英文药名：MYLOTARG(GEMTUZUMAB OZOGAMICIN)

中文药名：吉姆单抗 奥佐米星 米罗他

品牌药生产商：美国惠氏（Wyeth Pharmaceuticals）

药品介绍；

Mylotarg(gemtuzumab ozogamicin 注射剂)获得FDA的核准。美国家庭產品公司研发出一种新的化疗药物Mylotarg（gemtuzumab ozogamicin注射剂），这是依据单细胞繁殖抗体科技所研发而成的药物，已经获得美国食品暨药物管理局（ＦＤＡ）的核准。

吉妥单抗（gemtuzumab ozogamicin/Mylotarg）
抗CD33

【别名】Mylotarg 、CMA676、GO

【来源】重组人源化抗CD33单抗与细胞毒药物卡奇霉素的复合物。其中单抗为人鼠源氨基酸序列，与细胞毒抗肿瘤抗生素（卡奇霉素）偶联而成。

【作用机制】CD33表达于80%以上的急性髓性白血病（AML）患者白血病细胞上。本品静脉注射后，偶联屋中的抗体与复合物可被靶细胞胞饮。在细胞内，卡奇霉素从偶联物上水解游离，与DNA结合，使其双螺旋断列，导致细胞死亡。本品对表达CD33抗原的细胞毒性是不表达该抗原细胞的7万余倍。另外，由于造血干细胞不受药物治疗的影响，因而骨髓抑制较轻。作为一线药物治疗老年AML和高危MDS，Mylotarg 单药疗效不及化疗。目前正在进行Mylotarg 与氟达拉滨+阿糖胞苷、拓扑替康+阿糖胞苷和IL-11联合用药的临床研究。

【药动学】首次推荐剂量9mg/m2,静脉点滴持续2小时，半衰期45小时。第二次予以9mg/m2,半衰期延长至60小时，曲线下面积也比初次用药后增加一倍。

【适应症】首次复发的60岁以上CD33抗原阳性的急性髓细胞性白血病或不宜用细胞毒性药物治疗的CD33阳性的AML患者。

【不良反应】

全身反应：腹痛、乏力、背痛、寒战、发热、头痛、败血症、肿瘤溶解综合征。
循环系统：低血压、高血压、心律失常。
消化系统：食欲不振、恶心、呕吐、便秘、腹泻、腹胀、消化不良、胃炎、肝毒性、肝静脉血栓。
血液系统；骨髓抑制（较严重）、贫血、血小板减少、出血（鼻出血、脑出血、瘀斑、颅内出血、血尿、阴道出血）、弥漫性血管内凝血。
代谢系统：低钾血症、低镁血症、乳酸脱氢酶升高、高血糖。
肌肉骨骼：关节痛。
神经系统：抑郁、失眠、眩晕。
呼吸系统：呼吸困难、低氧血症、肺炎、咳嗽加重、咽炎、鼻炎。
皮肤及附属物：单纯疱疹、皮疹、局部反应、周围水肿。
【禁忌症】禁用于对本品或者本品中其他组成成分过敏的患者。

【规格】针剂，5mg/20ml；冻干粉剂。

【开发公司】Wyeth-Ayerst

Product Overview

MYLOTARG® (gemtuzumab ozogamicin for Injection)

