克拉屈滨注射剂[LEUSTATIN仿制药]Cladribine Injection

药店国别： 产地国家：美国 处方药：是 所属类别： 10毫克/10毫升/瓶 包装规格： 10毫克/10毫升/瓶 计价单位：瓶 生产厂家中文参考译名： 生产厂家英文名：FRESENIUS KABI 原产地英文商品名：Cladribine Injection (generic Leustatin) 10mg/10ml vial 原产地英文药品名：CLADRIBINE 中文参考商品译名：克拉屈滨(LEUSTATIN仿制药)1毫克/毫升 10毫升/瓶 中文参考药品译名：克拉屈滨 曾用名： 简介： 【药品名称】 克拉屈滨注射液 【化学名】 2-氯-6-氨基-9-(2-脱氧-β-D-赤型-呋喃戊糖基)嘌呤 【性状】 本品为无色或几乎无色的澄明液体。 【药理毒理】 药理作用：克拉屈滨的抑瘤活性与脱氧胞苷激酶和脱氧核苷酸激酶活性有关。它主要以被动转运进入细胞，在细胞内被脱氧胞苷激酶磷酸化，转化为克拉屈滨三磷酸，掺合到DNA分子中，妨碍DNA断裂后的修复作用，造成NAD和ATP的耗竭，破坏细胞代谢，影响细胞的DNA合成。因此本品对分化或静止期的淋巴细胞和单核细胞均有抑制DNA合成和修复的作用。毒理研究：遗传毒性：本品可造成DNA损失，引起哺乳动物细胞DNA链的断裂。本品可进入到人淋巴白细胞。在体外的Ames试验和中国仓鼠细胞染色体畸变试验中和体内的小鼠骨髓微核试验中，本品显示为DNA的断裂剂。生殖毒性：猕猴静脉给药，本品可引起精子细胞的生成抑制，但对人体生育力的影响不清楚。本品属妊娠D级的药品。致癌性：未进行本品的动物致癌试验研究，但根据遗传毒性研究结果不排除本品的致癌性可能。 【药代动力学】 尚缺乏克拉屈滨按目前临床推荐剂量用药时的中国人药代动力学资料。国外一项临床研究中入选肾功能正常的毛细胞白血病患者17名，按克拉屈滨0.09mg/kg/d的剂量连续静滴7日以上，测得平均稳态浓度为5.7ng/ml，总清除率为663.5ml/kg/h。对毛细胞白血病患者而言，本品的血清浓度和最终临床结果间未建立相关关系。另一项研究中包括各种血液恶性病患者8名，克拉屈滨按0.12mg/kg的剂量作2小时的静滴。滴注完毕时的平均血浆浓度为48±19ng/ml。可用双相或三相消除模型解释克拉屈滨在其中5位患者体内的消除过程。肾功能正常患者的终末半衰期为5.4h，清除率为978±422ml/kg/h，稳态分布容积为4.5±2.8L/kg。本品可以透过血脑屏障，脑脊液中的浓度约为血浆浓度的25%。血浆蛋白结合率约为20%。除已知的细胞毒作用机制外，目前尚不清楚本品在人体的代谢情况。实体瘤患者，按克拉屈滨3.5-8.1mg/m2/d的剂量连续静脉滴注5日，其尿排泄率平均为18%。目前尚未在肾功和肝功损伤患者体内进行克拉屈滨的消除研究。 【临床研究】 尚缺乏在中国人应用的临床研究资料。国外已在需治疗的、处于毛细胞白血病活动期的患者体内进行了克拉屈滨注射液的2项开放单中心临床研究。89位病人参与Scripps临床教学和研究基地的研究(研究A)，给药方案为静脉注射克拉屈滨注射液0.09mg/kg/d×7d。35位病人参与M.D.安德森癌症中心的研究(研究B)，给药方案为静脉注射3.6mg/m2/d×7da的克拉屈滨注射液。完全反应(CR)的标准为：外周血和骨髓毛细胞被清除，血红蛋白恢复至12g/dl，血小板计数为100×109/L，绝对中性粒细胞计数为1500×106/L。好的部分反应(GPR)标准为：血液学参数与完全反应的一致，骨髓毛细胞剩余量小于5%。部分反应(PR)标准为：骨髓毛细胞至少降低50%，且血液学参数与完全反应一致。病理复发标准为：骨髓毛细胞增至治疗前的25%。临床复发标准为：血细胞减少复发，特别是，血红蛋白降低值≥2g/dl，绝对中性粒细胞计数(ANC)降低值≥25%或血小板计数降低值≥50000。如果发现符合完全反应标准的病人随后出现骨髓毛细胞(<治疗前的25%)，我们将其归类为部分反应而不是完全反应的复发。可评价有效性的患者(N=106)，用上述血液学和骨髓反应标准评价其反应率，克拉屈滨注射液治疗后研究A和研究B的完全反应率分别为65%和68%，产生的联合完全反应率为66%。研究A和研究B的全部反应率(即完全反应+好的部分反应+部分反应)分别为89%和86%，联合全部反应率为88%。使用ITT(intention-to-treat)分析，且CR标准需有无脾肿大的依据(即体检时无可触及脾和CT扫描≤13cm)，研究A和研究B完全反应率分别为54%和53%，联合完全反应率为54%。研究A和研究B的全部反应率(CR+GPR+PR)分别为90%和85%，联合全部反应率为89%。完全反应病人反应(即骨髓、外周血无毛细胞和外周血参数正常化)的中位时间(治疗开始时测量)大约为4个月。由于骨髓吸引术和活组织检查未经常在外周血正常化时进行，所以实际上完全反应的中数时间可能比记录的时间稍短。试验截止时完全反应的中数持续时间为8-25个月。93位反应病人在试验截止时有7位的疾病有所进展，4位无外周血异常(病理过程)，仅局限于骨髓，3位病人出现外周血异常(临床过程)。7位对克拉屈滨注射液第一疗程无反应的病人接受了第二疗程的治疗。有足够随访、附加疗程的5位病人未改善其全部反应。 【适应症】 本品可试用于经干扰素治疗失败后活动性的伴有临床意义的贫血、中性粒细胞减少、血少板减少以及疾病相关症状的毛细胞白血病(HCL)治疗。 【用法与用量】 静脉滴注。治疗多毛细胞白血病时的建议剂量为克拉屈滨0.09mg/kg/d，作24小时的连续滴注，连用7天。不推荐其它的用药方案。根据己有经验，如患者对初始疗程无效，增加疗程不会获得更大利益。临用前按计算量。 【贮藏】 2-8度冷藏。 克拉屈滨英文版说明书 Brand Names: Cladribine Novaplus, LeustatinGeneric Name: cladribine (Pronunciation: CLAH drih been)----------------------------------------------------------------What is cladribine (Cladribine Novaplus, Leustatin)?Cladribine is a cancer (antineoplastic) medication. Cladribine interferes with the growth of cancer cells and slows their growth and spread in the body.Cladribine is used to treat a type of blood cancer (Hairy Cell Leukemia).Cladribine may also be used for purposes other than those listed in this medication guide.----------------------------------------------------------------What are the possible side effects of cladribine (CladribineNovaplus, Leustatin)?If you experience any of the following serious side effects, seek emergency medical attention or contact your doctor immediately:an allergic reaction (shortness of breath; closing of your throat;difficulty breathing; swelling of your lips, face, or tongue; or hives);decreased bone marrow function and blood problems (extreme fatigue;unusual bruising or bleeding; black, bloody or tarry stools; orfever, chills, sore throat, or signs of infection);muscle weakness;decreased or difficult urination, blood in the urine, or side pain;orfever.Other less serious side effects may be more likely to occur. Talk to your doctor if you experience:nausea, vomiting, diarrhea, or abdominal pain;loss of appetite;rash, itching or hives;cough;dizziness; orheadache.Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.