产地国家：日本 处方药：是 所属类别： 50毫克/片 56片/盒 包装规格： 50毫克/片 56片/盒 计价单位：盒 生产厂家英文名：Merck 原产地英文商品名：GRAZYNA(グラジナ錠)50mg/Tablets 56Tablets/box 原产地英文药品名：Grazoprevir Hydrate 中文参考商品译名：GRAZYNA(グラジナ錠)50毫克/片 56片/盒 中文参考药品译名：格拉瑞韦

简介：

新型丙肝药品GRAZYNA Tablets(Grazoprevir Hydrate，グラジナ錠)获日本批准上市 药物分类名称：抗病毒剂 商标名：GRAZYNA Tablets 50mg 一般名：グラゾプレビル水和物(Grazoprevir Hydrate) 化学名 (1aR,5S,8S,10R,22aR)-N-{(1R,2S)-1-[(Cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-5-(1,1-dimethylethyl)-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,10,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxamide monohydrate 分子式：C38H50N6O9S・H2O 分子量：784.92 性状 它是一种白色粉末。它易溶于N，N-二甲基甲酰胺或乙醇(99.5)，几乎不溶于水。处理注意事项为避免受潮，请将其保存为PTP纸张，并在取出之前将其从PTP纸张中取出。批准条件制定药品风险管理计划并适当实施。 药用药理学 1.作用机制Gurazopurebiru的NS3/4A蛋白酶，针对HCV NS3/4A蛋白酶抑制剂参与HCV多蛋白加工为病毒复制所需的成熟的病毒蛋白的生产。 2.抗病毒活性在生化检查，Gurazopurebiru的HCV基因型1a和1b，对NS3/4A蛋白酶2，3，4，5和6的酶活的抑制活性，其IC 50值分别为4〜690pM。在HCV复制子测定，Gurazopurebiru表示基因型1a，1b中，复制抑制活性对2,3,4,5-全长HCV复制子细胞和嵌合HCV复制子细胞的基因型6，EC 50值分别为0.4， 0.5,2.3,35,0.3,1.5和0.9nM。而且，从临床分离株属于基因型1a，1b中，(中值的EC 50值)复制抑制Gurazopurebiru的活性的嵌合复制子细胞2，3，4，5和6，分别0.8,0.3,2.9,5.85， 0.2,1.5和0.2 nM。 3.药物耐受性NS3/4A检查已掺入在蛋白酶抑制剂所观察到的已知突变Gurazopurebiru对HCV复制子细胞中的作用，通过Gurazopurebiru的活性基因型1a上NS3区域D168A / E / G / S / V突变从1/2减少到1/81。在F43S的NS3区域基因型1b，Y56F，37 Gurazopurebiru的活性从2/3由突变A156S / T / V和D168A / G / V)衰减到375分之1。Gurazopurebiru和以上组合国内II/III期Erubasubiru的试验中，在NS3区域病人的抗性突变在慢性丙型肝炎或代偿性肝硬化型肝炎患者投与开始前基因型检测1b中，未检测到患者的SVR12率分别为100%(101/101)和97%(208/215例)。分析了7名获得治疗无应答和序列信息的基因型1b患者的耐药突变。在治疗失败时没有发现患者对NS3区域有抗性。5名基因型1a患者在给药前检测到NS3区域内有或没有耐受突变的所有病例SVR 12。在两种药物中Grazzoprevir和Elvasville联合利巴韦林的联合分析中，海外II / III期试验的联合分析显示，在给药开始前检测到的NS3区域的抗性突变是基因型1b和基因型1a(包括Q80K)，未影响慢性丙型肝炎患者或C型代偿性肝硬化患者的治疗效果。 4.交叉耐受与其他NS3/4A蛋白酶抑制剂类似，在HCV基因型1复制子细胞系37)的体外交叉抗性试验中，格罗匹病毒活性通过NS3区域中的A156和D168突变而降低。 Grazoprevir的抑制活性不受NS5A抑制剂中发现的一系列抗性突变的影响。适应症改善慢性丙型肝炎或C型肝硬化血清群1(基因型1)中的病毒血症。 用法与用量 通常，成人每天一次接受100毫克。该药与Elvasville联合使用，给药期为12周。 临床结果 1.作为靶患有慢性丙型肝炎或代偿性肝硬化型肝炎患者II/III期研究的结果未处理的或处理过的先前国内基因型1与[疗法，其包含干扰素(IFN)](1a和1b)进行安慰剂随机，双盲，平行组比较测试(C型慢性肝炎患者)之间的受控的和开放标签的非对照研究(C代偿性肝硬化患者类型)，持续12周联合给药Gurazopurebiru和Erubasubiru。患者的HCV RNA量的百分比小于给药的为下表中所示的12周(SVR12比)结束后的检测极限。(参见表4中的SVR12率和整个亚组分析) 2.重度肾功能作为靶向与慢性丙型肝炎患者或代偿性肝硬化型肝炎患者基因型1与重度肾损伤注意外国的临床研究中的故障)用于病人，12个周联合Gurazopurebiru和Erubasubiru在国际阶段II / III期试验给药，患者的HCV RNA量的比例小于端部12周(SVR12比)后的检测限为99.1%(实施例一百一十六分之一百十五)。患者注)EGFR是具有小于30毫升/分钟/1.73平方米的受损肾功能相关的 包装 片剂50毫克：28片(PTP 7片x4)56片(8片PTP 8片) 制造供应商：MSD公司

