卡妥索单抗注射剂Removab 50 Mikrogramm Konzentrat说明书

药店国别： 产地国家：德国 处方药：是 所属类别： 50微克/注射器 包装规格： 50微克/注射器 计价单位：盒 生产厂家中文参考译名： 生产厂家英文名：Fresenius Biotech Gmbh 原产地英文商品名：Removab 50ug/SYRINGE 原产地英文药品名：atumaxomab 中文参考商品译名：Removab预填充注射剂 50微克/注射器 中文参考药品译名：卡妥索单抗 曾用名：

简介

英文药名：Removab(catumaxomab) 中文药名：卡妥|索单抗注射剂 生产厂家：费森尤斯公司 药品简介 商品名：Removab 药品名：Catumaxomab 开发商：本品由德国Trion Pharrna公司开发，于2009年4月首次在德国上市适应症本品为一三功能大鼠/小鼠杂交单克隆抗体，特异性靶向上皮细胞粘附分子(EpCAM)和CD3抗原。大部分肿瘤EpCAM抗原过表达。CD3作为T细胞受体的一部分表达于成熟T细胞。本品Fc区段第三个功能结合点可通过Fcγ受体和免疫辅佐细胞相互作用。 由于本品的结合特性，肿瘤细胞、T细胞和免疫辅佐细胞得以近距离接触，因此，既定的针对肿瘤细胞的免疫反应得以发生，这些免疫反应包括T细胞活化、抗体依赖细胞介导细胞毒作用(ADCC)，补体依赖细胞毒作用和吞噬作用。结果导致肿瘤细胞瓦解。 本品适用于标准治疗无效或不可行的因EpCAM阳性肿瘤所致的恶性腹水的治疗。 临床评价本品获准上市的依据是一项随机对照开放标示的Ⅱ/Ⅲ期临床研究(IP-REM-AC-01)结果。 该项临床研究考察了本品对258例无法再进行化疗的伴有恶性腹水的EpCAM阳性癌症患者的疗效，其中129例为卵巢癌患者，其余分别为胃肠癌、乳腺癌、胰腺癌以及其他癌患者，受试者按2：l的比例随机分成两组，其中一组(n=l70)在穿刺术后第0、3、7和10天以剂量递增的方式腹腔注射本品(10、20、50、150μg)，另一组(n=88)穿刺术后不给药;有157例患者接受了至少1个剂量的本品，131例患者则接受了4个剂量。 该研究设定的主要指标为无穿刺中位生存期(即给药结束后至需再行穿刺抽取腹水或死亡的时间)，结果显示治疗组和对照组的无穿刺中位生存期分别为46天和11天;与对照组相比，治疗组的给药结束后至需再行穿刺抽取腹水的时间、疾病进展的中位时间以及接受4种剂量本品治疗的患者的中位生存期均更长(77、111、86天对13、35、68天);此外，从医生和患者的问卷调查发现，本品治疗组患者的腹水症状也有所改善。 在对各种癌症的治疗中，卵巢癌的疗效最显著，本品治疗组(n=88)和对照组(n=44)的无穿刺中位生存期分别为52天和11天，到给药结束后需再行穿刺抽取腹水的时问分别为71天和1l天，给药结束后第二次穿刺抽取腹水的时间分别为26天和13天，疾病进展的中位时间分别为111天和35天，接受4种剂量本品治疗的患者的中位生存期比对照组长29天。 胃癌的疗效与之相似：本品治疗组和对照组的无穿刺中位生存期分别为44天和15天，给药结束后需再行穿刺抽取腹水的时间分别为118天和15天，接受4种剂量本品治疗的患者的中位生存期比对照组长27天。其他癌症患者中，本品治疗组和对照组的无穿刺中位生存期分别为30天和9天，给药结束后需再行穿刺抽取腹水的中位时间分别为69天和15天。给予本品治疗的卵巢癌患者的总生存期和无进展生存期均有所延长。 不良反应 普遍发生的不良反应(发生率≥10%)有淋巴细胞减少症，腹痛，恶心，呕吐，腹泻，发热，疲劳，寒战和疼痛。常见的不良反应(发生率在1%～10%之间)包括白细胞增多症，贫血，中性白细胞增多症，血小板病，心动过速，眩晕，肠梗阻，便秘，消化不良，腹胀，肠胃胀气，胃病，胃食管返流，口腔炎，虚弱，流感样病，胸痛，水肿，口渴，高胆红素血症，细胞溶解性肝炎，感染，硬红斑，尿路感染，食欲减退，低钠血症，低钙血症，低钾血症，低蛋白质血症，脱水，高血糖症，关节痛，背痛，肌痛，头痛，头晕，焦虑，失眠，少尿，白细胞尿，蛋白尿，血尿，呼吸困难，胸腔积液，皮疹，过敏性皮炎，皮肤反应，红斑，多汗症，瘙痒症，荨麻疹，低血压，高血压，面红，热潮红。比较罕见(发生率≤l%)的不良反应包括胃出血，肠梗阻，注射部位炎症，渗漏，导管感染，皮肤感染，惊厥，急性肾衰竭，肺栓塞，严重胸腔积液，严重过敏性皮炎，严重皮疹，严重表皮脱落，严重皮肤反应等。 本品不可腹腔推注或应用其它非腹膜内给药方式。细胞因子释放综合征：本品结合至免疫细胞和肿瘤细胞后将启动前炎性因子和细胞毒性细胞因子的释放，因此在本品治疗期间及之后，患者出现发热、恶心、呕吐和寒战等细胞因子释放综合征症状的情况非常普遍。呼吸困难和低/高血压也很常见。 在临床研究中，为控制疼痛和发热，在本品给药之前静脉注射1000 mg对乙酰氨基酚是常规处理。但是，尽管进行了预防性用药，仍有患者出现了3级以上的上述不良反应。除对乙酰氨基酚外，其它止痛/退热/抗炎标准用药也推荐使用。系统性炎症反应综合征不太常见，但也有发生，多半在本品注射后24小时内出现，表现为发热、心动过速、白细胞增多等。以止痛/退热/非甾体抗炎药预先进行预防，可降低风险。 用法与用量 本品经由腹腔输注。使用前需以50 mL 0.9%氯化钠溶液稀释，再通过恒速输液泵腹腔内给药。 本品推荐的给药方案为：第1剂：剂量为10 mg，给药时间为“第0天”;第2剂：剂量为20 mg，给药时间为“第3天”;第3剂：剂量为50 mg，给药时间为“第7天”;第4剂：剂量为100 mg，给药时间为“第10天”。给药间隔至少2天，可视不良反应情况适当延长。总治疗时间不超过20天。制剂本品为预填充注射剂，有两种规格，每支注射器分别装入0.1 mL(10μg)溶液和0.5 mL(50μg)溶液。规格：每支：10ug 50ug50ug厂家：德国 英文版说明书 Fresenius Biotechcatumaxomab (Removab®)Appraisal informationcatumaxomab (Removab®) 10 micrograms concentrate for solution for infusioncatumaxomab (Removab®) 50 micrograms concentrate for solution for infusionRemovab (catumaxomab) is now available to treat malignant ascites due to EpCAM-positive carcinomas where standard therapy is not available or not feasible.Catumaxomab is a hybrid rat-mouse monoclonal antibody that has binding sites for the epithelial cell adhesion molecule (EpCAM) and CD3, a component of the T cell receptor. It stimulates a range of immune responses against tumour cells.A randomised, open-label trial compared catumaxomab (as 4 intraperitoneal infusions) plus paracentesis with paracentesis alone in 258 patients with