慢性丙型肝炎（CHC）治疗创新新药Boceprevir(商品名Victrelis)被FDA批准上市，与长效干扰素派罗欣（通用名聚乙二醇干扰素α）和利巴韦林联用治疗 CHC 基因I型慢性丙肝感染，适用于患有代偿性肝脏疾病（包括肝硬化）的18岁及以上的成年患者，这些患者以前未经治疗或之前用干扰素和利巴韦林治疗失败。 FDA的药物评价和研究中心抗微生物产品室主任Edward Cox, M.D., M.P.H说：“对有丙型肝炎患者Victrelis是一个重要进展，”“这个新药对一个严重疾病提供一种有效治疗，和与当前可得到治疗比较提供更大机会治愈某些患者的丙型肝炎感染。” 批准日期： 2011年5月13日；公司：Merck VICTRELIS™ (波普瑞韦[boceprevir])胶囊 美国初始批准：2011 优先审评药物 作用机制 VICTRELIS是一种针对丙型肝炎病毒的直接作用抗病毒药[见微生物学]。 适应证和用途 VICTRELIS是一种丙型肝炎病毒(HCV)NS3/4A蛋白酶抑制剂适用于与聚乙二醇干扰素α和利巴韦林[ribavirin]联用基因型1感染慢性丙型肝炎CHC)的治疗，在有代偿性肝病(≥18岁)成年患者，包括肝硬变，既往未治疗或既往干扰素和利巴韦林治疗已失败患者。 VICTRELIS必须不作为单药治疗使用。 剂量和给药方法 800 mg 每天口服三次给药(每7-9小时)与食物(一餐或小吃). （1）VICTRELIS必须与聚乙二醇干扰素α和利巴韦林联用给药。 （2）为特殊给药指导参考聚乙二醇干扰素α和利巴韦林包装插件。 剂型和规格 胶囊：200mg 禁忌证 （1）因为VICTRELIS必须与聚乙二醇干扰素α和利巴韦林给药，也应用对聚乙二醇干扰素α和利巴韦林所有禁忌证。 （2）因为利巴韦林可能致出生缺陷和胎儿死亡，妊娠妇女中和女性伴侣妊娠男性禁忌boceprevir与聚乙二醇干扰素α和利巴韦林联用。 （3）与高度依赖CYP3A4/5清除的药物共同给药，和因为升高血浆浓度伴随严重和/或危及生命事件。 （4）强CYP3A4/5诱导剂where显著减低boceprevir血浆浓度可能伴随减低疗效。 警告和注意事项 VICTRELIS与利巴韦林和聚乙二醇干扰素α使用： （1）利巴韦林可能致出生缺陷和胎儿死亡：在女性患者和男性患者的女性伴侣中避免妊娠。治疗前患者必须有妊娠检验阴性；使用两种或更多方式避孕，和每月妊娠检验。 （2）贫血 –VICTRELIS增添至聚乙二醇干扰素α和利巴韦林与单独聚乙二醇干扰素α和利巴韦林比较是伴随另外的血红蛋白浓度减低。 （3）中性粒细胞减少 - VICTRELIS增添至聚乙二醇干扰素α和利巴韦林可能导致伴随单独聚乙二醇干扰素α和利巴韦林治疗中性粒细胞减少恶化。 不良反应 在临床试验中接受VICTRELIS与PegIntron和REBETOL联用成年受试者中最常报道的不良反应(大于35%受试者)是疲乏，贫血，恶心，头痛和味觉障碍。 药物相互作用 （1）VICTRELIS是一种CYP3A4/5强抑制剂和部分被CYP3A4/5代谢。治疗前和期间必须考虑药物-药物相互作用潜在可能。 特殊人群中使用 （1）肝硬变：尚未在有代偿肝硬变患者或有一种器官移植患者中研究安全性和疗效。 （2）与人类免疫缺陷病毒(HIV)合并感染：尚未确定有HCV和HIV合并感染患者中安全性和疗效。 （3）与乙型肝炎病毒(HBV)合并感染：尚未有HCV和HBV合并感染患者中研究安全性和疗效。 （4）儿童：尚未在儿童患者中研究安全性和疗效。 （5）可得到利巴韦林妊娠注册。 Victrelis (Boceprevir Capsules) Victrelis (boceprevir) is an inhibitor of the hepatitis C virus non-structural protein 3 (NS3) serine protease. Victrelis is specifically indicated in combination with peginterferon alfa and ribavirin for adults with chronic hepatitis C genotype 1 infection with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy. Victrelis is supplied as a capsule for oral administration. The recommended dose of Victrelis is 800 mg (four 200-mg capsules) three times daily (every 7-9 hours) with food. Refer to the peginterferon alfa and ribavirin package inserts for instructions on dosing. These highlights do not include all the information needed to use VICTRELIS safely and effectively. See full prescribing information for VICTRELIS. VICTRELIS™ (boceprevir) Capsules VICTRELIS (boceprevir) is an inhibitor of the hepatitis C virus (HCV) non-structural protein 3 (NS3) serine protease. Boceprevir has the following chemical name: (1R,5S)-N-[3-Amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide. The molecular formula is C27H45N5O5 and its molecular weight is 519.7. Boceprevir is manufactured as an approximately equal mixture of two diastereomers. Boceprevir is a white to off-white amorphous powder. It is freely soluble in methanol, ethanol and isopropanol and slightly soluble in water. CLINICAL PHARMACOLOGY: Mechanism of Action VICTRELIS is a direct acting antiviral drug against the hepatitis C virus. Microbiology Boceprevir is an inhibitor of the HCV NS3/4A protease that is necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS4A, NS4B, NS5A and NS5B proteins. Boceprevir covalently, yet reversibly, binds to the NS3 protease active site serine (S139) through an (alpha)-ketoamide functional group to inhibit viral replication in HCV-infected host cells. In a biochemical assay, boceprevir inhibited the activity of recombinant HCV genotype 1a and 1b NS3/4A protease enzymes, with Ki values of 14 nM for each subtype. INDICATIONS AND USAGE VICTRELIS™ (boceprevir) is indicated for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients (18 years and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy. The following points should be considered when initiating VICTRELIS for treatment of chronic hepatitis C infection: VICTRELIS must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin. VICTRELIS efficacy has not been studied in patients who have previously failed therapy with a treatment regimen that includes