新型丙型肝炎药物Olysio(Simeprevir)获得FDA批准治疗慢性丙型肝炎病毒感染,联合其他药物，用于丙型肝炎病毒（HCV）基因型1和4慢性丙型肝炎（CHC）成人患者的治疗。 FDA的药物评价和研究中心抗微生物产品室主任Edward Cox，M.D.说：“Olysio是第三个被FDA-批准的治疗慢性丙型肝炎病毒感染蛋白酶抑制剂，和提供卫生专业人员和患者对这个严重疾病有一个新，有效治疗”。 优先审评 批准日期：2013年11月22日；公司: Janssen Research & Development, LLC OLYSIO（simeprevir）胶囊，供口服使用 美国首次批准：2013 目前的主要变化 适应症和用法  11/2014 适应症和用法  10/2015 适应证和用法，使用限制  04/2015 剂量和给药方法   11/2014 剂量和给药方法  04/2015 剂量和给药方法  10/2015 禁忌  11/2014 警告和注意事项  04/2015 警告和注意事项  11/2014 适应症和用法 OLYSIO是丙型肝炎病毒（HCV）NS3/4A蛋白酶抑制剂用于治疗慢性丙型肝炎（CHC）基因型1或4的感染治疗作为组合的抗病毒治疗方案的组成部分。 使用限制： OLYSIO单药治疗不推荐。 OLYSIO与聚乙二醇干扰素α和利巴韦林的组合：筛选患者HCV基因型1A感染的病毒与NS3 Q80K多态性的存在，强烈建议，如果检测到与Q80K HCV基因型1A替代疗法应予以考虑。 OLYSIO不建议患者中度或重度肝功能不全（Child-Pugh分级B级或C）。 OLYSIO不建议在谁曾治疗失败对治疗方案，包括OLYSIO或其它HCV蛋白酶抑制剂的患者。 用法用量 一个150毫克胶囊每天服用一次同食。 OLYSIO应施用与其它抗病毒药物为CHC感染的治疗组合。 推荐治疗时间： OLYSIO与聚乙二醇干扰素α和利巴韦林的HCV基因型1或4单感染或HCV /人类免疫缺陷病毒-1（HIV-1）合并感染的患者：12周，随后的12个或36个额外的周聚乙二醇干扰素α和利巴韦林视之前响应状态和HIV-1共同感染​​的存在。 OLYSIO与索非布韦在HCV基因型1单感染患者： 初治或治疗经验的无肝硬化：12周 初治或治疗经验的肝硬化：24周。 用于组合使用OLYSIO其它抗病毒药物的具体剂量的说明，请参见它们各自的处方信息。 剂型和规格 胶囊：150毫克 禁忌 所有禁忌与OLYSIO用于CHC感染的治疗其它抗病毒药物也适用于它们在OLYSIO组合治疗中使用。 警告和注意事项 严重症状心动过缓当联合施用索非布韦和胺碘酮：严重症状的心动过缓，可能会发生在服用胺碘酮与索非布韦结合OLYSIO，特别是在患者的患者还接受β-阻断剂，或那些具有潜在心脏并发症和/或晚期肝病。不推荐用胺碘酮OLYSIO与索非布韦组合的共同施用。在患者没有替代治疗方案，心脏监测建议。 肝功能失代偿和肝功能衰竭：肝功能失代偿和肝功能衰竭，其中包括死亡病例的报道中晚期患者和/或失代偿性肝硬化。监测之前和期间OLYSIO联合治疗肝脏化学试验。 光敏性：在OLYSIO联合治疗严重的光敏反应已经被观察到。使用防晒措施，并限制在OLYSIO联合治疗阳光下曝晒。如果光敏反应发生考虑停药。 皮疹：皮疹已在OLYSIO联合治疗中观察到。如果严重皮疹发生停止OLYSIO。 不良反应 最常见的不良反应（发生率大于20％）： OLYSIO与在第一治疗12周聚乙二醇干扰素α和利巴韦林（具有高至少3％的频率发生，与安慰剂相比）：皮疹（包括光敏性），瘙痒和恶心。 OLYSIO用时12周或24周的治疗索非布韦：疲劳，头痛和恶心。 要报告疑似不良反应，请联系扬森产品，LP 1-800-扬森（1-800-526-7736）或FDA电话1-800-FDA-1088或www.fda.gov/medwatch。 药物相互作用 胺碘酮与索非布韦与OLYSIO组合联合给药，可能会导致严重的症状性心动过缓。 共同给药OLYSIO的药物是中等或强的诱导剂或CYP3A的抑制剂可显著影响simeprevir的血浆浓度。对于药物相互作用的可能性之前，必须先和治疗过程中考虑。 特殊人群中使用 HCV患者/ HIV-1的共感染：安全性和有效性进行了研究。 完整资料附件：http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1816fd68-0ed7-4a37-84bb-e298c5ab6e28 Important Safety Information Contraindications: Contraindications to P/R also apply to OLYSIOTM (simeprevir) combination treatment with P/R. OLYSIOTM in combination with P/R is contraindicated in pregnant women and in men whose female partners are pregnant because of the risks for birth defects and fetal death associated with ribavirin. Refer to the respective prescribing information for a list of the contraindications for P/R. Warnings and Precautions: Embryo-Fetal Toxicity (Use with P/R): Ribavirin may cause birth defects and/or death of the exposed fetus and animal studies have shown that interferons have abortifacient effects. Therefore, extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin therapy should not be started unless a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Refer also to the prescribing information for ribavirin. Female patients of childbearing potential and their male partners, as well as male patients and their female partners, must use two effective contraceptive methods during treatment and for 6 months after completion of treatment. Routine monthly