2013年8月12日，FDA批准Tivicay50mg片剂。Tivicay为每日一次的口服药物，是HIV整合酶抑制剂，旨在与其他抗逆转录病毒制剂联合用于既往已治疗过、或初治HIV-1成人和12岁及以上体重至少40千克儿童感染者。 Tivicay是一种整合酶链转移抑制剂干扰HIV繁殖所需酶之一。它是每天与其他抗病毒药物联用的服用药丸。 Tivicay被批准在宽广HIV感染患者群中使用。可用于治疗从未用过HIV治疗的HIV-感染成年(未治疗过)和HIV-感染成年既往曾用 HIV治疗 (经受过治疗)，包括曾用其他整合酶链转移抑制剂治疗过患者。Tivicay还被批准为年龄12岁和以上体重至少40公斤，未治疗过或经受过治疗的儿童但是既往未曾用过整合酶链转移抑制剂。 美国FDA药物评价和研究中心抗微生物产品室主任Edward Cox，M.D.，M.P.H. 说：“HIV-感染个体需要治疗方案个体化以配合其情况和他们的需求，”“对FDA批准新药像Tivicay增加已存在选择方案仍是优先政策。” 根据美国疾病控制和预防中心：每年约50,000美国人成为受HIV感染者和约2010年约15,500 死于该病。 在四项临床试验纳入2,539例参加者中评价Tivicay的安全性和疗效。依赖于试验，参加者被随机赋予接受Tivicay或Isentress (拉替拉韦[raltegravir])，各与其他抗病毒药联用，或Atripla，一个固定剂量的依非韦伦[efavirenz]，恩曲他滨[emtricitabine]和替诺福韦[tenofovir]联用。结果显示含Tivicay方案有效减低病毒负荷。 第五项试验作为对年龄12岁和以上及体重至少40公斤既往未用过整合酶链转移抑制剂HIV感染儿童，治疗方案的一部分，确定Tivicay的药代动力学，安全性和活性。 在临床研究期间观察到常见副作用包括难以睡眠(失眠)和头痛。严重副作用包括超敏性反应和在合并乙型和/或丙型肝炎参加者异常肝功能。Tivicay说明书给建议监视患者严重副作用。 Tivicay由总部在北卡罗来纳三角研究园GlaxoSmithKline制造。Isentress是由总部Merck白宫站上市而Atripla由总部加州旧金山Gilead。 TIVICAY (DOLUTEGRAVIR SODIUM) TABLET Pharmacological Class: HIV-1 integrase strand transfer inhibitor (INSTI). Active Ingredient(s): Dolutegravir 50mg; tablets. Company ViiV Healthcare Indication(s): In combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and children ≥12 years and ≥40kg. Pharmacology: Dolutegravir inhibits HIV-1 integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle. Clinical Trials: The efficacy of Tivicay was based on analyses of data from two trials, SPRING-2 and SINGLE, in treatment-naïve, HIV-1-infected subjects (n=1,641); one trial, SAILING, in treatment-experienced, INSTI-naïve HIV-1-infected subjects (n=715); and from VIKING-3 trial in INSTI-­experienced ­HIV-1-infected subjects (n=183) with virological failure and current or historical evidence of raltegravir and/or elvitegravir resistance. In the SPRING-2 trial, once-daily Tivicay versus twice-daily raltegravir in 822 HIV-infected, treatment-naïve patients, both in combination with a fixed-dose dual-NRTI treatment were evaluated. At week 48, the proportion of subjects who were virologically suppressed (HIV-1 RNA <50 copies/mL) was 88% for the regimen containing Tivicay and 86% for the regimen containing raltegravir, meeting the 10% non-inferiority criteria. In the SINGLE trial, once-daily Tivicay plus fixed-dose Epzicom versus the fixed-dose Atripla regimen in 833 HIV-infected, treatment-naïve patients were evaluated. At 48 weeks, the proportion of subjects who were virologically suppressed (HIV-1 RNA <50 copies/mL) was 88% for Tivicay regimen and 81% for Atripla which was statistically significant. For more information on clinical trials, see full labeling. Legal Classification: Rx Adults: ≥12 years and ≥40kg: treatment-naïve or treatment-experienced INSTI-naïve: 50mg once daily. Treatment-naïve or treatment-experienced INSTI-naïve with concomitant potent UGT1A/CYP3A inducers (eg, efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin): 50mg twice daily. INSTI-experienced with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance: 50mg twice daily. Children: <12 years or <40kg, or INSTI-experienced with documented or clinically suspected resistance to other INSTIs (raltegravir, elvitegravir): not established. Contraindication(s): Concomitant dofetilide. Warnings/Precautions: Discontinue if hypersensitivity reactions develop. Increased risk for worsening/development of elevated transaminases in patients with hepatitis B or C; monitor LFTs prior to starting and during therapy. Severe hepatic impairment: not recommended. INSTI-experienced patients (with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance) with severe renal impairment: decrease in dolutegravir concentrations may result in loss of efficacy and development of resistance. Pregnancy (Category B). Nursing mothers: not recommended. Interaction(s) May be affected by drugs that induce or inhibit UGT1A1, UGT1A3, UGT1A9, BCRP, and P-gp enzymes or transporters. Avoid concomitant nevirapine, oxcarbazepine, phenytoin, phenobarbital, carbamazepine, St. John’s wort. Avoid etravirine unless coadministered with atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. Concomitant efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin: adjust dose to 50mg twice daily. Concomitant cation-containing antacids, laxatives, sucralfate, oral iron/calcium supplements, and buffered drugs: give dolutegravir 2 hours before or 6 hours after. Concomitant metformin; monitor closely and adjust metformin dose if necessary. Adverse Reaction(s) Insomnia, headache; immune reconstitution syndrome, lab abnormalities. How Supplied: Tabs—30 LAST UPDATED: 8/30/2013 葛兰素史克HIV新药Tivicay获欧盟批准 2014年1月22日，葛兰素史克（GSK）、辉瑞（Pfizer）、盐野义（Shionogi）共同成立的HIV/AIDS合资企业ViiV Healthcare 1月21日宣布，HIV新药Tivicay（dolutegravir，50mg片剂）获欧盟委员会（EC）批准，联合其他抗逆转录病毒药物用于HIV成人感染者和12岁以上青少年感染者的治疗。 Tivicay的获批，是基于4个关键性III期临床试验（SPRING-2、SINGLE、SAILING、VIKING-3）的安全性和疗效数据。 Tivicay已于2013年8月获FDA批准，并于2013年10月获加拿大卫生部批准，联合其他抗逆转录病毒制剂，用于既往已治疗过、或初治HIV-1成人和12岁及以上体重至少40千克儿童感染者。 2016年Tivicay成主流 此前，独立分析公司Datamonitor Healthcare发布报告指出，Tivicay若获欧盟批准，必将对全球HIV市场产生巨大的影响，到2016年，Tivicay必将成为HIV治疗的主流整合酶抑制剂） Tivicay疗效优于Prezista或Isentress 在临床试验中，Tivicay疗效优于强生（JNJ）的蛋白酶抑制剂Prezista（darunavir，地瑞那韦），同时与当前的标准护理药物整合酶抑制剂Isentress（raltegravir，拉替拉韦）疗效相当。Isentress由默沙东（Merck & Co）开发。 Datamonitor Healthcare分析师Joseph Hedden称，Tivicay与其他一些竞争药物不同，该药不需要与药物促进剂联合用药，同时也具有一个非常有吸引力的耐药属性。在接下来几年里，以整合酶抑制剂销售额计算，这些属性将推动Tivicay至排名第一的位置。 关于Tivicay（dolutegravir）： Tivicay为每日一次的口服药物，是HIV整合酶抑制剂，旨在与其他抗逆转录病毒制剂联合用于既往已治疗过、或初治HIV-1成人和12岁及以上体重至少40千克儿童感染者。 关于III期临床项目： SPRING-2：在822例HIV感染者中开展，评价了每天1次Tivicay与每天2次raltegravir（拉替拉韦）与一种固定剂量双NRTI疗法联合治疗的疗效。48周时，含Tivicay方案有88%的患者实现病毒学抑制（HIV-1 RNA<50 c/ml），含raltegravir方案为86%，达到了10%的非劣性标准。 