依那西普说明书

药品名:依那西普(Etanercept)

英文名:Infliximab、Enbrel@(Amgen Inc 生产)、Remicade@(Centacor.Inc生产).

来源: 英利昔是利用重组DNA和单克隆抗体技术制备的人源化的人鼠嵌合搞TNFα受体单抗.
依那西普是完全由人Ig生产的抗TNFα受体单抗.

作用机制: 本品为二聚体融合蛋白,由人类75kD肿瘤坏死因子(tumor necrosis factor, TNF)受体的细胞外配体结合部分和人类IgG1Fc段连接而成.本品Fc段含有GH2区、CH3区铰链区,但是不含有CH1区.
近年来研究发现骨髓异常增生综合征(myelo-dysplastic syndrome, MDS)伴有程序化细胞死亡(凋亡)加速,并且这种细胞凋亡与过度表达TNFα有关.本品特异性地与TNFα受体结合,阻断TNFa与细胞表面TNFα受体的相互作用;此外,本品还可以调节TNFα诱导或者介导的生物学作用.

药代动力学:
1.吸收:单药25mg皮下注射.吸收较慢,平均69±34小时,达到血药峰浓度.每周两次,每次25mg皮下注射用药6个月后,平均血药浓度2.4±1.0 μg/ml.
2.分布:无资料.
3.半衰期:单药25mg皮下注射,清除率160±80ml/h.平均半衰期102±20小时.
4.清除:经体内蛋白质降解途径清除.
 
药物相互作用: 尚无相关资料.

适应证: 治疗低危/中危MDS、难治性贫血(RA)期伴有TNFa升高的病例.

单药有效率: 治疗MDS,有效率12.5%～30%.

剂型: 无菌白色不含防腐剂的冻干粉,每支含有Enbrel25mg,D-甘露醇40mg,蔗糖10mg,氨丁三醇1.2mg.依那西普为无菌冻干粉,每支含Remicade100mg.

剂量: 试验治疗MDS剂量(Remicade):3mg/kg静脉用药6次(第0、2、6、14、22、30周).Embrel,25mg皮下注射,每周2次,3个月为一疗程.

给药途径: 皮下注射或者静脉点滴.

配伍: 本品不宜与其他药品混合使用并且不应使用注射用水以外的溶媒溶药.

禁忌证: 败血症患者、已知对Embrel和Remicade或者制剂中其他成分过敏的患者禁用.心衰患者、老年患者、孕妇、哺乳期妇女慎用.

不良反应:
1.注射部位局灶反应:红斑、痛痒、疼痛、肿胀、出血、瘀伤。平均持续3~5天,一般不需停药.
2.感染:最常见下呼吸道感染,其他感染有:鼻炎、咽炎、肾盂肾炎、支气管炎、脓毒性关节炎、腹腔脓肿、蜂窝织炎、骨髓炎、伤口感染、肺炎、足部脓肿、腿部溃疡、腹泻、鼻窦炎、败血症。并有可能增加原有感染患者的死亡率.
3.心血管系统:心力衰竭、心肌梗死、心肌缺血、高血压、低血压、深静脉血栓、血栓性静脉炎。
4.消化系统：胆囊炎、胰腺炎、胃肠道出血、腹痛、消化不良、呕吐、食欲不振、口干、口腔溃疡。
5.肌肉骨骼系统:滑囊炎、多发性肌炎、关节痛、狼疮样综合征。
6.神经系统:头痛、眩晕、脑缺血、抑郁、多发性硬化、血管神精性水肿、偏瘫、脑卒中、癫痫、孤立性脱髓鞘病、横断性脊髓炎、视神精炎。
7.呼吸系统：咳嗽、呼吸困难、肺栓塞、间质性肺炎。
8.泌尿生死系统:膜性肾小球肾炎.
9.血液系统:淋巴结肿大、贫血、再生障碍性贫血、白细胞减少症、粒细胞减少症、全血减少、血小板减少症。
10.皮肤病变:脉管炎、皮下结节、风疹、皮疹、脱发。

临床应用规程：
1.用药前做血常规、心电图、超声心动图等检查，评定左室功能。
2.用药前准备好抢救过敏反应药物和简易呼吸器.
3.用英利昔前可预防性应用抗组胺药和解热镇痛药物.用依那西普前可仅用抗组胺类药.
4.监测血压、呼吸、心率等生命体征。
5.用药期间均需监测血象,进行左室功能评定.出现下述情况应考虑停药:确定相关的明显的血液学异常、严重过敏反应、狼疮样综合征。监测病情直至症状和体征恢复正常。
6.使用时以1ml无菌注射用水溶解.稀释剂应缓慢注入药瓶中,尽量避免摇动或剧烈震动.严禁将两支药品溶液混用,或者将一支中的药液倒入另一支中.如果药液出现褪色、絮状物、颗粒状物质，应废弃不用。

