Tretten (coagulation factor XIII A-subunit (recombinant))被美国FDA批准为世界上第一个可用于预防成人和儿童先天性第十三因子（FXIII）A亚基缺乏症出血重组治疗 TRETTEN，凝血因子XIII A-亚单位(重组) ——为静脉使用。为注射溶液冻干粉 商标名称：Tretten 通用名称：凝血因子XIII A亚基（重组） 生产公司：诺和诺德 治疗：Tretten（凝血因子XIII A亚基（重组））是人的因素XIII A亚基用于预防谁拥有罕见的凝血障碍的先天性第十三因子A亚基缺乏的病人出血的重组类似物。 TRETTEN Rx Pharmacological Class: Clotting factor. Active Ingredient(s): Coagulation Factor XIII A-Subunit (recombinant) 2000–3125 IU; per vial; lyophilized pwd for IV inj after reconstitution; preservative-free. Company Novo Nordisk Indication(s): Routine prophylaxis of bleeding in patients with congenital factor XIII (FXIII) A-subunit deficiency. Limitations of use: not for use in patients with congenital factor XIII B-subunit deficiency. Pharmacology: FXIII is the terminal enzyme in the blood coagulation cascade. When activated by thrombin at the site of vessel wall injury, FXIII maintains hemostasis through cross-linking of fibrin and other proteins in the fibrin clot. Activated recombinant FXIII has been shown to increase mechanical strength and resistance to fibrinolysis of the fibrin clot and contributes to enhance platelet and clot adhesion to injured tissue. Clinical Trials: The efficacy of Tretten for the prevention of bleeding in patients with congenital FXIII A-subunit deficiency was established in a multicenter, open-label, non-controlled trial over 52 weeks. The study included 41 subjects ≥6 years old with congenital FXIII A-subunit deficiency confirmed by genotyping. All patients received monthly doses of Tretten at 35 IU/kg. Bleeding episodes that required treatment with a FXIII-containing product were observed to evaluate the efficacy of monthly replacement therapy with Tretten on prevention of bleeding episodes. During the prophylaxis treatment period with Tretten for all 41 subjects, a mean annual rate of bleeding episodes that required treatment was determined to be 0.14 (95% CI: 0.058–0.332) per subject year. This was a statistically significant reduction from the historic bleeding rate of 1.68 per subject year for on-demand treatment. The age-adjusted rate of bleeding episodes that required treatment during the Tretten treatment period was 0.05 (95% CI: 0.0094–0.2501) per subject year with a model-based estimate corresponding to the mean age of 26.4 years. The mean annual bleeding rate was higher in patients <18 years of age compared to that in adults (0.362 vs. 0.040 bleeds/subject/year). An ongoing second trial enrolled 34 of the original 41 subjects and an additional 21 new subjects. The mean annual rate of bleeding episodes requiring treatment was determined to be 0.056 per subject year. The age-adjusted rate of bleeding episodes that required treatment during the Tretten treatment period was 0.022 (95% CI: 0.0045, 0.1023) per subject year with a model-based estimate corresponding to a mean age of 29.5 years. The annual mean bleeding rate was higher in patients aged <18 years compared to that in adults (0.127 vs. 0.026 bleeds/subject/year) with some overlap of the respective 95% confidence intervals. Legal Classification: Rx Adults & Children: Give by IV inj at a rate of max 1–2mL/min. Initially 35 IU/kg once monthly to achieve a target trough FXIII activity level ≥10% using a validated assay. Consider dose adjustment if adequate coverage not achieved. Do not administer with other infusion solutions. Warnings/Precautions: Should be initiated under supervision of an experienced physician. Discontinue immediately and treat appropriately if anaphylaxis or hypersensitivity reactions occur. Conditions that predispose to thrombosis; monitor for signs/symptoms of thrombosis after administration. Measure FXIII inhibitory antibody concentrations if expected plasma FXIII activity levels not attained or if breakthrough bleeding occurs. Pregnancy (Category C). Nursing mothers. Interaction(s) Thrombosis risk with concomitant factor VIIa; avoid. Adverse Reaction(s) Headache, pain in the extremities, injection site pain, increase in fibrin D-dimer levels; hypersensitivity reactions. How Supplied: Single-use vials—1 (w. diluent, supplies) LAST UPDATED: 4/4/2014 http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8664978e-1814-4930-aca5-97a24455f6df&type=display 诺和诺德罕见凝血障碍药物TRETTEN获FDA批准 2013年12月25日，TRETTEN（凝血因子XIII A亚基，重组）获FDA批准，用于先天性因子XIII（FXIII）A亚基缺乏症患者出血事件的常规预防（prophylaxis）。TRETTEN是唯一一种先天性FXIII A亚基缺乏症治疗药物。在临床试验中，TRETTEN已证明了其安全性和疗效，该药每月输液1次。 先天性FXIII A亚基缺乏症是一种严重、罕见的出血性疾病，治疗选择十分有限。该病患者对出血具有终身的易感性（susceptibility），包括自发性颅内出血。在美国，该病的患病率约为300万-500万分之一。根据2011年的数据，在全球范围内仅有1054例先天性FXIII A亚基缺乏症患者确诊，其中美国约有108例。 TRETTEN的获批，是基于III期临床项目的数据，该项目证明了TRETTEN治疗先天性FXIII A亚基缺乏症患者时的疗效和安全性。其中一项III期试验，涉及41例患者，研究结果表明，与未接受常规FXIII输液治疗的历史对照组相比，每月接受一次35IU/kg剂量TRETTEN输液预防性治疗的患者组，发生需治疗性出血发作的次数显著减少。 诺和诺德计划，在2014年初将TRETTEN推向美国市场。此外，TRETTEN也已获加拿大（商品名Tretten）及欧盟、瑞士、澳大利亚（商品名Novo Thirteen）批准。 关于先天性FXIII A亚基缺乏症（congenital FXIII A-subunit deficiency）： 先天性FXIII A亚基缺乏症是由于缺乏凝血因子XIII所致。该蛋白负责稳定血凝块的形成。在缺乏FXIII时，血凝块依然会形成，但不稳定，容易分解，导致延迟性出血