埃索美拉唑钠盐(原料药)标准 USP MC - Esomeprazole Sodium - 2012-07-23

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【药品名】埃索美拉唑

【药品名】埃索美拉唑【英文名】Esomeprazole【别名】埃索美拉唑；耐信；Nexium【剂型】片剂：20mg；40mg。

【药理作用】1.研究显示，耐信首过代谢减少，机体的内清除率降低，这将导致有更多的耐信滞留于血循环中，具有更高的曲线下面积(AUC)，使到达质子泵的数量增加，药物浓度更高。

就具有比奥美拉唑更好的作用。

2.同奥美拉唑一样，耐信到达壁细胞后，在分泌小管的酸性环境中转化为有活性的抑制剂次磺酰胺，结合到质子泵，表现出高度选择性的酸抑制效应。

重复给药后抑制效应增加，这与在治疗早期次磺酰胺和质子泵结合的时间过长可以产生累计效应有关，其中一些质子泵在给予下一个剂量时已经被抑制。

【药动学】本药口服后经小肠吸收进入血液，由于其弱碱性，迅速被吸收到胃壁细胞分泌小管的高酸环境中，与H结合，形成有活性的物质—次磺酰胺，埃索美拉唑达到最大血浆浓度的时间是1～2h。

单次用药的整体生物利用度为64%，重复给药后可达89%。

在平稳状态下健康个体其相对容积分布为0.22L/kg 体重，蛋白结合率为97%。

单次给药40mg后血浆消除半衰期为0.8h，每天重复给药时为1.2h，总血浆清除率在单次给药后约为17L/小时，重复给药时为9L/小时，两次给药间药物清除完全，无浓度积蓄现象。

因此，耐信的药动学具有时间和剂量的依赖关系。

耐信代谢主要是通过肝脏的CYP同工酶，CYP C和CYP A。

由于两个同工酶的光学选择性埃索美拉唑和R-异构体在它们之间的代谢比例显著不同，埃索美拉唑更多地经过CYP A途径，结果是埃索美拉唑比R-异构体和奥美拉唑有更低的体内清除率，尿中检测到的原药浓度小于1%，口服后80%以代谢产物形式从尿中排出，其余由粪便中排出。

R-奥美拉唑几乎由CYP C代谢。

耐信代谢后血浆中砜代谢物的水平要高于奥美拉唑代谢后的水平；R-异构体奥美拉唑的主要代谢产物为羟基代谢物的水平奥美拉唑组高于耐信组。

【适应症】1.胃食管反流性疾病(CER D) 糜烂性反流性食管炎，40mg/d，连服4～8周；治愈后20mg/d维持治疗防止复发。

埃索美拉唑回顾与临床应用研究进展

埃索美拉唑回顾与临床应用研究进展张小康;马昌翰;白洁;张大军【摘要】埃索美拉唑是一种质子泵抑制剂,可长时间有效抑制胃酸的分泌,同时可在一定程度上保护胃黏膜,是治疗酸相关性疾病的首选药物,被广泛应用于治疗胃十二指肠溃疡、胃食管反流病、应激性溃疡和非甾体抗炎药不良反应的预防.同时发现埃索美拉唑还具有抗氧化、抗炎及抗肿瘤等多重药理活性.【期刊名称】《沈阳医学院学报》【年(卷),期】2016(018)001【总页数】4页(P51-54)【关键词】埃索美拉唑;质子泵抑制剂;消化系统疾病;抗肿瘤【作者】张小康;马昌翰;白洁;张大军【作者单位】沈阳医学院基础医学院临床医学专业2013级16班,辽宁沈阳110034;基础医学院临床医学专业2014级22班;基础医学院临床医学专业2012级9班;基础医学院化学教研室【正文语种】中文【中图分类】R975埃索美拉唑( esomeprazole)是奥美拉唑的S-异构体，也是( PPI)家族中第1个单一光学异构体，于2004年11月进入我国医保目录。

在众多PPI中，埃索美拉唑24 h内抑酸效果最为显著［1］。

同时，除了泌酸增加外，酸相关性疾病还可有其他发病机制，如由氧化应激、非甾体抗炎药( NSAID)以及幽门螺杆菌感染所造成的胃黏膜损伤等［2］，而埃索美拉唑被广泛应用于治疗和维持胃食管反流病、胃溃疡，以及与抗生素联合应用根除幽门螺旋杆菌。

有研究指出，埃索美拉唑在治疗酸相关性疾病时，除了发挥抑制胃酸分泌的作用外，可能还有抗氧化、抗炎等作用［3］。

可与肿瘤细胞膜上的质子泵——V型ATP酶结合并抑制其活性，使肿瘤细胞内H+积聚并减弱适于肿瘤细胞生长的酸性微环境，进而起到抗肿瘤的作用。

本文将埃索美拉唑的药理学、药代动力学和药效学特性，及其临床应用进行综述。

埃索美拉唑为胃壁PPI的特异性抑制剂，通过特异性靶向作用机制减少胃酸分泌;为一弱碱，在壁细胞泌酸微管的低pH环境中浓集，转化为其活化形式次磺酰胺，然后通过二硫键与壁细胞H+-K+-ATP酶亚单位半胱氨酸残基上的巯基结合，使酶氧化失活，从而使壁细胞产生的H+不能被转运到胃腔，阻碍胃酸分泌的最后一步，对基础胃酸分泌和刺激的胃酸分泌均产生较强的抑制作用，进而达到升高胃内pH值的治疗效果［4］。

注射用埃索美拉唑纳

注射用埃索美拉唑纳商品名称：耐信注射剂通用名称：埃索美拉唑钠英文名称：Esomeprazole Sodium适应症:作为当口服疗法不适用时，胃食管反流病的替代疗法。

本品通常应短期用药（不超过7天），一旦可能就应转为口服治疗。

规格:40mg（以埃索美拉唑计）用法用量:对于不能口服用药的患者，推荐每日1次注射本品20-40 mg。

反流性食管炎患者应使用40mg，每日1次；对于反流疾病的症状治疗应使用20mg，每日1次。

给药方法注射用药：40mg和20mg配制的溶液均应在至少3分钟以上的时间内静脉注射。

滴注用药：40mg和20mg配制的溶液均应在10-30分钟的时间内静脉滴注。

使用指导：注射液的制备是通过加入5mL的0.9％氯化钠溶液至本品小瓶中供静脉使用。

滴注液的制备是通过将本品1支溶解至0.9％氯化钠溶液100 mL，供静脉使用。

配制后的注射用或滴注用液体均是无色至极微黄色的澄清溶液，应在12小时内使用，保存在30°C以下。

从微生物学的角度考虑最好立即使用。

配伍禁忌：配制溶液的降解对pH值的依赖性很强，因此药品必须按照使用指导应用。

本品只能溶于0.9％氯化钠中供静脉使用。

配制的溶液不应与其他药物混合或在同一输液装臵中合用。

不良反应:在埃索美拉唑口服或静脉给药的临床试验以及口服给药的上市后研究中，已确定或怀疑有下列不良反应。

这些反应按照发生次数分为以下几类(常见 - >1%，<10% ；偶见- >0.1%，<1% ；罕见 - >0.01%，<0.1% ；十分罕见 - <0.01%)。

