近日，美国FDA已经批准VIEKIRA XR缓释片的丙肝新药上市。VIEKIRA XR是每日一次的缓释制剂，与先前获批产品VIEKIRA PAK一样，有效成分是dasabuvir、ombitasvir、paritaprevir和ritonavir，用于治疗基因1型的慢性丙型肝炎病毒成人感染者。他们包括伴有代偿性肝硬化的患者，但不包括那些晚期肝硬化伴有失代偿性肝硬化的丙肝患者。
批准日期：2016年8月2日 公司：艾伯维（AbbVie）
VIEKIRA XR（达沙布韦/替比夫韦/帕里帕韦/利托那韦[dasabuvir，ombitasvir，paritaprevir/ritonavir]）缓释片，用于口服
美国最初批准：2014年
警告：乙型肝炎病毒再激活的风险患有HCV和HBV的患者查看完整的盒装警告的完整处方信息。
已报道乙型肝炎病毒（HBV）再激活，在某些情况下导致暴发性肝炎，肝衰竭和死亡。
作用机制
VIEKIRA XR结合了三种直接作用的丙型肝炎病毒抗病毒药物和独特的作用机制[见微生物学]。
利托那韦对HCV没有活性。利托那韦是一种有效的CYP3A抑制剂，可增加paritaprevir和整体药物暴露（即曲线下面积）的血浆药物浓度峰值和谷值。
适应症和用法
VIEKIRA XR包括dasabuvir，丙型肝炎病毒非核苷类NS5Bpalm聚合酶抑制剂，ombitasvir，丙型肝炎病毒NS5A抑制剂，paritaprevir，丙型肝炎病毒NS3/4A蛋白酶抑制剂和利托那韦，aCYP3A抑制剂，适用于成人治疗慢性丙型肝炎病毒（HCV）患者：
•基因型1b感染无肝硬化或代偿性肝硬化
•基因型1a感染无肝硬化或代偿性肝硬化与利巴韦林联合使用。
剂量和给药
在开始治疗之前进行测试：
•通过测量HBsAg和抗HBc，对所有患者进行HBV感染检测。
•评估肝脏失代偿的实验室和临床证据。
推荐剂量：每日一次服用三片。 VIEKIRA XR必须与膳食同时进行，因为在禁食条件下给药可能导致病毒学应答减少和可能产生耐药性。
治疗方案和患者人群的持续时间
患者人口                           治疗               持续时间  
基因型1a，无肝硬化             VIEKIRA XR +利巴韦林    12周
基因型1a，伴有代偿性肝硬化     VIEKIRA XR +利巴韦林    24周
基因型1b，有或没有代偿性肝硬化   VIEKIRA XR            12周
注意：对于未知基因型1亚型或混合基因型1感染的患者，遵循基因型1a给药建议。
根据既往治疗史，部分患者可考虑使用利巴韦林治疗12周的VIEKIRA XR [见临床研究]
HCV/HIV-1共感染：对于HCV/HIV-1共感染患者，请遵循上表中的剂量建议。
•肝移植受者：在具有正常肝功能和轻度纤维化（Metavir纤维化评分≤2）的肝移植受者中，推荐使用利巴韦林的VIEKIRA XR持续时间为24周。
剂量形式和强度
缓释片剂：200mg达沙韦韦，8.33mg ombitasvir，50mgparitaprevir和33.33mg利托那韦。
禁忌症
•中度至重度肝功能损害患者。
•如果VIEKIRA XR与利巴韦林一起服用，禁忌症toribavirin也适用于这种组合方案。
•与以下药物共同给药：高度依赖CYP3A清除;中等或强烈的CYP3A诱导剂或CYP2C8的强诱导剂;和CYP2C8的强抑制剂。
•已知对利托那韦的超敏反应（例如中毒性表皮坏死松解症，Stevens-Johnson综合征）。
警告和注意事项
•乙型肝炎病毒再次激活的风险：在开始HCV治疗之前，对所有患者进行HBV感染或早期HBV感染的证据。监测HCV/HBV合并感染患者的HBV再激活和肝炎发作的HCV治疗和治疗后随访。根据临床指示，启动适当的HBV感染患者管理。
•肝硬化患者肝功能失代偿和肝功能衰竭：肝功能失代偿和肝功能衰竭，包括肝脏移植或致命结果，主要见于晚期肝硬化患者。监测肝脏补偿的临床症状和体征。
•ALT升高：停用VIEKIRA XR（推荐替代避孕方法），停用含乙炔雌二醇的药物。在治疗的前4周对所有患者进行肝脏实验室检测。对于VIEKIRA XR的ALT升高，请关闭并遵循完整处方信息中的建议。
•与利巴韦林联合治疗相关的风险：如果VIEKIRA XR与利巴韦林一起使用，利巴韦林的警告和预防措施也适用于该组合方案。
•药物相互作用：伴随使用VIEKIRA XR和某些其他药物可能导致已知或潜在的重要药物相互作用，其中一些可能导致VIEKIRA XR的治疗效果丧失。
不良反应
在接受dasabuvir与ombitasvir，paritaprevir，利托那韦和利巴韦林组合的受试者中，最常报告的不良反应（大于10％的受试者）是疲劳，恶心，瘙痒，其他反应，失眠和虚弱。在接受阿扎比韦与ombitasvir，paritaprevir，没有利巴韦林的利托那韦组合的受试者中，最常见的不良反应（大于或等于5％的受试者）是恶心，瘙痒和失眠。
