产地国家：德国 处方药：是 所属类别： 140毫克/胶囊 120胶囊/瓶 包装规格： 140毫克/胶囊 120胶囊/瓶 计价单位：瓶 生产厂家英文名：Janssen-Cilag 原产地英文商品名：IMBRUVICA hard capsules 140mg/cap 120caps/box 原产地英文药品名：Ibrutinib 中文参考商品译名：IMBRUVICA硬胶囊 140毫克/胶囊 120胶囊/盒 中文参考药品译名：依鲁替尼 曾用名：拉铁尼伯

简介：

抗癌新药依鲁替尼(Imbruvica,Ibrutinib)获批准作为淋巴瘤,慢性淋巴细胞白血病用药IMBRUVICA®(依鲁替尼 Ibrutinib)胶囊口服使用美国初始批准：2013目前的主要变化适应证和用途 5/2016剂量和给药方法 5/2016警告和注意事项 3/2016作用机理Ibrutinib是BTK的小分子抑制剂。Ibrutinib形成与BTK活性位点的半胱氨酸残基形成共价键，从而抑制BTK的酶活性。BTK是B细胞抗原受体(BCR)和细胞因子受体途径的信号传导分子。BTK在通过的通路在必要时作B细胞贩卖，趋化性，和粘附的活化受体结果的B细胞表面信号的作用。非临床研究显示Ibrutinib抑制体外体内恶性B细胞增殖和存活以及细胞迁移和基板的粘合性。 适应症和用法：IMBRUVICA是指示对患者的治疗激酶抑制剂：套细胞淋巴瘤(MCL)是谁已收到至少一个以前的治疗。被授予加速审批的基础上整体回应率这一指标。这个指示继续批准均可在确证试验的临床效果验证队伍。慢性淋巴细胞白血病(CLL)/小淋巴细胞性淋巴瘤(SLL)。慢性淋巴细胞白血病(CLL)/小淋巴细胞性淋巴瘤(SLL)与17p缺失。华氏巨球蛋白血症(WM)。 用法用量：MCL：560毫克每天服用一次内服(4 140毫克胶囊，每天一次)。CLL/SLL和WM：420毫克，每天一次内服(三级140毫克胶囊，每天一次)。胶囊不宜口服用一杯水服用。不要打开，休息，或咀嚼胶囊。 剂型和规格：胶囊，140毫克 禁忌症：无 警告和注意事项： 出血：监测出血及管理。 感染：监测患者发热和感染，评估，aussitôt和治疗。 血细胞减少：月度检查全血细胞计数。 房颤：用于监控心房颤动和管理。 高血压：监测血压和治疗。 第二原发恶性肿瘤：其他恶性肿瘤，发生在患者，包括皮肤癌和癌 - 其他。 肿瘤溶解综合征(TLS)：评估基准风险，并采取预防措施。监测和治疗为TLS。 胚胎 - 胎儿毒性：能引起胎儿危害。建议的潜在风险女性胎儿和避免怀孕而服用药物和1个月后停止治疗。建议男性不要抚养一个被孩子在萨米时间。 不良反应：评论患者B细胞恶性肿瘤(MCL，CLL / SLL和WM)为白细胞减少，血小板减少，腹泻，贫血，肌肉骨骼痛，皮疹，恶心，青紫，疲劳，出血，最常见的不良反应(≥20%)发热。 Imbruvica第4个适应症获欧盟批准破性抗癌药Imbruvica(ibrutinib)近日获欧盟批准，用于既往已接受过至少一次治疗的Waldenstrom巨球蛋白血症(WM)成人患者，以及用于不适合化学-免疫疗法的WM成人患者的一线治疗。此次批准，使Imbruvica成为欧洲首个Waldenstrom巨球蛋白血症治疗产品，该适应症也是Imbruvica在欧洲获批的第4个适应症，之前已获批的3个适应症，分别为：复发性或难治性套细胞淋巴瘤(MCL)、慢性淋巴细胞白血病(CLL)、携带17p删除或TP53突变CLL。在美国，Imbruvica由强生旗下杨森(Janssen)与Pharmacyclics共同开发及商业化，强生同时拥有Imbruvica在欧洲、中东及非洲(EMEA)及其他国家和地区。Imbruvica新适应症的获批，是基于一项多中心II期研究。该研究涉及63例既往已接受中位数为2的既往疗法的(范围1-9)Waldenstrom巨球蛋白血症(WM)成人患者，调查了每日口服一次Imbruvica 420mg的疗效和耐受性。 数据显示，中位随访19个月(范围0.5-29个月)，与Imbruvica治疗相关的总缓解率为91%(ORR，主要终点)，11例(17%)实现轻微缓解(MR)、36例(57%)实现部分缓解(RR)、10例(16%)实现非常良好的部分缓解(VGPR)。患者启动治疗后，实现轻微缓解和部分缓解的中位时间分别为4周和8周。次要终点包括无进展生存期(PFS)和安全性。在治疗的24个月时，预计的无进展生存率和总生存率分别为69%(95% CI， 53.2 - 80.5)和95%(95% CI， 86.0 - 98.4)。 Imbruvica治疗组最常见不良反应(>20%)为中性粒细胞减少、血小板减少、腹泻、皮疹、恶心、肌肉痉挛、疲劳。Imbruvica治疗组有6%患者因不良反应停止治疗。总体而言，Imbruvica具有良好的耐受性，安全性与以往的研究一致。Imbruvica(ibrutinib)是一种首创的口服布鲁顿酪氨酸激酶(BTK)抑制剂，通过抑制肿瘤细胞复制和转移所需的BTK发挥抗癌作用。Imbruvica能够阻断介导恶性B细胞不可控地增殖和扩散的信号通路，帮助杀死并降低癌细胞数量，延缓癌症的恶化。 在临床试验中，Imbruvica单药及组合疗法针对广泛类型的血液系统恶性肿瘤展现出了强大的疗效，包括慢性淋巴细胞白血病(CLL)、套细胞淋巴瘤(MCL)、Waldenstrom巨球蛋白血症(WM)、弥漫性大B细胞淋巴癌(CLBCL)、滤泡性淋巴瘤(FL)、多发性骨髓瘤(MM)及边缘区淋巴瘤(MZL)等。Waldenstrom巨球蛋白血症(WM)是一种起源于B细胞的生长缓慢且罕见的血液肿瘤，患者确诊的平均年龄在63-68岁，该病在男性和女性中的发病率分别为百万分之7.3和4.2。基因组测序揭示，WM患者MYD88基因中存在一种常见的突变，触发了布鲁顿酪氨酸激酶(BTK)的激活。BTK是调控免疫细胞增殖和细胞存活所需的一种关键蛋白，在恶性B细胞的生存及扩散中发挥重要作用。

英文版说明书：

IMBRUVICA® (ibrutinib) Approved by U.S. FDA for the First-line Treatment of Chronic Lymphocytic LeukemiaApproval based on data from the Phase 3 RESONATE™-2 trial showing an 84% reduction in the risk of progression or death with IMBRUVICA compared to chlorambucil- First FDA-approved chemotherapy-free treatment option for first-line CLL patients- This is the 5th treatment indication for IMBRUVICAU.S. Food and Drug Administration (FDA) approved IMBRUVICA® (ibrutinib) as a first-line treatment for patients with chronic lymphocytic leukemia (CLL).1 The approval is based on data from the randomized, multi-center, open-label Phase 3 RESONATE™-2 (PCYC-1115) trial, which eva luated the use of IMBRUVICA versus chlorambucil in 269 treatment-naïve patients with CLL or small lymphocytic lymphoma (SLL) aged 65 years or older. The RESONATE-2 data were previously presented at the American Society of Hematology (ASH) Annual Meeting in December 2015 and also simultaneously published in The New England