| 简介：
部份中文索非布韦处方资料（仅供参考）
英文名：sofosbuvir
商品名：SOVALDI Tablets
中文名：索非布韦片
生产商：吉利德科学
药品介绍
近日，抗病毒新药Sovaldi（sofosbuvir，ソバルディ錠）已获日本劳动卫生福利部（MHLW）批准，用于基因型2 HCV感染者的治疗，治疗方式为Sovaldi联合利巴韦林（RBV）治疗12周。Sovaldi联合RBV是日本市场的首个全口服无干扰素治疗方案，该药也是吉利德在日本市场推出的首个丙肝治疗药物。
ソバルディ錠400mg
药物分类名称
抗病毒剂
批准日期：2015年5月
商標名
SOVALDI Tablets 400mg
一般名
ソホスブビル
Sofosbuvir（JAN）
化学名
1-Methylethyl N-［（S）-｛［（2R,3R,4R,5R）-5-（2,4-dioxo-3,4-dihydropyrimidin-1（2H）-yl）-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl］methoxy｝phenoxyphosphoryl］-L-alaninate
分子式
C22H29FN3O9P
分子量
529.45
構造式
性 状
白色至微黄白色粉末
可溶性
易溶于甲醇，丙酮，乙腈或乙醇（99.5），微溶于2-丙醇，微溶于乙酸乙酯，难溶于甲苯，二氯甲烷或庚烷。
熔点
约125°C
分布系数
log P = 1.62（1-辛醇/0.15mol/L氯化钾溶液）
批准条件
制定药品风险管理计划，适当实施。
药效药理
1. 作用机序
Sofosvir是一种核苷酸前药，被转化为尿苷三磷酸类型，其是肝细胞中的活性代谢物，活性代谢物是丙型肝炎病毒（HCV）复制必需的HCV非结构蛋白5B，（NS5B）RNA依赖性RNA聚合酶。 来自HCV基因型1b，2a，3a和4a的活性代谢物对NS5B聚合酶的50％抑制浓度（IC50值）为0.36?3.3μmol/L。活性代谢物不抑制人类DNA和RNA聚合酶，并且不抑制线粒体的表达。
2. 体外抗HCV活性
Sophosbuir抑制HCV基因型1-6复制子细胞中的RNA复制。HCV基因型1a，1b，2a，2b，3a，4a，5a和6a的稳定表达Sofosvir对复制子细胞的50％有效浓度（EC 50值）为0.040,0.11,0.050,0.015,0.050,0.040,0.015和0.014μmol/L）。野生型HCV基因型1a和1b，2A，2B，3A，4A，分别EC50值索非布韦用于瞬时表达的复制子细胞5a和6a0.030,0.022,0.147,0.013,0.034,0.036,0.022和0.046μmol/L为26）。来自临床分离株的含有HCV基因型1a（67例），1b（29例），2（15例）和3a（106例）NS5B区域的复制子细胞的Sophosubville的ECso值（中位数）分别为0.062,0.10,0.029和0.081μmol/L）。通过与Sofosvir和利巴韦林，干扰素α，NS5A抑制剂，NS3蛋白酶抑制剂或非核酸型NS5B抑制剂的组合观察到协同或协同的抗病毒活性。
3. 薬剤耐性
在使用HCV基因型1至6的复制子细胞的Sophosubville的体外耐受性测试中，在所有基因型复制子细胞系中观察到NS5B区域中的S282T突变。 用S282T突变转染的所有基因型复制子细胞对Sophosvir的敏感性降低，与对应的野生型相比，S282T突变株的EC50值增加了2.4?18.1倍。 此外，Sofosvir的活性保留在含有与利巴韦林，非核酸NS5B抑制剂，NS3蛋白酶抑制剂或NS5A抑制剂的抗性相关的突变的复制子细胞中。
所评估的国家III期临床试验的效力和安全性由代理和利巴韦林，病毒学复发患者的慢性丙型肝炎或5个例140的组合代偿性肝硬化型肝炎患者基因型2虽然承认，行政期间的突破不被承认。
5例复发患者均未发现NS5B区S282T耐药突变株与Sophosbuir易感性突变株。四个外国相在慢性丙型肝炎或III期临床试验的目标代偿性肝硬化型肝炎患者基因型3，NS5B抑制剂核苷施用相关的突变（L159F和V321A）是病毒学治疗失败所观察到的和在得到NS5B核苷酸序列患者中检测到，对于这些突变的所有处理的例子的外观率为3.1％（17案件出555例）。患者为患有慢性丙型肝炎或代偿性肝硬化型肝炎患者基因型4 3次外国临床试验中，它不给药期间观察到的病毒学治疗失败，11例出111例给药后确认复发。然而，在这些患者的基线或复发处未检测到S282T抗性突变或给药相关突变（L159F和V321A）。
适应病症
慢性丙型肝炎或C型补偿性肝硬化病毒血症的改善
（1）Celo组2（基因型2）
（2）不属于血清组1（基因型1）或血清组2（基因型2）的患者，
用法与用量
1.对于Celo组2（基因型2）：
与利巴韦林组合，通常成人每天接受400mg作为Sophosbuir，持续12周。
2.如果不符合Cerro组1（基因型1）或Celo组2（基因型2）：
与利巴韦林组合，通常成人每天接受400mg作为Sophosbuir，持续24周。
包装规格
片
400mg：28片，14片（7片×2）PTP
制造厂商
吉利德科学公司
提示：以上中文资料不够完整，使用者以原处方资料为准。
完整说明书附件：
https://www.info.pmda.go.jp/go/pack/6250042F1020_1_13/
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Sovaldi (Sofosbuvir)-400mg (14 Tablets)
SOVALDI Tablets 400mg（ソバルディ錠400mg）
Brand name : SOVALDI Tablets 400mg
Active ingredient: Sofosbuvir
Dosage form: yellow capsule-shaped tablet, major axis: 20 mm, minor axis: 9 mm, thickness: 7 mm
Print on wrapping: (printed on the bottle) ソバルディ錠400mg
Effects of this medicine
This medicine inhibits protein (NS5B RNA polymerase)involved in hepatitis C virus replication, and suppresses the proliferation of hepatitis C virus (antiviral effects). This medicine is used concomitantly with ribavirin.
It is usually used to treat chronic hepatitis C with or without compensated cirrhosis.
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 renal dysfunction.
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 1 tablet (400 mg of the active ingredient) at a time, once a day for 12 weeks. Strictly follow the instructions.
This medicine is used concomitantly with ribavirin. Follow the instruction about ribavirin.
If you miss a dose, take the missed dose as soon as possible. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. 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
For ribavirin used concomitantly with this medicine, teratogenic action (possibility to cause fetal malformation) has been reported in animal experiments. If you/your partner have/has a possibility of pregnancy, avoid pregnancy while you are taking ribavirin and for 6 months after you discontinue it. Also, you/your partner need to have a pregnancy test once a month in order to confirm that you/your partner do/does not become pregnant.
Avoid taking any food containing St. John's wort, as it may decrease the blood level of this medicine and diminish medicinal effects.
Possible adverse reactions to this medicine
The most commonly reported adverse reactions include anaemia, headache, dull, nausea and itch. 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.
palpitation and shortness of breath when going upstairs or uphill, headache, dizziness [anaemia]
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 the reach of children. Store away from direct sunlight, heat and moisture.
Discard the remainder. Do not store them.
Gilead Sciences K. K. Internal
Published: 7/2015
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.
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