A型血友病新药Hemlibra（emicizumab-kxwh）注射剂-20年来是首个用于防止或减少成人和儿童A型血友病患。 近日，美国FDA批准了Hemlibra(emicizumab - kxwh)用于防止或减少成人和儿童A型血友病患者出血的频率，这些患者体内有一种叫做因子VIII(FVIII)抑制剂的抗体。 "降低出血频率或防止出血事件是血友病患者疾病管理的重要组成部分。这一批准提供了一种新的预防治疗方法，它已经被证明可以显着减少因子VIII抑制剂的A型血友病患者出血的次数。" FDA药物评估和研究中心血液和肿瘤产品办公室主任Richard Pazdur博士说道。"另外，接受Hemlibra治疗的患者的生理功能也有所改善。" A型血友病是一种遗传性的凝血障碍，主要影响男性。据美国国立卫生研究院(National Institutes of Health)称，在美国，每5000个男性中就有一个患有血友病，其中大约80%的人为A型血友病。A型血友病患者缺少一种能产生凝血因子VIII的基因。患者可能会经历反复的严重出血，主要发生在关节内，结果可能会使关节严重受损。一些患者会产生FVIII抑制剂或抗体的免疫反应。这种抗体干扰了现有血友病治疗的有效性。 Hemlibra是一线疗法，通过桥接其他因子来恢复这些患者的凝血功能。Hemlibra是一种预防性的治疗，每周通过皮下注射。 批准日期：2017年11月20日  公司：美国基因泰克 HEMLIBRA(emicizumab-kxwh)注射，用于皮下 美国初步批准:2017年 最近的重大变化 适应症和用法:10/2018 剂量和管理:10/2018 作用机制 HEMLIBRA bridges激活因子IX和因子X，恢复有效止血所需的缺失激活因子VIII的功能。 适应症和用法 HEMLIBRA是一种双特异性因子IXa和因子x定向抗体，用于常规预防，以预防或减少年龄在新生儿及以上的患有血友病a(先天性因子VIII缺乏)的成人和儿童患者的出血发作频率。 剂量和管理 推荐的负荷剂量为3mg/kg，前4周每周皮下注射一次，随后维持剂量为:每周1次:1.5mg/kg或每两周1次3mg/kg,6毫克/公斤每四周一次。 重要的准备和管理指示见完整的处方信息。 剂型和强度 注: 30毫克/毫升的单剂量瓶 60mg/0.4mL单剂量瓶 105mg/0.7mL单剂量瓶 150mg/mL单剂量瓶 禁忌症 没有 警告和预防措施 实验室凝血试验干扰:HEMLIBRA干扰活化凝血时间(ACT)，活化部分凝血活蛋白时间(aPTT)，以及基于aPTT的凝血实验室测试，包括基于单因素分析的单因素分析，基于aPTT的活化蛋白C抗性(APC-R)，以及基于贝塞斯达分析的因子VIII (FVIII)抑制剂效价。不应使用固有通路凝块基础实验室检测。 不良反应 最常见的不良反应(发生率10%)是注射部位反应、头痛和关节痛。 包装提供/存储和处理 提供 HEMLIBRA (emicizumab-kxwh)注射液是一种无菌，无防腐剂，无色的微黄色溶液，单剂量小瓶，剂量强度: 30mg/1mL    30mg/mL   1vial  NDC 50242-920-01 60mg/0.4mL  150mg/mL  1vial  NDC 50242-921-01 105mg/0.7m  150mg/mL  1vial  NDC 50242-922-01 150mg/1mL   150mg/mL  1vial  NDC 50242-923-01 储存和处理 HEMLIBRA瓶储存在冰箱在2°C到8°C(36°F 46°F)在原始cartonto保护。不冻结。不动摇。 在给药前，如有必要，未开瓶的半天秤座可能被储存在外面，然后返回冷藏。制冷的温度和总时间不得超过30°C(86°F)和7天(温度低于30°C(86°F)),分别。一旦从瓶中取出，如果不立即使用，则丢弃半天秤座。扔掉任何没用过的海姆莱。 Hemlibra® (emicizumab-kxwh) Indication HEMLIBRA is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors. Important Safety Information Boxed WARNING: THROMBOTIC MICROANGIOPATHY and THROMBOEMBOLISM Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of > 100 U/kg/24 hours of activated prothrombin complex concentrate (aPCC) was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of HEMLIBRA if symptoms occur. Warnings and Precautions Thrombotic Microangiopathy (TMA) Associated with HEMLIBRA and aPCC Cases of thrombotic microangiopathy (TMA) were reported from clinical trials when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate (aPCC) was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis. In clinical trials, thrombotic microangiopathy was reported in 1.6% of patients (3/189) and in 8.3% of patients (3/36) who received at least one dose of aPCC. Patients presented with thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, without severe deficiencies in ADAMTS13 activity. Evidence of improvement was seen within one week following discontinuation of aPCC. One patient resumed HEMLIBRA following resolution of TMA. Consider the benefits and risks if aPCC must be used in a patient receiving HEMLIBRA prophylaxis. Monitor for the development of TMA when administering aPCC. Immediately discontinue aPCC and interrupt HEMLIBRA prophylaxis if clinical symptoms and/or laboratory findings consistent with TMA occur, and manage as clinically indicated. Consider the benefits and risks of resuming HEMLIBRA prophylaxis following complete resolution of TMA on a case-by-case basis. Thromboembolism Associated with HEMLIBRA and aPCC Thrombotic events were reported from clinical trials when on average a cumulative amount of >100 U/kg/24 hours of aPCC