2014年10月10日，美国FDA批准二联复方片ledipasvir/sofosbuvir(商标名：Harvoni 吉利德抗产品)扩展用于基因型4、5和6慢性丙型肝炎病毒（HCV）感染患者及合并感染HIV的患者。此外，Harvoni加利巴韦林12周疗程被批准作为一种替代疗法用于有24周Harvoni治疗经历的肝硬化基因型1患者。
这项获批用于HCV基因型4-6的补充新药申请（sNDA）基于开放试验1119与ELECTRON-2的结果。1119研究在既往未治疗及有过治疗经历的有或没有肝硬化的HCV基因型4或5患者中对 Harvoni 12周治疗进行了评价。
结果显示，93%的基因型4患者及 93%的基因型5患者达到SVR12。ELECTRON-2在既往未治疗或之前有过治疗的有或无肝硬化的基因型6HCV 感染患者中对Harvoni 12周治疗进行了评价。在这项研究中，96%的患者达到SVR12。
该用于HCV/HIV-1合并感染患者的补充新药申请基于3期开放式ION-4研究的数据，这项研究在合并感染有 HIV的患者中对Harvoni用于基因型1或4慢性 HCV 感染12周治疗进行了评价。数据证明，96%的患者达到SVR12。
这项研究包括HCV既往未治疗及有过治疗经历的患者，包括有补偿性肝硬化的患者。大多数患者正在使用三种HIV抗逆转录病毒方案中的其中一种，包括富马酸替诺福韦酯（TDF）和恩曲他滨，分别与依非韦伦、雷特格韦或利匹韦林配伍。
以Harvoni加利巴韦林12周治疗用于既往有过治疗的肝硬化 HCV 患者补充新药申请基于2期SIRIUS研究的数据，这项研究对 Harvoni 加利巴韦林12周治疗或在没有RBV的情况下以 Harvoni 24周治疗用于既往治疗失败的补偿性肝硬化HCV感染患者进行了评价。96%的Harvoni加利巴韦林12周治疗患者，97%的无RBV的Harvoni 24周治疗患者达到SVR12。
Harvoni证明在整个一系列患者人群中有较高的治愈率
Harvoni是首个也是唯一一个用于HCV治疗的单一片剂方案，该药物继续在一系列患者人群中有较高的治愈率及可耐受的副作用，包括在那些历来被认为最难以治愈的患者中，吉利德研发执行副总裁兼首席科学官 Bischofberger 博士称。我们很高兴Harvoni的标签及处方信息现在能够增加新适应证信息，用于这些重要的HCV患者人群。
欧洲药品管理局最近还批准更新Harvoni标签，允许Harvoni与利巴韦林合并用药的较短期治疗。具体地讲，这包括Harvoni加利巴韦林12周治疗用于有补偿性肝硬化、代偿失调性肝硬化的基因型1和4患者及肝移植后的HCV感染患者。
此次新的标签还包括进一步支持 Harvoni12周治疗用于合并感染HIV的基因型1或4患者及用于既往对 Sofosbuvir加利巴韦林（添加或不添加聚乙二醇干扰素）治疗失败患者的数据。
Harvoni (sofosbuvir/ledipasvir)推荐服用剂量：一般一天一次，每次服一片，同食物或空腹。

Harvoni(Ledipasvir and Sofosbuvir Tablets)
HARVONI Rx
Generic Name and Formulations:
Ledipasvir, sofosbuvir; 90mg/400mg; tabs.
Company:
Gilead Sciences, Inc.
Indications for HARVONI:
Chronic hepatitis C virus (HCV) infection in patients with: genotype 1, 4, 5, or 6 without cirrhosis or with compensated cirrhosis; genotype 1 with decompensated cirrhosis, in combination with ribavirin; or genotype 1 or 4 who are liver transplant recipients without cirrhosis or with compensated cirrhosis, in combination with ribavirin.
