MabCampath infusion 30mg/ml(Alemtuzumab 阿仑单抗注射剂) Campath/MabCampath——人源化单克隆抗体 Campath(欧洲商品名：MabCampath)是第一个对烷化剂或福达华治疗无效的患者仍具有显着疗效的药物。根据一项国际II期临床研究结果显示，经其它药物治疗复发或难治的CLL患者用Campath治疗后?可使其生存期显着延长1倍以上。目前，有关专家正致力于研究该药的新用法及联合用药，如研究与福达华等联合应用的疗效。     Campath是CD52抗体，可与表面携带CD52抗原的细胞相结合从而启动细胞破坏过程。通过这一方式，Campath可以清除外周血、骨髓及其它累及器官的淋巴细胞。由于T淋巴细胞同样携带CD52抗原，Campath已被成功地应用于前T细胞性白血病(T-PLL)及外周T细胞淋巴瘤的治疗。作为对福达华的补充，Campath在非清髓性移植中也发挥着重要作用。 目前，已有越来越多的肿瘤专家在早期治疗中选择Campath/MabCampath。 ▲MabCampath; 为第一及现时唯一一种被美国及欧洲准许使用在B细胞型CLL的新的药物。 ▲MabCampath;是一种单克隆抗体，能有效对化疗没有效用的病人产生疗效。 ▲MabCampath; 的原理是针对CD52抗原，这种抗原主要分布在B及T细胞的表面。 ▲MabCampath; 由于是一种抗体，会在淋巴细胞表面与CD 52抗原结合，并会引导身体的免疫系统破坏及吞噬在血液及骨髓结合后的细胞。  生产商：拜耳医药保健制药公司]  MabCampath infusion 30mg/ml(Alemtuzumab）注射静脉使用   适应症 CAMPATH是的CD52定向杀伤抗体作为单剂治疗B细胞慢性淋巴细胞白血病（B - CLL）表示。 剂量和用法 管理作为一个超过2小时的静脉滴注。 升级到建议剂量为30毫克/天每周三次，12周。 Premedicate与口服抗组织胺和乙酰氨基酚剂量前。 剂型和优势 30毫克/1毫升的单次使用小瓶。 禁忌 无。 警告和注意事项 血细胞减少： 获取完整的血球计数（CBC）和血小板计数在治疗期间和治疗后的CD4细胞计数在每周一班，直到恢复到≥200个细胞/μL。 停止对自身免疫性疾病或严重的血液学不良反应。 感染： Alemtuzumab导致严重的和长期的淋巴细胞，并增加感染的风险。如果发生严重的感染，不治疗，直到感染解析。 不要管理的活病毒疫苗，最近收到CAMPATH的患者。 不良反应 最常见的不良反应（≥10％）：血细胞减少，输液反应，巨细胞病毒（CMV）和其他感染，恶心，呕吐，腹泻，和失眠。 MabCampath 30mg/ml (Alemtuzumab) MabCampath 30mg/ml Description, Presentation and Dosage MabCampath 30mg/ml Description MabCampath 30mg/ml Drug Class Description Monoclonal antidobies MabCampath 30mg/ml Drug Description One ml contains 30 mg of alemtuzumab. Each vial contains 30 mg of alemtuzumab. Alemtuzumab is a genetically engineered humanised IgG1 kappa monoclonal antibody specific for a 21-28 kD lymphocyte cell surface glycoprotein (CD52). The antibody is produced in mammalian cell (Chinese Hamster Ovary) suspension culture in a nutrient medium. MabCampath 30mg/ml Generic Name Alemtuzumab MabCampath 30mg/ml Presentation MabCampath 30mg/ml Presentation Concentrate for solution for infusion. Colourless to slightly yellow concentrate. MabCampath 30mg/ml Manufacturer Genzyme Therapeutics Updated 23 November 2011 MabCampath 30mg/ml Dosage MabCampath 30mg/ml Adult Dosage MabCampath should be administered under the supervision of a physician experienced in the use of cancer therapy. Posology During the first week of treatment, MabCampath should be administered in escalating doses: 3 mg on day 1, 10 mg on day 2 and 30 mg on day 3 assuming that each dose is well tolerated. Thereafter, the recommended dose is 30 mg daily administered 3 times weekly on alternate days up to a maximum of 12 weeks. In most patients, dose escalation to 30 mg can be accomplished in 3-7 days. However, if acute moderate to severe adverse reactions such as hypotension, rigors, fever, shortness of breath, chills, rashes and bronchospasm (some of which may be due to cytokine release) occur at either the 3 mg or 10 mg dose levels, then those doses should be repeated daily until they are well tolerated before further dose escalation is attempted. Median duration of treatment was 11.7 weeks for first-line patients and 9.0 weeks for previously treated patients. Once a patient meets all laboratory and clinical criteria for a complete response, MabCampath should be discontinued and the patient monitored. If a patient improves (i.e. achieves a partial response or stable disease) and then reaches a plateau without further improvement for 4 weeks or more, then MabCampath should be discontinued and the patient monitored. Therapy should be discontinued if there is evidence of disease progression. Concomitant medicinal products Premedications Patients should