pregnancy tests must be performed during this time. Photosensitivity: Photosensitivity reactions have been observed with OLYSIOTM in combination with P/R, including serious reactions which resulted in hospitalization. Photosensitivity reactions occurred most frequently in the first 4 weeks of treatment with OLYSIOTM in combination with P/R, but can occur at any time during treatment. Photosensitivity may present as an exaggerated sunburn reaction, usually affecting areas exposed to light (typically the face, "V" area of the neck, extensor surfaces of the forearms, and dorsa of the hands). Manifestations may include burning, erythema, exudation, blistering, and edema. Use sun protective measures and limit sun exposure during treatment with OLYSIOTM in combination with P/R. Avoid use of tanning devices during treatment with OLYSIOTM in combination with P/R. Discontinuation of OLYSIOTM should be considered if a photosensitivity reaction occurs and patients should be monitored until the reaction has resolved. If a decision is made to continue OLYSIOTM in the setting of a photosensitivity reaction, expert consultation is advised. Rash: Rash has been observed in subjects receiving OLYSIOTM in combination with P/R. Rash occurred most frequently in the first 4 weeks of treatment with OLYSIOTM in combination with P/R, but can occur at any time during treatment. Severe rash and rash requiring discontinuation of OLYSIOTM have been reported. Most of the rash events in OLYSIOTM-treated patients were of mild or moderate severity. Patients with mild to moderate rashes should be followed for possible progression of rash, including the development of mucosal signs (e.g., oral lesions, conjunctivitis) or systemic symptoms. If the rash becomes severe, OLYSIOTM should be discontinued. Patients should be monitored until the rash has resolved. Sulfa Allergy: OLYSIOTM contains a sulfonamide moiety. In subjects with a history of sulfa allergy (n=16), no increased incidence of rash or photosensitivity reactions has been observed. However, there are insufficient data to exclude an association between sulfa allergy and the frequency or severity of adverse reactions observed with the use of OLYSIOTM. Use with P/R: OLYSIOTM must not be used as monotherapy. OLYSIOTM should be used in combination with both P/R. Therefore the prescribing information for P/R must be consulted before starting therapy with OLYSIOTM. Contraindications and Warnings and Precautions related to P/R also apply to OLYSIOTM combination treatment with P/R. Drug Interactions: Co-administration of OLYSIOTM with substances that are moderate or strong inducers or inhibitors of cytochrome P450 3A (CYP3A) is not recommended as this may lead to significantly lower or higher exposure of simeprevir, respectively. Adverse Reactions: In pooled Phase 3 studies, adverse reactions (all grades, at least 3% higher frequency) for OLYSIOTM with P/R vs. P/R alone in the first 12 weeks were rash (including photosensitivity) (28% vs. 