Indication and Usage
MYLOTARG is indicated for the treatment of patients with CD33+ acute myeloid leukemia in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy. The safety and efficacy of MYLOTARG in patients with poor performance status and organ dysfunction has not been established.
The effectiveness of MYLOTARG is based on overall response rates. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival, compared to any other treatment.  
Important Safety Information
WARNINGS: MYLOTARG should be administered under the supervision of physicians experienced in the treatment of acute leukemia and in facilities equipped to monitor and treat leukemia patients. There are no controlled trials demonstrating efficacy and safety using MYLOTARG in combination with other chemotherapeutic agents. Therefore, MYLOTARG should only be used as single agent chemotherapy and not in combination chemotherapy regimens outside clinical trials. Severe myelosuppression occurs when MYLOTARG is used at recommended doses.
HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS, INFUSION REACTIONS, PULMONARY EVENTS: MYLOTARG administration can result in severe hypersensitivity reactions (including anaphylaxis), and other infusion-related reactions which may include severe pulmonary events. Infrequently, hypersensitivity reactions and pulmonary events have been fatal. In most cases, infusion-related symptoms occurred during the infusion or within 24 hours of administration of MYLOTARG and resolved. MYLOTARG infusion should be interrupted for patients experiencing dyspnea or clinically significant hypotension. Patients should be monitored until signs and symptoms completely resolve. Discontinuation of MYLOTARG treatment should be strongly considered for patients who develop anaphylaxis, pulmonary edema, or acute respiratory distress syndrome. Since patients with high peripheral blast counts may be at greater risk for pulmonary events and tumor lysis syndrome, physicians should consider leukoreduction with hydroxyurea or leukapheresis to reduce the peripheral white count to below 30,000/µL prior to administration of MYLOTARG. (See WARNINGS.)
HEPATOTOXICITY: Hepatotoxicity, including severe hepatic veno-occlusive disease (VOD), has been reported in association with the use of MYLOTARG as a single agent, as part of a combination chemotherapy regimen, and in patients without a history of liver disease or hematopoietic stem-cell transplant (HSCT). Patients who receive MYLOTARG either before or after HSCT, patients with underlying hepatic disease or abnormal liver function, and patients receiving MYLOTARG in combinations with other chemotherapy are at increased risk for developing VOD, including severe VOD. Death from liver failure and from VOD has been reported in patients who received MYLOTARG. Physicians should monitor their patients carefully for symptoms of hepatotoxicity, particularly VOD. These symptoms can include: rapid weight gain, right upper quadrant pain, hepatomegaly, ascites, elevations in bilirubin and/or liver enzymes. However, careful monitoring may not identify all patients at risk or prevent the complications of hepatotoxicity. (See WARNINGS and ADVERSE REACTIONS sections.)
MYLOTARG is contraindicated in patients with a known hypersensitivity to gemtuzumab ozogamicin or any of its components and in lactating mothers. MYLOTARG may cause fetal harm when administered to a pregnant woman. The reported rate of Grade 3 or 4 thrombocytopenia, neutropenia, anemia, and bleeding were 99%, 98%, 52%, and 13%, respectively. Thirty percent of patients experienced severe infections, including sepsis (17%) and pneumonia (8%).
The most common adverse events (≥20%) were fever (82%), nausea (68%), chills (66%), vomiting (58%), thrombocytopenia (50%), leukopenia (47%), headache (37%), asthenia (36%), abdominal pain (32%), diarrhea (32%), epistaxis (28%), dyspnea (26%), hypokalemia (26%), sepsis (26%), anorexia (25%), stomatitis (25%), liver function tests abnormal (24%), constipation (23%), anemia (22%), local reaction (22%), herpes simplex (21%), and hypotension (20%).
MYLOTARG can produce a postinfusion symptom complex of fever and chills, and less commonly hypotension and dyspnea during the first 24 hours after administration. Patients should receive diphenhydramine 50 mg po and acetaminophen 650-1000 mg po 1 hour before MYLOTARG administration. Two additional doses of acetaminophen 650-1000 mg po every 4 hours may be given. Fever and chills were commonly reported despite premedication with diphenhydramine and acetaminophen. Vital signs should be monitored during infusion and for 4 hours following infusion. Methylprednisolone given prior to MYLOTARG infusion may ameliorate infusion-related symptoms.
Severe myelosuppression will occur in all patients given the recommended dose of this agent. Careful hematologic monitoring is required. Systemic infections should be treated.

