近日，泛基因型丙肝新药组合sofosbuvir 400mg/velpatasvir 100mg/voxilaprevir 100mg（商标名 VOSEVI）获美国批准上市，用于治疗伴有轻度肝硬化或无肝硬化的基因1~6型丙肝病毒感染成人患者。
Vosevi是一种固定剂量，组合片含两个以前批准的药物–索非布韦和velpatasvir–和一个新药，voxilaprevir。Vosevi是第一个被批准的治疗为患者以前曽被用直接作用抗病毒药索非布韦治疗对HCV抑制一种蛋白被称为NS5A其他药物。
FDA的药物评价和研究中心内抗微生物产品办公室主任Edward Cox，M.D.说：“直接作用抗病毒药预防病毒来自多重地[multiplying]和经常治愈的HCV。对在过去用其他HCV药物不能成功地治疗的有些患者Vosevi提供一种治疗选择”。
批准日期：2017年7月18日 公司：Gilead公司
VOSEVI™(索非布韦，velpatasvir，和voxilaprevir) 片，为口服使用
美国初次批准：2017
黑框：警告
警告：
在与 HCV和 HBV共感染患者肝炎B病毒再活化的风险
对完整黑框警告见完整处方资料
曽报道肝炎B病毒(HBV)再活化，在有些病例中导致爆发性肝炎，肝炎衰竭，和死亡
作用机制
VOSEVI是一股一个 索非布韦，velpatasvir，和voxilaprevir它是DAA剂固定剂量组合针对肝炎C病毒[见微生物学]。
适应证和用途
VOSEVI是一个索非布韦[sofosbuvir]，一个肝炎C病毒(HCV)核苷酸类似物NS5B聚合酶抑制剂，velpatasvir，一个HCV NS5A抑制剂，和voxilaprevir，一个HCV NS3/4ANS5A蛋白酶抑制剂固定剂量组合，和适用为成年患者有慢性HCV感染无肝硬化或有代偿的肝硬化(Child-Pugh A)患者的治疗：
● 基因型1，2，3，4，5，或6 感染和以前曽被用一个HCV方案含一个NS5A抑制剂治疗。
● 基因型1a或3感染和以前曽用一个HCV方案含索非布韦无一个NS5A抑制剂治疗。
o 在有基因型1b，2，4，5，或6感染以前用索非布韦无一个NS5A抑制剂治疗成年未显示VOSEVI超过索非布韦/velpatasvir的附加获益。
剂量和给药方法
●治疗开始前测试：通过测定HBsAg和anti-HBc测试所有患者对 HBV感染。
● 推荐的剂量：每天与食物口服一片(400mg的索非布韦，100mg的velpatasvir，和100mg的voxilaprevir)。
● 见下表中推荐方案和时间。
● 对有严重肾受损或肾病终末期患者不能做一个剂量推荐.
● 在有中度或严重肝受损患者(Child-Pugh B或C)不推荐VOSEVI。
剂型和规格
片：400mg 索非布韦，100mg velpatasvir，和100mg voxilaprevir
禁忌证
与利福平共同给药.
警告和注意事项
●肝炎B病毒再活化的风险：HCV治疗开始前测试所有患者为当前或以前HBV感染的证据。HCV 治疗期间和治疗随访后监视HCV/HBV共感染的患者对HBV 再活化和肝炎加剧。开始对HBV感染适当患者处理当临床有适应证时。
● 与胺碘酮共同给药心动过缓：严重症状性心动过缓 may occur in 患者 taking 胺碘酮[amiodarone]与VOSEVI，一种含索非布韦方案，特别是在患者还接受β阻断剂，或患者有潜在心脏并发症和/或晚期肝病。不推荐胺碘酮与VOSEVI的共同给药。在无另外活治疗选择患者中，推荐心脏监视。
不良反应
● 最常见不良反应(发生率大于或等于10%，所有级别)用VOSEVI治疗共12周观察到为头痛，疲乏，腹泻，和恶心。
药物相互作用
● P-gp诱导剂和/或中度至强效CYP诱导剂(如，圣约翰草[St. John’s wort]，卡马西平[carbamazepine])：索非布韦，velpatasvir，和/或voxilaprevir的浓度可能减低。不推荐使用VOSEVI与Pgp诱导剂和/或中度至强效CYP诱导剂。
●对潜在药物相互作用使用前咨询完整处方资料
包装规格/贮存和处置
每片VOSEVI片含400mg的索非布韦，100mg的velpatasvir，和100mg的voxilaprevir。片为米色，胶囊-形，膜-包衣，和一侧凹陷有“GSI”和其他一侧上“ 3 ”。每瓶含28片(NDC 61958-2401-1)，聚酯卷材，硅胶干燥剂，和用一种防儿童密闭盖密闭。
贮存在30 °C(86 ºF)以下。仅在原始容器这种分发。

U.S. Food and Drug Administration Approves Gilead’s Vosevi™ (Sofosbuvir/Velpatasvir/Voxilaprevir) for Re-Treatment of Adults with Chronic Hepatitis C Virus
Vosevi is the First Once-daily Single-Tablet HCV Regimen Approved as Salvage Therapy for Certain Patients and Completes Gilead’s Portfolio of Sofosbuvir-based HCV Direct-acting Antiviral (DAA) Treatments -
U.S. Food and Drug Administration (FDA) has approved Vosevi™ (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) tablets, a single-tablet regimen for the re-treatment of chronic hepatitis C virus (HCV) infection in adults with genotype 1, 2, 3, 4, 5 or 6 previously treated with an NS5A inhibitor-containing regimen, or with genotype 1a or 3 previously treated with a sofosbuvir-containing regimen without an NS5A inhibitor. The approval is based on data from the Phase 3 POLARIS-1 and POLARIS-4 studies, which evaluated 12 weeks of Vosevi in direct-acting antiviral-experienced chronic HCV-infected patients without cirrhosis or with compensated cirrhosis.
