药品信息:
--------------------------------------------------------------- 详细处方信息以本药内容附件PDF文件(201231918281615.pdf)的“原文Priscribing Information”为准 --------------------------------------------------------------- 部分中文戊柔比星处方资料(仅供参考)
戊柔比星注射液(valrubicin,VALSTAR )-卡介菌难治性膀胱原位癌 【通用名称】valrubicin,戊柔比星,抗癌药戊柔比星
【商品名】Valstar, Valtaxin
【化学名称】(2S一顺式)-[1,2,3,4,6,11-六氢-2,5,12-三经基-7-甲氧基-6,11-二氧代-4-[[2,3, 6-三脱氧基-3-[(三氟乙酰)氨基]-α-L-来苏吡喃基]-氧]-2-并四苯基]-2-氧代乙基戊酸酯。[理化性质]本品为橙黄色或橙红色粉末,熔点为135~136℃。具有强亲脂性,在二氯甲烷、乙醇、甲醇、丙酮中溶解,在水中几乎不溶。
【药理毒理】本品为蒽环类药物,主要作用为干扰正常DNA的分裂重组,可影响细胞的各种生物学功能,主要为干涉核酸代谢。易渗入细胞内,抑制核苷形成核酸,从而引起大量染色体损伤并使细胞周期停止于G2期。目前尚未对本品的致癌作用进行评价,但体外试验结果表明:本品可引起DNA损伤。鼠伤寒沙门菌和大肠埃希菌的体外试验结果表明:本品具有致突变作用。中国仓鼠卵细胞的染色体畸变试验结果表明:本品具有致畸作用。
【药动学】原位癌患者膀胱内滴注本品 800 mg后可渗入膀胱壁,且膀胱组织的平均总蕙环浓度高于人膀胱细胞(体外培养)的TC90,其主要代谢物N-三氟乙酰阿霉素和N-三氟乙酰阿霉素醇的量可忽略不计。6例患者的14个尿样研究结果显示,本品、N-三氟乙酰阿霉素和总蒽环的平均回收率分别为总给药量的98.6%,0.4%和99.0%。仅ng 量戊柔比星被吸收入血液。 膀胱内滴注本品后总蒽环AUC与膀胱壁状态有关。对经尿道膀胱肿瘤切除术(n=6)2周后的患者膀胱内滴注本品900 mg,经尿道切除术出现膀 )E穿孔的患者(n=1),及静滴本品600mg?m-2的患者(n=2),总蒽环AUC0-6h平均分别为78,18382和 11975 nmol?h?L-1。
【功能主治】化痰开道,抗癌消肿,用于食道癌及癌肿引起的食道梗阻。
【适应症】卡介菌难治性膀胱原位癌。
【用法用量】膀胱内滴注。推荐剂量为800 mg?次-1,每周I次,给药时间为6周。
【临床评价】90例卡介菌(BCG)难治性膀胱原位癌(CIS)患者中70%至少接受2疗程BCG治疗,30%接受1疗程BCG和至少1疗程其他药物(如丝裂霉素、噻替派或干扰素)治疗。本品的治疗开始于尿道切除和/或电灼疗法后至少2周。膀胱活组织切片检查和细胞学检查结果表明,第6个月16例(18%)患者出现完全反应,反应时间中值随分析方法的不同而变化。回顾性分析结果表明:经本品治疗后疾病复发的间隔时间比治疗前长;10例(11%)在随访过程中出现转移性或浸润性膀胱癌,治疗失败(应进行膀胱切除)和膀胱切除或晚期膀胱癌间隔的时间中值为17.5个月;4例死于转移性膀胱癌,6例发展为浸润性膀胱癌(T3),膀胱切除时1 例累及淋巴结。因膀胱切除时间延迟(因要求随访3个月以确定反应),故难确定晚期膀胱癌的发展进程。尽管本品治疗失败也常延迟或避免了膀胱切除。
【药物不良反应】230例患者膀胱内滴注本品 200~900 mg的临床研究中,不良反应(≥1%)如下:①全身系统:腹痛、虚弱、背痛、胸痛、发热、头痛、不适。②心血管系统:血管扩张。③消化系统:腹泻、肠胃胀气、恶心、呕吐。④血液和淋巴系统:贫血。⑤代谢和营养系统:高血糖、外周性水肿。⑥肌骨骼系统:肌痛。⑦神经系统:头昏。 ⑧呼吸系统:肺炎。⑨皮肤和附件:皮疹。⑩泌尿生殖系统:尿频、尿急、尿潴留、尿失禁、血尿(显微镜下)、夜尿症、排尿困难、尿道疼痛、尿道感染、膀胱痉挛、膀胱痛、膀胱炎。
【禁忌症】对蒽环类抗生素或聚乙二醇三聚蓖麻酯过敏、并发尿道感染、膀胱容积小(不能容纳本品稀释液)及膀胱穿孔或膀胱黏膜受损的患者禁用。
【贮存条件】遮光,密封,冷处保存。
Valstar Company: Anthra Pharmaceuticals Approval Status: Approved October 1998 Treatment for: Oncology Areas: Cancer & Oncology
General Information Valstar (Valrubicin) is used as an intravesical therapy of BCG-refractory carcinoma in situ (CIS) of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality.
Side Effects Irritable bladder symptoms.
Valstar is contraindicated in patients with known hypersensitivity to anthracyclines or Cremophor7 EL (polyoxyethyleneglycol triricinoleate). Patients with concurrent urinary tract infections should not receive Valstar. Valstar should not be administered to a patient with a small bladder capacity, i.e., unable to tolerate a 75 mL instillation.
Patients should be informed that Valstar has been shown to induce complete responses in only about 1 in 5 patients, and that delaying cystectomy could lead to development of metastatic bladder cancer, which is lethal. They should discuss with their physician the relative risk of cystectomy versus the risk of metastatic bladder cancer and be aware that the risk increases the longer cystectomy is delayed in the presence of persisting CIS.
Mechanism of Action Valrubicin is an anthracycline that affects a variety of inter-related biological functions, most of which involve nucleic acid metabolism. It readily penetrates into cells, where it inhibits the incorporation of nucleosides into nucleic acids, causes extensive chromosomal damage, and arrests cell cycle in G2. Although valrubicin does not bind strongly to DNA, a principal mechanism of its action, mediated by valrubicin metabolites, is interference with the normal DNA breaking-resealing action of DNA topoisomerase II.
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