*生血素
出处：按学科分类—医药、卫生 军事医学科学出版社《临床常用进口药物手册》第149页（14425字）
【中文释文】：
〔活性成分〕
重组人红细胞生成素-β
〔性状〕
冻干粉，溶解后可作皮下注射或静脉注射。
〔成分〕
生血素1000：每瓶含1000U红细胞生成素-β冻干粉，相当于8．3μg促红素-β，每瓶附一安瓿1ml注射用水；
生血素2000：每瓶含2000U红细胞生成素-β冻干粉，相当于16．6μg促红素-β，每瓶附一安瓿1m1注射用水；
生血素5000：每瓶含5000U红细胞生成素-β冻干粉，相当于41．5μg促红素-β，每瓶附一安瓿1ml注射用水；
生血素10000：每瓶含10000U红细胞生成素-β冻干粉，相当于83μg促红素-β，每瓶附一安瓿1ml注射用水。
〔适应证〕
生血素适用于因慢性肾衰竭引致贫血的透析病人。生血素适用于治疗未行透析慢性肾功能不全病者的症状性肾性贫血。
〔禁忌证〕
生血素禁用于高血压失控的病人及对此药过敏的病人。
〔妊娠和哺乳期〕
虽然动物测试显示生血素在治疗条件下无致畸效应，但在妊娠和哺乳期不主张使用生血素，因为现时在这方面的临床经验仍不足。
〔药物不良反应〕
心血管系统：在治疗期间出现的最常见不良反应为血压升高或高血压情况恶化，特别是血细胞比容迅速增高的病例。这些都能以适当药物治疗。如血压升高不能以药物控制，须暂时停用生血素。病人除应定时检测血压，还应在各次透析之间进行检测(尤其在治疗初期)。
伴有脑病样症状(如头痛、精神混乱、感觉中枢和／或运动中枢紊乱，例如谈话障碍、步态失调和阵挛性癫痫发作等)的高血压危象可能会在正常血压或低血压病人身上出现。对这类病人应立即予以密切检测，特别是出现急性针刺性偏头痛者。
血液：生血素可能导致血小板数量在正常范围内轻微上升，特别是经静脉注射，情况一般随继续治疗消失。虽然血小板增多症极为罕见，但亦建议在治疗最初8周时，定期检测血小板量。
使用生血素的血液透析病人，往往因红细胞压积升高而需增加肝素剂量。如肝素剂量不适当，可能会发生透析器堵塞。偶尔会出现分流处栓塞，特别是有低血压趋向或动静脉瘘呈现并发症(血管狭窄、动脉瘤)的病人，所以建议及早预防血栓塞发生(如使用阿斯匹林)。
大多数病例中治疗期间同时出现血清铁蛋白下降及红血球压积升高。所以如病人血清铁蛋白低于100ng／ml或转铁蛋白饱和度低于20%，需每天口服补充铁质200～300mg。在个别病例中，病人可能出现短暂性高钾血症，高磷酸盐血症，所以治疗期间应定期检测。
其他：个别病人曾出现类似过敏反应。
〔警告〕
正常人如错误使用(例如用作刺激药物)，可能会导致血细胞比容过多，因而引起各种致命的心血管系统并发症。
〔注意〕
小儿使用生血素还未积累足够的经验，2岁以下幼童暂不宜使用生血素。有恶性肿瘤、癫痫症、血小板增多、慢性肝衰竭的病人，使用生血素应当谨慎。
叶酸或维生素B12不足，会降低生血素的疗效。严重铝过多也会影响生血素的疗效。
对未行透析肾硬化病来说，使用生血素应看个体而定，因为促进肾衰竭加速的可能性不能排除。血清钾及磷酸盐必须定期检测，曾有极少数尿毒症病人在使用生血素后出现高钾情况，但其因果关系并不能确定。如发现高钾情况，应考虑停止使用生血素至钾回复正常水平止。
〔相互作用〕
到目前为止，临床结果还未显示生血素与其他药物有任何相互作用。
〔剂量〕
治疗目标为增加血细胞比容在30%～35%之间，每周平均增幅最少0．5%，最高水平不能超过35%。如存在高血压或心血管疾病，脑血管或末梢血管病症等情况，应按个体状况来确定每周升幅及目标水平。对部分病人来说，血细胞比容理想水平可能低于30%。
生血素治疗方案分两步骤：
1．治疗期
皮下注射：开始时治疗剂量为每周3×20U／kg。如发现血细胞比容增加不理想(每周增加少于0．5%)，可于每4周后每周剂量增加3×20U／kg。也可将每周剂量分成每日剂量。
静脉注射：开始时治疗剂量为每周3×40U／kg。如发现血细胞比容增加不理想(每周增加少于0．5%)，可于4周后每周剂量增加至3×80U／kg。其后每间隔1个月每周可再增多3×20U／kg。
以上两种给药途径，最高剂量不可超过每周720U／kg。
2．维持期 要达到维持血细胞比容在30%～35%之间，首先把剂量减至治疗期剂量的二半，然后每周或每2周调整剂量。
对儿童所做临床观察结果显示，平均来说，病人越年青，生血素维持剂量越高，然而，由于个别病人反应不同，难于估计，所以应按照建议剂量应用本药。
〔疗程〕
生血素一般用于终身治疗，但如有需要，可以随时终止疗程。
〔用法〕
生血素应在医务人员仔细监护及指导下使用。
由于曾发现个别过敏性反应病例，建议首次给药应在医务人员监护下进行。
生血素是以冻干粉存于小瓶内供应。
使用时将生血素溶解于附带的溶剂，但应马上使用(2h之内)。在使用前，确定溶液应呈无色无颗粒状态，透明或呈轻微乳状，方可使用。用剩药物应丢弃。
本药溶液可用于皮下注射或静脉注射。
静脉注射应在大约2min内完成。例如，在透析结束时经动静脉瘘管注入。非透析病人应采用皮下注射以避免刺伤外周静脉。
〔重要配伍禁忌〕
注意以下提示，避免引致不相配伍或影响活性：
1．切勿使用其他溶剂!