was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis. In clinical trials, thrombotic events were reported in 1.1% of patients (2/189) and in 5.6% of patients (2/36) who received at least one dose of aPCC. No thrombotic event required anticoagulation therapy. Evidence of improvement or resolution was seen within one month following discontinuation of aPCC. One patient resumed HEMLIBRA following resolution of thrombotic event. Consider the benefits and risks if aPCC must be used in a patient receiving HEMLIBRA prophylaxis. Monitor for the development of thromboembolism when administering aPCC. Immediately discontinue aPCC and interrupt HEMLIBRA prophylaxis if clinical symptoms, imaging, or laboratory findings consistent with thromboembolism occur, and manage as clinically indicated.Consider the benefits and risks of resuming HEMLIBRA prophylaxis following complete resolution of thrombotic events on a case-by-case basis. Laboratory Coagulation Test Interference HEMLIBRA affects intrinsic pathway clotting-based laboratory tests, including activated clotting time (ACT), activated partial thromboplastin time (aPTT), and all assays based on aPTT, such as one-stage factor VIII (FVIII) activity. Therefore, intrinsic pathway clotting-based laboratory test results in patients treated with HEMLIBRA should not be used to monitor HEMLIBRA activity, determine dosing for factor replacement or anti-coagulation, or measure FVIII inhibitor titers. Results affected by HEMLIBRA: aPTT; Bethesda assays (clotting-based) for FVIII inhibitor titers; one-stage, aPTT-based, single-factor assays; aPTT-based Activated Protein C Resistance (APC-R); ACT. Results unaffected by HEMLIBRA: Bethesda assays (bovine chromogenic) for FVIII inhibitor titers; thrombin time (TT); one-stage, prothrobin time (PT)-based, single-factor assays; chromogenic-based single-factor assays other than FVIII (see Drug Interactions for FVIII chromogenic activity assay considerations); immuno-based assays (ie, ELISA, turbidimetric methods); genetic tests of coagulation factors (e.g., Factor V Leiden, Prothrombin 20210). Most Common Adverse Reactions The most frequently reported adverse reactions observed in ≥ 10% of subjects treated with at least one dose of HEMLIBRA were injection site reactions, headache, and arthralgia. Adverse Reactions Characterization of aPCC Treatment in Pooled Clinical Trials There were 125 instances of aPCC treatment in 36 patients, of which 13 instances (10.4%) consisted of on average a cumulative amount of >100 U/kg/24 hours of aPCC for 24 hours or more; two of the 13 were associated with thrombotic events and three of the 13 were associated with TMA. No TMA or thrombotic events were associated with the remaining instances of aPCC treatment. Injection Site Reactions In total, 35 patients (19%) reported injection site reactions (ISRs). All ISRs observed in HEMLIBRA clinical trials were reported as mild to moderate intensity and 88% resolved without treatment. The commonly reported ISR symptoms were injection site erythema (7.4%), injection site pruritus (5.3%), and injection site pain (5.3%). Drug Interactions Clinical experience suggests that a drug interaction exists with HEMLIBRA and aPCC. There is a possibility for hypercoagulability with activated recombinant factor VII (rFVIIa) or FVIII with HEMLIBRA based on preclinical experiments. https://www.accessdata.fda.gov/drugsatfda_docs/label/ 2018/761083s002s004lbl.pdf