—痛风口服新类药Zurampic（lesinurad）-获美国FDA批准治疗血中高水平尿酸（高尿酸血症）与痛风关联病症 FDA的药品评价和研究中心中肺。过敏和风湿学产品室主任 Badrul Chowdhury，M.D.说："控制高尿酸血症对痛风的长期治疗是至关重要," "Zurampic为在其一生可能发生痛风的百万人们提供一种新治疗选择。" 批准日期：2015年12月22日；公司：AstraZeneca Pharmaceuticals LP ZURAMPIC®(lesinurad)片，供口服使用 美国初次批准：2015 作用机制 Lesinurad通过抑制涉及在肾脏中尿酸再吸收转运蛋白的功能减低血清尿酸水平。Lesinurad 抑制两个负责对尿酸再吸收根尖[apical]转运蛋白的功能，尿酸转运蛋白1(URAT1)和有机阴离子转运蛋白4(OAT4)，有IC50值分别为7.3和3.7μM。URAT1 是负责从肾小管腔被过滤的尿酸的再吸收的多数。OAT4是一个利尿剂-诱导高尿酸血症关联尿酸转运蛋白。Lesinurad与位于近端曲小管细胞的基底侧膜上尿酸再吸收转运蛋白SLC2A9(Glut9)无相互作用。 适应证和用途 ZURAMPIC是一种URAT1抑制剂适用与一种黄嘌呤氧化酶抑制剂联用为与痛风关联高尿酸血症的治疗在患者单独用一种黄嘌呤氧化酶抑制剂未实现目标血清尿酸水平。 使用限制： ⑴ 建议对无症状高尿酸血症的治疗不用ZURAMPIC。 ⑵ ZURAMPIC不应用作单药治疗。 剂量和给药方法 ⑴ ZURAMPIC被推荐在200mg每天1次与一种黄嘌呤氧化酶抑制剂联用，包括别嘌呤醇[allopurinol]或非布索坦[febuxostat]。ZURAMPIC的最大每天剂量是200mg。 ⑵ 未能服用ZURAMPIC与一种黄嘌呤氧化酶抑制剂可能增加肾不良反应风险。 ⑶ ZURAMPIC片应在早晨与食物和水服用。 ⑷应指导患者处于被很好水化。 ⑸ 开始ZURAMPIC前评估肾功能。如eCLcr是低于45mL/min不要开始ZURAMPIC。 ⑹如eCLcr持续地下降低于45mL/min终止ZURAMPIC。 剂型和规格 片：200mg。 禁忌证 严重肾受损，肾病终末期，肾移植受体，或用透析患者。 警告和注意事项 ⑴ 肾事件：ZURAMPIC开始后曽发生肾功能相关不良反应，在400mg剂量观察到较高发生率，用单药治疗发生率最高。用ZURAMPIC治疗开始和期间监视肾功能，尤其是有eCLcr低于60mL/min患者，和评价急性尿酸肾病的体征和症状. ⑵ 心血管事件：用ZURAMPIC观察到重大不良心血管事件；尚未确定因果相互关系。 不良反应 在12-个月对照临床试验中最常见不良反应(发生大于或等于2%用Zurampic治疗与一种黄嘌呤氧化酶抑制剂联用患者和比用单独黄嘌呤氧化酶抑制剂更频)是头痛，流感，血肌酐增加，和胃食管反流病。 药物相互作用 ⑴ 中度细胞色素P450 2C9(CYP2C9)抑制剂：谨慎使用。 ⑵ 敏感CYP3A底物：监视对CYP3A底物的疗效。 特殊人群中使用 ⑴ 肾受损：对有eCLcr低于45mL/min患者建议不使用。 ⑵ 肝受损：建议对有严重肝受损患者不使用。 包装供应 ZURAMPIC片, 200mg是蓝色，椭圆形，凹陷有“LES200”和被供应如下: 5片 | 瓶   NDC号   0310-1475-05 30片| 瓶   NDC号   0310-1475-30 90片| 瓶   NDC号   0310-1475-90 贮存和处置 避光。贮存在20°至25°C(68°至77°F); 外出允许从15°至30°C(59°至86°F)[见USP控制室温]。 Zurampic（lesinurad）200mg tablets是一种口服的选择性的尿酸的再吸收抑制剂-用于组合治疗高尿酸血症与痛风有关疾病。 【原研公司】阿斯利康公司 【国外上市注册、申报情况】 2015年12月22日获FDA批准上市，商品名Zurampic； 2016年2月18日获EMA批准上市，商品名Zurampic 产品特点 1.目前国内高尿酸血症患者的发病率为10%，即约有1.3亿的潜在人群，痛风已成为我国第二大代谢类疾病，越来越受到人们关注。 2.疗效优于非布索坦，副作用少临床试验表明，Lesinurad能剂量依赖性的降低血中尿酸水平，与非布索坦相比，Lesinurad能选择性抑制尿酸盐转运蛋白，不仅能降低尿酸的产生，同时增加尿酸的排泄，本品能明显降低血液中尿酸含量，从而改善痛风症状，预防痛风发作，副作用少，*严重肝脏及心血管副作用，患者难受性好。 临床试验证实，与单用非布索坦相比，所有剂量的Lesinurad与非布索坦联合均可使血尿酸<6 mg/dl的达标率为，而单独用非布索坦不能达标，高剂量的联合则使血尿酸<4mg/dl的达标率达，这能加速改善痛风症状，并加速痛风石的溶解。 Lesinurad与非布索坦的组合疗法能更快的改善痛风症状，减轻患者痛苦，耐受性好， 药物相互作用，有望成为广大痛风患者提供潜在的新治疗选择。 3.新作用机制，临床优势明显利斯拉德有独特的作用机制，本品是URAT1抑制剂，通过调节URAT1转运蛋白的活性，使尿酸分泌正常化，而调节URAT1转运蛋白的活性这一方法被认为是生理上降低尿酸水平的*适当的方法。 临床试验证实，利斯拉德单药治疗以及与黄嘌呤氧化酶（XO）抑制剂均能有效的降低体内血尿酸水平，利斯拉德能显著减少别嘌醇治疗*效的难治性痛风患者的血清尿酸水平，联合疗法的缓解率高达90%，对心电图没有影响，不会影响复极化，心脏安全性好，与KRYSTEXXA（pegloticase，静注）相比，每日一次的给药方案能极大的提高患者依从性，对不同肾功能损害程度的患者而言，利斯拉德的治疗效果不会受到影响。 Zurampic, lesinurad (RDEA594) About ZURAMPIC®(lesinurad)200mg tablets ZURAMPIC®(lesinurad) 200mg tablets inhibits the urate transporter, URAT1, which is responsible for the majority of the renal reabsorption of uric acid. By inhibiting URAT1, ZURAMPIC increases uric acid excretion and thereby lowers serum uric acid (sUA). ZURAMPIC also inhibits organic anion transporter (OAT) 4 a uric acid transporter involved in diuretic-induced hyperuricemia. In addition, in people, ZURAMPIC does not inhibit OAT1 and OAT3, which are drug transporters in the kidney associated with drug-drug interactions. About the ZURAMPIC Development Programme CLEAR1 