日前，美国FDA于2011年5月批准美国默克公司的慢性丙型肝炎治疗新药波普瑞韦（Boceprevir，商品名Victrelis）上市。Victrelis是默沙东研制的用于治疗基因1型丙型肝炎的新药。临床试验数据显示，当这种药物与现在药物共同使用时，能治愈60%以上的丙型肝炎患者（比较而言，单独使用现有药物的治愈率在20%～40%），而且，新药在提高治愈率的同时还能缩短治疗时间。

Victrelis也被称为boceprevir，是一种新型的丙型肝炎病毒蛋白毒抑制剂（丙型肝炎病毒蛋白毒是病毒复制所需要的），通过抑制这种病毒酶从而阻止病毒的复制。Victrelis借用了HIV治疗中的成功战略。

圣路易斯大学医学院内科学教授、Victrelis临床试验的研究人员布鲁斯·培根博士说：“与目前使用的标准治疗方法相比，Victrelis明显提高了患者达到无病毒查出水平的机会。对许多患者来说，Victrelis能缩短其治疗时间。”在默沙东开展的临床试验中，44%的以前未接受过治疗的丙型肝炎患者能在28周的时间完成治疗，而不是通常所需要的48周。

这种新药也有副作用：大约50%的患者在服用Victrelis后出现了贫血症状，这个比例是只使用现有药物患者的2倍；服用Victrelis的患者发生白细胞数量低的风险也更高。而且，患者需要服用大量的药片。

美国FDA批准丙肝治疗新药波普瑞韦

批准日期：2011年5月13日；公司：Merck

VICTRELIS(boceprevir)胶囊

美国初始批准：2011 优先审评药物
 
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：200 mg
 
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。

为报告怀疑不良反应，联系Schering Corporation，Merck & Co., Inc.的子公司电话1-877-888-4231或FDA电话1-800-FDA-1088或www.fda.gov/medwatch.

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) is indicated for use in combination with peginterferon alfa and ribavirin to treat chronic hepatitis C (HCV) genotype 1 infection in patients with compensated liver disease who are previously untreated or who have failed previous therapy.

Boceprevir is the first agent to directly target the hepatitis C virus

PHARMACOLOGY

Boceprevir directly inhibits the HCV NS3 protease, which is essential for viral replication.1

CLINICAL STUDIES

Two randomised, placebo-controlled double-blind phase 3 studies evaluated the efficacy of boceprevir in the treatment of chronic HCV genotype 1 infection, the most common form of the disease. Added to the current standard of care (pegylated interferon plus ribavirin), boceprevir 800mg 3 times daily significantly increased sustained virologic response rates (defined as an undetectable HCV RNA level after 24 weeks of follow-up) in both studies.

SPRINT-2 enrolled 1097 previously untreated patients, who were randomised to 1 of 3 treatment arms.2 Patients in all 3 arms underwent a 4-week lead-in period on peginterferon alfa-2b and ribavirin alone. The control group then received add-on placebo for 44 weeks, while the other 2 groups were assigned to add-on boceprevir for either 44 or 24 weeks. Treatment in the 24-week group was guided by response, with patients who had a detectable HCV RNA level between weeks 8 and 24 switching to placebo plus peginterferon alfa-2b and ribavirin for another 20 weeks.

Among non-black patients (n=938), sustained virologic response rates for boceprevir plus peginterferon and ribavirin were significantly greater than for placebo plus peginterferon and ribavirin: 68% (44 weeks’ treatment) and 67% (24 weeks’ treatment) versus 40% (p<0.001 for both). Black patients (n=159), who typically show a poorer response to HCV treatment, exhibited corresponding response rates of 53% (p=0.004), 42% (p=0.04) and 23%, respectively. Overall, treatment with boceprevir increased the likelihood of a sustained virologic response more than three-fold (p<0.001).2

RESPOND-2 enrolled 403 patients who had previously relapsed or failed to respond to peginterferon plus ribavirin.3 As in SPRINT-2, all participants underwent a 4-week lead-in period on peginterferon alfa-2b and ribavirin. Patients then received either additional placebo for 44 weeks, or boceprevir for 44 or 32 weeks; those in the 32-week group who had a detectable HCV RNA level at week 8 (but not at week 12) received placebo plus peginterferon and ribavirin for an additional 12 weeks.