Adult:
Test for HBV infection prior to initiation. 1 tab once daily. Genotype 1: Treatment-naïve without cirrhosis or with compensated cirrhosis (Child-Pugh A), or treatment-experienced without cirrhosis: treat for 12 weeks; treatment-naïve without cirrhosis who have pre-treatment HCV RNA <6 million IU/mL: can be considered for 8 weeks. Treatment-experienced with compensated cirrhosis: treat for 24 weeks; can be considered for 12 weeks with concomitant ribavirin (if eligible). Treatment-naïve and -experienced with decompensated cirrhosis (Child-Pugh B or C): treat for 12 weeks with ribavirin (see full labeling). Genotype 1 or 4: Treatment-naïve and -experienced liver transplant recipients without cirrhosis or with compensated cirrhosis: treat for 12 weeks with ribavirin. Genotype 4, 5, 6: Treatment-naïve and -experienced without cirrhosis or with compensated cirrhosis: treat for 12 weeks. HCV/HIV-1 co-infection: follow same dosage schedule. See full labeling.
Children:
<12yrs and <35kg: not established. Test for HBV infection prior to initiation. ≥12yrs or ≥35kg: 1 tab once daily. Genotype 1: Treatment-naïve without cirrhosis or with compensated cirrhosis (Child-Pugh A), or treatment-experienced without cirrhosis: treat for 12 weeks. Treatment-experienced with compensated cirrhosis: treat for 24 weeks. Genotype 4, 5, 6: Treatment-naïve and -experienced without cirrhosis or with compensated cirrhosis: treat for 12 weeks. HCV/HIV-1 co-infection: follow same dosage schedule. See full labeling.
Contraindications:
When co-administered with ribavirin, its contraindication also apply to this combination regimen (eg, Pregnancy Cat.X).
Warnings/Precautions:
Risk of HBV reactivation in patients coinfected with HCV/HBV. Test all patients for HBV infection by measuring HBsAg and anti-HBc; if positive serologic evidence, monitor for hepatitis flare or HBV reactivation during and at post-treatment follow-up; treat if clinically indicated. Increased risk of symptomatic bradycardia when concomitant amiodarone esp. patients also taking beta blockers or with cardiac comorbidities and/or advanced liver disease. Severe renal impairment (eGFR <30mL/min/1.73m2) or ESRD requiring hemodialysis. Decompensated cirrhosis. Pregnancy. Nursing mothers.
Interactions:
Concomitant certain immunosuppressants or chemotherapeutic agents: may increase risk of HBV reactivation. Concomitant amiodarone: not recommended; if no alternatives, monitor cardiac function (see full labeling). May increase absorption of concomitant P-gp and BCRP substrates. Concomitant P-gp inducers (eg, rifampin, St. John’s wort), other sofosbuvir-containing products, anticonvulsants (eg, carbamazepine, phenytoin, phenobarbital, oxcarbazepine), rifabutin, rifapentine, elvitegravir, cobicistat, emtricitabine, tenofovir DF, tipranavir/ritonavir, simeprevir, or rosuvastatin: not recommended. Separate dosing of antacids by 4hrs. May give H2-antagonists simultaneously or 12hrs apart (comparable to max famotidine 40mg twice daily). May give PPI doses (comparable to omeprazole ≤20mg) simultaneously under fasted conditions. May potentiate digoxin; monitor. Concomitant tenofovir DF regimens without a HIV protease inhibitor/ritonavir or cobicistat; monitor. Concomitant atazanavir/ritonavir or cobicistat + emtricitabine/tenofovir DF, darunavir/ritonavir or cobicistat + emtricitabine/tenofovir DF, or lopinavir/ritonavir + emtricitabine/tenofovir DF: consider alternatives; or if coadmin necessary, monitor.
Pharmacological Class:
HCV NS5A inhibitor + HCV NS5B polymerase inhibitor.
Adverse Reactions:
Fatigue, headache, asthenia, nausea, diarrhea, insomnia.
Note:
For ribavirin specific dosing and safety information, refer to the full prescribing information.
Generic Availability:
NO
How Supplied:
Tabs—28
http://www.gilead.com/~/media/files/pdfs/medicines/liver-disease/harvoni/harvoni_pi.pdf?la=en