be premedicated with oral or intravenous steroids, an appropriate antihistamine and analgesic 30-60 minutes prior to each MabCampath infusion during dose escalation and as clinically indicated thereafter. Prophylactic antibiotics Antibiotics and antivirals should be administered routinely to all patients throughout and following treatment. Dose modification guidelines There are no dose modifications recommended for severe lymphopenia given the mechanism of action of MabCampath. In the event of serious infection or severe haematological toxicity MabCampath should be interrupted until the event resolves. It is recommended that MabCampath should be interrupted in patients whose platelet count falls to < 25,000/μl or whose absolute neutrophil count (ANC) drops to < 250/μl. MabCampath may be reinstituted after the infection or toxicity has resolved. MabCampath should be permanently discontinued if autoimmune anaemia or autoimmune thrombocytopenia appears. The following table outlines the recommended procedure for dose modification following the occurrence of haematological toxicity while on therapy: Haematologic values Dose modification* ANC < 250/μl and/or platelet count 25,000/μl For first occurrence Withhold MabCampath therapy. Resume MabCampath at 30 mg when ANC  500/μl and platelet count  50,000/μl. For second occurrence Withhold MabCampath therapy. Resume MabCampath at 10 mg when ANC  500/μl and platelet count  50,000/μl. For third occurrence Discontinue MabCampath therapy. 50% decrease from baseline in patients initiating therapy with a baseline ANC  250/μl and/or a baseline platelet count  25,000/μl For first occurrence Withhold MabCampath therapy. Resume MabCampath at 30 mg upon return to baseline value(s). For second occurrence Withhold MabCampath therapy. Resume MabCampath at 10 mg upon return to baseline value(s). For th ird occurrence Discontinue MabCampath therapy. *If the delay between dosing is  7 days, initiate therapy at MabCampath 3 mg and escalate to 10 mg and then to 30 mg as tolerated Special populations Elderly (over 65 years of age) Recommendations are as stated above for adults. Patients should be monitored carefully. Patients with renal or hepatic impairment No studies have been conducted. Paediatric population The safety and efficacy of MabCampath in children aged less than 17 years of age have not been established. No data are available. Method of administration The MabCampath solution must be prepared according to the instructions. All doses should be administered by intravenous infusion over approximately 2 hours. MabCampath 30mg/ml Child Dosage The safety and efficacy of MabCampath in children aged less than 17 years of age have not been established. No data are available. MabCampath 30mg/ml Elderly Dosage Recommendations are as stated for adults. Patients should be monitored carefully. Drug Information Secondary MabCampath 30mg/ml Precautions, Reactions and Contraindications MabCampath 30mg/ml Special Precautions MabCampath 30mg/ml Special Precautions Acute adverse reactions, which may occur during initial dose escalation and some of which may be due to the release of cytokines, include hypotension, chills/rigors, fever, shortness of breath and rashes. Additional reactions include nausea, urticaria, vomiting, fatigue, dyspnoea, headache, pruritus, diarrhoea and bronchospasm. The frequency of infusion reactions was highest in the first week of therapy, and declined in the second or third week of