拉布立酶注射剂|Elitek (Rasburicase)
【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*3支/盒    7.5毫克/瓶+1安醅稀释液/套

ELITEK (rasburicase) Is the First Recombinant Uricolytic Agent Approved in the U.S.1,23

Rapid & Reliable ELITEK (rasburicase)
96% of adult patients experienced uric acid reduction ≤2 mg/dL 4 hours after 1st dose1,2
87% of adult patients receiving ELITEK (rasburicase) maintained uric acid concentrations ≤ 7.5 mg/dL from day 3 to day 71,2

Important Safety Information for ELITEK (rasburicase)
Anaphylaxis: ELITEK can cause severe hypersensitivity reactions including anaphylaxis. Immediately and permanently discontinue ELITEK in patients who experience a serious hypersensitivity reaction.

Hemolysis: Do not administer ELITEK to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Immediately and permanently discontinue ELITEK in patients developing hemolysis. Screen patients at higher risk for G6PD deficiency (e.g., patients of African or Mediterranean ancestry) prior to starting ELITEK.

Methemoglobinemia: ELITEK can result in methemoglobinemia in some patients. Immediately and permanently discontinue ELITEK in patients developing methemoglobinemia.

Interference with Uric Acid Measurements: ELITEK enzymatically degrades uric acid in blood samples left at room temperature. Collect blood samples in pre-chilled tubes containing heparin and immediately immerse and maintain sample in an ice water bath. Assay plasma samples within 4 hours of collection.

Among the 347 (265 pediatric; 82 adult) patients for whom all adverse reactions regardless of severity were assessed in Studies 1, 2 and 3, as well as an uncontrolled safety trial, the most frequently observed adverse reactions (incidence ≥10%) were vomiting (50%), fever (46%), nausea (27%), headache (26%), abdominal pain (20%), constipation (20%), diarrhea (20%), mucositis (15%), and rash (13%).

Among the 275 adult patients in Study 4, hypersensitivity reactions occurred in 4.3% of patients treated with the ELITEK alone and 1.1% of patients treated with the ELITEK/oral allopurinol combination. Hypersensitivity reactions included arthralgia, injection site irritation, peripheral edema, and rash. The most common Grade 3 or 4 adverse reactions regardless of relationship to study drug in the 3 arms of Study 4 (ELITEK alone; ELITEK combined with oral allopurinol; oral allopurinol alone) were sepsis (5.4%; 6.5%; 4.4%), hypophosphatemia (4.3%; 6.5%; 6.6%), anxiety (3.3%; 0%; 0%), abdominal pain (3.3%; 4.3%; 2.2%), hyperbilirubinemia (3.3%; 2.2%; 4.4%), and increased alanine aminotransferase (3.3%; 4.3%; 2.2%), respectively.

The following serious adverse reactions occurred with a difference in incidence of greater than or equal to 2% in patients receiving ELITEK compared to patients receiving oral allopurinol in randomized studies (Study 1 and Study 4): pulmonary hemorrhage, respiratory failure, supraventricular arrhythmias, ischemic coronary artery disorders, and abdominal and gastrointestinal infections.

Indication
ELITEK® is indicated for the initial management of plasma uric acid levels in pediatric and adult patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anti-cancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid. ELITEK is indicated for only a single course of treatment.

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原产地英文商品名:
ELITEK 7.5mg/vial+1amp diluent/kit
原产地英文药品名:
RASBURICASE
中文参考商品译名:
ELITEK 7.5毫克/瓶+1安醅稀释液/套
中文参考药品译名:
拉布立酶
生产厂家中文参考译名:
赛诺菲－圣德拉堡
生产厂家英文名:
Sanofi Synthelabo

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原产地英文商品名:
ELITEK 1.5mg/vial 3vials+3amps diluent/kit
原产地英文药品名:
RASBURICASE
中文参考商品译名:
ELITEK 1.5毫克/瓶 3瓶+3安醅稀释液/套
中文参考药品译名:
拉布立酶
生产厂家中文参考译名:
赛诺菲－圣德拉堡
生产厂家英文名:
Sanofi Synthelabo