美国FDA批准eltrombopag（Promacta）上市，用于治疗经糖皮质激素类药物、免疫球蛋白治疗无效或脾切除术后慢性特发性血小板减少性紫癜（ITP）患者的血小板减少。 批准日期：2008年11月20日；公司：GlaxoSmithKline，NOVARTIS PROMACTA（艾曲波帕 eltrombopag olamine）片剂 仅供口服使用 最初美国批准：2008 警告： 危险的肝毒性 请参阅完整的黑框警告的完整处方信息 PROMACTA可能引起肝毒性： ●测量血清丙氨酸转氨酶（ALT），天冬氨酸转氨酶（AST），胆红素之前PROMACTA，在剂量调整阶段，每2周和月以下建立了稳定的剂量开始。如果胆红素升高时，执行分级分离。 ●评估于3〜5天重复检测异常血清肝功能，如果异常被证实，监测血清肝功能每周直到异常（IES）解决，稳定或恢复到基线水平。 ●终止PROMACTA如果ALT水平增加至≥3X标准上限（ULN）的上限是： ●进取，或 ●迁延≥4周，或 ●伴随着提高直接胆红素，或 ●伴随着肝损伤或证据，肝功能失代偿的临床症状。 作用机序 艾曲波帕是一种口服生物可利用的，小分子的TPO受体激动剂，其与人TPO受体的跨膜结构域相互作用，并引发诱导骨髓祖细胞的巨核细胞的增殖和分化的信号级联。 适应症和用法 PROMACTA为慢性免疫（特发性）谁不得不皮质激素，免疫球蛋白，或脾切除一个响应不足血小板减少性紫癜的治疗血小板减少症的指示的血小板生成素受体激动剂。 PROMACTA只应在ITP患者的血小板减少症的程度和临床病症增加出血风险。PROMACTA不应以试图正常化血小板计数被用于使用。 用法用量 PROMACTA的起始剂量为50毫克，每天一次，对大多数患者;东亚血统的患者或患者的中度或重度肝功能不全时，起始剂量为25毫克，每天一次。 给空腹（1小时或2小时饭后）。 允许PROMACTA和其他药物，食品，或含多价阳离子（例如，铁，钙，铝，镁，硒和锌）补充剂之间有4小时的时间间隔。 调整每日剂量以实现并维持血小板，以减少出血的危险计数≥50×109/L 不要超过75毫克每日剂量。 停止PROMACTA如果血小板计数不4周后在最大剂量的增加，也停止PROMACTA重要肝脏检查异常或过度的血小板计数反应。 剂型和规格 25毫克和50毫克片剂，每个片剂，用于口服给药的，包含艾曲波帕，相当于25毫克或艾曲波帕游离酸的50毫克。 禁忌症 无。 警告和注意事项 PROMACTA可能引起肝毒性，观察血清转氨酶水平和胆红素的增加，肝化学必须治疗开始之前定期处理期间进行测量和。 以肝损伤患者服用时请务必小心。 PROMACTA是血小板生成素受体激动剂和TPO受体激动剂增加的发展或骨髓内网硬蛋白纤维沉积的进展的风险。监测外周血为骨髓纤维化的迹象。 停止可能会导致恶化血小板比是治疗之前存在。监测每周全血计数（CBCS），包括血小板计数为停药后至少4周。 剂量过大PROMACTA可以增加血小板计数，以产生血栓/血栓栓塞性并发症的水平。 PROMACTA可能增加恶性血液病的风险，尤其是在患者的骨髓增生异常综合征。 监视CBCS，包括血小板计数和外周血涂片，在治疗的与PROMACTA剂量调整阶段每周然后每月以下建立PROMACTA的稳定剂量的。 由于肝毒性和其他风险的风险，PROMACTA只能通过受限制的分配方案，要在限制销售计划招收，PROMACTA思虑，叫1-877-9-PROMACTA。 不良反应 最常见的不良反应（在超过1例接受PROMACTA并以较高的速率在PROMACTA发生与安慰剂）是：恶心，呕吐，月经过多，肌痛，感觉异常，白内障，消化不良，瘀斑，血小板减少，增加的ALT/AST和结膜出血。 药物相互作用 艾曲波帕是OATP1B1转运的抑制剂。密切监测患者的体征和过度暴露于那些OATP1B1底物的药物的症状（例如，瑞舒伐他汀），并考虑减少这些药物的剂量。 多价阳离子（例如，铁，钙，铝，镁，硒和锌）显著减少艾曲波帕的吸收; PROMACTA必须在4个小时的任何药物或含有多价阳离子如抗酸剂，乳制品，和矿物制品内可采取补充剂。 在使用特定PO。 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use PROMACTA safely and effectively. See full prescribing information for PROMACTA. PROMACTA (eltrombopag) tablets, for oral use Initial U.S. Approval: 2008 DESCRIPTION PROMACTA (eltrombopag) Tablets contain eltrombopag olamine, a small molecule thrombopoietin (TPO) receptor agonist for oral administration. Eltrombopag interacts with the transmembrane domain of the TPO receptor (also known as cMpl) leading to increased platelet production. Each tablet contains eltrombopag olamine in the amount equivalent to 12.5 mg, 25 mg, 50 mg, or 75 mg of eltrombopag free acid. CLINICAL PHARMACOLOGY Mechanism of Action Eltrombopag is an orally bioavailable, small-molecule TPO-receptor agonist that interacts with the transmembrane domain of the human TPO-receptor and initiates signaling cascades that induce proliferation and differentiation of megakaryocytes from bone marrow progenitor cells. Pharmacokinetics: Absorption: Eltrombopag is absorbed with a peak