要报告疑似不良反应，请联系AbbVie Inc.at 1-800-633-9110或FDA，电话1-800-FDA-1088或www.fda.gov/medwatch。
药物相互作用
•共同给予VIEKIRA XR可以改变某些药物的血浆浓度，某些药物可能会改变VIEKIRA XR的血浆浓度。在治疗前和治疗期间必须考虑药物相互作用的可能性。咨询完整的处方信息priorto和治疗期间潜在的药物相互作用。
•接受华法林治疗的患者建议经常监测国际标准化比值（INR）。
包装提供/存储和处理
VIEKIRA XR每月分发一箱，共治疗28天。每月每月包含四个每周纸箱。每周一次的纸箱包含七个每日剂量包。
每个儿童抗性日剂量包含三片。 NDC号码是0074-0063-28。
Dasabuvir，ombitasvir，paritaprevir和利托那韦200mg/8.33mg/50mg/33.33mg片剂呈黄色，薄膜包衣，长方形，一侧有“3QD”凹陷。
储存温度等于或低于30°C（86°F）。
完整说明资料附件：https://www.rxabbvie.com/pdf/viekiraxr_pi.pdf
U.S. FDA Approval of Once-Daily VIEKIRA XR™ (dasabuvir, ombitasvir, paritaprevir and ritonavir) for the Treatment of Genotype 1 Chronic Hepatitis C
U.S. Food and Drug Administration (FDA) has approved a New Drug Application (NDA) for VIEKIRA XR™ (dasabuvir, ombitasvir, paritaprevir and ritonavir) extended-release tablets. VIEKIRA XR is a once-daily, extended-release co-formulation of the active ingredients in VIEKIRA PAK® (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) and is for the treatment of patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection, including those with compensated cirrhosis (Child-Pugh A). VIEKIRA XR is not for people with decompensated cirrhosis.
VIEKIRA XR is the first co-formulated three direct-acting antiviral (DAA) treatment for adult patients with GT1 HCV. VIEKIRA XR is given once-daily as three oral tablets and must be taken with a meal. It is used without ribavirin (RBV) in GT1b patients and in combination with twice daily RBV in GT1a patients. The approval is supported by Phase 3 clinical trials for VIEKIRA PAK which include data that demonstrated 100 percent sustained virologic response 12 weeks following treatment (SVR12) in GT1b patients with 12 weeks of therapy without ribavirin and 95 percent SVR12 in GT1a patients when used with ribavirin for 12 or 24 weeks of therapy.
AbbVie. "The approval of VIEKIRA XR provides a new treatment option for genotype 1 hepatitis C patients in the U.S. with clinical trial data using the components of VIEKIRA XR demonstrating 100 percent cure rates in genotype 1b patients."