20%), pruritus (22% vs. 15%), nausea (22% vs. 18%), myalgia (16% vs. 13%), and dyspnea (12% vs. 8%). Use in Specific Populations: Race: Patients of East Asian ancestry exhibit higher simeprevir exposures. In clinical trials, higher simeprevir exposures have been associated with increased frequency of adverse reactions, including rash and photosensitivity. There are insufficient safety data to recommend an appropriate dose for patients of East Asian ancestry. The potential risks and benefits of OLYSIOTM should be carefully considered prior to use in patients of East Asian ancestry. Renal Impairment: No dose adjustment of OLYSIOTM is required in patients with mild, moderate or severe renal impairment. The safety and efficacy of OLYSIOTM have not been studied in HCV-infected patients with severe renal impairment (creatinine clearance below 30 mL/min) or end-stage renal disease, including patients requiring dialysis. Simeprevir is highly protein-bound; therefore, dialysis is unlikely to result in significant removal of simeprevir. Refer to the respective prescribing information for P/R regarding use in patients with renal impairment. Hepatic Impairment: No dose adjustment of OLYSIOTM is required in patients with mild hepatic impairment (Child-Pugh Class A); no dose recommendation can be given for patients with moderate or severe hepatic impairment (Child-Pugh Class B or C) due to higher simeprevir exposures. In clinical trials, higher simeprevir exposures have been associated with increased frequency of adverse reactions, including rash and photosensitivity. The safety and efficacy of OLYSIOTM have not been studied in HCV-infected patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). The combination of P/R is contraindicated in patients with decompensated cirrhosis (moderate or severe hepatic impairment). The potential risks and benefits of OLYSIOTM should be carefully considered prior to use in patients with moderate or severe hepatic impairment. Other HCV Genotypes: The safety and efficacy of OLYSIOTM in combination with P/R has not been established in patients with other HCV genotypes. Liver Transplantation: The safety and efficacy of OLYSIOTM alone or in combination with P/R have not been studied in liver transplant patients. 2013年11月25日，丙肝新药OLYSIO（simeprevir）已获FDA批准，联合聚乙二醇干扰素和利巴韦林（ribavirin），用于基因型1慢性丙型肝炎成人患者代偿性肝脏疾病（包括肝硬化）的治疗。 此前，FDA已于今年5月授予simeprevir新药申请（NDA）优先审查资格，同时该药于今年10月获得了FDA顾问委员会建议批准的积极意见。 Simeprevir监管文件的提交，部分由3个关键性III期临床试验数据支持：QUEST-1和QUEST-2在初治患者中开展，PROMISE则在基于干扰素疗法治疗后复发的患者中开展。 丙型肝炎（HCV）是一种血源性传染性肝脏疾病，若不及时治疗，可能对肝脏造成重大损害。在美国，约有320万丙型肝炎患者，每年约有1.5万人死于该病，大多死于丙型肝炎相关疾病，如肝硬化和肝癌。 关于OLYSIO（simeprevir）： Simeprevir是新一代NS3/4A蛋白酶抑制剂，为每日一次的口服药物，由Medivir公司和杨森（Janssen）联合开发，用于治疗慢性丙型肝炎成年患者的代偿性肝病，包括各个阶段的肝纤维化，其工作原理是通过阻断蛋白酶，来抑制HCV在肝脏细胞中的复制。 今年9月，simeprevir（在日本的商品名为Sovriad）获日本劳动卫生福利部（MHLW）批准，与聚乙二醇化干扰素和利巴韦林（ribavirin）联合用药，用于基因型-1慢性丙型肝炎病毒（HCV）感染者的治疗，这是simeprevir获得的全球首个监管批准。 simeprevir是一种新的直接作用抗病毒药物，也是第二代蛋白酶抑制剂，给药方式为：simeprevir+聚乙二醇干扰素+利巴韦林联合治疗12周，随后进行聚乙二醇干扰素+利巴韦林治疗12周或36周。