マイロターグ点滴静注用5mg

商標名
MYLOTARG Injection 5mg
一般名
ゲムツズマブオゾガマイシン（遺伝子組換え）
Gemtuzumab Ozogamicin (Genetical Recombination)〔JAN〕

化学名
Immunoglobulin G4 (human-mouse monoclonal hP67.6 γ4-chain anti-human antigen CD33), disulfide with human-mouse monoclonal hP67.6 κ-chain, dimer, conjugate with methyl (1R, 4Z, 8S, 13E)-13-[2-[[2-[[[p-(3-carbamoylpropoxy)-α-methylbenzylidene]hydrazino]carbonyl]-1,1-dimethylethyl]dithio]ethylidene]-8-[[4,6-dideoxy-4-[[[2,6-dideoxy-4-S-[4-[(6-deoxy-3-O-methyl-α-L-mannopyranosyl)oxy]-3-iodo-5,6-dimethoxy-o-toluoyl]-4-thio-β-D-ribo-hexopyranosyl]oxy]amino]-2-O-[2,4-dideoxy-4-(N-ethylacetamido)-3-O-methyl-α-L-threo-pentopyranosyl]-β-D-glucopyranosyl]oxy]-1-hydroxy-11-oxobicyclo[7.3.1]trideca-4,9-diene-2,6-diyne-10-carbamate

構造式

本質
ヒト免疫グロブリンG4の不変領域（κ鎖及びγ4鎖）及び可変領域フレーム配列並びにマウス抗CD33モノクローナル抗体の相補性決定領域からなるヒト化マウス抗CD33モノクローナル抗体に由来するcDNAの発現によりマウス骨髄腫細胞（NS0細胞）で産生される1,322個のアミノ酸残基からなる糖タンパク質（分子量：約150,000）とMicromonospora echinospora ssp.Calichensis菌から単離された細胞傷害性抗腫瘍抗生物質カリケアマイシンとの抱合体（分子量：約153,000）

承認条件

国内での治験症例が極めて限られており、また、治験において感染症、出血、肝機能障害等の重篤な副作用の発生が認められていることから、市販後、一定数の症例に係るデータが集積されるまでの間は、全症例を登録した使用成績調査を実施することにより、本剤使用患者の背景情報を把握するとともに、安全性及び有効性に関するデータを収集し、本剤の適正使用に必要な措置を講じること。

包装

〔バイアル〕　5mg×1

*製造販売
ファイザー株式会社（武田薬品工業株式会社）

完整处方附件：http://www.info.pmda.go.jp/go/pack/4239400D1030_2_02/

MYLOTARG® (gemtuzumab ozogamicin for Injection)新的用药方案

该试验纳入了280名病人，50~70岁，AML之前未经治疗。所有患者都接受标准化疗（柔红霉素和阿糖胞苷），其中一般患者还需接受吉妥单抗的治疗。
试验小组测试了吉妥单抗的新方案，比以前的试验剂量要低。过去的研究使用的诱导剂量：在第1和14天为9mg/m2，但是会增加血液学和肝毒性。
为了最大限度的减少毒性，他们选择使用更低的分割剂量，在第1、4、7天给予吉妥单抗诱导剂量为3mg/m2（最大剂量为5），在两个巩固化疗疗程的第1天再给予一次剂量。
分割方案允许高剂量吉妥单抗的传递但是不会增加额外的毒性，血液学毒性尤其是持久性血小板减少症，吉妥单抗比对照组更为常见，但是毒性造成的死亡没有增加。
研究人员报告说，加入吉妥单抗后可显著改善生存。

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原产地英文商品名:
MYLOTARG 5mg/20mL Vial
原产地英文药品名:
GEMTUZUMAB OZOGAMICIN
中文参考商品译名:
米罗他 5毫克/20毫升/瓶
中文参考药品译名:
吉姆单抗 奥佐米星
生产厂家中文参考译名:
美国惠氏
生产厂家英文名:
Wyeth Pharmaceuticals