----------------------------------------------------------------What is the most important information I should know about cladribine (Cladribine Novaplus, Leustatin)?Cladribine should only be administered under the supervision of a qualified healthcare provider experienced in the use of cancer chemotherapeutic agents.Serious side effects have been reported with the use of cladribine including: allergic reactions (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives); decreased bone marrow function and blood problems (extreme fatigue; easy bruising or bleeding; black, bloody or tarry stools; fever orchills; or signs of infection such as fever; chills, or sore throat); neurologic problems; kidney problems; and others. Talk to your doctor about the possible side effects from treatment with cladribine.----------------------------------------------------------------Who should not take cladribine (Cladribine Novaplus, Leustatin)?Before taking cladribine, tell your doctor if you havehave had recent vaccinations;liver disease;kidney disease; orbone marrow problems.You may not be able to take cladribine, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.Cladribine is in the FDA pregnancy category D. This means that cladribine is known to cause birth defects in an unborn baby.Do not take cladribine without first talking to your doctor if you are pregnant or could become pregnant during treatment.It is not known whether cladribine passes into breast milk. Do not take cladribine without first talking to your doctor if you are breast feeding a baby.----------------------------------------------------------------How should I use cladribine (Cladribine Novaplus, Leustatin)?Cladribine should only be administered under the supervision of a qualified healthcare provider experienced in the use of cancer chemotherapeutic agents.Your doctor will determine the correct amount and frequency of treatment with cladribine depending upon the type of cancer being treated and other factors. Talk to your doctor if you have any questions or concerns regarding the treatment schedule.Your doctor will probably want you to have regularly scheduled blood tests and other medical eva luations during treatment with cladribine to monitor progress and side effects.Skin accidentally exposed to cladribine should be rinsed thoroughly with soap and warm water.Your healthcare provider will store cladribine as directed by the manufacturer. If you are storing cladribine, follow the directions provided by your healthcare provider.----------------------------------------------------------------What happens if I miss a dose (Cladribine Novaplus, Leustatin)?Contact your doctor if you miss a dose of cladribine.----------------------------------------------------------------What happens if I overdose (Cladribine Novaplus, Leustatin)?If for any reason an overdose of cladribine is suspected, seek emergency medical attention or contact your healthcare provider immediately.Symptoms of a cladribine overdose tend to be similar to side effects caused by the medication, although often more severe.----------------------------------------------------------------What should I avoid while taking cladribine (Cladribine Novaplus, Leustatin)?Cladribine can lower the activity of your immune system making you susceptible to infections. Avoid contact with people who have colds, the flu, or other contagious illnesses and do not receive vaccines that contain live strains of a virus (e.g., live oral polio vaccine) during treatment with cladribine. In addition, avoid contact with individuals who have recently been vaccinated with a live vaccine.There is a chance that the virus can be passed on to you.Skin accidentally exposed to cladribine injection should be rinsed thoroughly with soap and warm water.----------------------------------------------------------------What other drugs will affect cladribine (Cladribine Novaplus, Leustatin)?Do not receive "live" vaccines during treatment with cladribine.Administration of a live vaccine may be dangerous during treatment with cladribine.Other medications may interact with cladribine. Talk to your doctor and pharmacist before taking any other prescription or over-the-counter medicines, including herbal products, during treatment with cladribine.----------------------------------------------------------------Where can I get more information?Your pharmacist has additional information about cladribine written for health professionals that you may read.Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.