Sustained virologic response rates were similar in patients who received 44 or 32 weeks of boceprevir (66% and 59%, respectively) and significantly higher with boceprevir than placebo (21%; p<0.001 for both).3

Adverse events most commonly associated with boceprevir were fatigue, nausea, headache, anaemia and dysgeusia.1 In SPRINT-2, anaemia necessitated dose reduction in 13% of control patients and 21% of boceprevir recipients, and discontinuation in 1% and 2%, respectively.1

In a pooled analysis of the two phase 3 studies, resistance-associated HCV amino acid variants were detected in 15% of boceprevir-treated patients and in 53% of those who did not achieve a sustained virologic response.1

VICTRELIS

Manufacturer:

Merck & Co., Inc.

Pharmacological Class:HCV NS3/4A protease inhibitor

Active Ingredient(s):Boceprevir 200mg; caps.

Indication(s):Chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin (PR) in adult patients with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy. Not for use as monotherapy.

Pharmacology:Boceprevir inhibits the hepatitis C virus (HCV) non-structural protein 3 serine protease by reversibly binding to an active site on this enzyme, thereby inhibiting viral replication in HCV-infected host cells.

Clinical Trials:In a placebo-controlled study, adding boceprevir to PR significantly increased the sustained virologic response rates compared to PR alone. In subjects with cirrhosis at baseline, the sustained virologic response was higher in those who were given boceprevir + PR for 44 weeks (after lead-in therapy with PR) compared to those given response-guided therapy based on results at treatment weeks 8 through 24.

In another study, in patients who failed previous therapy with PR, adding boceprevir to PR significantly increased the sustained virologic response rates compared to PR alone. In those with cirrhosis at baseline, sustained virologic response was higher in patients treated with boceprevir + PR for 44 weeks (after lead-in therapy with PR) compared to those who received response-guided therapy.

Legal Classification:

Rx

Adults:≥18yrs: Take with food. 800mg three times daily. Start after 4 weeks therapy with peginterferon and ribavirin. Without cirrhosis: continue treatment as indicated by HCV-RNA levels at weeks 8, 12, and 24 (see literature). With cirrhosis: continue for 44 weeks. Do not reduce dose. Discontinue if HCV-RNA levels indicate futility (see literature).

Children:<18yrs: not recommended.

Contraindication(s):Concomitant potent CYP3A4/5 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, St. John’s Wort) or narrow therapeutic index CYP3A4/5 substrates (eg, alfuzosin, cisapride, ergot derivatives, lovastatin, simvastatin, drosperinone, pimozide, sildenafil or tadalafil for PAH, triazolam, oral midazolam). Pregnant women and men whose partners are pregnant (note: ribavirin is Cat.X). Review peginterferon and ribavirin contraindications.

Warnings/Precautions:Female patients and partners must have (–) pregnancy test before therapy, use appropriate effective contraception, and undergo monthly pregnancy test. Monitor CBC w. differential, HCV-RNA. Co-infection with HBV or HIV. Decompensated cirrhosis. Organ transplant recipients. Pregnancy (Cat.B). Nursing mothers: not recommended.

Interaction(s):See literature. Concomitant rifabutin, salmeterol, efavirenz, concomitant colchicine in renal or hepatic impairment: not recommended. Potentiates CYP3A4/5 substrates (eg, amiodarone, bepridil, propafenone, quinidine, flecainide, trazodone, desipramine, azole antifungals, clarithromycin). Antagonizes ethinyl estradiol. Antagonized by potent CYP3A4/5 inhibitors. Monitor warfarin, digoxin, dihydropyridine calcium channel blockers, bosentan, protease inhibitors, immunosuppressants, opioids. Concomitant ketoconazole, itraconazole: max 200mg/day. Concomitant atorvastatin: max 20mg/day. Colchicine, PDE5 inhibitors for ED (eg, sildenafil, tadalafil, vardenafil), alprazolam, IV midazolam: reduce doses and monitor. Corticosteroids: avoid, monitor if needed.

Adverse Reaction(s):Fatigue, nausea, headache, dysgeusia, worsening anemia, neutropenia.

How Supplied:Bottles (12 caps/bottle)—28

Last Updated:6/21/2011

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原产地英文商品名:
VICTRELIS 200mg/cap 12caps/bottle 28bottles/box
原产地英文药品名:
BOCEPREVIR
中文参考商品译名:
VICTRELIS 200毫克/胶囊 12胶囊/瓶 28瓶/盒
中文参考药品译名:
BOCEPREVIR
生产厂家中文参考译名:
先灵
生产厂家英文名:
SCHERING