药品名称
药品名:依那西普(Etanercept)
英文名:Infliximab、Enbrel(Amgen Inc 生产)
生产厂家
Amgen Inc
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.
适应症
治疗低危/中危骨髓异常增生综合征（MDS）、难治性贫血(RA)期伴有TNFa升高的病例.
单药有效率: 治疗骨髓异常增生综合征（MDS）,有效率12.5%～30%.
剂型／规格
无菌白色不含防腐剂的冻干粉,每支含有依那西普25mg或50mg.
用法用量
试验治疗骨髓异常增生综合征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.
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。
任何疑问，请遵医嘱！
禁忌症
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.
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.
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。
包装规格：
25mg/Vial *4 小瓶 
50mg/ml *4 预充式注射剂

Medication name
Generic name: Etanercept - Injection

Brand name(s): Enbrel
Warning
Because etanercept works by blocking the immune system, it may lower your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection (such as fungal infections, bacterial infections including tuberculosis) or make any infection you have worse. Tell your doctor your medical history, especially of past/recent/current infections. Also, tell your doctor if you have lived or traveled in areas where certain fungal infections (such as coccidioidomycosis, histoplasmosis) are common or if you have been near someone with tuberculosis. Areas where these types of fungal infections are commonly found include the Ohio and Mississippi River valleys and the southwestern United States. You should be tested for tuberculosis (TB skin test or chest X-ray) before and during treatment with etanercept. See Side Effects section for symptoms of infections to watch out for, and get medical help right away if you develop any of these symptoms.The immune system is also important in preventing and controlling cancer. Though it is very unlikely to happen, there is a risk (especially in children/teens/young adults) of developing cancer (such as lymphoma, skin) due to this medication or due to your medical condition. Discuss the risks and benefits of treatment with your doctor. Tell your doctor right away if you develop symptoms such as unusual lumps/growths, swollen or painful abdomen, unexplained weight loss, persistent fever or night sweats.
Uses
This medication is used alone or in combination with an immunosuppressant (such as methotrexate) to treat certain types of arthritis (such as rheumatoid, psoriatic, juvenile idiopathic, and ankylosing spondylitis), as well as a skin condition called psoriasis. These conditions are caused by an overactive immune system (autoimmune disease). The immune system attacks the body's own healthy cells, causing inflammation in the joints and skin.Etanercept controls your body's defensive response by blocking the action of a certain natural substance (TNF) that is used by the immune system. Treatment decreases redness, itching and scaly patches in psoriasis as well as the pain, swelling and stiffness of joints in arthritis. This medication can stop the progression of disease and joint damage, resulting in improved daily functioning and quality of life.This medication treats but does not cure autoimmune diseases. Symptoms usually return within 1 month of stopping the medication.
How to use
Read the Medication Guide and the Patient Information Leaflet provided by your pharmacist before you start using this drug and each time you get a refill. If you have any questions, consult your doctor or pharmacist.Etanercept is injected under the skin of the thigh, abdomen, or upper arm, usually once or twice weekly exactly as prescribed by your doctor.Your dosage is based on your medical condition and response to treatment. Do not change your dose without first consulting your doctor. Use this medication regularly in order to get the most benefit from it. You should start to see an improvement in 1 to 2 weeks. It may take up to 3 months to receive the full benefit of this medication.If you will be giving yourself the injection, your doctor may want you to have the first injection in the medical office. Make sure you learn the proper way to inject this medication from your health care professional, as described in the Patient Information Leaflet from the manufacturer.Remove the medication from the refrigerator and allow it to warm to room temperature before injecting. This takes about 15 to 30 minutes. Do not shake the product. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid.Before injecting each dose, clean the injection site with rubbing alcohol. It is important to change the location of the injection site each time you use this drug to prevent problems under the skin. New injections should be given at least 1 inch (2.5 centimeters) from an old injection site. Do not inject into areas of the skin that are sore, bruised, red, or hard.Learn how to store and discard needles and medical supplies safely. Consult your pharmacist. Never reuse needles or syringes.Tell your doctor if your condition persists or worsens.