SINGLE：在833例初治HIV感染者中开展，评价了每天1次Tivicay+阿巴卡韦/拉米夫定相对于单一片剂Atripla的疗效。48周时，含Tivicay方案有88%的患者实现病毒学抑制（HIV-1 RNA<50 c/ml），Atripla方案为81%，数据具有统计学显着差异。Tivicay方案组有2%患者因不良事件中止治疗，Atripla方案组为10%。 SAILING：在719例经当前疗法治疗失败但未使用整合酶抑制剂治疗的患者中开展，评价了每天1次Tivicay和每天2次raltegravir（拉替拉韦）结合一种背景方案（2种制剂，其中至少1种完全活性剂）的疗效。24周时，含Tivicay方案有79%的患者实现病毒学抑制（HIV-1 RNA<50 c/ml），含raltegravir方案为70%，数据具有统计学显着差异。 VIKING-3：在183例正在接受治疗、且HIV已对数类HIV药物（包括整合酶抑制剂雷特格韦和/或elvitegravir）的成人感染者中开展。该项研究中，背景方案中添加Tivicay治疗7天后，HIV RNA水平下降达1.4 log10 c/ml。24周时，添加Tivicay方案有63%的患者实现病毒学抑制（HIV-1 RNA<50 c/ml）。 Tivicay用于12岁及以上、体重至少40千克儿童的适应症申请，是基于一项多中心、开发标签试验的安全性、药代动力学、药效评价数据。该项研究在既往未接受过整合酶抑制剂治疗的患者中开展。 TIVICAY Rx Generic Name and Formulations: Dolutegravir 50mg; tablets. Company: ViiV Healthcare Indications for TIVICAY: In combination with other antiretroviral agents for the treatment of HIV-1 infection. Adult Dose for TIVICAY: ≥12 years and ≥40kg: treatment-naïve or treatment-experienced INSTI-naïve: 50mg once daily. Treatment-naïve or treatment-experienced INSTI-naïve with concomitant potent UGT1A/CYP3A inducers (eg, efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin): 50mg twice daily. INSTI-experienced with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance: 50mg twice daily. Children's Dose for TIVICAY: <12 years or <40kg, or INSTI-experienced with documented or clinically suspected resistance to other INSTIs (raltegravir, elvitegravir): not established. Pharmacological Class: HIV-1 integrase strand transfer inhibitor (INSTI). Contraindications: Concomitant dofetilide. Warnings/Precautions: Discontinue if hypersensitivity reactions develop. Increased risk for worsening/development of elevated transaminases in patients with hepatitis B or C; monitor LFTs prior to starting and during therapy. Severe hepatic impairment: not recommended. INSTI-experienced patients (with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance) with severe renal impairment: decrease in dolutegravir concentrations may result in loss of efficacy and development of resistance. Pregnancy (Cat. B). Nursing mothers: not recommended. Interactions: May be affected by drugs that induce or inhibit UGT1A1, UGT1A3, UGT1A9, BCRP, and P-gp enzymes or transporters. Avoid concomitant nevirapine, oxcarbazepine, phenytoin, phenobarbital, carbamazepine, St. John’s wort. Avoid etravirine unless coadministered with atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. Concomitant efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin: adjust dose to 50mg twice daily. Concomitant cation-containing antacids, laxatives, sucralfate, oral iron/calcium supplements, and buffered drugs: give dolutegravir 2 hours before or 6 hours after. Concomitant metformin; monitor closely and adjust metformin dose if necessary. Adverse Reactions: Insomnia, headache; immune reconstitution syndrome, lab abnormalities. How Supplied: Tabs—30