眼睛：偶见视力模糊。

耳和迷路：偶见眩晕。

皮肤和皮下组织：偶见皮炎、瘙痒、皮疹、荨麻疹；罕见脱发、光过敏；十分罕见多形红斑、Stevens-Johnson综合征、中毒性表皮坏死溶解(TEN)。

骨骼肌、结缔组织和骨骼：罕见关节痛、肌痛；十分罕见肌无力。

呼吸、胸、纵隔：罕见支气管痉挛。

埃索美拉唑镁usp34

© ２０１０ＵＳＰＣＯｆｆｉｃｉａｌ５／１／１１－７／３１／１１ＵＳＰＭｏｎｏｇｒａｐｈｓ：Ｅｓｏｍｅｐｒａｚｏｌｅ．．．
页码，Байду номын сангаас／７
prepared atomic absorption standard solution. [NOTE—Store the solution in a plastic bottle. ] Standard solution A: Transfer 10.0 mL of Standard stock solution to a 500-mL volumetric flask, add 50 mL of 1 N hydrochloric acid, and dilute with water to volume. Transfer 20.0 mL of this solution to a 200-mL volumetric flask, and dilute with water to volume. [NOTE —This solution contains 2 µg/mL of magnesium. ] Standard solution B: Combine 5.0 mL of Standard solution A and 4.0 mL of Lanthanum solution , and dilute with water to 100.0 mL (0.1 µg/mL). Standard solution C: Combine 10.0 mL of Standard solution A and 4.0 mL of Lanthanum solution , and dilute with water to 100.0 mL (0.2 µg/mL). Standard solution D: Combine 15.0 mL of Standard solution A and 4.0 mL of Lanthanum solution , and dilute with water to 100.0 mL (0.3 µg/mL). Standard solution E: Combine 20.0 mL of Standard solution A and 4.0 mL of Lanthanum solution , and dilute with water to 100.0 mL (0.4 µg/mL). Standard solution F: Combine 25.0 mL of Standard solution A and 4.0 mL of Lanthanum solution , and dilute with water to 100.0 mL (0.5 µg/mL). [NOTE— Concentrations of the Standard solutions and the Sample solution may be modified to fit the linear or working range of the instrument. When using instruments with a linear calibration graph, the number of Standard solutions can be reduced. ] Blank solution: Transfer 4.0 mL of Lanthanum solution to a 100-mL volumetric flask, and dilute with water to volume. Sample solution: Transfer 250 mg of Esomeprazole Magnesium to a 100-mL volumetric flask, add 20 mL of 1 N hydrochloric acid, swirl until dissolved, and dilute with water to volume. Allow to stand for 30 min. Transfer 10.0 mL of this solution to a 200-mL volumetric flask, and dilute with water to volume. Transfer 10.0 mL of the solution to another 100 -mL volumetric flask, add 4.0 mL of Lanthanum solution , and dilute with water to volume. Spectrometric conditions (See Spectrophotometry and Light-Scattering 851 .) Mode: Atomic absorption spectrophotometer Flame: Air–acetylene Analytical wavelength: 285.2 nm Analysis Samples: Standard solution B, Standard solution C, Standard solution D, Standard solution E , Standard solution F, Blank solution , and Sample solution Determine the concentration, C s , in µg/mL, of magnesium in the Sample solution using the calibration graph. Calculate the percentage of magnesium in the portion of Esomeprazole Magnesium taken:

耐信针(片)

埃索美拉唑一、基本信息1.项目名称：埃索美拉唑钠原料药及注射剂，埃索美拉唑镁原料药及肠溶片英文名称：Esomeprazole Magnesium/ Esomeprazole Sodium商品名称：Nexium耐信(阿斯利康)化学名称：双-S-5-甲氧基-2-[(4-甲氧基-3,5-二甲基-2-吡啶基)甲基]亚磺酰基-1H-苯并咪唑镁三水合物分子式：C34H36MgN6O6S2•3H2O分子量：767.152.剂型：钠盐：原料药/粉针；镁盐：原料/肠溶片3.注册分类：钠盐：化药6+6；镁盐：化药3+64.规格：肠溶片20mg/40mg，粉针40mg5.性状：埃索美拉唑镁肠溶片内含埃索美拉唑肠溶颗粒(MUPS)20mg：浅粉红色，椭圆双凸形薄膜衣片40mg：粉红色，椭圆双凸形薄膜衣片6.适应症：胃食管反流性疾病(GERD)，糜烂性反流性食管炎的治疗，已经治愈的食管炎患者防止复发的长期维持治疗，胃食管反流性疾病(GERD)的症状控制，与适当的抗菌疗法联合用药根除幽门螺杆菌，并且愈合与幽门螺杆菌感染相关的十二指肠溃疡，防止与幽门螺杆菌相关的消化性溃疡复发7.用法用量：糜烂性反流性食管炎的治疗：40 mg，每日1次，连服4周。

对于食管炎未治愈或持续有症状的患者建议再服药治疗4周。

已经治愈的食管炎患者防止复发的长期维持治疗：20 mg，每日1次。

胃食管反流性疾病(GERD)的症状控制：没有食管炎的患者：20 mg，每日1次。

如果用药4周症状未获控制，应对患者作进一步的检查。

一旦症状消除，随后的症状控制可采用按需疗法，即需要时口服20 mg，每日1次。

与适当的抗菌疗法联合用药根除幽门螺杆菌：并且愈合与幽门螺杆菌相关的十二指肠溃疡、预防与幽门螺杆菌相关的消化性溃疡复发：埃索美拉唑镁肠溶片20 mg +阿莫西林1 g +克拉霉素500 mg，每日2次，共7天。

药片应和液体一起整片吞服，而不应当咀嚼或压碎。

对于存在吞咽困难的患者，可将片剂溶于半杯不含碳酸盐的水中(不应使用其他液体，因肠溶包衣可能被溶解)，搅拌，直至片剂完全崩解，立即或在30分钟内服用，再加入半杯水漂洗后饮用。

注射用埃索美拉唑钠最新标准USP-MC Esomeprazole for Injection 2012.07.24

Published on USP Medicines Compendium (https://)
Esomeprazole for Injection
For Comment Version 0.2
DEFINITION Esomeprazole for Injection contains an amount of esomeprazole sodium (C17H19N3NaO3S) equivalent to NLT 95.0% and NMT 105.0% of the labeled amount of esomeprazole (C17H19N3O3S).
rU = response of each impurity in the Sample solution rS = response of each appropriate USP Impurity RS from the Standard solution. [Note—If no USP Impurity RSs are available, use the response of esomeprazole.] CS = concentration of standard material in the Standard solution esomeprazole sodium in the Sample solution CU = nominal concentration of esomeprazole sodium in the Sample solution Acceptance criteria Any individual impurity: NMT 0.2%
Analysis Samples: Standard solution and Sample solution Calculate the percentage of the labeled amount of esomeprazole (C17H19N3O3S) in the Sample solution:

埃索美拉唑

埃索美拉唑与手性药物的研究与应用前景来源：INTERNET整理：王丽萍2005-7-8中华医药杂志2005年第5卷第5期摘要: Omeprazole，即奥美拉唑，化学结构为5-甲氧基-2-［［（4-甲氧基-3，5-二甲基-2-吡啶）甲基］亚砜］-1H-苯骈咪唑，是一类新型的抗消化性溃疡药和质子泵抑制剂，也是世界上第一个应用于临床的质子泵抑制剂（proton pump inhibitor，PPI），目前已在65个国家获准用于治疗各种与胃酸有关的疾病。

由于OPZ抑酸作用强，治愈率高......埃索美拉唑，即esomeprazole，商品名Nexiumò（中文译“耐信”），是由瑞典Astr aZeneca（阿斯特拉）公司分离合成的全球第异构体质子泵抑制剂（I-PPI）由于其疗效显著且用药量低，自2000年问世以来，已创下了全球销售额突破10亿美元的惊人记录。

面对如此骄人的成绩，人们不禁要问:是什么使得es-omeprazole有如此神奇的魔力，一枝独秀地傲然于世界医药市场?究其出身，esomeprazole是从meprazole（OPZ）而来。

Omeprazole，即奥美拉唑，化学结构为5-甲氧基-2-［［（4-甲氧基-3，5-二甲基-2-吡啶）甲基］亚砜］-1H-苯骈咪唑，是一类新型的抗消化性溃疡药和质子泵抑制剂，也是世界上第一个应用于临床的质子泵抑制剂（proton pump inhibitor，PPI），目已在65个国家获准用于治疗各与胃酸有关的疾病。

由于OPZ抑酸作用强，治愈率高、治愈时间短，可以消除难治性溃疡危象，而且安全可靠，已成为胃及十二指肠溃疡及反流性食管炎的重要药物，不仅成为世界最畅销的药品之一，创造了十亿美元的年销售记录，同时也极地推动了胃及十二指肠溃疡病治疗及相关领域的发展。

可是，OPZ分子中具有一个不对称的手性硫原子，存在两个光学异构体，（S）-构型和（R）-构型异构体，两种构型均具有药理活性，在代谢上表现为立体选择性（见图1）。

埃索美拉唑钠CTD申报资料

CD E
2
埃索美拉唑钠 CTD 申报资料
3.2.S.2.2 生产工艺和过程控制 3.2.S.2.2.1 化学反应式：
CD E
3
埃索美拉唑钠 CTD 申报资料
3.2.S.2.2.2 工艺流程图：
优菲拉唑避光氮气保护 H2O
甲苯 (2R,3R)-1,1,4,4,四苯基丁四醇钛酸四异丙酯
CO2
pH=7.3-7.8
CD E
1
埃索美拉唑钠 CTD 申报资料
3.2.S.2 生产信息 3.2.S.2.1 生产商生产商名称：连云港润众制药有限公司注册地址：连云港经济技术开发区大浦工业区金桥路 16 号邮电传编：222069 话：0518-86075959 真：0518-86075958
生产地址：连云港经济技术开发区大浦工业区金桥路 16 号邮电传编：222069 话：0518-86075959 真：0518-86075958
4
埃索美拉唑钠 CTD 申报资料
物料甲苯优菲拉唑 (2R,3R)-1,1,4,4-四苯基丁四醇钛酸四异丙酯 N,N-二异丙基乙胺异丙苯基过氧化氢甲醇钾
分子量 329.4 426.5 284.2 129.2 152.2 70.1
投料量（Kg）摩尔量 5.2 1.5 Y Z 0.044 X 0.383 4.55mol ymol zmol 0.34mol xmol 5.46mol
埃索美拉唑 N,N-二异丙基乙胺乙醇氢氧化钠异丙苯基过氧化氢 HPLC监测甲醇钾/ 甲醇埃索美拉唑钾盐甲醇
活性炭
过滤
浓缩乙酸乙酯
CD E
合ቤተ መጻሕፍቲ ባይዱ埃索美拉唑钾盐

埃索美拉唑镁标准-EP7.0

CHARACTERS Appearance: white or slightly coloured powder, slightly hygroscopic. Solubility : slightly soluble in water, soluble in methanol, practically insoluble in heptane.
ห้องสมุดไป่ตู้
TESTS
A. pXe=ntNa-nCoHl,3: 1-[(2-chlorophenyl)(methylimino)methyl]cycloC. X = O : (2-chlorophenyl)(1-hydroxycyclopentyl)methanone,
B. (2RS)-2-(2-chlorophenyl)-2-hydroxycyclohexanone,
identification CRS and the chromatogram obtained with reference solution (b) to identify the peak due to impurity E ; — use the chromatogram obtained with reference solution (a) to identify the peak due to impurity D. Relative retention with reference to esomeprazole (retention time = about 9 min) : impurity E = about 0.6 ; impurity D = about 0.8. System suitability : reference solution (a) : — resolution : minimum 3.0 between the peaks due to impurity D and omeprazole. If necessary, adjust the pH of the aqueous part of the mobile phase or its proportion of acetonitrile ; an increase in the pH will improve the resolution. Limits : — impurity D : maximum 0.2 per cent ; — impurity E : maximum 0.1 per cent; — unspecified impurities : for each impurity, maximum 0.10 per cent ; — total : maximum 0.5 per cent ; — disregard limit : 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (c) (0.05 per cent).

埃索美拉唑钠及冻干粉针剂

z 杂质合成及分析研究已结束；
研究进展
z 制剂已完成小试，确定生产厂家后即可进行中试放大；
z 前期质量研究已经完成，待中试完成后即可进行正式质
量标准研究；
预计进度
z 申报：2013 年 6 月完成； z 生产：2014 年底。
z 原料前期研究质量高。项目研究基础扎实，可快速完成后续研究工作。
南京承创医药科技有限公司
埃索美拉唑钠及冻干粉针剂
项目简介
项目摘要
项目名称
埃索美拉唑钠及冻干粉针剂
建议注册类别
6+6
国内外注册及上国外：多国上市。
市情况
国内：阿斯利康，商品名“耐信”，2009 年 3 月。
化合物专利 2014 年到期；
知识产权情况合成路线专利 2014 年到期；
镁盐的晶型专利 2018 年到期。
z 项目申报经验丰富，可确保快速完成报批程序。
1
南京承创医药科技有限公司
1．药品名称和剂型通用名：埃索美拉唑英文名：Esomeprazole 已有商品名：耐信（阿斯利康）化学名称： 5-甲氧基-2-((S)-((4-甲氧基-3,5-二甲基-2- 吡啶基)甲基)亚硫酰基)-1H苯并咪唑国内已上市的埃索美拉唑制剂有口服及注射二种剂型，口服给药为片剂，规格：40mg（以埃索美拉唑镁盐.3H2O）；注射剂为埃索美拉唑钠盐注射液，规格：40mg 的冻干粉。 2．化学结构式埃索美拉唑
3
南京承创医药科技有限公司
H2－受体拮抗剂、胃粘膜保护剂三足鼎立的格局。鉴于奥美拉唑的销售业绩下滑，2000 年，阿斯利康公司在推出了名副其实的换代产品埃索美拉唑，该药是全球第一个采用氧化合成技术生产的质子泵抑制剂，此项技术曾获诺贝尔奖。目前，埃索美拉唑已成为全球增长速度最快的质子泵子抑制剂产品，2005 年同比上一年又增长了 18％，已达到 46.33 亿美元。 2002 年埃索美拉唑获得 SFDA 批准后，阿斯利康以商品名“耐信”在中国推出，并于 2004 年 11 月进入了全国医保目录，市场得到启动。 6．申报注册分类 6+6 类 7．在中国专利情况 1）化合物专利到 2014 年 2）路线专利到 2014 年 3）镁盐的晶型专利到 2018 年 8．原料药工艺流程一般采用亚砜不对称氧化，如下