Precautions
Before using etanercept, tell your doctor or pharmacist if you are allergic to it; or to latex or natural dry rubber (found in the prefilled syringes or autoinjectors); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: active or recurrent infection (such as hepatitis B, HIV, tuberculosis), blood disorders (such as leukemia, anemia), weakened bone marrow, history of cancer (such as lymphoma), diabetes, heart failure, seizures, nervous system problems (such as multiple sclerosis), a certain liver problem (alcoholic hepatitis), blood vessel disorders (such as vasculitis).Do not have immunizations/vaccinations without the consent of your doctor, and avoid contact with people who have recently received oral polio vaccine. Consult your doctor about risks of exposure to chickenpox and other infections.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Caution is advised when using this drug in the elderly because they may be more prone to infections.It is recommended that children be up to date on all their childhood vaccinations before starting etanercept.During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this drug passes into breast milk and the effect on a nursing infant is unknown. Consult your doctor before breast-feeding.
Drug interactions
Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: abatacept, interleukin-1 blockers (such as anakinra, canakinumab, rilonacept), live vaccines (such as measles, mumps, polio, rubella, typhoid, varicella, yellow fever), other medications for autoimmune disease (such as azathioprine, cyclophosphamide, efalizumab, natalizumab).
Side effects
See also Warning section.Redness, itching, pain, or swelling at the injection site may occur. This usually starts 1-2 days after the injection and clears up in 3-5 days. Injection site reactions usually lessen after the first month. Headache may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you develop signs of infection while using this drug, such as: fever, chills, persistent sore throat, persistent cough, night sweats, trouble breathing, painful/frequent urination, unusual vaginal discharge, white patches in the mouth (oral thrush).Tell your doctor right away if you have any serious side effects, including: a rash on nose and cheeks (butterfly rash), dizziness, extreme fatigue, looking pale, hair loss, swelling of the arms/legs, unusual bruising/bleeding, severe headache, mental/mood changes, seizures, unexplained muscle weakness, numbness/tingling of the hands/feet, unsteadiness, vision changes, severe stomach/abdominal pain, persistent nausea/vomiting, dark urine, yellowing eyes/skin.An allergic reaction to this drug is unlikely, but get medical help right away if it occurs. Symptoms of an allergic reaction include: rash, itching/swelling (especially of the face/tongue/throat), dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
Missed dose
For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor or pharmacist immediately to establish a new dosing schedule. Do not double the dose to catch up.
Overdose
If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canada residents should call their local poison control center directly.
Notes
Do not share this medication with others.Laboratory and/or medical tests (such as complete blood count, liver function, TB test) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.This medication may interfere with certain lab tests. Be sure to tell the lab personnel that you are on this medication.
Storage
Store unopened vials and prefilled syringes in a refrigerator between 36-46 degrees F (2-8 degrees C) away from light and moisture. Do not freeze. Once mixed, this drug must be used within 14 days and should be stored in the original vial in the refrigerator. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Photos by medication strength
Enbrel 25 mg (1 mL) Sub-Q Kit
Enbrel 25 mg/0.5 mL (0.51 mL) Sub-Q Syringe
Enbrel 50 mg/mL (0.98 mL) Sub-Q Syringe

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。
日本批准依那西普(etanercept,Enbrel)用于类风湿性关节炎治疗
日本厚生省批准依那西普（etanercept，Enbrel）用于治疗对现有药物应答不足的类风湿性关节炎（RA）患者。 至此，本品已在全球70多个国家上市。
本品为一靶向肿瘤坏死因子（TNF）的完全人源化单克隆抗体药物，可缓解对传统抗关节炎药物应答不足的RA患者的体征和症状。其于1998年首次获得FDA批准用于治疗疼痛性关节疾病，长期安全性和疗效已在临床上得到了证明。本品可以单用治疗RA，以每周皮下注射2次的方式给药，在日本由惠氏公司和Takeda Pharmaceutical公司共同销售。本品最常见不良反应有注射部位反应、感染和头痛。

RA为一种可致残的慢性疾病。在日本大约有70万RA患者。严重的RA会引起机体免疫系统攻击关节内衬和结缔组织，致使关节疼痛和肿胀。如果不进行及时有效的治疗，还可能导致疲乏、残疾、畸形、器官损伤，甚至早死。在日本，畿患RA的女性患者人数是男性患者的4倍之多。RA可以在所有的年龄段包括儿童时期发病，其高发年龄段为25～50岁。