托泊替康副作用;别名:拓扑替康、Hycamtin;托泊替康适应症:小细胞肺癌、晚期转移性卵巢癌。;托泊替康药理学作用:本品为拓扑异构酶Ⅰ抑制剂。拓扑异构酶Ⅰ可诱导DNA单链可逆性断裂，使DNA螺旋松懈，本品与拓扑异构酶Ⅰ-DNA复合物结合并阻止这些单股断链的重新连接，其细胞毒作用是在DNA合成中，是S期细胞周期特异性药物。本品与拓扑异构酶Ⅰ和DNA形成的三元复合物和复制酶相互作用时产生双股DNA损伤。在体外，本品对L1210白血病细胞的作用比喜树碱弱，但对接种有L1210和P388白血病的大鼠的作用比喜树碱强。在体内，本品对Lewis肺癌和B16黑色素瘤的作用比喜树碱和9-氨基喜树碱强。
分类名称
一级分类：抗肿瘤药物 二级分类：抗肿瘤植物药 三级分类：
药品英文名
Topotecan
药品别名
金喜素、和美新、喜典、拓泊替康、Hycamtin
药物剂型
粉针剂：每瓶含本品2mg或4mg(以拓扑替康计)。
药理作用
本品为拓扑异构酶Ⅰ抑制剂。拓扑异构酶Ⅰ可诱导DNA单链可逆性断裂，使DNA螺旋松懈，本品与拓扑异构酶Ⅰ-DNA复合物结合并阻止这些单股断链的重新连接，其细胞毒作用是在DNA合成中，是S期细胞周期特异性药物。本品与拓扑异构酶Ⅰ和DNA形成的三元复合物和复制酶相互作用时产生双股DNA损伤。在体外，本品对L1210白血病细胞的作用比喜树碱弱，但对接种有L1210和P388白血病的大鼠的作用比喜树碱强。在体内，本品对Lewis肺癌和B16黑色素瘤的作用比喜树碱和9-氨基喜树碱强。
药动学
本药静脉滴注在体内呈二室模型，很容易分布到肝、肾等血流灌注好的组织，其结构中内酯环可逆性的pH依赖性地水解。本品半衰期为2～3h，与血浆蛋白结合率为6.6%～21.3%，药物可进入脑脊液中并蓄积，大部分(26%～80%)经肾脏排泄，其中90%在用药后12h排泄，小部分经胆汁排泄。
适应证
小细胞肺癌、晚期转移性卵巢癌。
禁忌证
对喜树碱类药物或其任何成分过敏者禁用。严重骨髓抑制、中性粒细胞＜1.5×109/L者禁用。妊娠、哺乳期妇女禁用。
不良反应
在限定剂量下本品可出现骨髓抑制等毒性反应，短时间和间歇用药主要表现为非累积性中性粒细胞减少，持续用药则包括血小板减少和贫血。非血液学毒性相关较轻，包括恶心、脱发、呕吐、腹泻、转氨酶轻度升高、疲乏、皮疹等。
用法用量
静脉输注，剂量为1.5mg/(m2·d)。每次约需30min，持续5天，21天为1疗程。先用4mL无菌注射用水溶解4mg的本品，然后再注入0.9%生理盐水或5%葡萄糖注射液中进行稀释，以供使用。
药物相应作用
专家点评
在一项公开的随机试验中，226例因使用顺铂或卡铂无效或复发的晚期卵巢癌妇女改用本品，并与紫杉醇作比较。使用本品治疗的112例患者中，22例有效，有效率为20%，用紫杉醇治疗的114例患者中，14例有效，有效率为12%。使用本品取得明显好转的平均时间为23周，用紫杉醇则为14周。在一项非对照性试验中，111例难治的晚期卵巢癌妇女，用药后16例疗效较好，占14%。疗效平均持续16周，平均存活52周。
Topotecan is a drug used to treat certain types of cancer. Topotecan is available under the trade name Hycamtin, and may also be referred to as topotecan hydrochloride or topotecan HCl.
Purpose
Topotecan is an antineoplastic agent used to treat small cell lung cancer, and certain cancers of the ovary.
