FDA批准艾替班特(Firazyr)治疗遗传性血管性水肿(HAE)急性发作
批准日期：2011年8月25日；本品在2008年11月7日首先被欧盟药品监督管理局批准由公司德国Jerini AG公司：美国为Shire plc公司
美国食品和药品监督管理局批准治疗年龄18岁和以上的一种罕见情况遗传性血管水肿(HAE)的急性发作。
HAE是一种蛋白被称为C1抑制剂低水平或功能不适当引起的局部，此蛋白涉及调节某些免疫系统和血液凝固通路功能。通常有家族史。在美国少于30,000人有HAE。
有HAE人们可能发生手，脚，肢体，面部，小肠，喉或气管迅速肿胀，可能造成畸形，残疾，或死亡。消化道肿胀可引起腹痛，恶心，和呕吐, 而气道肿胀使患者有窒息的危险。
FDA药品评价和研究中心的II药品评价办公室主任Curtis Rosebraugh, M.D., M.P.H.说“Firazyr提供治疗HAE急性发作的新选择和因为可以通过在腹部区注射自身给药，患者在认识到HAE发作时可自己治疗”。
在三项有开放延伸期对照临床试验中，其中225例患者接受1,076剂30 mg Firazyr显示Firazyr的安全性和疗效。患者用Firazyr被报道症状开始缓解中位治疗时间为2小时，安慰剂几乎20小时。
Firazyr是在美国第三个被批准治疗HAE发作的药物。2009年10月FD批准Berinert治疗HAE面部和副本发作，和2009年12月批准Kalbitor治疗年龄16岁和以上HAE急性发作患者。
FDA批准Firazyr有患者咨询资料包括注射指导。用Firazyr最常见副作用是注射部位反应，发热，肝酶升高，眩晕和皮疹。
FIRAZYR为皮下使用—FIRAZYR (艾替班特icatibant)注射剂
美国初始批准：2011
FIRAZYR
Manufacturer:
Shire US, Inc.
Pharmacological Class:
Bradykinin B2 receptor antagonist.
Active Ingredient(s):
Icatibant 10mg/mL; soln for SC inj; preservative-free.
Indication(s):
Treatment of acute attacks of hereditary angioedema (HAE).
Pharmacology:
Icatibant is a competitive antagonist selective for the bradykinin B2 receptor, with an affinity similar to bradykinin. Hereditary angioedema is caused by an absence or dysfunction of C1-esterase-inhibitor, a key regulator of the Factor XII/kallikrein proteolytic cascade that leads to bradykinin production. Bradykinin is a vasodilator which is thought to be responsible for the characteristic HAE symptoms of localized swelling, inflammation, and pain. Icatibant inhibits bradykinin from binding the B2 receptor and thereby treats the clinical symptoms of an acute, episodic attack of HAE.
Clinical Trials:
The efficacy and safety of Firazyr for the treatment of acute attacks of HAE in adults were studied in three controlled clinical trials. Response to therapy was primarily assessed using visual analog scores on a 100 mm scale and patient- and physician-reported symptom scores for abdominal and cutaneous pain and swelling.
Trial 1 was a randomized, placebo-controlled, double-blind, parallel-group study of 98 adult patients. Patients who had developed moderate-to-severe cutaneous or abdominal or mild-to-moderate laryngeal attacks of HAE were randomized to receive either Firazyr 30mg or placebo by SC injection. Patients with severe laryngeal attacks of HAE received open-label Firazyr 30mg. The primary endpoint was assessed using a 3-item composite visual analog score (VAS), comprised of averaged assessments of skin swelling, skin pain, and abdominal pain. Response was defined as at least a 50% reduction from the pretreatment composite 3-itemVAS score. The median time to 50% reduction in symptoms for patients with cutaneous or abdominal attacks treated with Firazyr (n=43) compared to placebo (n=45) was 2 hours versus 19.8 hours, respectively. Other evaluated endpoints included time to almost complete symptom relief (VAS<10 mm) and rescue medication use. In Trial 1, the median times to almost complete symptom relief were 8 versus 36 hours for Firazyr and placebo, respectively. In terms of rescue medication use, 3/43 (7%) patients treated with Firazyr used additional rescue medication in comparison to 18/45 (40%) patients treated with placebo.
In a second placebo-controlled trial and an active-controlled trial, a total of 26 and 35 patients, respectively, received Firazyr 30mg for the treatment of an acute HAE attack. Across the three trials, Firazyr had a median time to 50% reduction from baseline symptoms ranging from 2 to 2.3 hours.