注射用埃索美拉唑钠的研制及其稳定性考察

注射用埃索美拉唑钠的研制及其稳定性考察作者：徐晓娟唐云来源：《科技创新导报》 2014年第34期徐晓娟1 唐云1，2*（1.江苏正大丰海制药有限公司江苏盐城 224100；2.南京正大丰海医药科技有限公司江苏南京 210000）摘要：目的研究开发注射用埃索美拉唑钠。

筛选制剂处方和工艺，并建立其质量控制方法，考察其稳定性。

方法对络合剂种类及用量、原辅料加入顺序、中间体pH值及稳定性、过滤除菌、灌装量、冻干工艺及成品水分等进行筛选，确定其处方和工艺。

对制剂的性状、鉴别、碱度、有关物质、水分、异构体和含量等项目进行研究，建立质量控制方法，并考察其配伍稳定性及放样稳定性。

结果通过处方工艺筛选以及影响因素试验，确定了最佳处方和制备工艺。

按照优化出来的最佳处方及工艺，制备3批样品，并对其产品质量进行检测，结果均合格。

结论该制剂处方合理，制备工艺可行，质量可控，稳定性良好。

关键词：埃索美拉唑钠处方工艺质量控制稳定性中图分类号：R965 文献标识码：A 文章编号：1674-098X(2014)12(a)-0206-04Preparation and stability of Esomeprazole sodium injectionXu Xiaojuan1 Tang Yun1，2*（1.Jiangsu Chia Tai Fenghai Pharmaceutical Co.，Ltd.Yancheng Jiangsu，224100，China；2.Nanjing Chia Tai Fenghai Pharmaceutical Technology Co.，Ltd.Nanjing Jiangsu，210000，China）Abstract：Objective To develop the Esomeprazole sodium injection to meet the clinical requirements，formulation and the process parameters were screened and the quality control methods were established，then the stability was evaluated.Methods The types and amount of the complexing agents，adding order of raw and supplemental materials，the pH value and stability of intermediates，filtrating and removing bacteria，capacity of perfusion，freeze-drying process and moisture content of products were investigated to determine the formulation and process.The property of preparation，identification，pH value，related materials and content determination were studied to set up the quality control methods.Results Based on the screeningof formulation and process as well as the influence factors，the prescription and preparation process were obtained.The quality of the 3 batches sample was qualified which were prepared according to the optimized formula and preparationprocess.Conclusion The formulation is reasonable and the preparation process is feasible.The quality can be controlled and the products are stabile.Key Words：Esomeprazole sodium Formulation technology Quality control Stability随着社会发展，环境变迁，人口结构以及人们生活方式的改变，吸烟、饮酒、情绪紧张、药物刺激等因素引起的消化性溃疡发病率逐渐增高，给患者带来极大的痛苦，且生活质量下降。

nexium胃药说明书_美国胃药nexium的用法

nexium胃药说明书_美国胃药nexium的用法NEXIUM胃药(埃索美拉唑)它是一种抑酸保护胃粘膜的药物。

下面是小编整理的nexium胃药说明书，欢迎阅读。

nexium胃药说明书详细内容(欢迎点击) ◆nexium胃药的说明书◆nexium胃药一天吃几粒◆快速缓解胃痛的方法nexium胃药商品介绍【药品名称】埃索美拉唑镁肠溶片【商品名】耐信【英文商品名】Nexium【英文或拉丁名】Esomeprazole Magnesium Enteric-coated Tablets【汉语拼音】Aisuomeilazuomei Changrongpian【主要成分】埃索美拉唑镁【化学名】双-S-5-甲氧基-2-{ (4-甲氧基-3,5-二甲基-2-吡啶基)甲基亚磺酰基}-1H-苯并咪唑镁三水合物【结构式及分子式、分子量】分子式:C34H36MgN6O6S23H2O 分子量:767.15【nexium胃药价格】285.00nexium胃药的说明书【药理毒理】药效学特性埃索美拉唑是奥美拉唑的S-异构体，通过特异性的靶向作用机制减少胃酸分泌，为壁细胞中质子泵的特异性抑制剂。

奥美拉唑的R-异构体和S-异构体具有相似的药效学特性。

作用部位和机理埃索美拉唑为一弱碱，在壁细胞泌酸微管的高酸环境中浓集并转化为活性形式，从而抑制该部位的H+/K+-ATP酶(质子泵)，对基础胃酸分泌和刺激的胃酸分泌均产生抑制。

对胃酸分泌的影响口服埃索美拉唑20mg和40mg后，在一小时内起效。

重复给以20mg每天一次连续5天，在第5天服药后6~7小时测量，五肽胃泌素刺激引起的平均高峰泌酸量降低90%。

症状性GERD患者每天口服埃索美拉唑20mg和40mg，5天后24小时胃内pH4的时间平均值分别为13小时和17小时。

维持胃内pH4的时间至少8小时、12小时和16小时的患者比例在埃索美拉唑20mg时分别为76%、54%和24%;在40mg时分别为97%、92%和56%。

注射用埃索美拉唑钠

注射用埃索美拉唑钠（耐信）Esomeprazole Sodium for Injection(Nexium)本品为埃索美拉唑钠的无菌冻干品。

含埃索美拉唑钠以埃索美拉唑（C17H19N3O3S）计算，应为标示量的97.0%～109.0%。

【性状】本品为白色或类白色的冻干块状物或粉末。

【鉴别】（1）取本品1瓶，加水5ml使溶解，作为供试品溶液。

取0.008%硫酸镍溶液1ml，加供试品溶液0.5ml，摇匀，加1mol/L 氨溶液1ml，摇匀，加1%丁二酮肟的乙醇溶液1ml，摇匀，放置1分钟，溶液应不显色或显微黄色。

