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托珠单抗注射剂|Actemra(Tocilizumab Injection)

2012-05-10 16:22:20 作者：新特药房来源：中国新特药网天津分站浏览次数：938 文字大小：【大】【中】【小】

简介： 英文药名: Actemra(Tocilizumab Injection) 中文药名: IL-6受体单克隆抗体注射剂品牌药生产厂家: Roche Pharmaceuticals 药品说明美国FDA于2010年1月 8日批准Genentech和Roche公司新单抗Actemra ...

关键字：托珠单抗注射剂 Tocilizumab 商标名Actemra IL-6受体单克隆抗体中度至严重活动性类风湿性关节炎

英文药名: Actemra(Tocilizumab Injection)

中文药名: 托珠单抗注射剂

生产厂家: 基因泰克
药品说明
美国FDA于2010年1月 8日批准Genentech和Roche公司新单抗Actemra(tocilizumab)注射剂治疗中度至严重活动性类风湿性关节炎。公司副总裁认为“批准标识RA治疗向前重要一步，为此非常严重疾病患者提供一种新选择”。
一般描述：
ACTEMRA(tocilizumab)是一种免疫球蛋白IgG1(γ1，κ)子类重组人源化抗-人白介素6(IL-6)受体单抗，有典型的H2L2多肽结构。每条轻链和重链分别由214和448氨基酸组成。四条多肽链通过分子内和分子间二硫键连接，ACTEMRA的相对分子质量约148 kDa。
作用机制
Tocilizumab特异性结合至可溶性和膜结合IL-6受体(sIL-6R和mIL-6R)二者，和曾被显示抑制通过这些受体的IL-6-介导信号。IL-6是一种多效能促炎细胞因子，由各种细胞类型生成包括T-和B-细胞、淋巴细胞、单核细胞和纤维母细胞。IL-6 曾被显示被涉及不同生理学过程例如激活T-细胞、诱导免疫球蛋白分泌、启动肝脏急性期蛋白合成、和刺激造血祖细胞细胞增殖和分化。滑膜和内皮细胞也产生IL-6，通过炎性过程例如类风湿样关节炎影响，导致关节局部生成IL-6。
适应症：
ACTEMRA(tocilizumab)是白介素-6(IL-6)受体抑制剂用于类风湿性关节炎治疗：适用于一种或更多TNF 拮抗剂治疗反应不佳的中度至严重-活动性类风湿性关节炎成年患者。
用法用量：
类风湿性关节炎。ACTEMRA可单独使用或与氨甲喋呤或其它DMARD联用。
1. 成年推荐剂量每4周：患者对一种或更多TNF拮抗剂反应不佳：当与DMARD联用或单药治疗时，推荐起始量是4 mg/kg接着基于临床反应增至8 mg/kg。嗜中性绝对计数(ANC)低于2000/mm3, 血小板计数低于100,000/mm3，或ALT或AST高于正常上限(ULN)1.5倍患者建议不要开始用ACTEMRA。
2. 建议每次输注ACTEMRA剂量不要超过800mg。
3. 给药为静脉输注用无菌术稀释至100mL 0.9%氯化钠。在1小时期间单次静脉滴注。不要推注。
4. 调整剂量建议对某些剂量-相关实验室变化处理包括肝酶升高、白细胞减少、和血小板减少。
注意事项：
1. 严重感染-活动性感染，包括局部感染期间不要给予ACTEMRA。如发生严重感染，中断ACTEMRA直至感染被控制。
2. 胃肠道(GI)穿孔–患者可能处在增加风险，慎用。
3. 建议进行实验室监查–由于嗜中性、血小板、脂质、和肝功能检验治疗相关变化潜在后果。
4. 曾发生过敏或严重超敏反应。
5. 用ACTEMRA不应给予活疫苗。
不良反应：
最常见不良反应(发生率5%)：上呼吸道感染、鼻咽炎、头痛、高血压、ALT升高。
黑框警告：严重感染风险
1. 接受ACTEMRA患者中曾发生严重感染导致住院或死亡包括结核(TB)、细菌性、侵袭性真菌、病毒,和其它机会性感染。
2. 如发生严重感染，中断ACTEMRA直至感染被控制。
3. 进行潜伏TB检验；如阳性，在开始用ACTEMRA前先开始治疗TB。
活动性TB治疗期间监查所有患者，即使初始潜伏TB检验阴性。
包装规格：[注：本品美国上市包装，采购者以咨询为准]
ACTEMRA 162MG/0.9ML PFS PF 1/EA TOCILIZUMAB GENENTECH USA 50242-0138-01
ACTEMRA 20MG/ML 10ML SDV PF 1/EA TOCILIZUMAB "GENENTECH, INC." 50242-0136-01
ACTEMRA 20MG/ML 20ML SDV PF 1/EA TOCILIZUMAB "GENENTECH, INC." 50242-0137-01
ACTEMRA 20MG/ML 4ML SDV PF 1/EA TOCILIZUMAB "GENENTECH, INC." 50242-0135-01

