: The maintenance dose must be individualized for each patient on dialysis. In the US phase 3 multicenter trial in patients on hemodialysis, the median maintenance dose was 75 Units/kg TIW, with a range from 12.5 to 525 Units/kg TIW. Almost 10% of the patients required a dose of 25 Units/kg, or less, and approximately 10% of the patients required more than 200 Units/kg TIW to maintain their hematocrit in the suggested target range. In pediatric hemodialysis and peritoneal dialysis patients, the median maintenance dose was 167 Units/kg/week (49 to 447 Units/kg per week) and 76 Units/kg per week (24 to 323 Units/kg/week) administered in divided doses (TIW or BIW), respectively to achieve the target range of 30% to 36%.
If the transferrin saturation is greater than 20%, the dose of EPOGEN® may be increased. Such dose increases should not be made more frequently than once a month, unless clinically indicated, as the response time of the hemoglobin to a dose increase can be 2 to 6 weeks. Hemoglobin should be measured twice weekly for 2 to 6 weeks following dose increases. In adult patients with CRF not on dialysis, the dose should also be individualized to maintain hemoglobin levels between 10 to 12 g/dL. EPOGEN® doses of 75 to 150 Units/kg/week have been shown to maintain hematocrits of 36% to 38% for up to 6 months.
Lack or Loss of Response: If a patient fails to respond or maintain a response, an evaluation for causative factors should be undertaken (see WARNINGS: Pure Red Cell Aplasia, PRECAUTIONS: Lack or Loss of Response, and PRECAUTIONS: Iron Evaluation). If the transferrin saturation is less than 20%, supplemental iron should be administered.
Zidovudine-treated HIV-infected Patients
Prior to beginning EPOGEN®, it is recommended that the endogenous serum erythropoietin level be determined (prior to transfusion). Available evidence suggests that patients receiving zidovudine with endogenous serum erythropoietin levels>500 mUnits/mL are unlikely to respond to therapy with EPOGEN®.
In zidovudine-treated HIV-infected patients the dosage of EPOGEN® should be titrated for each patient to achieve and maintain the lowest hemoglobin level sufficient to avoid the need for blood transfusion and not to exceed the upper safety limit of 12 g/dL.
Starting Dose: For adult patients with serum erythropoietin levels ≤ 500 mUnits/mL who are receiving a dose of zidovudine ≤ 4200 mg/week, the recommended starting dose of EPOGEN® is 100 Units/kg as an IV or SC injection TIW for 8 weeks. For pediatric patients, see PRECAUTIONS: PEDIATRIC USE.
Increase Dose: During the dose adjustment phase of therapy, the hemoglobin should be monitored weekly. If the response is not satisfactory in terms of reducing transfusion requirements or increasing hemoglobin after 8 weeks of therapy, the dose of EPOGEN® can be increased by 50 to 100 Units/kg TIW. Response should be evaluated every 4 to 8 weeks thereafter and the dose adjusted accordingly by 50 to 100 Units/kg increments TIW. If patients have not responded satisfactorily to an EPOGEN® dose of 300 Units/kg TIW, it is unlikely that they will respond to higher doses of EPOGEN®.
Maintenance Dose: After attainment of the desired response (ie, reduced transfusion requirements or increased hemoglobin), the dose of EPOGEN® should be titrated to maintain the response based on factors such as variations in zidovudine dose and the presence of intercurrent infectious or inflammatory episodes. If the hemoglobin exceeds the upper safety limit of 12 g/dL, the dose should be discontinued until the hemoglobin drops below 11 g/dL. The dose should be reduced by 25% when treatment is resumed and then titrated to maintain the desired hemoglobin.
Cancer Patients on Chemotherapy
Although no specific serum erythropoietin level has been established which predicts which patients would be unlikely to respond to EPOGEN® therapy, treatment of patients with grossly elevated serum erythropoietin levels (eg, > 200 mUnits/mL) is not recommended. Therapy should not be initiated at hemoglobin levels ≥ 10 g/dL. The hemoglobin should be monitored on a weekly basis in patients receiving EPOGEN® therapy until hemoglobin becomes stable. The dose of EPOGEN® should be titrated for each patient to achieve and maintain the lowest hemoglobin level sufficient to avoid the need for blood transfusion (see recommended Dose Modifications, below).
Recommended Dose: The initial recommended dose of EPOGEN® in adults is 150 Units/kg SC TIW or 40,000 Units SC Weekly. The initial recommended dose of EPOGEN® in pediatric patients is 600 Units/kg IV weekly. Discontinue EPOGEN® following the completion of a chemotherapy course (see BOXED WARNINGS: Cancer ).
Surgery Patients
Prior to initiating treatment with EPOGEN® a hemoglobin should be obtained to establish that it is > 10 to≤13 g/dL.17 The recommended dose of EPOGEN® is 300 Units/kg/day subcutaneously for 10 days before surgery, on the day of surgery, and for 4 days after surgery.
An alternate dose schedule is 600 Units/kg EPOGEN® subcutaneously in once weekly doses (21, 14, and 7 days before surgery) plus a fourth dose on the day of surgery.18
All patients should receive adequate iron supplementation. Iron supplementation should be initiated no later than the beginning of treatment with EPOGEN® and should continue throughout the course of therapy. Deep venous thrombosis prophylaxis should be strongly considered(see BOXED WARNINGS).
PREPARATION AND ADMINISTRATION OF EPOGEN®
Do not shake. It is not necessary to shake EPOGEN®. Prolonged vigorous shaking may denature any glycoprotein, rendering it biologically inactive.
Protect the solution from light. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use any vials exhibiting particulate matter or discoloration.
Using aseptic techniques, attach a sterile needle to a sterile syringe. Remove the flip top from the vial containing EPOGEN®, and wipe the septum with a disinfectant. Insert the needle into the vial, and withdraw into the syringe an appropriate volume of solution.
Single-dose: 1 mL vial contains no preservative. Use one dose per vial; do not re-enter the vial. Discard unused portions.
Multidose: 1 mL and 2 mL vials contain preservative. Store at 2° to 8° C after initial entry and between doses. Discard 21 days after initial entry.
Do not dilute or administer in conjunction with other drug solutions. However, at the time of SC administration, preservative-free EPOGEN® from single-use vials may be admixed in a syringe with bacteriostatic 0.9% sodium chloride injection, USP, with benzyl alcohol 0.9% (bacteriostatic saline) at a 1:1 ratio using aseptic technique. The benzyl alcohol in the bacteriostatic saline acts as a local anesthetic which may ameliorate SC injection site discomfort. Admixing is not necessary when using the multidose vials of EPOGEN® containing benzyl alcohol.
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