VICTRELIS or other HCV NS3/4A protease inhibitors. VICTRELIS in combination with peginterferon alfa and ribavirin has not been studied in patients documented to be historical null responders (less than a 2-log10 HCV-RNA decline by treatment week 12) during prior therapy with peginterferon alfa and ribavirin. The clinical studies included subjects who were poorly interferon responsive. Subjects with less than 0.5-log10 HCV-RNA decline in viral load at Treatment Week 4 with peginterferon alfa plus ribavirin alone are predicted to have a null response (less than 2-log10 viral load decline at Treatment Week 12) to peginterferon alfa and ribavirin therapy. Poorly interferon responsive patients who were treated with VICTRELIS in combination with peginterferon alfa and ribavirin have a lower likelihood of achieving a sustained virologic response (SVR), and a higher rate of detection of resistance-associated substitutions upon treatment failure, compared to patients with a greater response to peginterferon alfa and ribavirin. USE IN SPECIFIC POPULATIONS Cirrhosis: Safety and efficacy have not been studied in patients with decompensated cirrhosis or in patients with an organ transplant. Co-infection with Human Immunodeficiency Virus (HIV): Safety and efficacy have not been established in patients co-infected with HCV and HIV. Co-infection with Hepatitis B Virus (HBV): Safety and efficacy have not been studied in patients co-infected with HCV and HBV. Pediatrics: Safety and efficacy have not been studied in pediatric patients. Ribavirin Pregnancy Registry available. CONTRAINDICATIONS All contraindications to peginterferon alfa and ribavirin also apply since VICTRELIS must be administered with peginterferon alfa and ribavirin. Because ribavirin may cause birth defects and fetal death, boceprevir in combination with peginterferon alfa and ribavirin is contraindicated in pregnant women and in men whose female partners are pregnant. Coadministration with drugs that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events. Potent CYP3A4/5 inducers where significantly reduced boceprevir plasma concentrations may be associated with reduced efficacy PRECAUTIONS WARNINGS AND PRECAUTIONS Use of VICTRELIS with Ribavirin and Peginterferon alfa: Ribavirin may cause birth defects and fetal death; avoid pregnancy in female patients and female partners of male patients. Patients must have a negative pregnancy test prior to therapy; use two or more forms of contraception, and have monthly pregnancy tests. Anemia - The addition of VICTRELIS to peginterferon alfa and ribavirin is associated with an additional decrease in hemoglobin concentrations compared with peginterferon alfa and ribavirin alone. Neutropenia - The addition of VICTRELIS to peginterferon alfa and ribavirin may result in worsening of neutropenia associated with peginterferon alfa and ribavirin therapy alone. DRUG INTERACTIONS VICTRELIS is a strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5. The potential for drug-drug interactions must be considered prior to and during therapy. ADVERSE REACTIONS The most commonly reported adverse reactions (greater than 35% of subjects) in clinical trials in adult subjects receiving the combination of VICTRELIS with PegIntron and REBETOL were fatigue, anemia, nausea, headache and dysgeusia. To report SUSPECTED ADVERSE REACTIONS, contact Schering Corporation, a subsidiary of Merck & Co., Inc., at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch DOSAGE AND ADMINISTRATION VICTRELIS must be administered in combination with peginterferon alfa and ribavirin. The dose of VICTRELIS is 800 mg (four 200-mg capsules) three times daily (every 7–9 hours) with food [a meal or light snack] (see Table 1). Refer to the peginterferon alfa and ribavirin Package Inserts for instructions on dosing. The following dosing recommendations differ for some subgroups from the dosing studied in the Phase 3 trials [see Clinical Studies (14)]. Response-Guided Therapy (RGT) is recommended for most individuals, but longer dosing is recommended in targeted subgroups (e.g., patients with cirrhosis). 