treatment, in patients treated with MabCampath both as first line therapy and in previously treated patients. If these events are moderate to severe, then dosing should continue at the same level prior to each dose escalation, with appropriate premedication, until each dose is well tolerated. If therapy is withheld for more than 7 days, MabCampath should be reinstituted with gradual dose escalation. Transient hypotension has occurred in patients receiving MabCampath. Caution should be used in treating patients with ischaemic heart disease, angina and/or in patients receiving an antihypertensive medicinal product. Myocardial infarction and cardiac arrest have been observed in association with MabCampath infusion in this patient population. Assessment and ongoing monitoring of cardiac function (e.g. echocardiography, heart rate and body weight) should be considered in patients previously treated with potentially cardiotoxic agents. It is recommended that patients be premedicated with oral or intravenous steroids 30-60 minutes prior to each MabCampath infusion during dose escalation and as clinically indicated. Steroids may be discontinued as appropriate, once dose escalation has been achieved. In addition, an oral antihistamine, e.g. diphenhydramine 50 mg, and an analgesic, e.g. paracetamol 500 mg, may be given. In the event that acute infusion reactions persist, the infusion time may be extended up to 8 hours from the time of reconstitution of MabCampath in solution for infusion. Profound lymphocyte depletion, an expected pharmacological effect of MabCampath, inevitably occurs and may be prolonged. CD4 and CD8 T-cell counts begin to rise from weeks 8-12 during treatment and continue to recover for several months following the discontinuation of treatment. In patients receiving MabCampath as first line therapy, the recovery of CD4+ counts to 200 cells/µl occurred by 6 months post-treatment, however, at 2 months post-treatment the median was 183 cells/µl. In previously treated patients receiving MabCampath, the median time to reach a level of 200 cells/μl is 2 months following last infusion with MabCampath but may take more than 12 months to approximate pretreatment levels. This may predispose patients to opportunistic infections. It is highly recommended that anti-infective prophylaxis (e.g. trimethoprim/sulfamethoxazole 1 tablet twice daily, 3 times weekly, or other prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and an effective oral anti-herpes agent, such as famciclovir, 250 mg twice daily) should be initiated while on therapy and for a minimum of 2 months following completion of treatment with MabCampath or until the CD4+ count has recovered to 200 cells/μl or greater, whichever is the later. Because of the potential for Transfusion Associated Graft Versus Host Disease (TAGVHD) it is recommended that patients who have been treated with MabCampath receive irradiated blood products. Asymptomatic laboratory positive Cytomegalovirus (CMV) viraemia should not necessarily be considered a serious infection requiring interruption of therapy. Ongoing clinical assessment should be performed for symptomatic CMV infection during MabCampath treatment and for at least 2 months following completion of treatment. Transient grade 3 or 4 neutropenia occurs very commonly by weeks 5-8 following initiation of treatment. Transient grade 3 or 4 thrombocytopenia occurs very commonly during the first 2 weeks of therapy and then begins to improve in