Amgen有限公司(安进公司)2007年9月28日宣布，欧盟委员会已批准扩展其达贝阿法依泊汀(darbepoetinalfa／Aranesp)适用对象至所有已在或尚未接受透析治疗之儿科慢性肾病或称慢性肾衰相关贫血个体治疗。
达贝阿法依泊汀最早是于2001年在欧盟获准上市的，它至今已用于270万肾病学和肿瘤学患者。但在治疗慢性肾病相关贫血方面，达贝阿法依泊汀原仅被批准用于11岁及以上人群。
阿法达贝泊汀(darbepoetinal—fa)，在美国和欧洲的商标名分别为Aranesp和Nespo。阿法达贝泊汀实是阿法依泊汀的改进型产品，其结构较之阿法依泊汀的重要差异在于它带有两个含烃链唾液酸，故半衰期无论是静脉、抑或皮下注射都延长了2倍，十分有利于简化给药方案，临床上可每2周、甚或每3周用药1次。
慢性肾病属进行性和不可逆疾病，它以肾损害和肾功能下降为特征。慢性肾病的最常见症状之一即为贫血，后者是因衰竭了的肾脏不再能够生产足量的促红细胞生成素、由此使得红血细胞生产和血红蛋白水平减少所致。贫血会严重影响患者的日常健康和生活质量，其具体表现包括疲劳、虚弱、呼吸短促、注意力分散、精神混乱、头晕或晕厥、皮肤苍白、心跳加快和反复感冒等。贫血还可致使发展潜在致死性的心血管疾病，此在全部慢性肾病人群中的流行率高至35～40％。
达贝阿法依泊汀于2001年首次获得欧盟批准，用于治疗11岁及以上儿童至成人的慢性肾病相关贫血。2002年，达贝阿法依泊汀又获准治疗正接受化疗之成人实体瘤患者贫血。2003年，此适应证的适用对象获准扩展至正接受化疗之成人非骨髓性恶性肿瘤癌症人群的有症状贫血治疗。2004年，达贝阿法依泊汀又获准可以每3周1次给药频率治疗正接受化疗之成人非骨髓性恶性肿瘤癌症患者贫血及能以每月1次剂量间隔方案治疗尚未进行透析之慢性肾病人群贫血。2006年，达贝阿法依泊汀标签再被更新至允许正进行透析之慢性肾病个体自每周1～3次给药重组人DNA促红细胞生成素类药物切换到每2周1次给药达贝阿法依泊汀疗法。
美国FDA发布警告, 阿法达贝泊汀(darbepoetin alfa,商品名Aranesp)对非化疗引起的癌症病人的贫血无效,不能减少其需要的红细胞输注率及改善疲乏症状,且增加死亡率。
阿法达贝泊汀是一种蛋白,与肾脏分泌的促红细胞生成素作用相似,通过刺激骨髓,促进红细胞生成。2001年被FDA批准用于治疗慢性肾功能衰竭引起的贫血,2002年获准用于非骨髓性恶性肿瘤化疗所致贫血患者。
临床上,阿法达贝泊汀有时被用于非化疗引起的贫血患者,为了验证其有效性和安全性,一项大型、多中心、随机、安慰剂对照的研究被进行,该研究共纳入989例未接受化疗或放疗的活动期恶性肿瘤患者,60%的患者为疾病晚期。
结果显示,阿法达贝泊汀组16周内红细胞输注率为18%,而安慰组剂为24%,两组比较无统计学差异(P=0.15;危险比0.89);治疗组绝对死亡率高于安慰剂组(49%对46%;风险比1.25)。
因此,FDA告诫医务人员,阿法达贝泊汀的适应人群为因化疗所致贫血及产品说明书的适应证,而不应标签外用药。

Aranesp® is contraindicated in patients with uncontrolled hypertension. Patients with chronic renal failure (CRF) experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels in two clinical studies. Patients with CRF and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular events and mortality than other patients. These events included myocardial infarction, stroke, congestive heart failure, and hemodialysis vascular access thrombosis. A rate of hemoglobin rise of > 1 g/dL over 2 weeks may contribute to these risks. Seizures have occurred in patients with CRF participating in Aranesp® clinical trials.

Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients treated with Aranesp®. This has been reported predominantly in patients with CRF receiving ESAs by subcutaneous administration. PRCA has also been reported in patients receiving ESAs while undergoing treatment for hepatitis C with interferon and ribavirin. A sudden loss of response to Aranesp®, accompanied by severe anemia and low reticulocyte count, should be evaluated. If anti-erythropoietin antibody-associated anemia is suspected, withhold Aranesp® and other ESAs. Aranesp® should be permanently discontinued in patients with antibody-mediated anemia. Patients should not be switched to other ESAs as antibodies may cross-react.

Aranesp®(Darbepoetin)

SHORT DESCRIPTION: Aranesp is an erythropoiesis-stimulating drug, very similar in structure and action to the body's own endogenous Erythropoietin. Aranesp differs from the recombinant human Erythropoietin in Epogen (Epoetin Alfa) mainly in its duration of activity. This new protein maintains its levels in the blood for approximately three times longer, which is an extremely significant difference. Aranesp dosage is one injection each week.

LONG DESCRIPTION: Aranesp is an erythropoiesis-stimulating drug, very similar in structure and action to the body's own endogenous Erythropoietin. It is manufactured by Amgen, the world's largest biotechnologies company. In fact, it is also the same company that first brought recombinant Erythropoietin (Epoetin Alfa) to the market in 1984. In structure Darbepoetin Alfa differs from human Erythropoietin only slightly, and has all the same biological activity. Human Erythropoietin is normally released by the kidneys in response to hypoxia, or low blood oxygen levels. It in turn triggers bone marrow to increase red blood cell production, and is likewise vital to the regulation of normal red blood cell concentrations. Darbepoetin Alfa can likewise be used to augment erythropoiesis when the body is not maintaining adequate red blood cell levels on its own. It is approved by the FDA for the treatment of anemia (low red blood cell count) specifically associated with chronic renal failure or chemotherapy.

Aranesp differs from the recombinant human Erythropoietin in Epogen (Epoetin Alfa) mainly in its duration of activity. This new protein maintains its levels in the blood for approximately three times longer, which is an extremely significant difference. This means that with Aranesp, patients are required to administer the product much less frequently. While Epogen is usually given on a schedule of three times a week, Aranesp requires only one injection each week. This course enhances patient comfort quite a bit, and is especially useful when the patient is visiting the doctor for drug administration. Studies comparing this form of therapy to the use of standard recombinant Erythropoietin note that users need approximately the same amount of drug, it is just given in larger doses with more time between applications.

Erythropoiesis stimulating drugs are very popular in endurance sports, such as long distance running and cycling. In these sports maximum oxygen carrying capacity is of paramount importance to the performance of the athlete. We are all too familiar with the decades old practice of manually removing and later reinfusing blood plasma for the sake of increasing red blood cell count and endurance capacity for a sport, commonly referred to as "blood doping". Drugs like Aranesp and Epogen accomplish the same thing as this decades old practice, and are essentially just new forms of "chemical blood doping". In practice they can be just as effective as their antiquated counterpart, even more so. These agents are also used at times in bodybuilding circles, where the erythropoiesis stimulating effect may help bring out a greater look of masculinity when the body fat percentage is sufficiently low. It is likewise more of a "pre-contest" drug.

While Aranesp and Epogen can be just as effective as the practice of blood doping, be warned that these drugs can also be just as dangerous. A number of athlete deaths have been attributed to the use of these agents over the past several years, caused by an over-thickening of the blood due to abnormally high red cell concentrations. One must take extreme caution when using these drugs, making sure to meticulously measure red blood cell counts to be sure that the drug is not having an effect that could turn out to be life threatening. Take note also that Aranesp is now detectable during urine analysis, making it unsafe for drug-tested sports.