symptomatic malignant ascites due to EpCAM-positive carcinomas. Median puncture-free survival, the primary endpoint, was significantly longer with catumaxomab than with drainage alone (46 days vs 11 days; p<0.0001). Median time to the next therapeutic puncture was also significantly increased in the catumaxomab group compared with the drainage-alone group (77 days versus 13 days; p<0.0001) and there was a trend towards increased overall survival with catumaxomab (72 days vs 68 days; p=0.0846).----------------------------------------------------Removab concentrate for solution for infusionWhat is it and how is it used?Removab contains the active substance catumaxomab, a monoclonal antibody. It recognises a protein on the surface of cancer cells and recruits immune cells to destroy them.Removab is used to treat malignant ascites,when standard treatment is not available or no longer feasible. Malignant ascites is an accumulation of fluid in the abdominal space (peritoneal cavity) resulting from certain types of cancer.What do you have to consider before using it?Do not use Removabif you are allergic (hypersensitive) to catumaxomab or any of the other ingredients of Removab (see section 6)if you are allergic (hypersensitive) to murine proteins (from rat and / or mouse)Take special care with RemovabIt is important to tell your doctorif you have any of the following:undrained fluid in your abdominal cavitycold hands and feet, light headedness, difficulty passing urine, increased heart rate, and weakness (symptoms of low blood volume)weight gain, weakness, shortness of breath and fluid retention (symptoms of low blood protein levels)feeling dizzy and faint (symptoms of low blood pressure)problems with your heart and circulationkidney or liver problemsan infection.Removab should not be used in children and adolescents under 18 years of age.Before you start using Removab your doctor will check your:Body Mass Index (BMI), which depends on your height and weightKarnofsky Index, a measure of your general performance status. You are required to have a BMI above 17 (after drainage of the ascites fluid) and a Karnofsky Index above 60 to use this medicine.Taking other medicinesPlease tell your doctor or pharmacist if you are taking or have recently taken any other medicines including those obtained without a prescription.Pregnancy and breast-feedingYou should not use Removab if you are pregnant unless clearly necessary. Talk to your doctor if you are, might be or are planning to become pregnant.If you are breast-feeding, talk to your doctor before starting treatment.Driving and using machinesThere are no studies on the effects of Removab on the ability to drive and use machines.However, if you experience side effects such as dizziness or chills during or after administration, you should not drive or use machines until they disappear.How is it used?You will be given Removab under the supervision of a doctor experienced in treating cancer. After the Removab infusion you will be observed as decided by your doctor.Before starting and during treatment, you will be given other medicines to reduce fever, pain or inflammation caused by Removab.A catheter will be placed in your abdominal space (intraperitoneal) for