2.1 VICTRELIS Combination Therapy: Patients Without Cirrhosis Who Are Previously Untreated or Who Are Previous Partial Responders or Relapsers to Interferon and Ribavirin Therapy Initiate therapy with peginterferon alfa and ribavirin for 4 weeks (Treatment Weeks 1–4). Add VICTRELIS 800 mg (four 200-mg capsules) orally three times daily (every 7–9 hours) to peginterferon alfa and ribavirin regimen after 4 weeks of treatment. Based on the patient's HCV-RNA levels at Treatment Week (TW) 8, TW12 and TW24, use the following Response-Guided Therapy (RGT) guidelines to determine duration of treatment (see Table 1). Response-Guided Therapy was not studied in subjects who had less than a 2-log10 HCV-RNA decline by treatment week 12 during prior therapy with peginterferon alfa and ribavirin. If considered for treatment, these subjects should receive 4 weeks of peginterferon alfa and ribavirin followed by 44 weeks of VICTRELIS 800 mg orally three times daily (every 7–9 hours) in combination with peginterferon alfa and ribavirin. In addition, consideration should be given to treating previously untreated patients who are poorly interferon responsive (as determined at TW 4) with 4 weeks peginterferon alfa and ribavirin followed by 44 weeks of VICTRELIS 800 mg orally three times daily (every 7–9 hours) in combination with peginterferon alfa and ribavirin in order to maximize rates of SVR . 2.2 VICTRELIS Combination Therapy: Patients with Cirrhosis Patients with compensated cirrhosis should receive 4 weeks peginterferon alfa and ribavirin followed by 44 weeks VICTRELIS 800 mg (four 200-mg capsules) three times daily (every 7–9 hours) in combination with peginterferon alfa and ribavirin. 2.3 Dose Modification Dose reduction of VICTRELIS is not recommended. If a patient has a serious adverse reaction potentially related to peginterferon alfa and/or ribavirin, the peginterferon alfa and/or ribavirin dose should be reduced or discontinued. Refer to the peginterferon alfa and ribavirin Package Inserts for additional information about how to reduce and/or discontinue the peginterferon alfa and/or ribavirin dose. VICTRELIS must not be administered in the absence of peginterferon alfa and ribavirin. 2.4 Discontinuation of Dosing Based on Treatment Futility Discontinuation of therapy is recommended in all patients with 1) HCV-RNA levels of greater than or equal to 100 IU/mL at TW 12; or 2) confirmed detectable HCV-RNA levels at TW24 HOW SUPPLIED DOSAGE FORMS AND STRENGTHS Capsules: 200 mg How Supplied VICTRELIS 200 mg capsules are comprised of a red-colored cap with the Merck logo printed in yellow ink, and a yellow-colored body with "314" printed in red ink. The capsules are packaged into a carton with 28 bottles containing 12 capsules (NDC 0085-0314-02). Storage and Handling VICTRELIS Capsules should be refrigerated at 2–8°C (36–46°F) until dispensed. Avoid exposure to excessive heat. For patient use, refrigerated capsules of VICTRELIS can remain stable until the expiration date printed on the label. VICTRELIS can also be stored at room temperature up to 25°C (77°F) for 3 months. Keep container tightly closed. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202258lbl.pdf --------------------------------------------- 产地国家：美国 原产地英文商品名: VICTRELIS 200mg/cap  336bottles/box 原产地英文药品名: BOCEPREVIR 中文参考商品译名: VICTRELIS 200毫克/胶囊  336胶囊/盒 中文参考药品译名: 波普瑞韦 生产厂家中文参考译名: 默克制药 生产厂家英文名: Merck --------------------------------------------- 产地国家：德国 原产地英文商品名: VICTRELIS 200mg/cap 336caps/box 原产地英文药品名: BOCEPREVIR 中文参考商品译名: VICTRELIS 200毫克/胶囊 336/盒 中文参考药品译名: 波普瑞韦 生产厂家中文参考译名: 默克制药 生产厂家英文名: Merck --------------------------------------------- 产地国家：德国 原产地英文商品名: VICTRELIS 200mg/cap  84cap/box 原产地英文药品名: BOCEPREVIR 中文参考商品译名: VICTRELIS 200毫克/胶囊  84胶囊/盒 中文参考药品译名: 波普瑞韦 生产厂家中文参考译名: 默克制药 生产厂家英文名: Merck