2．切勿与其他药物混合使用!
3．切勿使用玻璃注射用具，应使用塑料制品!
〔贮存〕
生血素应贮存于2～8℃(冷藏箱)。
运输时，冷藏温度如遭间断，时间不可超过5d及温度一定不超过25℃。
〔有效期〕
生血素必须在印于盒上的有效期内使用。
〔包装〕
生血素1000，生血素2000：每盒10瓶冻干粉和10安瓿注射溶剂。
生血素5000，生血素10000：每盒5瓶冻干粉和5安瓿注射溶剂。
切勿让儿童触及!
OPC-安瓿开启方法：不需使用锉刀!
如何开启新设计OPC安瓿：
1．手持安瓿，保持蓝点向上位置。振摇或叩击安瓿使溶剂不留于安瓿茎部。
2．手持安瓿，保持蓝点向上位置。拿稳茎部，向外折断。
〔生产厂家〕
德国Boehringer mannheim GmbH
【外文释文】：
Active ingredient
Epoetin beta．(Synonyms：rhEPO and recombinant humanerythropoietin)．
Presentation
Freeze-dried substance for subcutaneous or intravenous administration after dissolution．
Composition
Recormon 1 000：1 vial contains 1 000 international units epoetin beta as a freeze-dried substance，corresponding to 8．3 μg epoetin beta．
1 solvent ampoule contains 1 ml water for injections．
Recormon 2 000：1 vial contains 2 000 international units epoetin beta as a freeze-dried substance，corresponding to 16．6μg epoetin beta．
1 solvent ampoule contains 1 ml water for injections．
Recormon 5 000：1 vial contains 5 000 international units epoetin beta as a freeze-dried substance，corresponding to 41．5μg epoetin beta．
1 solvent ampoule contains 1 ml water for iniections．
Recormon 10 000：1 vial contains 10 000 international units epoetin beta as a freezedried substance，corresponding to 83 μg epoetin beta．
1 solvent ampoule contains 1 ml water for injections．
Indication
Recormon is used for the treatment of anaemia associated with chronic renal failure in patients on dialysis．Recormon is used for the treatment of symptomatic renal anaemia in patients with chronic renal insufficiency not yet undergoing dialysis．
Contraindications
Recormon must not be used in poorly controllable hypertension and known hypersensitivity to the medication．
Use in pregnancy and lactation period
Animal studies revealed that no teratogenic effects occur under therapeutic conditions．However，Recormon should not be used during pregnancy and lactation as at present insufficient clinical experience has been gained in these fields．
Adverse drug reactions
Cardiovascular system：the most frequent adverse reaction during treatment with Recormon is an increase in blood pressure or aggravation of existing hypertension，especially in cases of rapid PCV increase．These increases in blood pressure can be treated with drugs．If blood pressure rises cannot be controlled by drug therapy，a transient interruption of Recormon therapy is recommended．Regular monitoring of blood pressure is recommended，also between dialyses(particularly at the beginning of therapy)．Hypertensive crisis with encephalopathy-like symptoms(e．g．headache，confusion，sensorimotor disorderssuch as speech disturbance，impaired gait-up to tonoclonic seizures)may occur，also in individual patients with normal or low blood pressure．This requires the immediate attention of a physician and intensive medical care．Particular attention should be paid to sudden stabbing migraine-like headaches as a possible warning signal．
Blood：There may be a moderate dose-dependent rise in the platelet count within the normal range during treatment with Recormon，especially after intravenous administration．This regresses during the course of continued therapy．Development of thrombocytosis is very rare．It is recommended that the platelet count is regularly monitored during the first 8 weeks of therapy．An increase in heparin dose during haemodialysis is frequently required during the course of therapy with Recormon as a result of the increased packed cell volume．Occlusion of the dialysis system is possible if heparinization is not optimum．Shunt thromboses may occur，especially in patients who have a tendency to hypotension or whose arteriovenous fistulae exhibit complications(e．g．stenoses，aneurysms)．Early shunt revision and thrombosis prophylaxis，e．g．with acetylsalicylic acid，is therefore recommended in these patients．
In most cases，a fall in serum ferritin values simultaneous with a rise in packed cell volume is observed．Therefore oral iron substitution with 200 to 300 mg Fe2+／day is recommended in all patients with serum ferritin values below 100 ng／ml or transferrin saturation below 20%．In isolated cases，transient hyperkalaemia and hyperphosphataemia may occur．These parameters should be monitored regularly．
Others：Anaphylactoid reactions have been observed in isolated cases．
Warning
Misuse by healthy persons(e．g．for doping)may lead to an excessive increase in packed cell volume．This may be associated with life-threatening complications of the cardiovascular system．
Special precautions for use