the whole treatment period, until the day after your last infusion.Removab is given as 4 intraperitoneal infusions with increasing dose (10, 20, 50 and 150 micrograms), separated at least by a 2-day break.If you have any further questions on the use of this product, ask your doctor.What are possible side effects?Like all medicines, Removab can cause side effects, although not everybody gets them.These side effects may occur with certain frequencies, which are defined as follows: very common: affects more than 1 user in 10common: affects 1 to 10 users in 100uncommon: affects 1 to 10 users in 1,000rare: affects 1 to 10 users in 10,000very rare: affects less than 1 user in 10,000not known: frequency cannot be estimated from the available data.Serious side effectsSome of these side effects may be serious and require medical treatment. You should tell a doctor immediately if you experience any of these serious side effects.Very common serious side effects:Abdominal painFeverCommon serious side effects:Abdominal pain accompanied by difficulty passing stoolsShortness of breathUncommon serious side effects:Very fast heart beat, fever, shortness of breath, feeling faint or light-headed within 24 hours of infusion.Blockage in the gut or bowelBleeding in the stomach, shown by the vomiting of blood or the passage of red or black stoolsInflammation and pain or burning and stinging in the area around the catheterInfection of the skinFitsLung problems including blood clot in the lungs or accumulation of fluid around the lungs which cause chest pain and breathlessnessSevere skin reactions such as flaking of the skin, rash and sensitive skinSevere kidney problemsOther side effectsVery common side effects:Feeling sick (nausea), vomiting and diarrhoeaTiredness, pain and chillsReduction in number of white blood cellsCommon side effects:Increased number of white blood cellsIncreased clotting factorsReduction in red blood cells (anaemia)Decreased blood levels of calcium, potassium and sodiumDecreased blood protein levelsHigh blood sugarA very fast heart beatSpinning sensationConstipation, indigestion, stomach problems, heartburn, passing wind and mouth ulcersFlu-like symptomsFluid retentionDizzinessor headacheChest painIncreased sweating, feeling thirsty and weakLiver problems and yellowing of the skin (jaundice)Infectionsincluding bladder infectionsLumps under the skin on the back of the legs that may become sores and leave scarsIncreased protein levels or white blood cells in urineLoss of appetiteDehydrationBack pain, aching muscles and jointsFeeling anxious and having difficulty sleeping.Passing small amounts of urine or finding blood in the urineSkin redness, itchy rash, hives, sensitive skin or a sudden widespread rashHigh or low blood pressureFlushing and hot flushes.If any of the side effects become serious or if you notice any side effects not listed in this leaflet, tell your doctor or nurse.How should it be stored?Keep out of the reach and sight of children.Do not use Removab after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.Store in a refrigerator (2°C – 8°C). Do not freeze. Store in the original package in order to protect from light.https://europepmc.org/articles/PMC2840231