and CLEAR2 (see prior release on this topic here ) were pivotal Phase III studies that evaluated the efficacy and safety of a once daily dose of ZURAMPIC in combination with allopurinol compared to allopurinol alone. In CLEAR1 and CLEAR2, ZURAMPIC when used in combination with allopurinol, met the primary endpoint in both studies with approximately twice as many patients achieving the serum uric acid (sUA) goal of <6.0mg/dL (360 µmol/L) by month 6, compared to those treated with allopurinol alone. CRYSTAL (see prior release on this topic here ) was a pivotal Phase III study that evaluated the efficacy and safety of a once daily dose of ZURAMPIC in combination with febuxostat 80mg compared to febuxostat 80mg alone in gout patients with tophi (visible deposits of urate crystals in joints and skin). Patients were administered febuxostat 80mg orally once daily for 3 weeks before randomisation. In CRYSTAL, results showed ZURAMPIC 200mg in combination with febuxostat demonstrated greater (nominal p<0.05) sUA lowering to the target for tophaceous gout of <5.0mg/dL (300 µmol/L) compared to febuxostat alone at all months except at the time of the primary endpoint, month 6 (56.6% vs. 46.8%, non significant). In the subgroup of patients with baseline sUA ≥5.0mg/dL (300 µmol/L) (i.e. those above recommended sUA treatment target for tophaceous gout on febuxostat alone), ZURAMPIC 200mg in combination with febuxostat resulted in more subjects reaching target sUA of <5.0mg/dL (300 µmol/L) compared to febuxostat alone at month. In a pooled analysis of the three clinical trials, the safety profile was similar for ZURAMPIC 200mg in combination with an XOI to that of an XOI alone, with the exception of an increased incidence of predominantly reversible serum creatinine (sCr) elevations. About Hyperuricemia and Gout Gout is a serious, chronic, progressive, and debilitating form of inflammatory arthritis that affects more than 15.8 million people in major markets.* The underlying cause of gout is hyperuricemia (elevated sUA), which leads to the deposition of crystals primarily in the joints and in other tissues. This can result in recurrent attacks of inflammatory arthritis and, if left uncontrolled, could lead to chronic, progressive arthritis, and tophus (visible deposits of urate crystals) formation. The goal of sUA lowering treatment is to reduce sUA levels to the target level of <6.0mg/dL (360 µmol/L) as recommended by both the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). In those with greater disease severity and urate burden, such as those with tophi, guidelines recommend lowering sUA to <5.0mg/dL (300 µmol/L) to achieve better disease control. Among patients treated in clinical trials, less than 50% of patients on allopurinol 300mg reached sUA target levels <6.0mg/dL (360 µmol/L). For patients who cannot reach target on an XOI alone, the current ACR and EULAR guidelines recommend adding an agent that increases uric acid excretion. *Major markets include the United States, France, Germany, Italy, Spain, the United Kingdom and Japan