concentration occurring 2 to 6 hours after oral administration. Based on urinary excretion and biotransformation products eliminated in feces, the oral absorption of drug-related material following administration of a single 75 mg solution dose was estimated to be at least 52%. An open-label, randomized, crossover study was conducted to assess the effect of food on the bioavailability of eltrombopag. A standard high-fat breakfast significantly decreased plasma eltrombopag AUC0-8 by approximately 59% and Cmax by 65% and delayed tmax by 1 hour. The calcium content of this meal may have also contributed to this decrease in exposure. Distribution: The concentration of eltrombopag in blood cells is approximately 50% to 79% of plasma concentrations based on a radiolabel study. In vitro studies suggest that eltrombopag is highly bound to human plasma proteins (>99%). Eltrombopag is a substrate of BCRP, but is not a substrate for P-glycoprotein (P-gp) or OATP1B1. Metabolism: Absorbed eltrombopag is extensively metabolized, predominantly through pathways including cleavage, oxidation, and conjugation with glucuronic acid, glutathione, or cysteine. In vitro studies suggest that CYP1A2 and CYP2C8 are responsible for the oxidative metabolism of eltrombopag. UGT1A1 and UGT1A3 are responsible for the glucuronidation of eltrombopag. Elimination: The predominant route of eltrombopag excretion is via feces (59%), and 31% of the dose is found in the urine. Unchanged eltrombopag in feces accounts for approximately 20% of the dose; unchanged eltrombopag is not detectable in urine. The plasma elimination half-life of eltrombopag is approximately 21 to 32 hours in healthy subjects and 26 to 35 hours in ITP patients. INDICATIONS AND USAGE PROMACTA is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Limitations of use: --PROMACTA should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. --PROMACTA should not be used in an attempt to normalize platelet counts CONTRAINDICATIONS None. PRECAUTIONS WARNINGS AND PRECAUTIONS --PROMACTA may cause hepatotoxicity. Increases in serum aminotransferase levels and bilirubin were observed. Liver chemistries must be measured before the initiation of treatment and regularly during treatment. --Thrombotic/thromboembolic complications may result from increases in platelet counts with PROMACTA. Portal vein thrombosis has been reported in patients with chronic liver disease receiving PROMACTA. Monitor platelet counts regularly. --Monitor CBCs with differentials (including platelet counts) weekly during the dose adjustment phase of therapy with PROMACTA and then monthly following establishment of a stable dose of PROMACTA. DRUG INTERACTIONS --Eltrombopag is an inhibitor of OATP1B1 and BCRP transporters. Monitor