Journal of Medicine. IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company and Janssen Biotech, Inc."This approval represents a significant leap forward for patients diagnosed with CLL who may want to consider an alternative first-line treatment to traditional chemotherapy," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "AbbVie is committed to making significant improvements in the lives of patients with hematologic malignancies and will continue to explore ways to improve treatment options for patients."The preva lence of CLL is approximately 115,000 patients in the U.S.2 with approximately 15,000 newly diagnosed patients every year.3 CLL is a disease of elderly patients, with an average diagnosis age of 71.3The National Comprehensive Cancer Network (NCCN) recently published an update to its clinical practice guidelines for non-Hodgkin's lymphomas, granting IMBRUVICA a category 1 recommendation for certain CLL patients, the highest recommendation assigned by the organization. Specifically, NCCN recommends IMBRUVICA as a first-line treatment option for frail CLL patients with significant comorbidities, as well as for CLL patients with or without del 17p or the genetic mutation TP53 who are 70 years or older, or younger patients with significant comorbidities. The NCCN guidelines inform prescribing and reimbursement practices in many institutions in the U.S. and internationally."The progression-free survival data seen in these previously untreated CLL patients are strong and encouraging," said Dr. Jan Burger, M.D., Ph.D., Associate Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX and the RESONATE-2 lead study investigator.* "This is especially important for first-line CLL patients, when considering the safety profile. This treatment represents another option for these patients."IMBRUVICA is now approved to treat CLL patients regardless of their treatment history (treatment-naïve and previously-treated patients). In addition, IMBRUVICA is approved to treat high-risk CLL patients with del 17p,1 a genetic aberration that occurs when part of chromosome 17, the location of the tumor suppressor gene p53, has been lost or deleted.4IMBRUVICA significantly prolonged progression-free survival (PFS; primary endpoint) as determined by an Independent Review Committee (IRC), reducing the risk of progression or death by 84% versus chlorambucil (hazard ratio [HR], 0.161 [95% confidence interval: 0.091, 0.283]; median PFS: not reached for IMBRUVICA vs. 18.9 months [95% confidence interval: 14.1, 22.0] for chlorambucil).1 IMBRUVICA was also associated with a significantly higher IRC-assessed overall response rate (ORR: a composite of complete and partial responses; 82.4% vs. 35.3%; P<0.0001) versus chlorambucil.1 Five patients (3.7 percent) in the IMBRUVICA arm achieved a complete response, compared to two patients (1.5 percent) in the chlorambucil arm.1The safety of IMBRUVICA in this patient population was consistent with previously reported studies. The adverse reactions (AR) reported in the U.S. Prescribing Information reflect exposure to IMBRUVICA with a median duration of 17.4 months versus a median exposure to chlorambucil of 7.1 months: nearly 2.5 times longer exposure for IMBRUVICA. Warnings and Precautions include hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, second primary malignancies, embryo-fetal toxicity and tumor lysis syndrome. The most commonly occurring adverse reactions of all Grades in CLL patients treated with IMBRUVICA in the RESONATE-2 trial (>20%) were diarrhea, musculoskeletal pain, cough and rash.IMPORTANT SAFETY INFORMATIONWARNINGS AND PRECAUTIONSHemorrhage - Fatal bleeding events have occurred in patients treated with IMBRUVICA®. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA®.The mechanism for the bleeding events is not well understood. IMBRUVICA® may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA® for at least 3 to 7 days pre- and postsurgery depending upon the type of surgery and the risk of bleeding.Infections - Fatal and nonfatal infections have occurred with IMBRUVICA® therapy. Grade 3 or greater infections occurred in 14% to 26% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA®. eva luate patients for fever and infections and treat appropriately.Cytopenias - Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 9%) occurred in patients treated with IMBRUVICA®. Monitor complete blood counts monthly.Atrial Fibrillation - Atrial fibrillation and atrial flutter (range, 6% to 9%) have occurred in patients treated with IMBRUVICA®, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. Atrial fibrillation should be managed appropriately and if it persists, consider the risks and benefits of IMBRUVICA® treatment and dose modification.Hypertension - Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA® with a median time to onset of 4.5 months (range, 0.03 to 18.40 months). Monitor patients for new-onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA®. Adjust existing antihypertensive medications and/or initiate antihypertensive treatment as appropriate.Second Primary Malignancies - Other malignancies (range, 5% to 16%) including non-skin carcinomas (range, 1% to 4%) have occurred in patients treated with IMBRUVICA®. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4% to 13%).Tumor Lysis Syndrome - Tumor lysis syndrome has been infrequently reported with IMBRUVICA® therapy. Assess the baseline risk (eg, high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate.Embryo-Fetal Toxicity - Based on findings in animals, IMBRUVICA® can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA® and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.ADVERSE REACTIONSThe most common adverse reactions (?20%) in patients with B-cell malignancies (MCL, CLL, WM) were thrombocytopenia* (57%, 53%, 43%), diarrhea (51%, 48%, 37%), anemia* (41%, 37%, 13%), neutropenia* (47%, 46%, 44%), musculoskeletal pain (37%, 32%†, NA‡), fatigue (41%, 29%, 21%), bruising (30%, 25%†, 16%†), nausea (31%, 24%, 21%), rash (25%, 23%†, 22%†), and upper respiratory tract infection (34%, 19%, 19%).*Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).†Includes multiple ADR terms.‡Not applicable; no associated ADRs.The most common Grade 3 or 4 non-hematologic adverse reactions (?5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%). Approximately 4% (CLL), 14% (MCL), and 11% (WM) of patients had a dose reduction due to adverse reactions.Approximately 4%-10% (CLL), 9% (MCL), and 6% (WM) of patients discontinued due to adverse reactions. Most frequent adverse reactions leading to discontinuation were pneumonia, subdural hematomas, and atrial fibrillation (1% each) in CLL patients and subdural hematoma (1.8%) in MCL patients.DRUG INTERACTIONSCYP3A Inhibitors - Avoid coadministration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA® dose.CYP3A Inducers - Avoid coadministration with strong CYP3A inducers.SPECIFIC POPULATIONSHepatic Impairment - Avoid use in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA® dose.