贮存：
原药避光贮于2～8℃。溶解后最多只能保存14天。

注：以下产品不同规格和不同价格，购买时请以电话咨询为准！
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原产地英文商品名:
ENBREL 50MG/ML/SYRINGE/BOX
原产地英文药品名:
ETANERCEPT
中文参考商品译名:
恩利 50毫克/毫升/注射器/盒
中文参考药品译名:
依那西普
生产厂家中文参考译名:
IMMUNEX
生产厂家英文名:
IMMUNEX

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原产地英文商品名:
ENBREL 25mg/25ml/vial 4vials/box
原产地英文药品名:
ETANERCEPT
中文参考商品译名:
恩利 25毫克/25毫升/瓶 4瓶/盒
中文参考药品译名:
依那西普
生产厂家中文参考译名:
IMMUNEX
生产厂家英文名:
IMMUNEX

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原产地英文商品名:
ENBREL 25mg/0.5ml/syringe 4syringes/Box
原产地英文药品名:
ETANERCEPT
中文参考商品译名:
恩利 25毫克/0.5毫升/注射剂 4注射剂/盒
中文参考药品译名:
依那西普
生产厂家中文参考译名:
IMMUNEX
生产厂家英文名:
IMMUNEX

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About Enbrel® (etanercept)
How does ENBREL work?
ENBREL is a type of protein called a tumor necrosis factor (TNF) blocker that blocks the action of a substance your body makes called TNF. Tumor necrosis factor is made by your body's immune system. People with immune diseases such as RA, JRA, AS, psoriatic arthritis, and plaque psoriasis have too much TNF in their bodies.

About moderate to severe rheumatoid arthritis
About moderate to severe juvenile rheumatoid arthritis
About ankylosing spondylitis
About psoriatic arthritis
About chronic moderate to severe plaque psoriasis
 
Important information about taking prescription ENBREL 
ENBREL can reduce the amount of TNF in the body. And while ENBREL can block the damage that too much TNF can cause, it can also lower the ability of your immune system to fight infections. So, taking ENBREL can make you more prone to getting infections or make any infection that you may have worse. To find out more about prescription ENBREL, talk with your doctor. Your doctor is the best source of information. You can also view the Important Safety Information. If you have additional questions, call 1-888-4ENBREL (1-888-436-2735). This line is open Monday through Friday, 8:00 am to 11:00 pm, Eastern Time.
 
How ENBREL is taken 
Administering ENBREL can be convenient. ENBREL is a protein and is injected (by you or someone else) just under the skin. Once you've filled your prescription, schedule a training session with your doctor's office to learn the proper techniques for self-injection. During this session, you may administer your first dose of ENBREL. You'll learn what you need to know at the doctor's office to inject ENBREL at home.
 
Proven experience 
ENBREL has more than 14 years of collective clinical experience.

The first ENBREL clinical trials began in 1992. Since its approval for moderate to severe rheumatoid arthritis in 1998, ENBREL has also been approved for use in treating moderate to severe juvenile rheumatoid arthritis (JRA), psoriatic arthritis, ankylosing spondylitis (AS), and moderate to severe plaque psoriasis.
 
Established safety profile 
The safety profile for ENBREL during clinical trials showed:
Rates of serious adverse events were comparable to control patients in rheumatoid arthritis, psoriatic arthritis, and plaque psoriasis clinical trials.

The most common adverse events reported were injection site reactions, infections, and headache.

Routine laboratory monitoring specific for ENBREL therapy is not required; however, careful medical management and supervision of patients are recommended. Tell your doctor if you are prone to infection or have had hepatitis B.
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Learn More: 
rheumatid arthritis  
juvenile rheumatoid arthritis  
psoriatic arthritis  
ankylosing spondylitis  
plaque psoriasis
 
What important safety information do I need to know about taking prescription ENBREL?
ENBREL is a type of protein called a tumor necrosis factor (TNF) blocker that blocks the action of a substance your body's immune system makes called TNF. People with an immune disease, such as rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, or psoriasis, have too much TNF in their bodies. ENBREL can reduce the amount of active TNF in the body to normal levels, helping to treat your disease. But, in doing so, ENBREL can also lower the ability of your immune system to fight infections.