patients closely for signs and symptoms of excessive exposure to the drugs that are substrates of OATP1B1 and BCRP (e.g., rosuvastatin) and consider reduction of the dose of these drugs. --Polyvalent cations (e.g., iron, calcium, aluminum, magnesium, selenium, and zinc) significantly reduce the absorption of eltrombopag; PROMACTA must not be taken within 4 hours of any medications or products containing polyvalent cations such as antacids, dairy products, and mineral supplements. USE IN SPECIFIC POPULATIONS --Pregnancy: PROMACTA may cause fetal harm. Enroll pregnant patients in the PROMACTA pregnancy registry by calling 1-888-825-5249. --Nursing Mothers: A decision should be made to discontinue PROMACTA or nursing, taking into account the importance of PROMACTA to the mother. --Reduce the initial dose in patients with hepatic impairment (Child-Pugh Class A, B, C). ADVERSE REACTIONS The most common adverse reactions (occurring in 3% of patients receiving PROMACTA and at a higher rate in PROMACTA versus placebo) were: nausea, diarrhea, upper respiratory tract infection, vomiting, increased ALT, myalgia, urinary tract infection, oropharyngeal pain, increased AST, pharyngitis, back pain, influenza, paresthesia, and rash. DOSAGE AND ADMINISTRATION Use the lowest dose of PROMACTA to achieve and maintain a platelet count 50 x 109/L as necessary to reduce the risk for bleeding. Dose adjustments are based upon the platelet count response. Do not use PROMACTA in an attempt to normalize platelet counts [see Warnings and Precautions ]. In clinical studies, platelet counts generally increased within 1 to 2 weeks after starting PROMACTA and decreased within 1 to 2 weeks after discontinuing PROMACTA. Take PROMACTA on an empty stomach (1 hour before or 2 hours after a meal). Allow at least a 4-hour interval between PROMACTA and other medications (e.g., antacids), calcium-rich foods (e.g., dairy products and calcium fortified juices), or supplements containing polyvalent cations such as iron, calcium, aluminum, magnesium, selenium, and zinc. Initial Dose Regimen Initiate PROMACTA at a dose of 50 mg once daily, except in patients who are of East Asian ancestry (such as Chinese, Japanese, Taiwanese, or Korean) or who have mild to severe hepatic impairment (Child-Pugh Class A, B, C). For patients of East Asian ancestry, initiate PROMACTA at a reduced dose of 25 mg once daily. For patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, C), initiate PROMACTA at a reduced dose of 25 mg once daily [see Use in Specific Populations ]. For patients of East Asian ancestry with hepatic impairment (Child-Pugh Class A, B, C), consider initiating PROMACTA at a reduced dose of 12.5 mg once daily. Monitoring and Dose Adjustment After