英文药名：HARVONI Combination Tablets（Ledipasvir Acetonate/sofosbuvir） 中文药名：雷迪帕韦/索非布韦配合錠 生产厂家：吉利德科学公司 ハーボニー配合錠 治疗类别名称 抗病毒药物 批准日期：2015年9月 商品名：HARVONI Combination Tablets 通用名：Ledipasvir Acetonate（雷迪帕韦）/sofosbuvir（索非布韦） 给药途径：片剂，口服 作用机制 HARVONI是ledipasvir和sofosbuvir一种固定剂量组合复方，是对丙肝病毒直接主要抗病毒药物[见微生物学]. 适应证和用途 HARVONI是一个ledipasvir，一种丙肝病毒(HCV)NS5A抑制剂，和sofosbuvir，一种HCV核苷酸类似物NS5B聚合酶抑制剂的固定剂量组合复方，和适用在成年中为慢性丙肝(CHC)基因型1感染的治疗。 剂量和给药方法 ⑴ 推荐剂量：1片(90mg ledipasvir和400mg sofosbuvir)口服每天1次有或无食物。 ⑵ 推荐治疗时间： ⒈未治疗过有或无肝硬化：12周 ⒉经历治疗无肝硬化：12周 ⒊经历治疗有肝硬化：24周 ⑶ 对有严重肾受损或肾病终末期患者不能做推荐剂量 剂型和规格 片：90mg/400mg 禁忌证 无 警告和注意事项 不建议与其他含sofosbuvir其他药物使用，包括SOVALDI。 不良反应 用HARVONI治疗共8，12或24周观察到最常见不良反应(发生率大于或等于10%，所有级别)是疲乏和头痛。 药物相互作用 ⑴ P-gp诱导剂(如，利福平[rifampin]，圣约翰草[St. John’s wort])：可能改变ledipasvir和sofosbuvir的浓度。不建议HARVONI与P-gp诱导剂使用。 ⑵ 使用前为药物相互作用潜在咨询完整处方资料。 附：在日本上市的处方资料：http://www.info.pmda.go.jp/go/pack/6250107F1026_1_10/ --------------------------------------- 上市国家：日本 原产地英文商品名: HARVONI Combination Tablets(ハーボニー配合錠：90mg/400mg)/tab 14tabs/box 原产地英文药品名: Ledipasvir Acetonate/sofosbuvir 中文参考商品译名: Harvoni复方片(ハーボニー配合錠：90毫克/400毫克)/片 14片/盒 中文参考药品译名: 雷迪帕韦/索非布韦 生产厂家英文名: Gilead Sciences Inc 生产厂家中文参考译名: 吉利德科学公司 --------------------------------------- 上市国家：日本 原产地英文商品名: HARVONI Combination Tablets(ハーボニー配合錠：90mg/400mg)/tab 28tabs/bottle 原产地英文药品名: Ledipasvir Acetonate/sofosbuvir 中文参考商品译名: Harvoni复方片(ハーボニー配合錠：90毫克/400毫克)/片 28片/瓶 中文参考药品译名: 雷迪帕韦/索非布韦 生产厂家英文名: Gilead Sciences Inc 生产厂家中文参考译名: 吉利德科学公司 Ledipasvir-Sofosbuvir (Harvoni) Class and Mechanism: Ledipasvir is a potent inhibitor of HCV NS5A, a viral phosphoprotein that plays an important role in viral replication, assembly, and secretion. Sofosbuvir is a nucleotide analog inhibitor of hepatitis C virus NS5B polymerase—the key enzyme mediating HCV RNA replication. The triphosphate form of sofosbuvir (GS-461203) mimics the natural cellular uridine nucleotide and is incorporated by the HCV RNA polymerase into the elongating RNA primer strand, resulting in chain termination The fixed-dose combination of ledipasvir and sofosbuvir (Harvoni) is manufactured by Gilead Sciences. Indications: The fixed dose combination ledipasvir-sofosbuvir (90 mg/400 mg) is FDA-approved for the treatment of chronic hepatitis C genotype 1 in both treatment-naive and treatment-experienced patients. The treatment duration depends on prior treatment experience and the presence or absence of cirrhosis. Treatment experience is defined as patients who have failed treatment with either peginterferon plus ribavirin or peginterferon plus ribavirin plus a HCV protease inhibitor. •Genotype 1 treatment-naïve patients with or without cirrhosis: 12 weeks •Genotype 1 treatment-experienced patients without cirrhosis: 12 weeks •Genotype 1 treatment-experienced patients with cirrhosis: 24 weeks •Treatment experience is defined as patients who have failed treatment with either peginterferon plus ribavirin or peginterferon plus ribavirin plus a HCV protease inhibitor. •Note: a treatment duration of 8 weeks can be considered in treatment-naive patients without cirrhosis who have a baseline HCV RNA level less than 6million IU/mL. Dosing: Ledipasvir-sofosbuvir (90 mg/400mg) is a fixed-dose combination tablet The recommended dosage is one tablet once daily, with or without food. •For patients with mild to moderate renal impairment, no dosage adjustment of ledipasvir/sofosbuvir is recommended. There are insufficient data regarding the safety and efficacy of ledipasvir/sofosbuvir in patients with severe renal impairment (eGFR less than 30 ml/min/1.73m2) or end-stage renal disease requiring dialysis.  