部分中文阿舒瑞韦处方资料（仅供参考）

英文名：Asunaprevir

商标名：Sunvepra Capsules

中文名：阿舒瑞韦胶囊

日文名：スンベプラカプセル100mg

生产商：百时美施贵宝

药品简介

药物分类名称

抗病毒剂/HCV NS3/4A蛋白酶抑制剂

批准日期：2014年9月

欧文商標名

Sunvepra Capsules

一般名：アスナプレビル（Asunaprevir）

化学名：1,1-Dimethylethyl｛（2S）-1-［（2S,4R）-4-（｛7-chloro-4-methoxyisoquinolin-1-yl｝oxy）-2-（｛（1R,2S）-1-［（cyclopropanesulfonyl）carbamoyl］-2-ethenylcyclopropyl}carbamoyl）pyrrolidin-1-yl］-3,3-dimethyl-1-oxobutan-2-yl｝carbamate

分子式：C35H46ClN5O9S

分子量：748.29

構造式：

性状：

Asnaprevir是一种白色至微黄色的白色粉末。 它极易溶于乙腈或二甲基亚砜，微溶于乙醇（99.5），几乎不溶于水。

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

Asnaprevir是一种HCV NS3/4A蛋白酶抑制剂。 NS3/4A蛋白酶参与HCV多蛋白加工，用于病毒复制所必需的成熟病毒蛋白质生产。

2.抗病毒活性

在生化检查，Asunaprevir显示了HCV基因型1的NS3 / 4A蛋白酶的强效抑制效果（1a和1b）（IC 50值：1A 0.7〜1.8nmol / L，1b的0.3nmol / L），对基因型2（2a和2b）的抑制作用较弱（IC 50值：2a 15 nmol / L，2 b 78 nmol / L）。在HCV复制子测定，Asunaprevir表明基因型1a的抑制作用，EC 50值分别复制子1B和2A 4nmol / L，1.2nmol / L，和230nmol / L。

此外，在使用HCV复制子测定的组合研究中，asnaprevir与Daclatasville，干扰素α或利巴韦林组合显示出加和或协同作用。

3.药物耐受性

在同时给予asnaprevir和daclatasville盐酸盐的基因型1b慢性丙型肝炎患者的临床试验中，通常在Daclattusville观察到asnaprevir的抗药性替代（替代NS3-D168） （更换NS5A-Y93和/或L31）。

作为在asnaprevir存在下培养HCV复制子细胞的结果，发生了对asnaprevir的抗性。 通过分析耐受基因型1b复制子的NS3蛋白酶结构域的基因，在活性位点的氨基酸残基中发现了突变，并且NS3蛋白酶的D168被取代为A，G，H，V或Y具有抗性。 确认这是一个原因。 具有这些取代的基因型1b的重组复制子的EC 50值是野生型的16至280倍。

4.交叉耐受

具有抗性替代阿斯普雷韦的HCV复制子对具有不同作用机制的直接作用抗病毒剂如NS5A抑制剂足够敏感。 在通过给予telaprevir对HCV RNA没有阴性的慢性丙型肝炎患者中检测到的V36和T54的NS3中的氨基酸取代对asnaprevir的抗HCV活性仅有轻微影响，但是R155K，V36M + R155K和 在A156T / V中，asnaprevir的抗HCV活性降低至1/55至1/6。 此外，在NS3的F43，Q80，R155，A156和D168中发现Simépville的主要耐受性替代，并且这些取代的asnaprevir的EC50值为simprevir的EC50值的约1/26至1/2。

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

成人口服给药为100mg，每日两次，作为asenaprevir。该药与Daclatasville盐酸盐联合使用，给药期为24周。

包装

胶囊

100毫克：28粒（14粒×2）PTP

制造供应商

Bristol-Myers Squibb Co.Ltd。

完整资料附件：http://www.info.pmda.go.jp/go/pack/6250039M1027_1_21/

Hepatitis C new drug daclatasvir+asunaprevir oral solution approved by Japan

On July 7, 2014, the Japanese Ministry of Health, Labor and Welfare approved the company's daclatasvir (Daklinza) + asunaprevir (Sunvepra) combination for the treatment of hepatitis C virus (HCV) genotype 1 infection, including treatment Those who have modern compensatory cirrhosis.

Daclatasvir is a potent, all-gene NS5A replication complex inhibitor; and asunaprevir is an NS3/4A protease inhibitor. In Japan, the combination of these two drugs was the first non-interferon, ribavirin-free oral regimen that was formally approved for the treatment of HCV infection. This therapy combines the NS5A inhibitor daclatasvir and the NS3/4A protease inhibitor asunaprevir. This therapy is primarily designed to treat patients with genotype 1 hepatitis C. This is also the first full oral hepatitis C therapy in the world to officially enter the market.

In Japan, the daclatasvir+asunaprevir combination regimen is for patients with chronic HCV genotype 1 infection with or without compensatory cirrhosis. These patients cannot tolerate or apply interferon-based treatment regimens or interferon-containing treatments. The protocol has no response; the combination is intended to improve viremia in this population.

Daclatasvir is a potent, all-gene NS5A replication complex inhibitor; while asunaprevir is a NS3/4A protease inhibitor. In Japan, the combination of these two drugs was the first non-interferon-free, ribavirin-free oral regimen that was formally approved for the treatment of HCV infection.

At the press conference, Bristol-Myers Squibb said that about 70% of the Japanese hepatitis C carriers were infected with the HCV gene type 1b. Dr. Kazuaki-Chayama of Hiroshima University in Japan said that there is a unique population of HCV patients in Japan, many of whom are older and cannot tolerate or respond to traditional treatments. Therefore, it is urgent to seek an effective treatment plan for this group of people.

Dr. Chayama believes that the daclatasvir+asunaprevir combination regimen has been officially approved by the Japanese authorities, and for many of these HCV-infected people in Japan, for the first time, a new medication option has been obtained.

In Japan, the daclatasvir+asunaprevir combination regimen is for patients with chronic HCV genotype 1 infection with or without compensatory cirrhosis. These patients cannot tolerate or apply interferon-based treatments or interferon-containing treatments. The protocol has no response; the combination is intended to improve viremia in this population.

The research team led by Dr. Chayama conducted a phase III clinical trial. The results showed that Japanese HCV genotype 1 infected patients received the daclatasvir+asunaprevir regimen, and 84.7% of patients achieved a sustained virological response (SVR24) 24 weeks after the end of treatment.

Among patients with hepatitis C who were unable to tolerate or were not eligible for interferon regimen over the age of 65, 91.9% of patients achieved SVR24 after treatment with this regimen; the proportion of patients with modern compensatory cirrhosis at baseline reached an SVR24 ratio of 90.9%.

Only 5% of the subjects discontinued treatment because of adverse reactions. Among them, the incidence of serious adverse events was low (5.9%), and almost no serious adverse reactions occurred in more than one patient. Overall, nasopharyngitis is the most common adverse reaction (30.2%).