新型丙肝药品GRAZYNA Tablets(Grazoprevir Hydrate，グラジナ錠)获日本批准上市 グラジナ錠50mg 治疗类别名称 抗病毒药物 商標名 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 構造式 性状 白色粉末。N，易溶于N-二甲基甲或乙醇（99.5），并且几乎不溶于水。 操作注意事项 为了避免潮湿，保存PTP板的遗体，从PTP板之前，为了给药取出。 条件批准 在建立药品风险管理，要正确使用。 药效药理 1. 作用机序 Gurazopurebiru是对HCV NS3/4A蛋白酶抑制剂。NS3/4A蛋白酶参与HCV多处理所必需的病毒复制的成熟病毒蛋白的生产。 2.抗病毒活性 在生化检查，Gurazopurebiru所述HCV基因型1a，1b中，显示了对NS3 / 4A蛋白酶2，3，4，5和6，它们的IC 50值分别为4〜690pM酶抑制活性。 在HCV复制子测定法中，Gurazopurebiru指示针对2，3，4和全长HCV复制子细胞和基因型6的嵌合HCV复制子细胞的5基因型1A，1B，复制抑制活性，EC 50值分别为0.4，0.5,2.3,35,0.3,1.5，是0.9nM。 此外，基因型1a从临床分离物衍生，1b中，（中位数EC 50值）的复制在2，3，4，5和6，分别0.8,0.3,2.9,5.85嵌合复制子细胞抑制Gurazopurebiru的活性，0.2,1.5和是0.2nm的。 3. 薬剤耐性 NS3/4A了检查Gurazopurebiru对已掺入了蛋白酶抑制剂看到的已知突变HCV复制子细胞中的作用，通过的Gurazopurebiru的活性基因型1A中的NS3区D168A/E/G/S/V突变那里被衰减为1/2至1/81。在F43S的NS3区基因型1b，Y56F，所述Gurazopurebiru的活性从2/3由A156S/T/V和D168A/ G/V的突变衰减到三百七十五分之一 Gurazopurebiru，更结合国内II/III期试验的Erubasubiru，基因1b型。 每个那是不是耐药患者基因突变的患者100％SVR12率已经被检测到，NS3区域的检测管理的慢性丙型肝炎或C型代偿期肝硬化患者（例如一百○一分之一百○一）和97开始之前这是％（215分之208例）。七个患者基因型1b的抗性突变的分析而获得的治疗无应答和序列信息。未在治疗非响应时间进行检测的NS3区的耐药变种的病人。 5名患者基因型1a的是，无论存在或不存在，已先于给药开始检测到NS3区耐药突变的，它是在所有情况下SVR12实现。 在II/III期研究海外Gurazopurebiru和组合Erubasubiru利巴韦林，以及两种药物，已被前政府开始检测的NS3区域（包括Q80K）基因1b型和基因型1a的耐药突变组合的汇总分析也丝毫不影响患者的慢性丙型肝炎或C型代偿性肝硬化患者的任何的治疗效果 4. 交差耐性 在HCV基因型1复制子细胞系的体外交叉电阻测试，在Gurazopurebiru活性37降低由A156和D168类似NS3区和其它NS3/4A蛋白酶抑制剂）的突变看到。一系列在NS5A抑制剂发现抗性突变，影响观察Gurazopurebiru的抑制活性。 适应症 在慢性丙型肝炎或C病毒血症的改善补偿血清1肝硬化型（基因型1） 用法与用量 成年人，每天一次，每次100毫克给药。该药物是与Erubasubiru组合使用时，施用期是12周。 包装规格 片剂 50毫克：片剂56（PTP8粒×7） 制造厂商 MSD有限公司 注：以上中文资料仅参考，使用以原处方为准：http://www.info.pmda.go.jp/go/pack/6250043F1024_1_02/ GRAZYNA Tablets 50mg（Grazoprevir hydrate） GRAZYNA Tablets 50mg（グラジナ錠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 50mg Effects of this medicine This 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 medicine The 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.Internal Published: 11/2016 The 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 drugs Merck 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