most patients. Therefore, haematological monitoring of patients is indicated. If a severe haematological toxicity develops, MabCampath treatment should be interrupted until the event resolves. MabCampath treatment may be reinstituted following resolution of the haematological toxicity. MabCampath should be permanently discontinued if autoimmune anaemia or autoimmune thrombocytopenia appears. Complete blood counts and platelet counts should be obtained at regular intervals during MabCampath therapy and more frequently in patients who develop cytopenias. It is not proposed that regular and systematic monitoring of CD52 expression should be carried out as routine clinical practice. However, if retreatment is considered, it may be prudent to confirm the presence of CD52 expression. In data available from first line patients treated with MabCampath, loss of CD52 expression was not observed around the time of disease progression or death. Patients may have allergic or hypersensitivity reactions to MabCampath and to murine or chimeric monoclonal antibodies. Medicinal products for the treatment of hypersensitivity reactions, as well as preparedness to institute emergency measures in the event of reaction during administration is necessary. Males and females of childbearing potential should use effective contraceptive measures during treatment and for 6 months following MabCampath therapy. No studies have been conducted which specifically address the effect of age on MabCampath disposition and toxicity. In general, older patients (over 65 years of age) tolerate cytotoxic therapy less well than younger individuals. Since CLL occurs commonly in this older age group, these patients should be monitored carefully. In the studies in first line and previously treated patients no substantial differences in safety and efficacy related to age were observed; however the sizes of the databases are limited. 抗CD52抗体Alemtuzumab(Campath 1H)-获FDA批准治疗慢性淋巴细胞白血病上市的人源化单克隆抗体生物“静脉注射”剂 Alemtuzumab是抗CD52人源化单克隆抗体。CD52在正常T和B淋巴细胞和恶性淋巴细胞呈高表达，却不表达于造血干细胞。一项多中心的临床研究促促使FDA于2001年批准Alemtuzumab用于治疗B细胞慢性淋巴细胞白血病。93例B细胞性慢性淋巴细胞性白血病患者均为烷化剂和氟达拉滨治疗失败患者。 Alemtuzumab的用法为30 mg/次静脉注射，每周三次，共12周。总缓解率为33%，其中完全缓解率为2%。总的中位进展时间为4.7个月，其中肿瘤缓解者的中位进展时间为9.5个月；总的生存时间为12个月，而肿瘤缓解者的生存时间为32个月。常规给予抗菌素和抗病毒药以减小免疫抑制相关性机会性感染的发生。副作用为输液反应，另有27%的患者发生3至4度感染（主要为细菌性）[24]。一项II期临床研究显示，Alemtuzumab治疗慢性淋巴细胞性白血病的缓解率为87%，其中完全缓解率达19%。而且经过18个月仍未达到治疗失败时间[25]。目前，Alemtuzumab、Rituximab和氟达拉滨三药联合治疗慢性淋巴细胞性白血病的临床研究正在进行中。也有人尝试将Alemtuzumab用于治疗T细胞淋巴瘤。 人源化单克隆抗体MabCampath在EC获准 人源化单克隆抗体alemtuzumab（商品名 MabCampath）已在EC获准用于治疗B-细胞慢性淋巴白血病（B－CLL）。计划于 8月份在欧洲上市。 MabCampath适用于曾用烷化剂治疗或用氟达拉滨（ fludarabine）治疗失败的 CLL病人，在4月EC CPMP推荐批准该产品用于此病人群，条件是公司要进行一项Ⅲ期临床试验，以确认其安全性和有效性。 CLL是成人白血病最流行的一种形式，在欧洲有约6万例病人，估计每年有8000新诊断病例。该病的特点是癌性白血病淋巴细胞不可控制的积聚。 MabCampath通过与 CD52 抗原在白血病细胞表面结合，并通过抗体依赖性细胞溶解作用将它们杀死。 alemtuzumah已在美国销售。在美国由 Berlex公司以商品名Campath上市，随后该产品于5月在EC获准。M＆I公司于1999年提出最初的生物制品许可证申请（ BLA），但 FDA认为申请资料还不充分。一年以后，FDA 的肿瘤药顾问委员会推荐批准该产品，但要求公司进行附加的安全性临床试验。在EC， MabCampath将由Schering AG公司上市。M&I公司在日本和东亚保留所有权。 --------------------------------------------------------------- 产地国家：美国 原产地英文商品名: CAMPATH 30MG/ML/VIAL 3VIALS/BOX 原产地英文药品名: ALEMTUZUMAB 中文参考商品译名: 坎帕斯 30毫克/毫升/瓶 3瓶/盒 中文参考药品译名: 阿仑单抗 生产厂家中文参考译名: ILEX PHARMACEUTICALS 生产厂家英文名: ILEX PHARMACEUTICALS --------------------------------------------------------------- 产地国家：德国 原产地英文商品名: MabCampath  30MG/ML/VIAL 3VIALS/BOX 原产地英文药品名: ALEMTUZUMAB 中文参考商品译名: 坎帕斯 30毫克/毫升/瓶 3瓶/盒 中文参考药品译名: 阿仑单抗 生产厂家中文参考译名: 拜耳医药 生产厂家英文名: Bayer medicine