另取0.03%乙二胺四醋酸二钠溶液与水各0.5ml，分别作为阳性对照溶液和空白溶液，同法操作。

阳性对照溶液应不显色或显微黄色，空白溶液应显粉红色。

（2）取奥美拉唑对照品10mg，精密称定，置100ml量瓶中，加磷酸盐缓冲液（pH11.4）（取磷酸钠6.8g和二水合磷酸氢二钠6.2g，加水适量使溶解并稀释至1000ml，摇匀，pH值应为11.3～11.6）15ml 使溶解，加水稀释至刻度，摇匀，精密量取5ml，置25ml量瓶中，加磷酸盐缓冲液（pH11）（取磷酸盐缓冲液（pH11.4）10ml，加水稀释至100ml）稀释至刻度，摇匀，作为对照品溶液；另取本品，加磷酸盐缓冲液（pH11）溶解并定量稀释制成每1ml中约含埃索美拉唑0.01mg的溶液，作为供试品溶液。

照高效液相色谱法（中国药典2005年版二部附录ⅤD）测定，采用手性色谱柱，以α1-酸性糖蛋白（α1-acidglycoprotein）键合硅胶为填充剂，以乙腈-磷酸盐缓冲液（pH6.2）（取磷酸二氢钠2.4g和二水合磷酸氢二钠0.45g，加水适量使溶解并稀释至1000ml，摇匀，pH值应为6.1～6.3）（75∶425）为流动相，检测波长为280nm。

精密量取对照品溶液与供试品溶液各20μl，分别注入液相色谱仪，记录色谱图，对照品溶液中第二个被洗脱峰为埃索美拉唑峰，保留时间约为4分钟，奥美拉唑两个对映体峰的分离度应符合要求。

