艾代拉里斯片Zydelig Tablets 100mg(Idelalisib)

药店国别： 产地国家：美国 处方药：是 所属类别： 100毫克/片 60片/盒 包装规格： 100毫克/片 60片/盒 计价单位：盒 生产厂家中文参考译名： 生产厂家英文名：Gilead Sciences 原产地英文商品名：Zydelig 100mg/tab 60tabs/box 原产地英文药品名：idelalisib 中文参考商品译名：Zydelig 100毫克/片 60片/盒 中文参考药品译名：idelalisib 曾用名： 简介： 近日，美国FDA批准Idelalisib(商品名：Zydelig)的三个适应症：和利妥昔单抗(Rituxan)联合治疗复发的慢性淋巴细胞白血病(CLL)、作为单药治疗复发性滤泡B细胞非霍奇金淋巴瘤(FL)和复发性小淋巴细胞淋巴瘤(SLL)。FDA对后两个适应症是加速批准，且患者之前都至少接受过两次全身治疗批准日期：2014年7月23日 公司：吉利德科学ZYDELIG®(艾代拉里斯[idelalisib])片剂，供口服使用最初的美国批准：2014年警告：致命和严重毒性：肝，重性腹泻，结肠炎，肺炎，感染和肠胃穿孔查看完整的盒装警告的完整处方信息。 •Zydelig治疗的患者中有16%至18%发生致命性和/或严重肝毒性。在治疗前和治疗期间监测肝功能。中断，然后减少或停止Zydelig。Zydelig治疗的患者中有14%至20%发生致命性和/或严重和严重腹泻或结肠炎。监测严重腹泻或结肠炎的发展。中断，然后减少或停止Zydelig。•4%的Zydeligtreated患者发生致命性和/或严重肺炎。监测肺部症状和双侧间质浸润。中断或停止Zydelig。•Zydelig治疗的患者中有21%至48%发生致命和/或严重感染。监测感染的体征和症状。如果怀疑有感染，则中断Zydelig。•临床试验中Zydeligtreated患者可能会发生严重肠道穿孔。如果怀疑肠穿孔，请停止Zydelig。 作用机制 Idelalisib是PI3K激酶的抑制剂，其在正常和恶性B细胞中表达。Idelalisib诱导细胞凋亡和抑制细胞增殖恶性B细胞和原发性肿瘤细胞中。Idelalisib抑制几种细胞信号传导包括B细胞受体(BCR)信号传导和CXCR4和CXCR5信号传导，其参与B细胞向淋巴结和淋巴结的运输和归巢骨髓。用idelalisib治疗淋巴瘤细胞导致抑制趋化性和粘附性，并降低细胞活力。 适应症和用法 Zydelig是一种激酶抑制剂，用于治疗以下患者：•复发性慢性淋巴细胞性白血病(CLL)联合利妥昔单抗应用于单用利妥昔单抗因其他合并症而被认为是适当治疗的患者。•已接受至少两种全身治疗的患者中的滤泡性B细胞非霍奇金淋巴瘤(FL)复发。•至少接受过两次全身治疗的患者的复发性小淋巴细胞性淋巴瘤(SLL)。 使用限制： Zydelig未被指出，不建议用于任何患者的一线治疗。Zydelig未被指出，不建议与苯达莫司汀和/或利妥昔单抗联合用于治疗FL。总体而言，FL和SLL获得了加速批准反应速度。改善患者的生存或疾病相关症状尚未确定。继续批准这些适应证可能取决于临床受益的证实在验证性试验中。 剂量和给药 建议起始剂量：口服150毫克，每日两次。剂型和强度片剂：150mg，100mg。 禁忌症 严重过敏反应史，包括过敏反应和中毒性表皮坏死松解症。 警告和注意事项 •严重皮肤反应：监测患者发生严重皮肤反应并停止Zydelig。•过敏反应：监测患者的过敏反应并停止Zydelig。•嗜中性白血球减少症：监测血液计数。•胚胎-胎儿毒性：Zydelig可能会对胎儿造成伤害。建议妇女在服用Zydelig时对胎儿有潜在风险并避免怀孕。 不良反应 单药治疗Zydelig治疗的患者最常见的不良反应(发生率≥20%)为腹泻，疲劳，恶心，咳嗽，发热，腹痛，肺炎和皮疹。联合试验中Zydelig治疗患者最常见的不良反应(发生率≥30%)为腹泻，肺炎，发热，疲劳，皮疹，咳嗽和恶心。常见的实验室异常包括嗜中性白血球减少症，ALT升高和AST升高。 药物相互作用 •强效CYP3A抑制剂：如果没有其他疗法，则需要额外监测。•强CYP3A诱导剂：避免合用强效CYP3A诱导剂。•CYP3A底物：避免共同给药敏感的CYP3A底物。 在特定人群中使用哺乳期： 建议妇女不要母乳喂养。外上市情况美国：片剂150mg，100mg(2014.7.23);Gilead Sciences, Inc.公司持有;商品名Zydelig欧盟：片剂150mg，100mg(2014.9.18);Gilead Sciences International Ltd公司持有;商品名Zydelig临床优势Zydelig(idelalisib)是一种首创的高度选择性、口服有效的磷酸肌醇3-激酶delta(PI3K-delta)抑制剂。一项Ⅲ期临床试验(NCT01732913)显示在危险因素分层的所有亚组中，idelalisib组均显著延长了预估无进展生存期，idelalisib组患者总生存显著改善，并且具有显著更高的淋巴结反应率(93%、4%)。与利妥昔单抗单药治疗相比，艾代拉利司+利妥昔单抗联合疗法对研究的主要终点疾病无进展生存期具有显著的积极影响，表现出了高度统计学显著功效。 对于患有复发性血癌的人来说，它能够显著延长患者的无进展生存期。在一系列临床研究中显示出良好的治疗前景，且安全性及耐受性均较好。产品简介Idelalisib是首个上市的口服、选择性的磷酸肌醇3-激酶delta(PI3K-delta，P110-delta)抑制剂。P110-delta参与改变B淋巴细胞的免疫环境，对这类肿瘤细胞的活化、增殖、生存和迁移(trafficking)起着关键作用。Idelalisib的加速批准是基于一个单臂、多中心、开放标签的积极二期临床结果。 该临床实验招募了123位复发性的“惰性”非霍奇金淋巴瘤(iNHL)和小淋巴细胞淋巴瘤(SLL)患者。病人每天接受两次，每次150毫克艾代拉里斯治疗，一级实验终点是总应答率(ORR)，二级实验终点是应答时间和无进展生存期。其中FL和SLL患者的总应答率分别为54%和58%。后者应答时间的中位数为11.9个月。这个结果和标准疗法的通常疗效相比相当或更好。艾代拉利司(Idelalisib)的获批上市，为慢性淋巴细胞白血病(CLL)的治疗在ibrutinib之后又带来一个新的选择。在美国，慢性淋巴细胞白血病(CLL)在成人白血病患者中人数排第二，预计2014年会增添超过15000名新患者。包括Idelalisib和ibrutinib在内的CLL新药研发，有望把CLL从死刑判决演变成一种可控制的慢性疾病。 