Serious infections, including tuberculosis (TB), have happened in patients taking ENBREL. Some of these serious infections have been fatal. Many serious infections occurred in people prone to infection. Serious infections have also occurred in patients with advanced or poorly controlled diabetes. Do not start ENBREL if you have an infection or are allergic to ENBREL or its components. Once on ENBREL, if you get an infection or have any sign of an infection, including fever, cough, or flu-like symptoms, or have open sores, tell your doctor. Your doctor should test you for TB before starting ENBREL and should monitor you closely for signs and symptoms of TB.

Serious nervous system disorders, such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes have been reported. There have been rare reports of serious blood disorders (some fatal).

In medical studies, more cases of lymphoma (a type of cancer) were seen in patients taking TNF blockers compared to similar patients who were not taking TNF blockers. The risk of lymphoma may be several-fold higher in people with rheumatoid arthritis and psoriasis; the role of TNF blockers in the development of malignancies is unknown.

Tell your doctor if you:
Think you have, are being treated for, have signs of, or are prone to infection
Have any open sores
Have or have had TB or hepatitis B
Have ever been treated for heart failure
Have ever had or develop a serious nervous system disorder
Develop symptoms such as persistent fever, bruising, bleeding, or paleness while taking ENBREL
Common side effects in adult clinical trials were injection site reaction, infection and headache.

In a medical study of patients with JIA, infection, headache, abdominal pain, vomiting, and nausea occurred more frequently than in adults. The kinds of infections reported were generally mild and similar to those usually seen in children. Other serious adverse reactions were reported, including serious infection and depression/personality disorder.

If you have any questions about this information, be sure to discuss them with your doctor. You are encouraged to report negative side effects of prescription drugs to the FDA. If you have any questions about this information, be sure to discuss them with your doctor. Please see full Prescribing Information.

INDICATIONS
Moderate to Severe Rheumatoid Arthritis (RA)

ENBREL is indicated for reducing signs and symptoms, keeping joint damage from getting worse, and improving physical function in patients with moderate to severe rheumatoid arthritis. ENBREL can be taken with methotrexate or used alone.

In medical studies, ENBREL was shown to be effective in about 2 out of 3 adults with RA who used it, and has been shown to begin working in as few as 2 weeks, with most patients receiving benefit within 3 months. In an RA medical study, 55% of patients had no progression of joint damage.
 
Moderate to Severe Polyarticular Juvenile Idiopathic Arthritis (JIA)

ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in children ages 2 years and older.

In medical studies, ENBREL was shown to be effective in about 3 out of 4 children with JIA who used it. For these JIA patients, ENBREL has been shown to begin working in approximately 2 to 4 weeks.

Psoriatic Arthritis
ENBREL is indicated for reducing signs and symptoms, keeping joint damage from getting worse, and improving physical function in patients with psoriatic arthritis. ENBREL can be used in combination with methotrexate in patients who do not respond adequately to methotrexate alone.

In medical studies, ENBREL was shown to be effective in about 50% of psoriatic arthritis patients who used it. Clinical responses were apparent at the time of the first visit (4 weeks) and were maintained through 6 months of therapy.
 
Ankylosing Spondylitis (AS)
ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.

In a medical study, ENBREL was shown to be effective in about 3 out of 5 adults with AS who used it. Clinical responses were seen at 2 weeks in 46% of patients, with 59% of patients receiving benefit within 8 weeks.
 
Moderate to Severe Plaque Psoriasis
ENBREL is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

In medical studies, nearly half of patients saw a significant improvement in their plaque psoriasis within 3 months of using ENBREL. Overall, 3 out of 4 patients saw improvement. ENBREL can work fast; many patients saw improvement within 2 months. ENBREL has been shown to be effective through 12 months of therapy.