阿斯利康公司埃索美拉唑钠最新原版英文说明书

HIGHLIGHTS OF PRESCRIBING INFORMATION •Hypomagnesemia has been reported rarely with prolonged treatmentThese highlights do not include all the information needed to use NEXIUM I.V. safely and effectively. See full prescribing information for NEXIUM I.V.NEXIUM® I.V. (esomeprazole sodium) for Injection, for intravenous use Initial US Approval: 2005---------------------------RECENT MAJOR CHANGES-----------------------Warnings and Precautions, Interaction with Clopidogrel (5.4) 10/2012 Warnings and Precautions, Clostridium difficile associated 09/2012 diarrhea (5.3)Warnings and Precautions, Concomitant use of NEXIUMwith Methotrexate (5.9) 01/2012-------------------------INDICATIONS AND USAGE--------------------------NEXIUM I.V. is a proton pump inhibitor indicated for the treatment of Gastroesophageal Reflux Disease (GERD) with erosive esophagitis (EE) in adults and pediatric patients greater than one month of age, when oral therapy is not possible or appropriate. (1.1)-----------------------DOSAGE AND ADMINISTRATION-------------------GERD – with Erosive Esophagitis• Adults: Dose is either 20 mg or 40 mg esomeprazole given once daily by intravenous injection (no less than 3 minutes) or intravenous infusion(10 minutes to 30 minutes). (2.1)• Pediatric: Give the following doses once daily as an intravenous infusion over 10 minutes to 30 minutes• 1 year to 17 years: (2.1)o Body weight less than 55 kg: 10 mgo Body weight 55 kg or greater: 20 mg• 1 month to less than 1 year of age: 0.5 mg/kg (2.1)---------------------DOSAGE FORMS AND STRENGTHS------------------NEXIUM I.V. for Injection is supplied as a freeze-dried powder containing 20 mg or 40 mg of esomeprazole per single-use vial. (3)----------------------------CONTRAINDICATIONS-----------------------------Patients with known hypersensitivity to any component of the formulation or to substituted benzimidazoles (angioedema and anaphylaxis have occurred).(4)-----------------------WARNINGS AND PRECAUTIONS--------------------• Symptomatic response to therapy with NEXIUM does not preclude the presence of gastric malignancy. (5.1)• Atrophic gastritis has been noted with long-term omeprazole therapy.(5.2)• PPI therapy may be associated with increased risk of Clostridium difficile associated diarrhea. (5.3)• Avoid concomitant use of NEXIUM I.V. with clopidogrel. (5.4)• Bone Fracture: Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. (5.5)with PPIs (5.6)• Avoid concomitant use of NEXIUM with St John’s Wort or rifampin due to the potential reduction in esomeprazole levels (5.7, 7.2)• Interactions with diagnostic investigations for Neuroendocrine Tumors: Increases in intragastric pH may result in hypergastrinemia and enterochromaffin-like cell hyperplasia and increased chromogranin A levels which may interfere with diagnostic investigations for neuroendocrine tumors. (5.8, 12.2)-----------------------------ADVERSE REACTIONS----------------------------Most common adverse reactions (≥1%):• Headache, flatulence, nausea, abdominal pain, injection site reaction, diarrhea, dry mouth, dizziness/vertigo, constipation and pruritus (6.1)To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or /medwatch. ---------------------------------DRUG INTERACTIONS------------------------• NEXIUM I.V. inhibits gastric acid secretion and may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (e.g. ketoconazole, iron salts, erlotinib, and digoxin).Patients treated with NEXIUM and digoxin may need to be monitored for digoxin toxicity. (7)• Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.(7)• NEXIUM I.V. may reduce the plasma levels of atazanavir, nelfinavir, and saquinavir. (7)• Concomitant treatment with a combined inhibitor of CYP2C19 and CYP3A4, such as voriconazole, may result in more than doubling of the esomeprazole exposure. (7)• May increase systemic exposure of cilostazol and an active metabolite.Consider dose reduction (7)• Clopidogrel: NEXIUM I.V. decreases exposure to the active metabolite of clopidogrel. (7)• Tacrolimus: NEXIUM may increase serum levels of tacrolimus (7.2)• Methotrexate: NEXIUM may increase serum levels of methotrexate(7.3)------------------------USE IN SPECIFIC POPULATIONS-------------------• Pregnancy: Based on animal data, may cause fetal harm. Limited human data. (8.1)• Nursing Mothers: Caution should be exercised when administered to a nursing woman. (8.3)• Hepatic Insufficiency: For patients with severe liver impairment (Child Pugh Class C), a dose of 20 mg of NEXIUM should not be exceeded. (2,8.6, 12.3)See 17 for PATIENT COUNSELING INFORMATIONRevised: 10/2012_______________________________________________________________________________FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE1.1 Treatment of Gastroesophageal Reflux Disease (GERD) withErosive Esophagitis2 DOSAGE AND ADMINISTRATION2.1 GERD with Erosive Esophagitis2.2 Preparations for Use and Administration3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Risk of Concomitant Gastric Malignancy5.2 Atrophic Gastritis5.3. Clostridium difficile associated diarrhea5.4 Interaction with Clopidogrel5.5 Bone Fracture5.6 Hypomagnesemia5.7 Concomitant use of NEXIUM with St John's Wort or Rifampin5.8 Interactions with Investigations for Neuroendocrine Tumors5.9 Concomitant use of NEXIUM with Methotrexate6 ADVERSE REACTIONS6.1 Clinical Trials Experience with Intravenous NEXIUM6.2 Clinical Trials Experience with Oral NEXIUM6.3 Postmarketing Experience7 DRUG INTERACTIONS7.1 Interactions With Investigations of Neuroendocrine Tumors7.2 Tacrolimus7.3 Methotrexate8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Hepatic Impairment10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics12.4 Microbiology13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility14 CLINICAL STUDIES14.1 Acid Suppression in Gastroesophageal Reflux Disease(GERD)16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information are not listed.________________________________________________________________________2 FULL PRESCRIBING INFORMATION1. INDICATIONS AND USAGE1.1 Treatment of Gastroesophageal Reflux Disease(GERD) with Erosive EsophagitisNEXIUM I.V. for Injection is indicated for the short-termtreatment of GERD with erosive esophagitis in adults andpediatric patients 1 month to 17 years, inclusively as analternative to oral therapy when oral NEXIUM is not possibleor appropriate.DOSAGE AND ADMINISTRATIONNEXIUM I.V. for Injection should not be administeredconcomitantly with any other medications through the sameintravenous site and or tubing. The intravenous line shouldalways be flushed with either 0.9% Sodium ChlorideInjection, USP, Lactated Ringer’s Injection, USP or 5%Dextrose Injection, USP both prior to and after administrationof NEXIUM I.V. for Injection.The admixture should be stored at room temperature up to30°C (86°F) and should be administered within the designatedtime period as listed in the Table 1 below. No refrigeration isrequired.Table 1Diluent Administer within:0.9% Sodium Chloride 12 hoursInjection, USPLactated Ringer’sInjection, USP12 hours5% Dextrose 6 hoursInjection, USPParenteral drug products should be inspected visually forparticulate matter and discoloration prior to administration,whenever solution and container permit.As soon as oral therapy is possible or appropriate, intravenoustherapy with NEXIUM I.V. for Injection should bediscontinued and the therapy should be continued orally.Special PopulationsHepatic Insufficiency: No dosage adjustment is necessary inpatients with mild to moderate liver impairment (Child PughClasses A and B). For patients with severe liver impairment(Child Pugh Class C), a dose of 20 mg of NEXIUM shouldnot be exceeded [see Use in Specific Populations (8.6) andClinical Pharmacology, Pharmacokinetics (12.3)].2.1 GERD with Erosive EsophagitisAdultsThe recommended adult dose is either 20 mg or 40 mgesomeprazole given once daily by intravenous injection (noless than 3 minutes) or intravenous infusion (10 minutes to30 minutes).Safety and efficacy of NEXIUM I.V. for Injection as atreatment of GERD patients with erosive esophagitis for morethan 10 days have not been demonstrated.PediatricThe recommended doses for children ages 1 month to 17years, inclusive, are provided below. Dose should be infusedover 10 minutes to 30 minutes.1 year to 17 years:Body weight less than 55 kg: 10 mgBody weight 55 kg or greater: 20 mg1 month to less than 1 year of age: 0.5 mg/kg2.2 Preparations for Use and AdministrationAdultsIntravenous Injection (20 mg or 40 mg vial) over no less than3 minutesThe freeze-dried powder should be reconstituted with5 mL of 0.9% Sodium Chloride Injection, USP.Withdraw 5 mL of the reconstituted solution andadminister