完整说明书附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2e5365ff-cb2a-4b16-b2c7-e35c6bf2de13
Actemra（tocilizumab）托珠单抗
ACTEMRA (tocilizumab)是一种免疫球蛋白IgG1(γ1，κ)子类重组人源化抗-人白介素6(IL-6)受体单抗，有典型的H2L2多肽结构。每条轻链和重链分别由214和448氨基酸组成。四条多肽链通过分子内和分子间二硫键连接，ACTEMRA的相对分子质量约148 kDa。
美国FDA于2010年1月 8日批准Genentech和Roche公司新单抗Actemra (tocilizumab)注射剂治疗中度至严重活动性类风湿性关节炎。Actemra/tocilizumab，其靶标主要针对免疫系统特异阶段，即RA发病过程中引起关节损害的炎症阶段。
2013年10月，罗氏（Roche）皮下注射剂型Actemra（通用名：tocilizumab）获FDA批准，用于既往经一种或多种疾病修饰抗风湿药物（DMARDs）治疗反应不足的中度至重度活动性类HH风湿性关节炎HH（RA）成人患者的治疗。此次批准，是Actemra在4年内获得的第6个FDA批准，此前FDA已批准Actemra用于中度至重度活动性类HH风湿性关节炎HH成人患者的治疗、用于2岁及以上活动性多关节幼年特发性关节炎和全身型幼年特发性关节炎的治疗。
2014年5月，皮下注射（SC）剂型Actemra（通用名：tocilizumab）获加拿大卫生部批准，用于对一种或多种疾病修饰抗风湿药物（DMARDs）和/或肿瘤坏死因子（TNF）拮抗剂响应不足的中度至重度活动性类HH风湿性关节炎HH（RA）成人患者的治疗。
罗氏公司Actemra是首个也是唯一一个获加拿大批准，可同时用于静脉注射给药（IV）和皮下注射给药（SC）的人源化HH白细胞介素6HHHH受体HH拮抗剂HH单克隆抗体HH。与静脉注射（IV）剂型Actemra，Actemra SC可用作单药疗法，也可与甲氨蝶呤（MTX）或其他非生物类DMARDs联合用药。临床试验中，Actemra SC和Actemra IV具有同等的疗效和安全性。
Actemra(tocilizumab)
ACTEMRA®(tocilizumab) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.
ACTEMRA(tocilizumab) is an interleukin-6 (IL-6) receptor inhibitor indicated for treatment of:
Rheumatoid Arthritis:
Adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.
INDICATION
ACTEMRA is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies.
ACTEMRA is indicated for the treatment of active systemic juvenile idiopathic arthritis in patients 2 years of age and older.
Serious Infections
Serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial, invasive fungal, viral, and other opportunistic infections have occurred in patients receiving ACTEMRA. ACTEMRA should not be administered during an active infection, including localized infections. If a serious infection develops, ACTEMRA should be interrupted until the infection is controlled.
Prior to initiating ACTEMRA, a test for latent TB should be performed. If the test is positive, treatment for TB should be started prior to starting ACTEMRA. All patients should be monitored for active TB during treatment, even if initial latent TB test is negative.
The benefits and risks of treatment should be considered prior to initiating ACTEMRA in patients:
with chronic or recurrent infection
who have been exposed to TB
who have a history of serious or opportunistic infections
who have resided or traveled in areas of endemic TB or mycoses
with underlying conditions that may predispose them to infection
Patients should be closely monitored for signs and symptoms of infection during and after treatment with ACTEMRA.
CONTRAINDICATION
ACTEMRA should not be administered to patients with known hypersensitivity to ACTEMRA.
WARNINGS AND PRECAUTIONS
Gastrointestinal Perforations
ACTEMRA should be used with caution in patients who may be at increased risk for gastrointestinal (GI) perforation. Patients presenting with new-onset abdominal symptoms should be evaluated promptly for early identification of GI perforation
Laboratory Monitoring
Neutrophils, platelets, lipids and hepatic transaminases should be monitored as changes in these parameters were associated with treatment with ACTEMRA. Dosage modifications or interruptions may be required. Please see full prescribing information for more information.
Immunosuppression
The impact of treatment with ACTEMRA on the development of malignancies is not known, but malignancies were observed in clinical studies with ACTEMRA. ACTEMRA is an immunosuppressant, and treatment with immunosuppressants may result in an increased risk of malignancies.
Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis and death, have occurred with infusion of ACTEMRA. ACTEMRA should only be administered by a healthcare professional with appropriate medical support to manage anaphylaxis. If anaphylaxis or other clinically significant hypersensitivity reaction occurs, administration of ACTEMRA should be stopped immediately and ACTEMRA should be permanently discontinued. Do not administer ACTEMRA to patients with known hypersensitivity to ACTEMRA.
Clinically significant hypersensitivity reactions, including anaphylaxis associated with ACTEMRA and requiring treatment discontinuation were reported in 0.1% (3 out of 2644) in the rheumatoid arthritis 24 week, controlled trials and in 0.2% (8 out of 4009) in the all-exposure population. These reactions were generally observed during the second to fourth infusion of ACTEMRA. Appropriate medical treatment should be available for immediate use in the event of a serious hypersensitivity reaction.
Anaphylaxis was reported in 1 out of 112 patients (less than 1%) treated with ACTEMRA during the SJIA controlled and open label extension study.
Demyelinating Disorders
Patients should be closely monitored for signs and symptoms of demyelinating disorders. Prescribers should exercise caution in considering the use of ACTEMRA in patients with preexisting or recent-onset demyelinating disorders.
Active Hepatic Disease and Hepatic Impairment
Treatment with ACTEMRA is not recommended in patients with active hepatic disease or hepatic impairment.
Vaccinations
Live vaccines should not be given with ACTEMRA. Patients should be brought up to date on all recommended vaccinations, except for live vaccines, prior to initiation of ACTEMRA therapy.
ADVERSE REACTIONS
RHEUMATOID ARTHRITIS (RA)
The most common serious adverse reactions were serious infections. In the ACTEMRA monotherapy clinical study, the rate of serious infections was 3.6 per 100 patient-years in the ACTEMRA group and 1.5 per 100 patient-years in the methotrexate group. The rate of serious infections in the 4 mg/kg and 8 mg/kg ACTEMRA plus DMARD groups was 4.4 and 5.3 events per 100 patient-years, respectively, compared to 3.9 events per 100 patient-years in the placebo plus DMARD group.
In the 5 Phase III clinical trials the most common adverse reactions (≥5% of patients treated with ACTEMRA) through 6 months were:

ACTEMRA 8mg/kg Monotherapy
(%) Methotrexate
(%) ACTEMRA 4mg/kg + DMARDs
(%) ACTEMRA 8mg/kg + DMARDs
(%) Placebo + DMARDs
(%)

URTI 7 5 6 8 6

Nasopharyngitis 7 6 4 6 4

Headache 7 2 6 5 3

Hypertension 6 2 4 4 3

Increased ALT 6 4 3 3 1
ADVERSE REACTIONS
SYSTEMIC JUVENILE IDIOPATHIS ARTHRITIS (SJIA)
The most common adverse events (at least 5%) seen in ACTEMRA treated patients in the 12 week controlled portion of the study were: upper respiratory tract infection, headache, nasopharyngitis and diarrhea.
Infections
In the 12 week controlled phase, the rate of all infections in the ACTEMRA group was 345 per 100 patient-years and 287 per 100 patient-years in the placebo group. In the ongoing open label extension (Part II), the overall rate of infections was 304 per 100 patient-years.
In the 12 week controlled phase, the rate of serious infections in the ACTEMRA group was 11.5 per 100 patient years. In the ongoing open label extension, the overall rate of serious infections was 11.4 per 100 patient years. The most commonly reported serious infections included pneumonia, gastroenteritis, varicella, and otitis media.
Macrophage Activation Syndrome
In the 12 week controlled study, no patient in any treatment group experienced macrophage activation syndrome (MAS) while on assigned treatment; 3 per 112 (3%) developed MAS during open-label treatment with ACTEMRA. One patient in the placebo group escaped to ACTEMRA 12 mg per kg at Week 2 due to severe disease activity, and ultimately developed MAS at Day 70. Two additional patients developed MAS during the long-term extension. All 3 patients had ACTEMRA dose interrupted (2 patients) or discontinued (1 patient) for the MAS event, received treatment, and the MAS resolved without sequelae. Based on a limited number of cases, the incidence of MAS does not appear to be elevated in the ACTEMRA SJIA clinical development experience; however no definitive conclusions can be made.
Infusion Reactions
Infusion related reactions were defined as all events occurring during or within 24 hours after an infusion. In the 12 week controlled phase, 4% of ACTEMRA and 0% of placebo treated patients experienced events occurring during infusion.
Within 24 hours after infusion, 16% of patients in the ACTEMRA treatment group and 5% of patients in the placebo group experienced an event. In the ACTEMRA group the events included rash, urticaria, diarrhea, epigastric discomfort, arthralgia and headache. One of these events, urticaria, was considered serious.
Anaphylaxis
Anaphylaxis was reported in 1 out of 112 patients (less than 1%) treated with ACTEMRA during the controlled and open label extension study.
USE IN PREGNANCY
There are no adequate and well-controlled studies in pregnant women. ACTEMRA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. To monitor the outcomes of pregnant women exposed to ACTEMRA, pregnancy registry has been established. Physicians are encouraged to register patients by calling 1-877-311-8972 or register online at。
PATIENT COUNSELING INFORMATION
Patients should be advised of the potential benefits and risks of ACTEMRA. Physicians should instruct their patients to read the Medication Guide before starting ACTEMRA therapy. Inform patients that ACTEMRA may lower their resistance to infections and instruct patients of the importance of contacting their doctor immediately when symptoms of an infection appear. Inform patients that some patients receiving ACTEMRA have had serious side effects in the stomach and intestines and instruct patients of the importance of contacting their doctor immediately when symptoms of severe, persistent abdominal pain appear.
Please see full Prescribing Information including Boxed Warning for additional important safety information.