initiating PROMACTA, adjust the dose to achieve and maintain a platelet count =50 x 109/L as necessary to reduce the risk for bleeding. Do not exceed a dose of 75 mg daily. Monitor clinical hematology and liver tests regularly throughout therapy with PROMACTA and modify the dosage regimen of PROMACTA based on platelet counts as outlined in Table 1. During therapy with PROMACTA, assess CBCs with differentials (including platelet count) weekly until a stable platelet count has been achieved. Obtain CBCs with differentials (including platelet counts) monthly thereafter. Table 1. Dose Adjustments of PROMACTA In patients with hepatic impairment (Child-Pugh Class A, B, C), after initiating PROMACTA or after any subsequent dosing increase wait 3 weeks before increasing the dose. Modify the dosage regimen of concomitant ITP medications, as medically appropriate, to avoid excessive increases in platelet counts during therapy with PROMACTA. Do not administer more than one dose of PROMACTA within any 24-hour period. Discontinuation Discontinue PROMACTA if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks of therapy with PROMACTA at the maximum daily dose of 75 mg. Excessive platelet count responses, as outlined in Table 1, or important liver test abnormalities also necessitate discontinuation of PROMACTA HOW SUPPLIED DOSAGE FORMS AND STRENGTHS 12.5 mg, 25 mg, 50 mg, and 75 mg tablets. Each tablet, for oral administration, contains eltrombopag olamine, equivalent to 12.5 mg, 25 mg, 50 mg, or 75 mg of eltrombopag free acid. FDA批准PROMACTA（艾曲泊帕）治疗罕见血液病 GlaxoSmithKline (GSK) 宣布PROMACTA® (艾曲泊帕)已获美国食品药品监督局(FDA)完全批准。PROMACTA® (艾曲泊帕)是一种口服药，可升高慢性免疫性(特发性)血小板减少性紫癜(ITP是一种罕见的血液病)患者的血小板数量，而这类患者经激素、免疫球蛋白以及脾切除治疗效果不佳。 PROMACTA于2008年5月首次被FDA指定为治疗罕见病的药物，并于当年11月获得加速批准用来治疗慢性ITP。FDA的加速批准程序为药物获得暂时的上市批准提供了途径，从而解决了急需该药的患者需求。而完全的批准则需完成上市后的临床试验及临床效果验证。 “完全批准PROMACTA要基于临床研究，让医生与患者更为广泛地了解其疗效及安全性”GlaxoSmithKline制药部的Steven Stein, MD, V.P. 说。“PROMACTA的例子证明了FDA加速批准程序大力支持患者急需疗法的研发。可选治疗方案受限的患者可应用PROMACTA治疗，与此同时，GSK进行的临床研究也取得了额外的疗效与安全性方面的数据。 关于慢性ITP 慢性ITP是一种以血液中血小板破坏增多和(或)血小板生成不足为特征的疾病，可导致瘀伤及出血风险增加。据估计，美国约有60,000例患者被诊断为慢性ITP。这些患者常出现小血管出血症状，可引起瘀伤或鼻出血。 处方信息更新（PI） PROMACTA处方信息的主要变化为PI在禁忌和注意事项栏列举的初始剂量方案及血栓/血栓栓塞并发症。标签如今也包括来自RAISE(一项在ITP患者中进行的为期6个月的随机双盲安慰剂对照研究)的疗效与安全性数据。 新版PI还纳入了2年的安全性资料(来自一项在慢性ITP患者中进行的开放标签单组延期研究)。上述研究显示：不良反应发生的类型与安慰剂对照研究中报道的相似。 PI的其它变化包括更新了下述信息：药物剂量调整，肝毒性危险、骨髓网硬蛋白形成、血栓/血栓栓塞并发症、血小板减少复发、恶性血液病、白内障风险，不良事件信息，药物相互作用，在特定患者人群（肝肾损伤）中的应用及药代动力学部分。 黑框警告与重要安全信息 PROMACTA可引起肝脏毒性，同时还会伴随血清转氨酶水平及胆红素的升高。开始治疗前及治疗期间应定期检测肝功能。请参见黑框警告中的全部处方信息。 PROMACTA因其肝毒性风险、骨髓网硬蛋白形成、骨髓纤维化、血栓/血栓栓塞并发症、血小板减少复发风险及PROMACTA停药后出血风险以及恶性血液病、恶性肿瘤恶化、白内障风险，而仅能通过所谓的PROMACTA CARES限制性分配程序获得。 其它PROMACTA信息 PROMACTA是一种口服的血小板生成素受体激动剂，临床前及临床研究显示其可刺激巨核细胞（可生成血小板的骨髓细胞）的增殖与分化。