Recormon should not be used in children below the age of 2 years as at present insufficient clinical experience has been gained．Recormon should be used with caution in the presence of malignant tumours，epilepsy，thrombocytosis and chronic liver failure．Folic acid and vitamin B12 deficiencies should be ruled out as they reduce the effectiveness of Recormon．Severe aluminium overload may compromise the effectiveness of Recormon．The indication for Recormon treatment of nephrosclerotic patients not yet undergoing dialysis should be defined individually as a possible acceleration of progression of renal failure cannot be ruled out with certainty．Serum potassium and phosphate levels should be monitored regularly during Recormon therapy．Potassium elevation has been reported in a few uraemic patients receiving Recormon，though causality has not been established．If an elevated or rising potassium level is observed，then consideration should be given to ceasing Recormon administration until the level has been corrcted．
Interaction
The clinical results obtained so far do not indicate any interaction of Recormon with other substances．
Dosage(single and weekly dose)
The aim of treatment is to increase the packed cell volume to 30%-35%whereby the weekly increase should be at least 0．5%．A value of 35%should not be exceeded．
In the presence of hypertension or existing cardiovascular，cerebrovascular or peripheral vascular diseases，the weekly increase in PCV and the target PCV should be determined individually taking into account the clinical picture．In some patients the optimum PCV may be below 30%．Treatment with Recormon is divided into two stages：
Correction phase：
·Subcutaneous administration
The initial dosage is 3×20 U／kg body weight and week．The dosage may be increased every 4 weeks by 3× 20 U／kg body weight and week if the increase of packed cell volume is not adequate(less than 0．5%per week)．The weekly dose can also be divided into daily doses．
·Intravenous administration
The inital dosage is 3 × 40 U／kg body weight and week．The dosage may be raised after 4 weeks to 3×80 U／kg body weight and week if the increase of packed cell volume is not adequate(less than 0．5%per week)．Further increments of 3 × 20 U／kg body weight and week are possible at monthly intervals．
For both routes of administration，the maximum dosage should not exceed 720 U／kg body weight and week．
·Maintenance phase：
To maintain a packed cell volume of between 30%-35%，the dosage is initially reduced to half of the previously administered amount．Subsequently，the dose is adujsted at intervals of one or two weeks individually for the patient(maintenance dose)．
Results of clinical studies in children have shown that，on average，the younger the pa tients，the higher the Recormon doses．Nevertheless，the recommended dosing schedule should be followed as the individual response cannot be predicted．
Duration of treatment
Treatment with Recormon is usually a life-long therapy．It can，however，be interrupted，if necessary at any time．
Method of administration
This product should only be used under consultant supervision，usually in a hospital setting．Since anaphylactoid reactionswere observed in isolated cases，it is recommended that the first dose be administered under medical supervision．
Recormon is supplied as a freeze-dried substance in vials．This is dissolved with the contents of the accompanying solvent ampoule．The reconstituted solution should be used immediately，i．e．within 2 hours．Only solutions which are clear or slightly opalescent，colourless and practically free of visible particles may be injected．Any medication remaining in the vial after use should be discarded．
The reconstituted solution can be administered subcutaneously or intravenously．
In case of intravenous administration，the solution should be injected over approx．2 minutes，e．g．in haemodialysis patients via the arterio-venous fistula at the end of dialysis．For non-haemodialyzed patients，subcutaneous administration should always be preferred in order to avoid puncture of peripheral veins．
Most important incompatibilities
To avoid incompatibility or loss of activity，the following instructions must be observed：
·Do not use any other solvent
·Do not mix with other drugs
·Do not use glass，but only plastic materials for injection
Instructions for storage
Recormon must be stored at a temperature of 2-8℃(refrigerator)．For the purpose of transport，the cooling chain may be interrupted for a period of up to 5 days at room temperature(≤25℃)．
Expiry date
Recormon should not be used after the expiry date printed on the pack．
Presentations and pack sizes
Recormon 1000，Recormon 2000：
10 vials with freeze-dried substance and 10 ampoules with solvent．
Recormon 5 000，Recormon 10 000：
5 vials with freeze-dried substance and 5 ampoules with solvent．
Keep all medicines out of the reach of children!
Note on usage of OPC(One-Point-Cut)ampoules：
Filing no longer necessary!How to use the new OPC ampoules．
Hold the ampoule with the blue point upwards．Shake or tap the ampoule to get any fluid in the stem into the body of the ampoule．
Hold the ampoule with the blue point upwards．Take hold of the stem and snap off away from you．
Manufacturer
Boehring Mannheim GmbH Germany