美国食品和药物管理局（FDA）在今年1月18日批准Immunex公司的药物Enbrel用于治疗银屑病关节炎新适应症，这是FDA第一次批准银屑病关节炎治疗药物。FDA曾在2001年9月就批准对Enbrel新适应症作快速审查处理。

Enbrel是一种批准用于治疗中度到重度类风湿性关节炎的药物，预计全美有150万人患有这种由于免疫系统紊乱造成的关节和软骨疼痛及膨胀的疾病。

银屑病关节炎是一种严重的慢性炎症疾病，可引起关节疼痛、肿胀，很容易导致失能。传统的治疗包括非甾体抗炎药，皮质内固醇和改善用抗风湿药，如氨甲蝶呤和环孢菌素。以前的统计资料表明全美大约有30万银屑病关节炎患者，但是Immunex在本周三宣称由国家银屑病基金会进行的最新统计表明当前美国有100万银屑病患者。

银屑病基金会的主管Gail Zimmerman介绍说，“银屑病关节炎与其他类型的关节炎不同，患者除皮肤表面有带磷红色斑块外，还伴有关节疼痛和膨胀症状。目前对银屑病关节炎的治疗仅仅是借鉴了其他治疗方法，并不是对每位患者都有效。”

该药物通过结合到特定蛋白使之失去活性而起到治疗作用，后者在正常的免疫功能和类风湿性关节炎及银屑病关节炎引起的反馈反应中都起关键性作用。Enbrel的副作用除注射部位皮肤有反馈作用外，对呼吸系统和其他部位也有潜在的感染性。

ENBREL使牛皮癣患者的病情迅速改善。

《英国皮肤学杂志》发表的资料显示，ENBREL在剂量减少之后为牛皮癣患者带来持续的疗效。
 
新泽西州麦迪逊, 6月29日/美通社-亚洲网/《大剂量改善治疗回应》。
 
Wyeth 公司(NYSE: WYE)旗下的Wyeth Pharmaceuticals今天宣布，2005年6月出版的《英国皮肤学杂志》发表的第叁阶段试验资料显示，与每周两次25毫克的剂量相比，在使用最大剂量（每周两次50毫克）时，ENBREL(*) (etanercept)在12周使牛皮癣患者的病情迅速改善，回应更快。在每周两次50毫克的治疗组，当剂量在第12周减少一半时，多数病人在24周试验剩馀时间仍有持续的疗效。
 
Walsgrave Hospital & George Eliot Hospital的皮肤病专家John Berth-Jones说：“这些资料显示，在开始采用每周两次50毫克的ENBREL治疗三个月时，病人的牛皮癣症状迅速地明显减轻，随後再进行叁个月的每周两次的25毫克的後续治疗。特别值得注意的是，在改为维护剂量时治疗回应没有丧失。”
 
据估计，牛皮癣患者占全世界人口的大约2%。在欧洲，估计有510万牛皮癣患者。这种疾病的特点皮肤长期发炎。这种炎症导致皮肤出现红肿，常常痛苦不堪，有损于外貌。越来越多的肿瘤骨疽因素在牛皮癣病灶中被发现，据认为与牛皮癣的形成和维护有关。
 
这项分析研究了对欧洲、美国和加拿大583名患者的24周研究的资料。被研究的人口患有活动的临床上稳定地牛皮癣，涉及身体表面的23%。此外，参加试验的患者平均患有19年的牛皮癣，中间牛皮癣面积和严重性指数(PASI)为16.4。PASI是衡量牛皮癣的程度和严重性的获得证实的临床衡量尺度。在头12周的研究中，患者被随机分为叁个双盲对照组：第一组获得每周两次50毫克的皮下剂量ENBREL；第二组获得每周两次25毫克的剂量；第叁组获得每周两次皮下安慰剂治疗。在第二个12周，所有患者都以公开标签的方式获得每周两次的25毫克ENBREL 注射。

在剂量减少期间仍然保持疗效
 
研究结果根据初步终点的实现和维持进行分析，在12周衡量的皮肤损伤基线有75%或更高的改善。结果随後在24周重新评估。在第一个12周的时间点，每周两次50毫克的治疗组有49%获得PASI 75，而每周两次25毫克治疗组为34%，安慰剂组为3%。在第24周，所有患者都获得了额外12周的每周两次25毫克的ENBREL治疗，剂量减少一半的患者有54%实现了PASI 75，在连续每周两次25毫克的患者为45%，在服用ENBREL 每周两次25毫克之後采用12周安慰剂的治疗组为28%。此外，在每周两次50毫克剂量第12周实现PASI 75的患者有77%在第24周的研究中保持PASI 75的回应。

疗效迅速
 
早在研究的第2周，PASI基线的平均百分比改善在获得每周两次50毫克ENBREL的治疗组就与安慰剂治疗组有明显的区别。此外，获得ENBREL的患者的回应在研究中取决于剂量，采用ENBREL进行每周两次50毫克治疗 (10%)与安慰剂组（2%）相比，早在第4周的PASI 75回应就有明显的差别。采用ENBREL进行每周两次25毫克治疗 (20%)与安慰剂组（3%）相比，早在第8周的PASI 75回应就有明显的差别。此外，每周两次50毫克治疗组与每周两次25毫克治疗组相比，早在第12周的PASI 75回应有明显的差别(P = 0.004)。