PROMACTA由GlaxoSmithKline 与 Ligand Pharmaceuticals (Nasdaq: LGND)通过联合研究发现，而 GlaxoSmithKline进行了开发。 https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=9578 ---------------------------------------------------- 注：以下产品不同规格和不同价格，采购以咨询为准 ---------------------------------------------------- 产地国家：美国 原产地英文商品名: PROMACTA 12.5mg/tablets 30tablets/bottles 原产地英文药品名: eltrombopag 中文参考商品译名: PROMACTA 12.5毫克/片 30片瓶 中文参考药品译名: 艾曲泊帕 生产厂家英文名: NOVARTIS ---------------------------------------------------- 产地国家：美国 原产地英文商品名: PROMACTA 25mg/tablets 30tablets/bottles 原产地英文药品名: eltrombopag 中文参考商品译名: PROMACTA 25毫克/片 30片瓶 中文参考药品译名: 艾曲泊帕 生产厂家英文名: NOVARTIS ---------------------------------------------------- 产地国家：美国 原产地英文商品名: PROMACTA 50mg/tablets 30tablets/bottles 原产地英文药品名: eltrombopag 中文参考商品译名: PROMACTA 50毫克/片 30片瓶 中文参考药品译名: 艾曲泊帕 生产厂家英文名: NOVARTIS ---------------------------------------------------- 产地国家：美国 原产地英文商品名: PROMACTA 75mg/tablets 30tablets/bottles 原产地英文药品名: eltrombopag 中文参考商品译名: PROMACTA 75毫克/片 30片瓶 中文参考药品译名: 艾曲泊帕 生产厂家英文名: NOVARTIS ---------------------------------------------------- 产地国家：美国 原产地英文商品名: PROMACTA 12.5mg/tablets 30tablets/bottles 原产地英文药品名: eltrombopag 中文参考商品译名: PROMACTA 12.5毫克/片 30片瓶 中文参考药品译名: 艾曲泊帕 生产厂家英文名: GlaxoSmithKline ---------------------------------------------------- 产地国家：美国 原产地英文商品名: PROMACTA 25mg/tablets 30tablets/bottles 原产地英文药品名: eltrombopag 中文参考商品译名: PROMACTA 25毫克/片 30片瓶 中文参考药品译名: 艾曲泊帕 生产厂家英文名: GlaxoSmithKline ---------------------------------------------------- 产地国家：美国 原产地英文商品名: PROMACTA 50mg/tablets 30tablets/bottles 原产地英文药品名: eltrombopag 中文参考商品译名: PROMACTA 50毫克/片 30片瓶 中文参考药品译名: 艾曲泊帕 生产厂家英文名: GlaxoSmithKline ---------------------------------------------------- 产地国家：美国 原产地英文商品名: PROMACTA 75mg/tablets 30tablets/bottles 原产地英文药品名: eltrombopag 中文参考商品译名: PROMACTA 75毫克/片 30片瓶 中文参考药品译名: 艾曲泊帕 生产厂家英文名: GlaxoSmithKline ---------------------------------------------------- 产地国家：日本 原产地英文商品名: REVOLADE Tablets（レボレード錠）25mg/tablets 70tablets/bottles 原产地英文药品名: Eltrombopag Olamine 中文参考商品译名: REVOLADE（レボレード錠）25毫克/片 70片瓶 中文参考药品译名: 艾曲泊帕 生产厂家英文名: GlaxoSmithKline ---------------------------------------------------- 产地国家：日本 原产地英文商品名: REVOLADE Tablets（レボレード錠）12.5mg/tablets 70tablets/box 原产地英文药品名: Eltrombopag Olamine 中文参考商品译名: REVOLADE（レボレード錠）12.5毫克/片 70片/盒 中文参考药品译名: 艾曲泊帕 生产厂家英文名: GlaxoSmithKline 日本的资料附件：http://www.info.pmda.go.jp/go/pack/3999028F1025_2_02/ ---------------------------------------------------- 产地国家：德国 原产地英文商品名:  REVOLADE 25mg/tablets 28tablets/box 原产地英文药品名: eltromboag 中文参考商品译名:  REVOLADE  25毫克/片 28片/盒 中文参考药品译名: 艾曲泊帕 生产厂家英文名: GlaxoSmithKline ---------------------------------------------------- 产地国家：德国 原产地英文商品名:  REVOLADE 50mg/tablets 28tablets/box 原产地英文药品名: eltromboag 中文参考商品译名:  REVOLADE  50毫克/片 28片/盒 中文参考药品译名: 艾曲泊帕 生产厂家英文名: GlaxoSmithKline