DEFITELIO(DEFIBROTIDE SODIUM)SOLUTION IV获FDA批准在接受来自血或骨髓干细胞移植患者对罕见病第一个治疗 FDA的药品评价和研究中心中血液学和肿瘤室主任Richard Pazdur，M.D.说：“准满足移植社会接受化疗和HSCT患者治疗这个罕见但频繁致命性合并症显著需求。” 优先审评状态和孤儿药物指定 批准日期：2016年3月30日；公司 Jazz Pharmaceuticals plc DEFITELIO(去纤维钠 defibrotide-sodium)注射液，为静脉使用 作用机制 去纤维钠的作用机制尚未完全阐明。在体外，去纤维钠增强纤溶酶水解纤维蛋白凝块的酶活性。研究评价去纤维钠对内皮细胞(ECs)药理学效应是主要地在人微血管内皮细胞系中进行。在体外，去纤维钠增加组织纤溶酶原激活剂(t-PA)和血栓调节蛋白表达，和减低von Willebrand因子(vWF)和纤溶酶原激活剂抑制剂-1(PAI-1)表达，因此减低EC活化和增加EC-介导的纤维蛋白溶解。去纤维钠保护ECs免受化疗，肿瘤坏死因子-α(TNF-α)，血清饥饿，和灌注所致损伤。 适应证和用途 DEFITELIO是适用为有肝小静脉闭塞病(VOD)，也称为肝窦阻塞综合征(SOS)，造血干细胞移植(HSCT)后有肾或肺功能失调成年和儿童患者的治疗。 剂量和给药方法 给予DEFITELIO 6.25mg/kg每6小时给予作为2-小时静脉输注。 治疗共最小21天。如21天后VOD的体征和症状没有解决。继续治疗直至解决。 剂型和规格 注射液：200mg/2.5mL(80mg/mL)在一个单次-患者-使用小瓶。 禁忌证 ⑴同时给药与全身抗凝剂或纤维蛋白溶解疗法。 ⑵对DEFITELIO或对任何赋形剂已知超敏性。 警告和注意事项 ⑴出血：监视患者对出血。如发生显著出血不给或终止DEFITELIO。 ⑵超敏性反应：如发生严重或危及生命过敏反应，终止DEFITELIO，按照标准医护治疗，和监视直至体征和症状解决。 不良反应 用DEFITELIO治疗最常见不良反应(发生率 ≥10%和独立的因果关系)为低血压，腹泻，呕吐，恶心和鼻出血。 药物相互作用 DEFITELIO可能增强抗血栓形成/纤溶蛋白溶解药物的活性。 如何供应/贮存和处置 DEFITELIO(去纤维钠)注射液是在一个单次-患者-使用，透明玻璃小瓶作为一个清澈，浅黄色至棕色，无菌，无防腐剂溶液为静脉输注供应。每小瓶(NDC 68727-800-01)含200 mg/2.5 mL(在一个浓度80 mg/mL)的去纤维钠。 DEFITELIO(去纤维钠)注射液的每个纸箱(NDC 68727-800-02)含10个小瓶。 贮存DEFITELIO(去纤维钠)注射液在20°C-25°C(68°F-77°F)；外出允许15° C至30°C(59°F至 86°F)间(见USP控制室温)。 First and Only FDA-Approved Therapy for Patients with this Rare, Potentially Fatal Complication FDAgranted marketing approval for Defitelio® (defibrotide sodium) for the treatment of adult and pediatric patients with hepatic VOD, also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following HSCT. "FDA's approval of Defitelio underscores the importance of Defitelio to children and adults as the first and only proven treatment for this rare and often deadly complication of stem-cell transplantation.  Defitelio is a clinically significant therapeutic advance because it is a potentially curative intervention for patients with VOD, which may save lives with a single course of therapy.  Before today, patients in the U.S. had no approved options," said Bruce Cozadd, chairman and chief executive officer of Jazz Pharmaceuticals.  "The commercial availability of Defitelio in the U.S. demonstrates Jazz Pharmaceuticals' continued commitment to bringing meaningful new treatments to patients to fill high unmet medical needs." The FDA approval of Defitelio is supported by efficacy data from three clinical studies in patients with hepatic VOD with renal or pulmonary dysfunction following HSCT who were treated with Defitelio at the recommended 6.25 mg/kg every 6 hours; results are provided in the table below. The safety of Defitelio to support approval is based on data from 176 patients in the clinical development program for the treatment of VOD with renal and/or pulmonary dysfunction following HSCT who were treated with Defitelio.  The most common adverse reactions (incidence =10% and independent of causality) with Defitelio treatment were hypotension (low blood pressure), diarrhea, vomiting, nausea and epistaxis (nose bleeds).The most common serious adverse reactions (incidence =5% and independent of causality) were hypotension (11%) and pulmonary alveolar hemorrhage (7%). "VOD/SOS is a devastating condition, which can develop without warning after stem-cell transplantation and can progress rapidly causing severe kidney or lung dysfunction and lead to multi-organ failure.  Thus, it can derail a patient's recovery from the curative intent of a stem-cell transplant, with patients who develop VOD/SOS and multi-organ failure facing an overall mortality rate of over 80%," said Paul G. Richardson, M.D., director of clinical research at the LeBow Institute for Myeloma Therapeutics and the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute and the RJ Corman Professor of Medicine at Harvard Medical School.  "Defitelio thus fulfills an unmet need having shown a consistent Day+100 patient survival benefit across three large prospective studies.  Importantly, Defitelio provides transplant teams with the first approved treatment option that can help return patients to the road to recovery." About Defitelio Defitelio® (defibrotide sodium) injection 80mg/mL is indicated for the treatment of adult and pediatric patients with hepatic VOD, also known as SOS, with renal or pulmonary dysfunction following HSCT.  