Thus, no dosage recommendation has been given for patients with severe renal impairment or end-stage renal disease requiring dialysis. •For patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, or C), no dosage adjustment is recommended, but the safety and efficacy of ledipasvir/sofosbuvir in patients with decompensated cirrhosis has not been established. Clinical Use: The combination of ledipasvir-sofosbuvir has primarily been studied as an all-oral (interferon-free) combination regimen in treatment-naive and treatment-experienced patients with genotype 1 chronic HCV infection. Phase 3 studies (ION-1, ION-2, and ION-3) have consistently shown SVR12 rates greater than 90% with a 12-week course of ledipasvir-sofosbuvir in patients with genotype 1 chronic HCV.  For treatment-experienced patients with cirrhosis, the SVR12 rates were significantly better with 24 weeks of therapy than with 12 weeks. A subanalysis of the ION-3 trial showed that treatment-naive patients without cirrhosis had excellent SVR12 rates with only 8 weeks of ledipasvir-sofosbuvir if their pre-treatment HCV RNA level was less than 6 million IU/mL. For the treatment of patients with genotype 1 infection, the addition of ribavirin to ledipasvir-sofosbuvir did not provide significant benefit. The approved clinical use for ledipasvir-sofosbuvir is only for genotype 1 chronic HCV-infected adults. Ledipasvir-sofosbuvir does not have a specific indication for HIV-infected persons. Adverse Effects: Available data from clinical trials has demonstrated the combination of ledipasvir-sofosbuvir has been very well tolerated. The most common reported adverse effects are fatigue and headache. Major Drug Interactions: Ledipasvir-sofosbuvir has significant drug-drug interactions with P-gp inducers (e.g., St. John's wort and rifampin). The concomitant use of ledipasvir-sofosbuvir with P-gp inducers is not recommended. Additional drug-drug interactions may occur with ledipasvir-sofosbuvir and other medications and these are detailed in the Ledipasvir-sofosbuvir (Harvoni) Full Prescribing Information. Resistance: In vitro, ledipasvir can select for the primary NS5A mutations Q30E and Y93H with genotype 1a and Y93H with genotype 1b; these mutations confer high-level reduced susceptibility to ledipasvir. In phase 3 trials, the most common mutations detected at failure for genotype 1a were Q30R, Y93H or N, and L31M; with genotype 1b, the most common mutation was Y93H. In vitro, the substitution S282T is associated with a 2- to 18-fold reduced susceptibility to sofosbuvir. The S282T mutation was not detected in any of the lepidasvir-sofosbuvir phase 3 trials. Ledipasvir has excellent in vitro activity against the NS5B S282T mutants. Similarly, sofosbuvir retains full activity against the NS5A ledipasvir-associated mutations. Prescribing Information: Ledipasvir-sofosbuvir (Harvoni) Full Prescribing Information. Summary: The fixed dose combination of ledipasvir-sofosbuvir provides a very attractive and effective one pill once a day option for treatment of genotype 1 chronic hepatitis C infection. This regimen is the first FDA-approved interferon- and ribavirin-free regimen to treat hepatitis C. Three phase 3 trials (ION-1, ION-2, and ION-3) have demonstrated SVR rates consistently above 90%. The 24-week regimen for treatment-experienced cirrhotic patients is very expensive. Although ledipasvir-sofosbuvir is FDA approved only for genotype 1 HCV, it is a recommended therapy for patients with genotype 4, 5, or 6 in the American Association for the Study of Liver Diseases, Infectious Diseases Society of America, and International Antiviral Society USA (AASLD/IDSA/IAS-USA) guidance. In addition, although ledipasvir-sofosbuvir is not specifically FDA-approved for HIV-infected patients, it will likely generate significant interest for use in this arena based on results from the ION-4 trial.