As of late 2003, clinical trials are underway in Italy and France to test the effectiveness of topotecan in treating tumors of the brain (glioblastomas) and autonomic nervous system (neuroblastomas). In the French study, topotecan is given together with radiotherapy while the Italian trial uses topotecan as part of combination chemotherapy. Early results indicate that the drug may be useful in treating cancers of the nervous system as well as ovarian and small-cell lung cancers.
Description
Topotecan is a synthetic derivative of the naturally occurring compound camptothecin. Camptothecin belongs to a group of chemicals called alkaloids, and is extracted from plants such as Camptotheca acuminata. Captothecin was initially investigated as a chemotherapeutic agent due to its anti-cancer activity in laboratory studies. The chemical structure and biological action of topotecan is similar to that of camptothecin and irinotecan.
Topotecan inhibits the normal functioning of the enzyme topoisomerase I. The normal role of topoisomerase I is to aid in the replication, recombination and repair of deoxyribonucleic acid (DNA). Higher levels of topoisomerase I have been found in certain cancer tumors compared to healthy tissue. Inhibiting topoisomerase I causes DNA damage. This damage leads to apoptosis, or programmed cell death.
Topotecan is used in patients whose cancer of the ovary has recurred or progressed after platinum-based treatment such as cisplatin. Topotecan is also used to treat relapse of small cell lung cancer that initially responded to other drugs. Increases in survival times have been observed in patients treated with topotecan compared to control populations treated with paclitaxel.
Tumors that are targeted by topotecan sometimes develop resistance to the drug. Although the reasons for this resistance are not fully understood as of late 2003, researchers think that they may be related either to inadequate amounts of drug in the tumor or to alterations in topoisomerase I that make the enzyme resistant to topotecan.
Recommended Dosage
Patients should be carefully monitored before and during topotecan treatment for bone marrow function.
Topotecan is administered intravenously over 30 minutes once per day for five consecutive days followed by 16 days of rest. This schedule may be repeated every 21 days. The initial dose of topotecan may be adjusted downward depending on patient tolerance to the toxic side effects of topotecan.
The dose of topotecan may be reduced in patients with kidney dysfunction.
No dose modification is necessary for patients with liver impairment.
No dose modification is necessary for elderly patients.
Precautions
Topotecan should be used only under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Certain complications will only be possible to manage if the necessary diagnostic and treatment resources are readily available. Topotecan should not be used in patients with bone marrow depression before starting treatment. Skin that comes in contact with topotecan must be washed thoroughly with soap and warm water.
The dose of topotecan may be reduced in patients with moderate kidney dysfunction. Topotecan is not recommended for use in patients with severe kidney dysfunction.
Topotecan should not be administered to pregnant women. Women of child bearing age are advised not to become pregnant during treatment. Women should discontinue nursing prior to taking topotecan.
Side Effects
Suppression of bone marrow function is the most serious side effect commonly observed in this treatment and can lead to death. Bone marrow reserves should be monitored by blood cell counts for all patients before and during topotecan treatment. The suppression of bone marrow is not cumulative over time. Additional side effects including nausea and vomiting, anorexia, diarrhea, constipation, headache and hair loss (alopecia) may occur.
Interactions
Suppression of bone marrow is more severe when topotecan is given with platinum drugs. G-CSF (filgrastim) may extend the duration of bone marrow suppression. If G-CSF is used, it should not be administered until day six of the 21-day course.
药品中文名称 注射用盐酸托泊替康
药品名称说明
药品英文名称 Topotecan Hydrochloride for Injection
药品中文商品名 和美新
药品英文商品名 Hycamtin
中文剂型 注射剂
英文剂型
药品规格 4mg
包装规格 1瓶，5瓶/盒
注册证号 H20030519
原注册证号
注册证号说明
分包装文号
公司中文名称
公司英文名称 GlaxoSmithKline
公司中文地址
公司英文地址 Conshohicken,PA 19428
公司中文国别 美国
公司英文国别 U.S.A.
生产厂商中文名
生产厂商英文名 GlaxoSmithKline PLC
生产厂国内地址
生产厂国内地址 Conshohicken,PA 19428
生产厂中文国别 美国
生产厂英文国别 U.S.A.
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