【药品名称】拉布立酶注射剂
   
【药物别名】 Fasturtec

拉布立酶(rasburicase).Sanofi-Synthelabo 公司生产的重组尿酸氧化酶Rasburicase为冻干粉针制剂,商品名为Fasturtec ，Elitek

该药于2001 年6月在德国和英国以Fasturtec 的商品名首次批准上市。现已整个欧洲以及在美国上市，在美国以Elitek的名称于2002年7月被批准上市，用于预防及治疗血癌所引起的高尿酸血症注射液。

【药理毒理】

高尿酸血症是白血病和淋巴瘤及其治疗的一种常见并发症。对于骨髓增生性疾病或造血系统恶性肿瘤病人，核酸的分解代谢是恶性细胞群增加更新的结果，从而增加嘌呤的代谢，导致尿酸血浓度的增高。癌症的积极治疗方案可引起细胞溶解增多和嘌呤代谢物的释放。肿瘤溶解综合征的特征为严重高尿酸血症、高磷酸盐血症、高钾血症、高钙血症和急性肾衰。作为高尿酸血症的结果，当尿中的尿酸达到过饱和，肾小管和远端收集系统出现尿酸结晶会引起肾功能不全。 尽管控制代谢异常可降低急性肾衰的危险性，然而，在开始治疗后，晚期伯基特淋巴瘤和B细胞急性淋巴细胞白血病患儿25%仍会出现急性肾衰。 高尿酸血症的标准预防或治疗方案为使用别嘌醇（allopurinol）治疗，进行尿液碱化，水合和渗透性利尿。别嘌醇通过抑制黄嘌噙氧化酶阻滞尿酸形成，但会增加肾脏排泄尿酸前体（次黄嘌呤和黄嘌呤）的负荷。与次黄嘌呤不同，黄嘌呤在尿中比尿酸难溶。有时别嘌醇治疗的病人也可出现黄嘌呤肾病和结石。此外，对于病人体内存留的尿酸的排泄，使用别嘌醇治疗无效。
本品为由来自曲霉菌DNA克隆的酿酒酿母（Saccharomyces cerevisae）基因工程突变株产生的重组尿酸氧化酶。尿酸氧化酶可催化尿酸的氧化，形成尿囊素，后者为一种比较容易排泄的代谢物，其溶解度为尿酸的5～10倍。大多数哺乳动物体内均有内源性尿酸氧化酶，但人体则缺乏这种酶。法国Sanofi Synthelabo公司生产的非重组尿酸氧化酶，由黄曲霉培养液纯化而得，治疗高尿酸血症疗效较别嘌醇显着。然而，非重组产品发生急性过敏反应（如支气管痉挛，低氧血症）者约为5%，包括以往无过敏史的病人或罹患高铁血红蛋白血症和6-磷酸葡萄糖脱氢酶（G-6-PD）缺乏的溶血性贫血病人。
   
【药 动 学】输注本品一日0.2mg/kg，约2～3天可达到稳态血药浓度，消除半衰期约为19小时，儿童和青少年较成年人的本品清除率高。肾或肝功能不全病人无需进行剂量调整。本品开始输注后24小时内呆使尿酸浓度降至2～3mg/dl以下。高尿酸血症病人使用本品治疗4小时，尿酸水平达到正常，而使用别嘌醇则需要24小时才能达到正常。给药期间一般可保持低尿酸水平，此外，在进行化疗时或化疗后，可能会出现一过性尿酸升高。 本品为由经基因工程改造的酿酒酿母株产生的重组尿酸氧化酶。分子量约为34kDa。在血液学肿瘤病人化疗初期使用本品可预防和治疗高尿酸血症，进而预防急性肾衰。本品应在化疗前或化疗早期使用。目前尚缺乏有关联合治疗的资料。

【适 应 证】本品为重组尿酸氧化酶，可用于治疗和预防具有高危肿瘤溶解综合征的血液恶性肿瘤病人的急性高尿酸血症，尤其适用于化疗引起的高尿酸血症病人。
   
【不良反应】使用本品可能出现的常见不良反应有发热，恶心，呕吐和皮疹。发生率分别为6.8%，1.7%,1.4%和1.4%。腹泻（0.9%），头痛0.9%,过敏(0.6%)等较少见。
   
