英文药名：Krystexxa(Pegloticase Injection) 中文药名：聚乙二醇重组尿酸酶注射剂 生产厂家：SAVIENT PHARMS 药品介绍 KRYSTEXXA（聚乙二醇重组尿酸酶 pegloticase）注射剂，用于静脉输注 美国首次批准：2010年 警告： 分析和输注反应请参阅完整的处方信息以获取完整的警告。 据报道在KRYSTEXXA给药期间和之后发生过敏反应和输注反应。 KRYSTEXXA应在医疗保健场所和准备管理过敏反应和输液反应的医疗保健提供者管理。 患者应该预先服用抗组胺药和皮质类固醇。 在施用KRYSTEXXA后，应当对患者进行密切监测一段适当的过敏反应时间。 在输注前监测血清尿酸水平，如果水平增加至6mg/dL以上，特别是当观察到高于6mg/dL的2个连续水平时，考虑停止治疗。 近期主要变化 剂量和管理，管理 4/2012 警告和注意事项，过敏 4/2012 警告和注意事项，输液反应 4/2012 作用机制 KRYSTEXXA是一种尿酸特异性酶，是一种重组尿酸酶，通过催化尿酸氧化成尿囊素，从而降低血清尿酸，达到治疗效果。尿囊素是一种惰性和水溶性嘌呤代谢物。它容易被消除，主要是通过肾脏排泄。 适应症和用法 KRYSTEXXA®（聚乙二醇重组尿酸酶）是一种聚乙二醇化尿酸特异性酶，用于治疗常规治疗难治的成人患者的慢性痛风。 重要使用限制： KRYSTEXXA不推荐用于治疗无症状高尿酸血症。 剂量和给药 对于成年患者8mg，每两周静脉输注。 不要作为静脉推注或推注给药。 在开始KRYSTEXXA之前停止口服降低尿酸的药物 每次输注前监测血清尿酸水平。 患者应该预先服用抗组胺药和皮质类固醇。 管理在医疗保健设置由医疗保健提供者准备管理过敏反应。 KRYSTEXXA混合物只能通过重力进给，注射泵或输液泵静脉输注不少于120分钟。 剂量形式和强度 1mL稀释的无菌浓缩物，含有8mg聚乙二醇重组尿酸酶蛋白，以尿酸酶蛋白量表示。 禁忌症 葡萄糖-6-磷酸脱氢酶（G6PD）缺乏：在开始KRYSTEXXA之前，由于溶血和高铁血红蛋白血症的风险，应当筛选具有G6PD缺乏的高风险（例如，非洲和地中海血统的风险）的患者。 警告和注意事项 过敏反应：用KRYSTEXXA治疗的患者发生过敏反应。任何输注可发生过敏反应，包括第一次输注，并且通常在输注的2小时内显现。然而，还报道了迟发型超敏反应。KRYSTEXXA应在医疗保健场所和准备管理过敏反应的医疗保健提供者管理。患者应该预先服用抗组胺药和皮质类固醇。在施用KRYSTEXXA后，应当对患者进行密切监测一段适当的过敏反应时间。 输液反应：用KRYSTEXXA治疗的患者发生输液反应。KRYSTEXXA应在医疗保健场所和准备管理输液反应的医疗保健提供者管理。 患者应该预先服用抗组胺药和皮质类固醇。密切监测患者输液反应的体征和症状。在输注反应的情况下，输注应该被减慢，或停止并以较慢的速率重新启动。如果发生严重的输注反应，则停止输注并根据需要进行治疗。输注反应的风险在失去治疗反应的患者中较高。 痛风耀斑：在开始抗高尿酸血症治疗（包括用KRYSTEXXA治疗）时经常观察到痛风发作的增加。如果治疗期间出现痛风，KRYSTEXXA不需要停止。至少在治疗的前6个月推荐痛风预防（即，非甾体抗炎药（NSAID）或秋水仙碱），除非医学上禁忌或不耐受。 充血性心力衰竭：KRYSTEXXA尚未在充血性心力衰竭患者中正式研究，但一些临床试验中的患者发生了加重。在充血性心力衰竭患者中使用KRYSTEXXA时要小心，并在输液后密切监测患者。 不良反应 最常见的不良反应（发生在KRYSTEXXA治疗的患者的至少5％中）是痛风发作，输注反应，恶心，挫伤或瘀斑，鼻咽炎，便秘，胸痛，过敏反应和呕吐。 供应/存储和处理 提供 KRYSTEXXA是一种在磷酸盐缓冲盐水中的透明无色无菌溶液，用于稀释后静脉输注。 KRYSTEXXA在一次性使用的2mL玻璃小瓶中提供，带有Teflon®涂层（无胶乳）橡胶注射塞，可提供KRISTEXXA 8mg尿酸酶蛋白1mL体积。 存储和处理 在使用前，KRYSTEXXA必须储存在纸箱中，并在2°C至8°C（36°F至46°F）之间的任何时候保持冷藏。 防光。 不要摇晃或冻结。 不要在超过有效期限后使用。 NDC：54396-801-01 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5f4574d1-401f-4647-83e5-28c0f4a122a7 --------------------------------------------------------- 【原产地英文商品名】KRYSTEXXA 8mg/ml/vial 【原产地英文药品名】PEGLOTICASE 【中文参考商品译名】KRYSTEXXA 8毫克/毫升/瓶 【中文参考药品译名】聚乙二醇重组尿酸酶 【生产厂家中文参考译名】SAVIENT PHARMS 【生产厂家英文名】SAVIENT PHARMS Pegloticase（KRYSTEXXA™）是聚乙二醇化的尿酸酶，用于传统治疗无效的慢性痛风 Pegloticase是静脉注射药物 美国FDA批准了Savient Pharmaceuticals公司的Krystexxa (pegloticase)用于治疗那些使用现有疗法难以治疗的成人慢性痛风患者。 痛风是由于人体尿酸盐过多导致，人体内尿酸太多时，会在关节或软组织处形成结晶，从而引起关节处间歇性的红肿、热、痛或僵硬等症状。痛风的发生与肥胖、高血压、高血脂、糖尿病等有密切联系，常见于男性、绝经后女性及患有肾病的人群中。 常规的治疗痛风的方法是通过用药降低患者体内的尿酸盐水平， Krystexxa (pegloticase)是一种酶，通过将尿酸降解为无毒的产物随尿液排出体外，达到降低尿酸水平的作用。经过对212例患者6个月的临床试验，证明了该药物的有效性。 但由于四分之一的病人在接受新药后会有严重的过敏反映，因此建议医疗人员在使用该药物时可适当联合使用皮质类固醇及抗组胺药，来降低过敏反应的症状。其他副作用还有痛风发作、头晕、注射部位肿起、过敏、便秘、胸部疼痛及呕吐等。 另外内科医生提醒，该药物在给伴有充血性心力衰竭的患者使用时应当特别注意，因为还没有这类人群的用药分析数据。 KRYSTEXXA(PEGLOTICASE)INJECTABLE INJECTION KRYSTEXXA is the first and only FDA-approved medicine for chronic refractory gout, a type of arthritis that occurs when uric acid build up in the blood remains high and inflammation persists even after treatment with conventional therapies. According to estimates, chronic refractory gout impacts approximately 50,000 people in the United States.1 Indications and Usage KRYSTEXXA (pegloticase) is a PEGylated uric acid specific enzyme indicated for the treatment of chronic gout in adult patients refractory to conventional therapy. Gout refractory to conventional therapy occurs in patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated. Important Limitations of Use KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia IMPORTANT SAFETY INFORMATION INDICATION KRYSTEXXA® (pegloticase) is a PEGylated uric acid–specific enzyme indicated for the treatment of chronic gout in adult patients refractory to conventional therapy. Gout refractory to conventional therapy occurs in patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated. Important Limitations of Use: KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia. WARNING: ANAPHYLAXIS AND INFUSION REACTIONS •Anaphylaxis and infusion reactions have been reported to occur during and after administration of KRYSTEXXA. •Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours of the infusion. However, delayed-type hypersensitivity reactions have also been reported. •KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions. •Patients should be premedicated with antihistamines and corticosteroids. •Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA. •Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed. CONTRAINDICATIONS •Glucose-6-phosphate dehydrogenase (G6PD) Deficiency: Before starting KRYSTEXXA, confirm patients are not G6PD deficient. Patients at higher risk for G6PD deficiency (e.g., those of African and Mediterranean ancestry) should be screened because of the risk of hemolysis and methemoglobinemia, however any patient could be affected. WARNINGS AND PRECAUTIONS •Anaphylaxis: Anaphylaxis occurred in patients treated with KRYSTEXXA. Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours of the infusion. However, delayed-type hypersensitivity reactions have also been reported. KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis. Patients should be premedicated with antihistamines and corticosteroids. Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA. •Infusion Reactions: Infusion reactions occurred in patients treated with KRYSTEXXA. KRYSTEXXA should be administered in a healthcare setting and by healthcare providers prepared to manage infusion reactions. Patients should be premedicated with antihistamines and corticosteroids. Monitor patients closely for signs and symptoms of infusion reactions. In the event of an infusion reaction, the infusion should be slowed, or stopped and restarted at a slower rate. If a severe infusion reaction occurs, discontinue infusion and institute treatment as needed. The risk of an infusion reaction is higher in patients who have lost therapeutic response. ◦Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed. ◦Concomitant use of KRYSTEXXA and oral urate-lowering agents may blunt the rise of serum uric acid levels. It is recommended that patients discontinue oral urate-lowering agents and not institute therapy with oral urate-lowering agents while taking KRYSTEXXA. •Gout Flares: An increase in gout flares is frequently observed upon initiation of antihyperuricemic therapy, including treatment with KRYSTEXXA. If a gout flare occurs during treatment, KRYSTEXXA need not be discontinued. Gout flare prophylaxis with a nonsteroidal anti-inflammatory drug (NSAID) or colchicine is recommended starting at least 1 week before initiation of KRYSTEXXA therapy and lasting at least 6 months, unless medically contraindicated or not tolerated. •Congestive Heart Failure: KRYSTEXXA has not been formally studied in patients with congestive heart failure, but some patients in clinical trials experienced exacerbation. Exercise caution when using KRYSTEXXA in patients who have congestive heart failure, and monitor patients closely following infusion. •Re-treatment: No controlled clinical data is available on the safety and efficacy of re-treatment with KRYSTEXXA after stopping treatment for longer than 4 weeks. Patients receiving re-treatment may be at increased risk for anaphylaxis and infusion reactions and should be monitored carefully. ADVERSE REACTIONS The most commonly reported serious adverse reactions in the pivotal trial with the approved regimen of 8 mg KRYSTEXXA administered every 2 weeks were gout flares, infusion reactions, and anaphylaxis. Most common adverse reactions: gout flares (77%), infusion reactions (26%), nausea (12%), contusion or ecchymosis (11%), nasopharyngitis (7%), constipation (6%), chest pain (6%), anaphylaxis (5%), and vomiting (5%). In addition to events occurring in greater than 5%, exacerbation of pre-existing congestive heart failure occurred in 2%.