英文版说明书 Treatment of Three B-cell Blood Cancers, United States of AmericaZydelig (idelalisib), a phosphoinositide 3-kinase (PI3K) delta inhibitor, is indicated for the treatment of three B-cell blood cancers: relapsed chronic lymphocytic leukaemia (CLL), follicular lymphoma (FL) and small lymphocytic lymphoma (SLL). The drug is developed and marketed by Gilead Sciences.The US Food and Drug Administration (FDA) approved Zydelig (idelalisib) for the treatment of CLL, FL and SLL in July 2014.Gilead Sciences received a positive opinion on Zydelig's marketing authorisation application (MAA) from the Committee for Medicinal Products for Human Use (CHMP) of European Medicines Agency (EMA) for the treatment of CLL and FL in July 2014. The drug is currently under review by the EMA.The three B-cell blood cancersCLL is a blood cancer in which the bone marrow overproduces B-lymphocytes. Its symptoms include fatigue, bleeding, anaemia and infections. It is estimated that about 120,000 people in the US are affected by CLL, and 4,500 people die from it each year.FL and SLL are two types of blood cancers that grow at a slow pace in the lymph system. FL occurs when B-lymphocytes grow in groups to form nodules, while SLL occurs when the B-lymphocytes overgrow in the lymph nodes. The symptoms of FL and SLL include high fever, weight loss and enlarged lymph nodes. It is estimated that about 148,000 people in the US are living with FL and SLL.Zydelig's mechanism of actionZydelig inhibits phosphoinositide 3-kinase (PI3K) delta, a main protein involved in the activation, viability, proliferation and migration of B-cells. The drug works by blocking the pathways that cause B-cell viability.Zydelig is available in the form of 100mg and 150mg dosed tablets for oral administration.Clinical trials on ZydeligThe FDA approval of Zydelig for the treatment of CLL patients was based on the results obtained from a phase III clinical trial known as Study 116. The CHMP gave a positive opinion on Zydelig based on the same clinical trial.Study 116 was a randomised and placebo-controlled clinical study. It enrolled 220 patients with relapsed CLL for whom standard chemotherapy was not suitable. One set of the patients was treated with Zydelig and rituximab while the others received rituximab alone.However, the study was ended by the Data Monitoring Committee in October 2013 due to the statistically significant benefit in progression-free survival (PFS) in the Zydelig arm in comparison to the placebo plus rituximab arm. The study also revealed that the median PFS was not reached in the Zydelig plus rituximab arm, while it was 5.5 months in the placebo plus rituximab arm.The FDA granted accelerated approval for Zydelig for the treatment of FL and SLL based on the data received from a Phase II single-arm study named Study 101-09. The study was conducted on patients for whom Zydelig was considered as monotherapy and those who are refractory to rituximab and alkylating agent containing chemotherapy.The study results demonstrated that Zydelig achieved an overall response rate of 54% in FL patients and 58% in SLL patients. The most common adverse reactions found in the Zydelig-administered patients included pyrexia, diarrhoea, fatigue, cough, nausea, abdominal pain, chills and rash. The most frequent serious adverse reactions recorded in the combination were pneumonia, sepsis, pyrexia, febrile neutropenia and diarrhoea.The most common lab abnormalities included hypertriglyceridemia, neutropenia and hyperglycaemia.