“Direct-acting antiviral regimens have transformed HCV treatment and have allowed health care providers the fortunate opportunity to cure many patients. However, for patients who require re-treatment, there remains an unmet clinical need for an effective and well-tolerated option,” said Ira Jacobson, MD, Chairman of the Department of Medicine at Mount Sinai Beth Israel, New York City and a principal investigator in the Vosevi clinical trials. “Treatment with Vosevi resulted in high cure rates in clinical studies of patients who were not previously cured with several widely-prescribed DAA regimens and will provide physicians with an important new therapeutic option that could offer hope for their hardest-to-treat patients.”
Vosevi has a boxed warning in its product label regarding the risk of hepatitis B virus (HBV) reactivation in HCV/HBV coinfected patients. See below for important safety information.
Vosevi is the latest single-tablet regimen in Gilead’s portfolio of sofosbuvir-based DAA treatments that offer people living with HCV a short course of therapy to cure their HCV, with the convenience associated with once-daily single-tablet regimens. Since 2013, Gilead has brought to market four HCV treatments, including 3 single-table regimens. To date, more than an estimated 1.4 million patients worldwide have been treated with sofosbuvir-based regimens.
“The evolution of Gilead’s portfolio of HCV single-tablet regimens has been driven by our commitment to address previously unmet needs and put the possibility of cure within reach for as many HCV patient populations as possible,” said John F. Milligan, PhD, Gilead’s President and Chief Executive Officer. “The approval of Vosevi completes our portfolio by fulfilling the unmet need for an effective regimen for patients who could not be cured, despite prior treatment with certain DAA regimens.”
The approval of Vosevi is supported by data from the POLARIS-1 study evaluating 12 weeks of treatment among adults with HCV genotype 1, 2, 3, 4, 5 or 6 with or without compensated cirrhosis who had failed prior treatment with an NS5A inhibitor-containing regimen, as well as data from the POLARIS-4 study evaluating 12 weeks of treatment among adults with HCV genotypes 1a and 3 with or without compensated cirrhosis who had failed prior treatment with a sofosbuvir-containing regimen that did not include an NS5A inhibitor. In these populations across the two studies, 340 of the 353 patients treated with Vosevi (96 percent) achieved the primary endpoint of SVR12, defined as maintaining undetectable viral load 12 weeks after completing therapy.
The most common adverse events (≥10% of patients) among patients who received Vosevi were headache, fatigue, diarrhea and nausea. The proportion of subjects who permanently discontinued treatment due to adverse events was 0.2% for subjects who received Vosevi for 12 weeks.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with Vosevi. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
Contraindications
Vosevi is contraindicated with rifampin.
Warnings and Precautions
Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with Vosevi due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir containing regimen. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
Risk of Reduced Therapeutic Effect Due to Concomitant Use of Vosevi with P-gp Inducers and/or Moderate to Potent Inducers of CYP2B6, CYP2C8 or CYP3A4: St. John’s wort and carbamazepine are not recommended for use with Vosevi as they may significantly decrease sofosbuvir, velpatasvir, and/or voxilaprevir plasma concentrations.
Adverse Reactions
The most common adverse reactions (≥10%, all grades) with Vosevi were headache, fatigue, diarrhea, and nausea.
Drug Interactions
Coadministration of Vosevi is not recommended with phenytoin, phenobarbital, oxcarbazepine, rifabutin, rifapentine, atazanavir, lopinavir, tipranavir/ritonavir, efavirenz, rosuvastatin, pitavastatin, and cyclosporine due to changes (decreased or increased) in concentrations of sofosbuvir, velpatasvir, voxilaprevir, and/or the other agent.
Consult the full Prescribing Information for Vosevi for more information on potentially significant drug interactions, including clinical comments.
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm567467.htm