富马酸吉列替尼，富马酸吉列替尼片gilteritinib（XOSPATA Tablets 40mg）

药店国别：无 产地国家：美国 处方药：是 所属类别： 40毫克/片 90片/瓶 包装规格： 40毫克/片 90片/瓶 计价单位：瓶 生产厂家中文参考译名：无 生产厂家英文名：Astellas 原产地英文商品名：XOSPATA 40mg/tablets 90tablets/bottles 原产地英文药品名：gilteritinib 中文参考商品译名：XOSPATA片 40毫克/片 90片/瓶 中文参考药品译名：富马酸吉列替尼 曾用名：无

简介

近日，美国食品和药物管理局（FDA）批准Xospata（gilteritinib），用于经FDA批准的一种检测方法证实存在FLT3突变的复发性或难治性（药物难治）急性髓性白血病（AML）成人患者的治疗。 Xospata是一种口服疗法，此次批准，使该药成为FDA批准用于复发性或难治性AML患者群体的首个也是唯一一个FLT3靶向制剂，同时也标志着安斯泰来进入了美国血液癌症治疗领域。 批准日期：2018年11月29日 公司：安斯泰来（Astellas）XOSPATA(富马酸吉列替尼[gilteritinib])片 供口服使用 首次美国批准：2018 作用机理 Gilteritinib是一种抑制多受体酪氨酸激酶的小分子，包括FMS样酪氨酸激酶3（FLT3）。Gilteritinib对外源性表达FLT3的细胞FLT3-ITD、酪氨酸激酶结构域突变(TKD)FLT3-D835Y和FLT3-ITD-D835Y具有抑制FLT3受体信号转导和增殖的能力，并诱导表达FLT3-ITD的白血病细胞凋亡。 适应症及用法 XOSPATA是一种激酶抑制剂，用于治疗复发或难治性急性髓系白血病（AML）合并FLT3的成人患者。通过FDA批准的测试检测突变。 剂量与给药：每天口服一次，每次120毫克。 剂型和强度药片：40毫克。 禁忌症：对吉特替尼或任何赋形剂过敏。在临床试验中观察到过敏反应。 警告和注意事项 •后部可逆性脑病综合征（PRES）：发生PRES的患者停止XOSPATA。 •延长QT间期：中断和减少QTcF>500msec的XOSPATA住院患者的剂量。纠正XOSTATA给药前和期间的低钾血症或低镁血症。 •胰腺炎：在发展为胰腺炎的患者中中断和减少剂量。 胚胎胎儿毒性：XOSPATA可导致胎儿损伤给孕妇服用的告知胎儿的潜在风险，并使用有效的避孕方法。 不良反应 最常见的不良反应(≥20%)为肌痛/关节痛、转氨酶升高、疲劳/不适、发热、非感染性腹泻、呼吸困难、水肿、皮疹、肺炎、恶心、口腔炎、咳嗽、头痛、低血压、头晕和呕吐。 药物相互作用 联合P-gp和强CYP3A诱导剂：避免同时使用。 强CYP3A抑制剂：考虑替代疗法。如果不能避免同时使用强CYP3A抑制剂，则更频繁地监测患者XOSPATA的不良反应。 在特定人群中的使用哺乳期：建议妇女不要母乳喂养。 包装供应/储存和搬运 如何供应XOSPATA(gilteritinib)40mg片剂以浅黄色、圆形、薄膜包衣片形式提供，并经阿斯泰拉标志和“235”的同一面。XSOPTA片剂可在以下包装尺寸中使用：·瓶90片儿童抵抗关闭，（NDC 04691425-90）保管部将XOSPATA片在20℃至25℃（68°F至77°F）下储存；允许在15℃至30℃之间移动（59°F至86°F）[参见美国药典控制室温]。保存在原始容器中。

英文版说明

pdfXOSPATA(gilteritinib) Approved by U.S. FDA for Adult Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) with a FLT3 MutationU.S. Food and Drug Administration (FDA) approved XOSPATA® (generic name: gilteritinib) for the treatment of adult patients who have relapsed or refractory (resistant to treatment) Acute Myeloid Leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test. XOSPATA is an oral therapy and the first and only FLT3-targeting therapy to be approved by the FDA for this population.The American Cancer Society estimates that in 2018, approximately 19,000 people will be diagnosed with AML in the U.S. AML has been associated with various genetic mutations. XOSPATA has demonstrated inhibitory activity against two different mutations, FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain (TKD).2 Impacting approximately 30 percent of AML patients, the FLT3-ITD mutation is associated with worsened disease free survival and overall survival. , FLT3-TKD mutations impact approximately 7 percent of AML patients4 and, although the impact of these mutations is less clear, they have been associated with treatment resistance.“Our ability to use precision medicine to help patients with FLT3-mutated AML takes an important step forward with the approval of XOSPATA,” said Alexander Perl, M.D., Abramson Cancer Center, University of Pennsylvania. “There is an urgent need in the clinic for more targeted agents to help patients whose disease is either refractory to the initial therapy, or who have relapsed."“XOSPATA offers new hope to patients for whom the treatment path forward is unclear,” said Steven Benner, M.D., senior vice president and global therapeutic area head, Oncology Development, Astellas. “For the first time, people with relapsed or refractory FLT3 mutation-positive AML have an FDA approved FLT3-targeting treatment available to them. The approval of XOSPATA is also a proud, landmark moment for our oncology program and marks the first approval of a medicine that will be the cornerstone of our new presence in blood cancers.”The FDA’s approval of XOSPATA was based on an interim analysis of the following endpoints in the ADMIRAL clinical trial: the rate of complete remission (CR)/complete remission with partial hematologic recovery (CRh); the duration of CR/CRh (DOR); and the rate of conversion from transfusion dependence to transfusion independence. The CR/CRh rate was 21%. The median duration of CR/CRh was 4.6 months. The rate of conversion from transfusion dependence to transfusion independence was 31.1% for any 56 day post-baseline period. For patients who achieved a CR/CRh, the median time to first response was 3.6 months (range, 0.9 to 9.6 months). The CR/CRh rate was 29 of 126 in patients with FLT3-ITD or FLT3-ITD/TKD and 0 of 12 in patients with FLT3-TKD only.Full results from the ADMIRAL trial will be submitted for presentation at an upcoming medical meeting.The safety eva luation of XOSPATA was based on 292 patients with relapsed or refractory AML treated with 120 mg gilteritinib daily. The median duration of exposure to XOSPATA was 3 months (range 0.1 to 42.8 months). The most frequent non-hematological serious adverse reactions (≥5%) reported in patients were pneumonia (19%), sepsis (13%), fever (13%), dyspnea (7%) and renal impairment (5%). Overall, 22 of 292 patients (8%) discontinued XOSPATA treatment permanently due to an adverse reaction. The most common adverse reactions (>1%) leading to discontinuation were pneumonia (2%), sepsis (2%) and dyspnea (1%). The most common adverse reactions (≥20%) were myalgia/arthralgia (42%), transaminase increased (41%), fatigue/malaise (40%), fever (35%), non-infectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%) and vomiting (20%).Previously, XOSPATA was granted both Orphan Drug designation and Fast Track designation by the U.S. FDA. Gilteritinib also received Orphan Designation from the European Commission (EC) and Orphan Drug Designation from the Japan Ministry of Health, Labor and Welfare (MHLW). The MHLW also granted SAKIGAKE designation to gilteritinib for FLT3mut+ relapsed/refractory AML and approved the treatment for this population in September 2018.