The FDA granted the Defitelio application priority review status.  Defitelio also received orphan drug designation for the treatment of hepatic VOD. Important Safety Information Defitelio should not be given to patients who are: •Currently taking anticoagulants or fibrinolytics •Allergic to Defitelio or any of its ingredients Defitelio may increase the risk of bleeding in patients with VOD and should not be given to patients with active bleeding.  During treatment with Defitelio, patients should be monitored for signs of bleeding.  In the event that bleeding occurs during treatment with Defitelio, treatment should be temporarily or permanently stopped.  Patients should tell the doctor right away about any signs or symptoms of hemorrhage such as unusual bleeding, easy bruising, blood in urine or stool, headache, confusion, slurred speech, or altered vision.  Defitelio may cause allergic reactions including anaphylaxis.  Patients who develop signs and symptoms of anaphylaxis such as trouble breathing, severe itching, skin rash or hives, or swelling of the face, lips, mouth or tongue should seek medical attention immediately. The most common side effects of Defitelio are decreased blood pressure, diarrhea, vomiting, nausea and nose bleeds.  Please see full Prescribing Information for Defitelio before prescribing. In Europe, defibrotide is marketed under the name Defitelio®?(defibrotide).  In October 2013, the European Commission granted marketing authorization to Defitelio under exceptional circumstances for the treatment of severe VOD in patients undergoing HSCT therapy.  It is the first and only approved treatment in Europe for severe VOD.  In Europe, Defitelio is indicated in patients over one month of age.  It is not indicated in patients with hypersensitivity to defibrotide or any of its excipients or with concomitant use of thrombolytic therapy. DEFITELIO Rx Select the drug indication to add to your list DEFITELIO Miscellaneous gastrohepatic disorders  Only 4 drugs may be compared at once Remove Selected Compare Selected Generic Name and Formulations: Defibrotide sodium 200mg/2.5mL; soln for IV infusion after dilution; preservative-free. Company: Jazz Pharmaceuticals plc Select therapeutic use: Miscellaneous gastrohepatic disorders RECENT UPDATES Monograph added. Indications for DEFITELIO: Treatment of hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation. Adults and Children: Confirm patient is hemodynamically stable on ≤1 vasopressor. Give by IV infusion over 2hrs. 6.25mg/kg every 6hrs for at least 21 days; if VOD unresolved after 21 days, continue until resolution or up to max 60 days. Treatment modification: see full labeling. Contraindications: Concomitant systemic anticoagulant or fibrinolytic therapy. Warnings/Precautions: Increased risk of bleeding; monitor. Active bleeding: do not initiate. Discontinue permanently if severe or life-threatening hypersensitivity reaction or recurrent significant bleeding occurs. Withhold if persistent, severe or potentially life-threatening bleeding occurs; consider resuming when bleeding has stopped. Discontinue ≥2hrs prior to an invasive procedure; resume as soon as any procedure-related bleeding risk has resolved. Pregnancy: potential risk of miscarriage. Nursing mothers: not recommended. Interactions: See Contraindications. Discontinue concomitant anticoagulants and fibrinolytics before initiating Defitelio. Pharmacological Class: Anticoagulant. Adverse Reactions: Hypotension, diarrhea, vomiting, nausea, epistaxis; hemorrhage, hypersensitivity reactions. Generic Availability: NO How Supplied: Single-use vials—10 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2c3db989-d7ad-41ed-9ebf-698dcf6c24ec ---------------------------------------------- 产地国家：美国 原产地英文商品名: Defitelio injection 200mg/2.5mL(80mg/mL)/vial 10vial/box  原产地英文药品名: defibrotide sodium 中文参考商品译名: Defitelio注射液 200毫克/2.5毫升（80毫克/毫升）/瓶 10瓶/盒 中文参考药品译名: 去纤苷酸 生产厂家中文参考译名: 爵士制药 生产厂家英文名: Jazz Pharmaceuticals, Inc