【用法用量】本品推荐剂量为一日0.20mg/kg，于30分钟内静脉滴注。用药时加至50ml的9mg/ml氯化钠溶液（0.9% w/v)中。本品治疗时间一般为5～7天。 本品用药不影响化疗药物的用药时间和化疗方案。但输注本品的输注管不应与输注化疗药物的同用，以预防可能的药的间的不相容性。如不能使用不同的输液管，则应在输注化疗药物和本品之间使用氯化钠溶液洗净。
   
【制剂规格】本品为1.5mg/ml瓶装粉针剂。 1.5mg/ml*3支/盒
【开发厂家】(法国)Sanofi-Synthelabo公司

FASTURTEC

Fasturtec Information

Fasturtec is a brand name for a medicine known under the generic name of Rasburicase. This is a drug that stimulates the organism increasing the rate at which it breaks down uric acid, used as part of the chemotherapeutic treatment administered in certain cases of cancer. This drug may only be administered under the direct supervision of a health care professional, authorized and specialized in the manipulation and administration of chemotherapeutic agents.

Fasturtec Indications

Fasturtec is a chemotherapeutic product employed during treatment for certain types of cancer. It is used to treat abnormal increases of uric acid levels that may result from the tumor breakdown. Specialized health care professionals may direct the administration of this medicine for the treatment of other medical conditions that are not mentioned / included here. For further information on the additional uses of this medicinal product it is recommended to consult a specialized health care provider.

Fasturtec Warnings

Fasturtec should not be administered to patients that are suffering from a glucose 6-phosphate dehydrogenase deficiency, to individuals that are suffering from hemolytic reactions or methemoglobinemia or to patients that are allergic to this drug or any of its ingredients. Before starting a therapy course with this drug, several tests may be performed to establish the safety of the treatment.

Fasturtec may not be safe for use in patients that are or may become pregnant during the course of the therapy. Also, this drug may not be suitable for use in patients that are breast feeding a baby. In you are pregnant, plan to become pregnant or are nursing a baby, you should consult with your personal physician, as he or she will be able to inform you of the exact risks and benefits of the Fasturtec treatment and help you determine what treatment plan is best suited to your case.

Other medical conditions may also affect your Fasturtec treatment. As such, you should ensure that the prescriber is familiar with your general health condition and medical history.

Fasturtec Intake Guidelines

Fasturtec may only be administered by a specialized health care professional, who is authorized in the handling and administering of chemotherapeutic agents; the administration should take place in a hospital setting. Typically, the patient is kept under medical observation in a clinic or a hospital for a few days after the initial dose, in order for the health care professional to closely monitor the patient’s response to the treatment and to detect any reactions that may appear. After the initial time period, the monitoring will continue through regular blood testing and clinical examinations. The follow-up visits are equally important in order to ensure the safety of the Fasturtec treatment, and it is strongly recommended that the patient does not miss any of the scheduled appointments with his or her health care specialist.

Fasturtec Dosage

The exact Fasturtec dosage, administration frequency and treatment duration will be established by the examining health care specialist, as he or she will take into account a number of factors that may vary from one patient to another. These factors include, but are not limited to: the patient’s age, the type of cancer he or she is suffering from, his or her general health condition and the response to the treatment. The Fasturtec doses will be administered in a clinic or hospital, under the direct supervision of the specialized health care professional.

Fasturtec Overdose

As Fasturtec is only administered under the direct supervision of a specialized health care professional, an overdose with this drug is unlikely. However, if an overdose is suspected, the patient should receive emergency medical attention as severe complications may appear. The exact symptoms of an overdose with this drug have not been established at this point; however it is suspected that a Fasturtec overdose is manifested through an exacerbation of the side effects that may be associated with this drug.

Fasturtec Missed Dose

Fasturtec is only administered in a clinic or hospital by a specialized health care professional. As such, missing any doses of the medicine is highly unlikely. However, this is possible in certain situations (such as in the case of an outpatient clinic). If you miss a dose of the medicine, it is strongly recommended to contact your personal health care provider for further information. Prompt measures need to be taken in order for the situation to be corrected.