耐药性好
接受ENBREL治疗的患者的副作用和炎症的数目和种类类似于安慰剂治疗组。注射部位的反应是最常见的报告事件（50毫克ENBREL组和25毫克组分别18%和13%，而安慰剂组为6%)。研究人员报告说，在12周的研究中，ENBREL仍有很强的耐药性。

关于ENBREL

Wyeth Pharmaceuticals公司在北美以外销售ENBREL。它由Immunex（现在是Amgen (Nasdaq: AMGN)的一部分）发现，与Wyeth Pharmaceuticals联合开发。两间公司在北美共同推广ENBREL。

在欧洲联盟，ENBREL已经获准用于治疗成年人的轻度到中度牛皮癣。这些患者对包括cyclosporine、methotrexate或PUVA在内的其他治疗方法没有回应，或者禁忌，或者不能忍耐。ENBREL还获准单独或与methotrexate结合使用，治疗成年人的活动期风湿性关节炎，这些患者对治疗关节炎药物（包括methotrexate (除非有禁忌)的回应不够。ENBREL还用于治疗以前没有采用methotrexate治疗的成年人的严重的活动期风湿性关节炎。在风湿性关节炎患者身上，ENBREL单独使用，或与methotrexate结合使用，它可放慢用X光发现的与疾病有关的结构损伤。ENBREL还获准用于治疗4至17岁活动期多关节慢性关节炎。这些患者对methotrexate的回应不够或者不能忍受。ENBREL还获准用于治疗成年人的活动期渐进性牛皮癣关节炎，因为他们对以前的治疗关节炎药物的响应不够，它还用于治疗成年人的严重活动期强直性脊柱炎。他们对常规药物的回应不够。
 
自从ENBREL六年前推出以来，医生已经熟悉ENBREL的好处和长期耐药性。全世界超过28万患者采用这种药物治疗。ENBREL (etanercept) 的作用是把肿瘤骨疽 (TNF)粘合。它在正常免疫功能和造成牛皮癣、牛皮癣关节炎和RA的发炎过程的一系列反应中起着重要的作用。把ENBREL与TNF粘合使粘合的 TNF在生物上失去活性，这可能大大减轻发炎活动。
 
自从这种产品第一次推出以来，采用ENBREL的患者出现过严重的感染，有些造成死亡。患者应该告诉医生，他们是否有炎症，或者是否容易发炎。患者如果有炎症或者对ENBREL或其成份过敏，就不应该开始使用ENBREL。容易发炎的患者应该慎用ENBREL。

该药有引起多种硬化症和/或眼部神经炎症等严重神经系统疾病的报告。患者应该告诉医生，他们是否有任何这样的疾病，或者在开始用ENBREL之後出现这些疾病。患者还应该告诉医生，他们是否进行过心衰竭的治疗。严重血液疾病，造成死亡的情况也鲜有报告。

患者如果出现持续的发热、青肿、出血或苍白，应该立即通知医生。现在尚不清楚ENBREL是否引起过这些神经系统或血液疾病。 如果一名患者的医生确认有严重的血液问题，患者可能需要停用ENBREL。
 
在牛皮癣患者的叁项双盲安慰剂对照试验中观察到的最常见的副作用是感染（占患者的27%-29% )、注射部位反应(14%-16%)、头痛(9%-12%)以及注射部位ecchymoses (6%-8%)。在662个患者暴露年，没有机会性感染或肺病的报告。

在用ENBREL对1261名患者进行15个月的双盲、开放标签研究中，牛皮癣患者出现过23例恶性副作用。

在对风湿性关节炎（RA）的5项双盲对照临床试验中，最常见的副作用是感染（占患者的49%）、注射部位反应（31%）、头痛（12%）以及呼吸疾病（10%）。恶性副作用罕见。

牛皮癣关节炎和强直性脊柱炎患者身上观察到的副作用与RA临床试验中观察到的副作用类似。
 
在对青少年关节炎患者的研究中，感染（占患者的62%）、头痛（19%)、腹痛（19%)、呕吐(13%)和恶心(9%)比成年常见。罕见的严重副作用是水痘 (3%)、肠胃炎 (3%)、严重感染, (2%)、抑郁症/性格疾病(1%)、皮肤溃疡(1%)、上消化道发炎(1%)和糖尿病(1%)。