Aranesp comes in the dosage strengths of 25, 40, 60, 100, 200 and 300 mcg/ml. When shopping, you will quickly learn that this is not a cheap drug. Due to the high cost for the new erythropoiesis stimulating agents, they are often the targets of counterfeit drug manufacturing operations. But these operations cater not to the black market like underground steroid makers, but push their drugs through legitimate channels - into the pharmacies where they are sold to unsuspecting consumers, often with diluted dosages. This has been a big issues as of late, suggesting that it may be a good idea to get your scripts filled (if you get them) thorough the larger pharmacy chains, which are unlikely to purchase their drugs through pharmaceutical wholesalers.

中文阿法达贝泊汀处方资料

Aranesp的劑量調整是依照適應症而有所不同。由於有較長的血中半衰期，Aranesp的給藥頻率少於Epoetin alfa (例如：當Epoetin alfa 每週給藥3次，Aranesp則應每週給藥一次)。
_____起始劑量_____
_____治療貧血_____
治療慢性腎衰竭患者的貧血症狀，Aranesp的建議起始劑量為每公斤體重0.45毫微克，靜脈注射或皮下注射每週一次。因為患者的個體差異，Aranesp給藥應逐漸校正到維持患者的血紅素濃度不超過目標值12g/dL。b.從Epoetin alfa治療轉換成Aranesp︰因為AranespR具有較長的血漿半衰期，給藥的頻率相對比Epoetin alfa少。若患者先前Epoetin alfa每週給藥2到3次，則Aranesp應每週給藥一次。若患者先前Epoetin alfa每週給藥一次，則Aranesp應每兩週給藥一次。原先的給藥途徑維持不變(靜脈注射或皮下注射)。

________劑量調整_________

增加Aranesp的藥量時，頻率每個月不應多於一次。如果患者的血紅素濃度上升並接近12g/dL，就需要降低大約25%的Aranesp給藥劑量。如果患者的血紅素濃度持續上升，Aranesp就需要暫時停藥直到血紅素濃度下降，血紅素濃度回復後再度給藥，Aranesp的起始劑量就需要降低大約25%的原來給藥劑量。如果患者的血紅素濃度在兩週內上升超過1g/dL，就需要降低大約25%的Aranesp給藥劑量。
_______維持劑量__________
如果患者的血紅素濃度超過12g/dL以上，則應依照上述調整劑量。則應依照上述調整劑量。Aranesp的劑量調整必須個別化，以確保每位患者能夠維持適當的血紅素濃度。

___接受化學治療之癌症患者︰_____

建議之起始劑量為2.25mcg/kg皮下注射每週1次。每患者之劑量應調整以維持目標血紅素值。治療6週後，假如血紅素值增加少於1.0g/dL，則Aranesp之劑量應增至4.5mcg/kg。假如於兩週內血紅素值增加超過1.0g/dL，或血紅素值超過12g/dL，則劑量應減少約25%。假如血紅素值超過13g/dL，則劑量應暫時保留直到血紅素值降至12g/dL。基於此點，再重新治療之劑量應比先前劑量減少大約25%。

_____調配及給藥時注意事項_______

a.請勿振搖Aranesp，劇烈振搖可能造成Aranesp蛋白變性，導致Aranesp喪失生物活性。
b.在調配Aranesp之前，應先檢視藥品溶液是否有顆粒或變色的情形。請勿使用有顆粒或變色Aranesp藥品溶液。
c.請勿稀釋Aranesp。
d.請勿將Aranesp與其他藥品溶液混合調配。
e.Aranesp為單劑量玻璃瓶裝而且不含防腐劑，開封後未使用的藥品請丟棄。請勿儲存未使用的藥品。

【原产地英文商品名】Aranesp 150MCG/0.75ML/VIAL
【原产地英文药品名】DARBEPOETIN ALFA IN ALBUMN SOL
【中文参考商品】阿法达贝泊汀 150微克/0.75毫升/支注射液
【中文参考药品】阿法达贝泊汀
【临床试验期】完成
【中文适应病症参考】伴随非骨髓样恶性肿瘤
【中文适应病症参考】贫血症
中文适应病症参考】恶性肿瘤
【中文适应病症参考】癌症
【生产厂家中文参考】美国安进公司
【生产厂家英文名】Amgen, Inc