Fasturtec Side Effects

Fasturtec may lead to the appearance of, or may aggravate pre-existing blood conditions such as hemolytic reactions or methemoglobinemia. Such situations are rare, but severe. Also, in some cases the patient may suffer from an allergic reaction to this medicine, requiring immediate medical attention. If any symptoms of an allergic reaction appear (hives, rashes, dizziness, chest pain, swelling of the lips, face or tongue, bluish coloring of the lips or skin, breathing problems) the patient should immediately contact his or her personal health care specialist.

More common side effects associated with Fasturtec therapy include abdominal pain, diarrhea, rashes, fever, headaches, constipation or sores on the mucosal membrane of the mouth. Other side effects may appear as well. Any unexpected signs or symptoms that may appear during the Fasturtec treatment should be immediately brought to the attention of the supervising health care specialist.

Fasturtec Drug Reactions

Fasturtec may interact with other drugs and medicines, both prescription and over the counter. As such, it is best that you let your personal health care professional know of any other medication you are taking before starting a therapy course with this drug. In some cases, special adjustments to the dosage may be required or you may need special monitoring during the treatment. Also, you should inform the supervising health care specialist before starting any new medication therapy while you are following a treatment course with Fasturtec.

【拉布立酶注射剂临床应用】

Pui等报道，131例接受治疗的病人（21岁以下，88例男孩，43例女孩）中，因白血病或淋巴瘤而出现高尿酸血症，或认为存在着发生这一并发症的高度危险，进行多中心公开标签的非随机无对照研究。这些病人血清乳酸脱氢酶升高。研究分为两个阶段，第一阶段是剂量调整期（确定有效剂量），第二阶段是治疗期（确定有效性和安全性）。第一阶段起始剂量为一日0．15mg/kg，基于志愿者的研究结果以及非重组产品的等效剂量。而后每次增加 0.05mg/kg。调整后不再增加剂量。前11例病人使用本品0．15mg/kg治疗，能有效地纠正或预防高尿酸血症。而第12例病人，为年仅13岁的男孩，患有 Ⅲ期小型未分化非霍奇全淋巴瘤（NHL），4小时尿酸浓度出现一过性增高，尿酸水平为21．1mg/dl。根据研究设计，采用0．2mg/kg高剂量本品治疗。其后 14例病人的治疗证明，该剂量有效并用于治疗期。治疗期中2例在48小时时出现高尿酸血症，在24小时后消除。在48小时后有2例出现高尿酸血症，但经过治疗无1例持续24小时以上。131例病人的研究显示，本品的任何一种剂量均可显著降低尿酸浓度。而不管病人是否存在高尿酸血症。尽管由于强化化疗，两组病人中位尿酸浓度在整个疗程中均保持或接近0．5mg/dl。

Lascombes等报道的结果也类似，其为多中心公开标签研究，有107例新近诊断的具有出现高危高尿酸血症危险的NHL和继续淋巴细胞白血病（ALL）或急性非淋巴样白血病（ANL）患者参与，其中17例为成人，90例为儿童。在诱导化疗期，本品剂量为一日0.15mg/kg。

Goldman等进行的公开标签随机多中心的本品和别嘌醇对照研究，52例白血病或淋巴瘤儿科病人（年龄0.3～17岁）参与，按照尿酸水平（＜8mg/dl或＞ 8mg/dl）和疾病（淋巴瘤或白血病）分层。

使用本品治疗的病人，血中尿酸水平下降较快，并且在整个诱导化疗期间，始终维持在较低水平。在治疗的初始96小时内尿酸水平下降72％。随机接受本品的病人，首剂用药后4小时，血浆尿酸浓度降低86％。而别嘌醇组病人相应的为12％。此外，接受本品的基础高尿酸血症病人（10例）在4小时以内均达到5mg/dl以下的尿酸水平。而对照组，在开始使用别嘌醇治疗时的高尿酸血症病人无1例尿酸水平达到5mg/dl以下。2项研究均报道，本品治疗中肾功能出现变化。Pui等报道，高尿酸血症组及非高尿酸血症组病人肾功能均得到稳步改善。治疗第6 天肾功能均处于正常范围。开始使用本品治疗后无1 例病人需要透析，尽管25例病人患有与高比率肾脏并发症相关的恶性肿瘤。

Goldman等则报道，1例病人接受别嘌醇治疗，研穷期间由进行透析。与此不同，使用本品治疗的病人，肾功能不全和高尿酸血症在治疗期间得到改善而无需透析。