There are six major HCV genotypes (GT1-6) and GT1 is the most preva lent form of HCV in the U.S., accounting for approximately 74 percent of all cases.1 Hepatitis C continues to be an important public health issue, with the Centers for Disease Control and Prevention (CDC) estimating that in the U.S. approximately 2.7 million people are chronically infected with HCV.
The approval of VIEKIRA XR is supported by data from seven Phase 3 clinical trials in more than 2,300 patients who received VIEKIRA PAK with or without RBV for 12 or 24 weeks and two bioavailability studies comparing the formulations.
USE
VIEKIRA XR™ (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets/VIEKIRA PAK® (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) (VIEKIRA) are prescription medicines used with or without ribavirin to treat adults with genotype 1 chronic (lasting a long time) hepatitis C (hep C) virus infection.
VIEKIRA can be used in people who have compensated cirrhosis.
VIEKIRA is not for people with advanced cirrhosis (decompensated). If people have cirrhosis, they should talk to a doctor before taking VIEKIRA.
IMPORTANT SAFETY INFORMATION
When taking VIEKIRA in combination with ribavirin, people should read the Medication Guide that comes with ribavirin, especially the important pregnancy information.
What is the most important information to know about VIEKIRA?
VIEKIRA may cause severe liver problems, especially in people with certain types of cirrhosis. These severe liver problems can lead to the need for a liver transplant, or can lead to death.
VIEKIRA can cause increases in liver function blood test results, especially if people use ethinyl estradiol-containing medicines (such as some birth control products).
Ethinyl estradiol-containing medicines (combination birth control pills or patches, such as Lo Loestrin® FE, Norinyl®, Ortho Tri-Cyclen Lo®, Ortho Evra®; hormonal vaginal rings such as NuvaRing®; and the hormone replacement therapy medicine, Fem HRT®) must be stopped before starting treatment with VIEKIRA. If these medicines are used as a method of birth control, another method must be used during treatment with VIEKIRA, and for about 2 weeks after treatment with VIEKIRA ends. A doctor can provide instruction on when to begin taking ethinyl estradiol-containing medicines.
A doctor should do blood tests to check liver function during the first 4 weeks of treatment and then as needed.
A doctor may tell people to stop taking VIEKIRA if signs or symptoms of liver problems develop. A doctor must be notified right away if any of the following symptoms develop or if they worsen during treatment with VIEKIRA: tiredness, weakness, loss of appetite, nausea, vomiting, yellowing of the skin or eyes, color changes in stools, confusion, or swelling of the stomach area.
About VIEKIRA XR
The components of VIEKIRA XR* have been studied in a broad range of genotype 1 (GT1) patients with chronic hepatitis C virus (HCV) infection, ranging from treatment-naïve to difficult to treat patients, such as those with compensated (mild, Child-Pugh A) cirrhosis of the liver, HCV/HIV-1 co-infection, liver transplant recipients with normal hepatic function and mild fibrosis, and those who have failed previous treatment with pegylated interferon (pegIFN) and ribavirin (RBV).
The extended-release co-formulation of these components, VIEKIRA XR, consists of 200 mg of dasabuvir, 8.33 mg of ombitasvir, 50 mg of paritaprevir, and 33.33 mg of ritonavir per tablet, and is dosed three tablets once daily. VIEKIRA XR must be taken with a meal, and tablets should be swallowed whole. People should not drink alcohol within four hours of taking VIEKIRA XR. VIEKIRA XR is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B and C) due to risk of potential toxicity. VIEKIRA XR is taken for 12 weeks, except in GT1a patients with cirrhosis and all liver transplant recipients with normal hepatic function and mild fibrosis, who should take it for 24 weeks. Ribavirin should be co-administered in GT1a patients and in all patients who have received a liver transplant.
Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. Paritaprevir is used in combination with AbbVie's ombitasvir with or without dasabuvir for the treatment of hepatitis C.
*Given as a fixed-dose combination of ombitasvir 25mg (an NS5A inhibitor), paritaprevir 150mg (an NS3/4A protease inhibitor), and ritonavir 100mg (an HIV-1 protease inhibitor), dosed once daily with a meal, and dasabuvir 250mg (a non-nucleoside NS5B palm polymerase inhibitor), dosed twice daily with a meal.