英文版说明书

GRAZYNA Tablets 50mg（Grazoprevir hydrate）GRAZYNA Tablets 50mg Brand name : GRAZYNA Tablets 50 mg　Active ingredient: Grazoprevir hydrate　Dosage form: white tablet with gray flecks, major axis: 13.89 mm, minor axis: 6.73 mm, thickness: 5.65 mm　Print on wrapping: （Face）GRAZYNA 50mg, 779, グラジナ 50mg（Back）グラジナ 50mgEffects of this medicineThis medicine inhibits proteases involved in hepatitis C virus replication, thereby suppressing hepatitis C virus multiplication (antiviral action). It is used with elbasvir.It is usually used to treat chronic hepatitis C or compensated cirrhosis type C.Before using this medicine, be sure to tell your doctor and pharmacist•If you have previously experienced any allergic reactions (itch, rash, etc.) to any medicines.If you have liver dysfunction.If you have ever diagnosed as hepatitis B.•If you are pregnant or breastfeeding.•If you are taking any other medicinal products. (Some medicines may interact to enhance or diminish medicinal effects. Beware of over-the-counter medicines and dietary supplements as well as other prescription medicines.)Dosing schedule (How to take this medicine)•Your dosing schedule prescribed by your doctor is ((to be written by a healthcare professional))•In general, for adults, take 2 tablets (100 mg of grazoprevir) at a time, once a day, for 12 weeks. Strictly follow the instructions.•This medicine is used concomitantly with elbasvir. Follow the instruction about elbasvir.•Remove the medicine from a press-through package (PTP) immediately before use.•If you miss a dose, consult with your doctor or pharmacist. You should never take two doses at one time.•If you accidentally take more than your prescribed dose, consult with your doctor or pharmacist.•Do not stop taking this medicine unless your doctor instructs you to do so.Precautions while taking this medicine•Avoid taking any food containing St. John's wort, since it may decrease the blood level of the medicine and diminish medicinal effects.Possible adverse reactions to this medicineThe most commonly reported adverse reactions include headache, general malaise, diarrhea, constipation and rash. If any of these symptoms occur, consult with your doctor or pharmacist.The symptoms described below are rarely seen as initial symptoms of the adverse reactions indicated in brackets. If any of these symptoms occur, stop taking this medicine and see your doctor immediately.•general malaise, loss of appetite, nausea/vomiting [liver dysfunction]The above symptoms do not describe all the adverse reactions to this medicine. Consult with your doctor or pharmacist if you notice any symptoms of concern other than those listed above.Storage conditions and other information•Keep out of reach of children. Store away from direct sunlight, heat and moisture.•Do not take the tablets out of the PTP sheet to avoid moisture.•Discard the remainder. Do not store them.MSD K.K.InternalPublished: 11/2016The information on this sheet is based on approvals granted by the Japanese regulatory authority. Approval details may vary by country. Medicines have adverse reactions (risks) as well as efficacies (benefits). It is important to minimize adverse reactions and maximize efficacy. To obtain a better therapeutic response, patients should understand their medication and cooperate with the treatment.November 21, 2016, MSD K.K. companies listed in Japan elbasvir and grazoprevir two new drugsMerck has been listed in Japan for two oral hepatitis C drugs, 50 mg of Erelsa (elbasvir) tablets and 50 mg of Grazyna (grazoprevir hydrate) tablets, respectively. NS5A inhibitors Erelsa and NS3/ 4A protease inhibitors and Grazyna were developed by Merck & Co for the treatment of viremia in patients with genotype 1 chronic hepatitis C or compensatory cirrhosis, one dose per day for 12 weeks The Erelsa and Grazyna showed a history of patients with different backgrounds (different treatment history, gender, IL28B genotype, presence or absence of resistance, etc.) in clinical trials of genotype 1 chronic hepatitis C patients in Japan Effectiveness and safety, including moderate to severe renal impairment in patients