In all three controlled trials, patients were eligible for treatment of subsequent attacks in an open-label extension. Patients were treated with Firazyr 30mg and could receive up to 3 doses of Firazyr 30mg administered at least 6 hours apart for each attack. A total of 225 patients were treated with 1,076 doses of 30mg Firazyr for 987 attacks of acute HAE in these trials. In an assessment of the first 5 Firazyr-treated attacks (621 doses for 582 attacks), the median times to a 50% reduction from the pretreatment composite 3-item VAS score were similar across attacks (2, 2, 2.4, 2, 1.5 hours). The majority (93%) of these attacks of HAE were treated with a single dose of Firazyr.
Legal Classification:
Rx
Adults:
≥18yrs: 30mg SC in abdominal area; may give additional doses at intervals of at least 6 hours if response inadequate or symptoms recur. Max 3 doses/24hrs.
Children:
<18yrs: not recommended.
Warnings/Precautions:
Advise patients to seek medical attention after treating laryngeal attack given the potential for airway obstruction. Elderly. Labor & delivery. Pregnancy (Cat.C). Nursing mothers.
Interaction(s):
May attenuate the antihypertensive effect of ACE inhibitors.
Adverse Reaction(s):
Inj site reactions, pyrexia, transaminase increase, dizziness, rash.
How Supplied:
Single-use prefilled syringe (3mL)—1, 3
制造商：
Shire的美国公司
类药物：
缓激肽B2受体拮抗剂。
活性成分（S）：
艾替班特10mg/ml的;为SC注射soln;不含防腐剂。
指示（S）：
治疗遗传性血管水肿（HAE）急性发作。
药理：
艾替班特是一个竞争激烈的缓激肽B2受体的选择性拮抗剂，与一个类似激肽的亲和力。遗传性血管性水肿是由C1酯酶抑制剂，一个关键的调节因子XII /激肽释放酶水解级联反应，导致缓激肽的生产的缺失或功能障碍引起的。缓激肽是一种血管扩张，这被认为是负责为局部红肿，发炎，疼痛的特点栓塞症状。艾替班特抑制缓激肽B2受体结合，从而将临床症状的一种急性，栓塞幕攻击。
临床试验：
治疗成人栓塞急性发作的疗效和安全Firazyr三个对照临床试验研究。对治疗的反应，主要是评估使用视觉模拟评分在100毫米的规模和病人和医生报告的腹部和皮肤的疼痛和肿胀的症状评分。
1审判是一项随机，安慰剂对照，双盲，平行组的98名成年患者的研究。曾开发中度至重度皮肤或腹部轻度至中度的喉攻击或栓塞患者随机接受Firazyr为30mg或安慰剂皮下注射，。严重喉攻击栓塞患者接受开放标签Firazyr为30mg。主要终点是评估使用了3项综合视觉模拟评分法（VAS），平均评估皮肤红肿，皮肤疼痛，腹痛组成。反应定义为预处理复合3 itemVAS得分至少减少50％。皮肤或腹部的攻击与Firazyr治疗的病人，症状减少50％的平均时间为（N = 43），相较于安慰剂组（n = 45），2小时和19.8小时，分别。其他评估指标包括几乎完全缓解症状（VAS <10毫米）和抢救药物的使用时间。在试验1中，几乎完全缓解症状的平均时间分别为8与36小时Firazyr和安慰剂分别。在抢救药物的使用方面，3 / 43（7％）与Firazyr治疗的病人使用四十五分之一十八（40％）与安慰剂治疗的患者相比额外的抢救用药。
在第二个安慰剂对照试验，并积极的对照试验，26日和35例，分别为治疗急性HAE的攻击，收到Firazyr 30毫克。在三个试验中，Firazyr了2至2.3小时不等的症状从基线减少50％的中位数时间。
在所有这三个对照试验中，患者随后的攻击在开放标签扩展治疗的资格。病人的治疗与Firazyr 30毫克，并可能获得高达3 Firazyr为30mg剂量每次攻击间隔至少6个小时管理。共有225例患者共收治1076 987急性HAE的攻击，在这些试验中的剂量为30mg Firazyr。在评估第5 Firazyr处理的攻击（621剂量为582攻击），平均时间从预处理减少50％的复合3项VAS评分在攻击（2，2，2.4，2，1.5类似小时）。 HAE的这些袭击的大多数（93％）的Firazyr单剂量治疗。
法律分类：
接收
成人：
≥18yrs：为30mg腹部SC;可能会在间隔至少6个小时的额外剂量，如果响应不足或症状复发。最多3个doses/24hrs。
儿童：
<18yrs：不推荐。
警告/注意事项：
建议患者寻求治疗喉攻击的气道阻塞的潜在后就医。老人。劳动和交付。怀孕（Cat.C）。哺乳的母亲。
相互作用（S）：
可能会减少ACE抑制剂的降压作用。
不良反应（S）：
注射部位反应，发热，转氨酶增加，头晕，皮疹。
如何提供：
一次性使用的预充式注射器（3ML）-1，3
最后更新：
二○一一年十一月十八日 |