an intravenous injection over no less than 3minutes.Intravenous Infusion (20 mg or 40 mg) over 10 minutes to 30 minutesA solution for intravenous infusion is prepared by firstreconstituting the contents of one vial with 5 mL of 0.9% Sodium Chloride Injection, USP, Lactated Ringer’s Injection, USP or 5% Dextrose Injection, USP and further diluting the resulting solution to a final volume of 50 mL.The solution (admixture) should be administered as an intravenous infusion over a period of 10 minutes to 30 minutes.The reconstituted solution should be stored at room temperature up to 30°C (86°F) and administered within 12 hours after reconstitution. No refrigeration is required. Pediatric PopulationIntravenous Infusion over 10 minutes to 30 minutes (0.5mg/kg) for patients ages 1 month to less than 1 year of ageA solution for intravenous infusion is prepared by firstreconstituting the contents of one vial with 5 mL of 0.9%Sodium Chloride Injection, USP and further diluting theresulting solution to a final volume of 50 mL. Theresultant concentration after diluting to a final volume of50 mL is as follows:40 mg vial: 0.8 mg/mL20 mg vial: 0.4 mg/mLWithdraw appropriate amount of volume for desired dose(0.5 mg/kg) and administer as an intravenous infusion over10 minutes to 30 minutesIntravenous Infusion (10 mg and 20 mg) over 10 minutes to 30 minutes for Pediatric Patients, ages 1 year to 17 years of age40 mg vialA solution for intravenous infusion is prepared by firstreconstituting the contents of one vial with 5 mL of 0.9%Sodium Chloride Injection, USP and further diluting theresulting solution to a final volume of 50 mL. Theresultant concentration after diluting to a final volume of50 mL is 0.8 mg/mL.20 mg dose: Withdraw 25 mL of the final solution andadminister as an intravenous infusion over 10 minutes to30 minutes10 mg dose: Withdraw 12.5 mL of the final solution andadminister as an intravenous infusion over 10 minutes to30 minutes20 mg vialA solution for intravenous infusion is prepared by firstreconstituting the contents of one vial with 5 mL of 0.9%Sodium Chloride Injection, USP and further diluting theresulting solution to a final volume of 50 ml. The resultantconcentration after diluting to a final volume of 50 mL is0.4 mg/mL.20 mg dose: Administer the final solution (50 mL) as anintravenous infusion over 10 minutes to 30 minutes10 mg dose: Withdraw 25 mL of the final solution andadminister as an intravenous infusion over 10 minutes to30 minutes3 DOSAGE FORMS AND STRENGTHSNEXIUM I.V. for Injection is supplied as a freeze-dried whiteto off-white powder containing 20 mg or 40 mg ofesomeprazole per single-use vial.4 CONTRAINDICATIONSPatients with known hypersensitivity to any component of theformulation or to substituted benzimidazoles (angioedema andanaphylaxis have occurred).5 WARNINGS AND PRECAUTIONS5.1 Risk of Concomitant Gastric MalignancySymptomatic response to therapy with NEXIUM does notpreclude the presence of gastric malignancy.5.2 Atrophic GastritisAtrophic gastritis has been noted occasionally in gastriccorpus biopsies from patients treated long-term withomeprazole, of which esomeprazole is an enantiomer.5.3 Clostridium difficile associated diarrheaPublished observational studies suggest that PPI therapy likeNEXIUM may be associated with an increased risk ofClostridium difficile associated diarrhea, especially inhospitalized patients. This diagnosis should be considered fordiarrhea that does not improve [see Adverse Reactions (6.2)].5.4 5.5 5.6 5.7 Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Interactions with ClopidogrelAvoid concomitant use of NEXIUM I.V. with clopidogrel. Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications, such as esomeprazole, that inhibit CYP2C19 activity. Concomitant use of clopidogrel with 40 mg esomeprazole reduces the pharmacological activity of clopidogrel. When using NEXIUM I.V. consider alternative anti-platelet therapy. [see Drug Interactions (7 and Pharmacokinetics (12.3)]Bone FractureSeveral published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines. [see Dosage and Administration (2) and Adverse Reactions (6.3)] HypomagnesemiaHypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically. [See Adverse Reactions (6.3)]Concomitant use of NEXIUM with St John’s Wort or RifampinDrugs which induce CYP2C19 or CYP3A4 (such as St John’s Wort or rifampin) can substantially decrease esomeprazole concentrations [see Drug Interactions (7)]. Avoid concomitant use of NEXIUM with St John’s Wort or rifampin.5.8 5.96 6.1 Interactions with Investigations for Neuroendocrine TumorsSerum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Providers should temporarily stop esomeprazole treatment before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.Concomitant use of NEXIUM with Methotrexate Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration a temporary withdrawal of the PPI may be considered in some patients. [see Drug Interactions (7.3)] ADVERSE REACTIONSClinical Trials Experience with Intravenous NEXIUM Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.AdultsThe safety of intravenous esomeprazole is based on results from clinical trials conducted in three different populations including patients having symptomatic GERD with or without a history of erosive esophagitis (n=199), patients with erosive esophagitis (n=160), and healthy subjects (n=204). Adverse experiences occurring in >1% of patients treated with intravenous esomeprazole (n=359) in trials are listed below by body system:Symptomatic GERD and Erosive Esophagitis TrialsThe data described below reflect exposure to NEXIUM I.V for Injection in 359 patients. NEXIUM I.V. for Injection was studied only in actively-controlled trials. The population was 18 to 77 years of age; 45% Male, 52% Caucasian, 17% Black, 3% Asian, 28% Other, and had either erosive reflux esophagitis (44%) or GERD (56%). Most patients received doses of either 20 or 40 mg either as an infusion or an injection.Table 2Adverse reactions occurring at an incidence≥ 1% in the NEXIUM I.V. group% of patientsEsomeprazoleIntravenous Adverse Reactions (n=359)Headache 10.9Flatulence 10.3Nausea 6.4Abdominal pain 5.8Diarrhea 3.9Mouth dry 3.9Dizziness/vertigo 2.8Constipation 2.5Injection site reaction 1.7Pruritus 1.1Intravenous treatment with esomeprazole 20 and 40 mgadministered as an injection or as an infusion was found tohave a safety profile similar to that of oral administration ofesomeprazole.PediatricIn a randomized, open-label, multi-national study to evaluatethe pharmacokinetics of repeated intravenous doses of oncedaily esomeprazole, esomeprazole was well tolerated inpediatric patients 1 month to 17 years old, inclusive. Thesafety results are consistent with the known safety profile ofesomeprazole and no unexpected safety signals wereidentified. [See Clinical Pharmacology (12.3)]6.2 Clinical Trials Experience with Oral NEXIUMAdultThe safety of oral NEXIUM was evaluated in over 15,000patients (aged 18 to 84 years) in clinical trials worldwideincluding over 8,500 patients in the United States and over6,500 patients in Europe and Canada. Over 2,900 patientswere treated in long-term studies for up to 6-12 months. Ingeneral, NEXIUM was well tolerated in both short and long-term clinical trials.The safety in the treatment of healing of erosive esophagitiswas assessed in four randomized comparative clinical trials,which included 1,240 patients on NEXIUM 20 mg, 2,434patients on NEXIUM 40 mg, and 3,008 patients onomeprazole 20 mg daily. The most frequently occurringadverse events (≥1%) in all three groups were headache (5.5, 5.0, and 3.8, respectively) and diarrhea (no difference among the three groups). Nausea, flatulence, abdominal pain, constipation, and dry mouth occurred at similar rates among patients taking NEXIUM or omeprazole.Additional adverse events that were reported as possibly or probably related to NEXIUM with an incidence <1% are listed below by body system:Body as a Whole: abdomen enlarged, allergic reaction, asthenia, back pain, chest pain, chest pain substernal, facial edema, peripheral edema, hot flushes, fatigue, fever, flu-like disorder, generalized edema, leg edema, malaise, pain, rigors; Cardiovascular: flushing, hypertension, tachycardia; Endocrine: goiter; Gastrointestinal: bowel irregularity, constipation aggravated, dyspepsia, dysphagia, dysplasia GI, epigastric pain, eructation, esophageal disorder, frequent stools, gastroenteritis, GI hemorrhage, GI symptoms not otherwise specified, hiccup, melena, mouth disorder, pharynx disorder, rectal disorder, serum gastrin increased, tongue disorder, tongue edema, ulcerative stomatitis, vomiting; Hearing: earache, tinnitus; Hematologic: anemia, anemia hypochromic, cervical lymphadenopathy, epistaxis, leukocytosis, leukopenia, thrombocytopenia; Hepatic: bilirubinemia, hepatic function abnormal, SGOT increased, SGPT increased; Infections and Infestations: Clostridium difficile associated diarrhea; Metabolic/Nutritional: glycosuria, hyperuricemia, hyponatremia, increased alkaline phosphatase, thirst, vitamin B12 deficiency, weight increase, weight decrease; Musculoskeletal: arthralgia, arthritis aggravated, arthropathy, cramps, fibromyalgia syndrome, hernia, polymyalgia rheumatica; Nervous System/Psychiatric: anorexia, apathy, appetite increased, confusion, depression aggravated, dizziness, hypertonia, nervousness, hypoesthesia, impotence, insomnia, migraine, migraine aggravated, paresthesia, sleep disorder, somnolence, tremor, vertigo, visual field defect; Reproductive: dysmenorrhea, menstrual disorder, vaginitis; Respiratory: asthma aggravated, coughing, dyspnea, larynx edema, pharyngitis, rhinitis, sinusitis; Skin and Appendages: acne, angioedema, dermatitis, pruritus, pruritus ani, rash, rash erythematous, rash maculo-papular, skin inflammation, sweating increased, urticaria; Special Senses: otitis media, parosmia, taste loss, taste perversion; Urogenital: abnormal urine, albuminuria, cystitis, dysuria, fungal infection, hematuria, micturition frequency, moniliasis, genital moniliasis, polyuria; Visual: conjunctivitis, vision abnormal.Endoscopic findings that were reported as adverse eventsinclude: duodenitis, esophagitis, esophageal stricture,esophageal ulceration, esophageal varices, gastric ulcer,gastritis, hernia, benign polyps or nodules, Barrett’sesophagus, and mucosal discoloration.The incidence of treatment-related adverse events during 6month maintenance treatment was similar to placebo. Therewere no differences in types of related adverse events seenduring maintenance treatment up to 12 months compared toshort-term treatment.Two placebo-controlled studies were conducted in 710patients for the treatment of symptomatic gastroesophagealreflux disease. The most common adverse events that werereported as possibly or probably related to NEXIUM werediarrhea (4.3%), headache (3.8%), and abdominal pain (3.8%).The following potentially clinically significant laboratorychanges in clinical trials, irrespective of relationship toNEXIUM, were reported in ≤ 1% of patients: increasedcreatinine, uric acid, total bilirubin, alkaline phosphatase,ALT, AST, hemoglobin, white blood cell count, platelets,serum gastrin, potassium, sodium, thyroxine and thyroidstimulating hormone [see Clinical Pharmacology, EndocrineEffects (12.2) for further information on thyroid effects].Decreases were seen in hemoglobin, white blood cellcount,platelets, potassium, sodium, and thyroxine.PediatricThe safety of oral NEXIUM was evaluated in 316 pediatricand adolescent patients aged 1 to 17 years in four clinicaltrials for the treatment of symptomatic GERD [see ClinicalStudies (14.2)]. In 109 pediatric patients aged 1 to 11 years,the most frequently reported (at least 1%) treatment-relatedadverse reactions in these patients were diarrhea (2.8%),headache (1.9%) and somnolence (1.9%). In 149 pediatricpatients aged 12 to 17 years the most frequently reported (atleast 2%) treatment-related adverse reactions in these patientswere headache (8.1%), abdominal pain (2.7%), diarrhea (2%),and nausea (2%). No new safety concerns were identified inpediatric patients.6.3 Postmarketing ExperienceThe following adverse reactions have been identified duringpost-approval use of NEXIUM. Because these reactions arereported voluntarily from a population of uncertain size, it isnot always possible to reliably estimate their frequency orestablish a causal relationship to drug exposure.Postmarketing Reports -There have been spontaneous reportsof adverse events with postmarketing use of esomeprazole.These reports occurred rarely and are listed below by bodysystem:Blood And Lymphatic System Disorders: agranulocytosis,pancytopenia; Eye Disorders: blurred vision; GastrointestinalDisorders: pancreatitis; stomatitis; microscopic colitis;Hepatobiliary Disorders: hepatic failure, hepatitis with orwithout jaundice; Immune System Disorders: anaphylacticreaction/shock; Infections and Infestations: GI candidiasis;Metabolism and nutritional disorders: hypomagnesemia;Musculoskeletal And Connective Tissue Disorders: muscularweakness, myalgia, bone fracture; Nervous System Disorders:hepatic encephalopathy, taste disturbance; PsychiatricDisorders: aggression, agitation, depression, hallucination;Renal and Urinary Disorders: interstitial nephritis;Reproductive System and Breast Disorders: gynecomastia;Respiratory, Thoracic and Mediastinal Disorders:bronchospasm; Skin and Subcutaneous Tissue Disorders:alopecia, erythema multiforme, hyperhidrosis, photosensitivity, Stevens-Johnson syndrome, toxic epidermalnecrolysis (TEN, some fatal).Other adverse events not observed with NEXIUM, butoccurring with omeprazole can be found in the omeprazolepackage insert, ADVERSE REACTIONS section.7 DRUG INTERACTIONSEsomeprazole is extensively metabolized in the liver byCYP2C19 and CYP3A4.In vitro and in vivo studies have shown that esomeprazole isnot likely to inhibit CYPs 1A2, 2A6, 2C9, 2D6, 2E1 and 3A4.No clinically relevant interactions with drugs metabolized bythese CYP enzymes would be expected. Drug interactionstudies have shown that esomeprazole does not have anyclinically significant interactions with phenytoin, warfarin,quinidine, clarithromycin or amoxicillin. Post-marketingreports of changes in prothrombin measures have beenreceived among patients on concomitant warfarin andesomeprazole therapy. Increases in INR and prothrombin timemay lead to abnormal bleeding and even death. Patientstreated with proton pump inhibitors and warfarinconcomitantly may need to be monitored for increases in INRand prothrombin time.Esomeprazole may potentially interfere with CYP2C19, themajor esomeprazole metabolizing enzyme. Coadministrationof esomeprazole 30 mg and diazepam, a CYP2C19 substrate,resulted in a 45% decrease in clearance of diazepam. Increased plasma levels of diazepam were observed 12 hours after dosing and onwards. However, at that time, the plasma levels of diazepam were below the therapeutic interval, and thus this interaction is unlikely to be of clinical relevance. ClopidogrelClopidogrel is metabolized to its active metabolite in part by CYP2C19. Concomitant use of esomeprazole 40 mg results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition. Avoid concomitant administration of NEXIUM I.V. with clopidogrel. When using NEXIUM I.V., consider use of alternative anti-platelet [see Pharmacokinetics (12.3)]. Omeprazole acts as an inhibitor of CYP 2C19. Omeprazole, given in doses of 40 mg daily for one week to 20 healthy subjects in cross-over study, increased C max and AUC of cilostazol by 18% and 26%, respectively. C max and AUC of one of its active metabolites, 3,4-dihydro-cilostazol, which has 4-7 times the activity of cilostazol, were increased by 29% and 69%, respectively. Co-administration of cilostazol with esomeprazole is expected to increase concentrations of cilostazol and its above mentioned active metabolite. Therefore, a dose reduction of cilostazol from 100 mg twice daily to 50 mg twice daily should be considered. Concomitant administration of esomeprazole and a combined inhibitor of CYP2C19 and CYP3A4, such as voriconazole, may result in more than doubling of the esomeprazole exposure. Dose adjustment of esomeprazole is not normally required for the recommended doses. However, in patients who may require higher doses, dose adjustment may be considered.Drugs known to induce CYP2C19 or CYP3A4 (such as rifampin) may lead to decreased esomeprazole serum levels. Omeprazole, of which esomeprazole is an enantiomer, has been reported to interact with St. John’s wort, an inducer of CYP3A4. In a cross-over study in 12 healthy male subjects, St John’s wort (300 mg three times daily for 14 days) significantly decreased the systemic exposure of omeprazole in CYP2C19 poor metabolizers (C max and AUC decreased by37.5% and 37.9%, respectively) and extensive metabolizers(C max and AUC decreased by 49.6% and 43.9%, respectively). Avoid concomitant use of St. John’s Wort or rifampin with NEXIUM.。

FDA宣布埃索美拉唑和奥美拉唑不会增加心血管事件风险

FDA宣布埃索美拉唑和奥美拉唑不会增加心血管事件风险佚名
【期刊名称】《世界临床药物》
【年(卷),期】2008(29)1
【摘要】曾有2项研究资料提示，严重胃食道反流性疾病患者长期使用埃索美拉唑（esomeprazole，Nexium）或奥美拉唑（omeprazole．Prilosec）可能增加心血管事件风险。

对此，FDA对这2个药物进行了安全审查。

2007年12月，FDA宣布审查结果说，没有证据表明埃索美拉唑和奥美拉唑会增加心血管事件的风险。

【总页数】1页(P4-4)
【关键词】心血管事件;埃索美拉唑;奥美拉唑;FDA;esomeprazole;风险;宣布;研究资料
【正文语种】中文
【中图分类】R544.1;R975
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