英文药名：PROMACTA®（Eltrombopag） 中文药名:艾曲泊帕片 艾曲波帕 生产商：Ligand制药公司和葛兰素史克 药品介绍 通用名为Eltrombopag的Promacta（SB-497115）是口服的小分子血小板生成素受体激动剂，由美国Ligand制药公司和英国制药巨头葛兰素史克共同开发，并于2008年被美国食品药品监管局批准上市，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。在美国和欧洲大约有140,000该类患者。 ITP是一种罕见的血液疾病，表现为血小板损害或血小板数量不足，使患者出现淤伤或出血的风险增加。Eltrombopag可与人体跨膜区的血小板生成素受体作用，产生信号放大，从而诱导骨髓巨核细胞的增殖和分化。该药主要用于对糖皮质激素类、球蛋白药物或接受脾切除术后效果不理想的慢性血小板减少性紫癜患者。 Promacta在2011年的临床实验中对治疗丙型肝炎血液相关的并发症显示良好疗效。 PROMACTA Generic Name for PROMACTA Eltrombopag (as olamine) 25mg, 50mg; tabs. Legal Classification: Rx Pharmacological Class for PROMACTA Thrombopoietin receptor agonist. Manufacturer of PROMACTA GlaxoSmithKline Pharmaceuticals Indications for PROMACTA Thrombocytopenia due to chronic immune (idiopathic) thrombocytopenic purpura (ITP) in adults who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Adult dose for PROMACTA Take on empty stomach. Initially 50mg once daily. Moderate to severe hepatic impairment or East Asian ancestry: initially 25mg once daily. Titrate to maintain platelet count ≥50x109/L; max 75mg once daily. Adjust dose based on platelet count: see literature. Children's dosing for PROMACTA Not recommended. Warnings/Precautions for PROMACTA Monitor CBC, platelet count, and peripheral blood smears for cytopenias and abnormal morphologies; discontinue if no increase in platelet count occurs after 4 weeks at max dose, or if excessive increase in platelet count occurs (eg, >400x109/L), or if evidence of bone marrow fibrosis occurs (eg, cytopenias, nucleated RBCs). Monitor liver function closely before, during, and after treatment (see literature); discontinue if ALT >3xULN and is progressive or persistent for ≥4 weeks, or if it occurs with evidence of hepatic injury; reinitiation of therapy: not recommended; if restarted, use lower dose and monitor carefully. Do baseline eye exam; monitor for cataracts. Thromboembolism risk factors. Myelodysplastic syndromes. Renal impairment. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions for PROMACTA Do not take within 4 hours of food/drugs containing polyvalent cations (eg, Fe+2, Ca+2, Al+3, Mg+2, Se+2, Zn+2). May potentiate substrates of organic anion transporter polypeptide 1B1 (eg, benzylpenicillin, most statins, methotrexate, nateglinide, repaglinide, rifampin); monitor and consider reducing their doses. May be potentiated by strong inhibitors of CYP1A2 (eg, ciprofloxacin, fluvoxamine) or CYP2C8 (eg, gemfibrozil, trimethoprim), and with moderate or strong inhibitors of UGT1A1 or UGT1A3. Adverse Reactions for PROMACTA Nausea, vomiting, menorrhagia, myalgia, paresthesia, cataract, ecchymosis, thrombocytopenia, increased ALT/AST, conjunctival hemorrhage, increased risk of hematologic malignancies; thrombotic events with excessive increases in platelet counts; worsened thrombocytopenia after discontinuation. Notes for PROMACTA Note: Physicians, pharmacies, and patients must enroll in Promacta Cares program. Register pregnant patients taking eltrombopag by calling (888) 825-5249. How is PROMACTA supplied? Tabs—30 Related Disease: Thrombocytopenia   PROMACTA is 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 increases the risk for bleeding. PROMACTA should not be used in an attempt to normalize platelet counts. Important Safety Information BOXED WARNING PROMACTA may cause hepatotoxicity. Patients receiving therapy with PROMACTA must have regular monitoring of serum liver tests (see Laboratory Monitoring). Discontinue PROMACTA if ALT levels increase to ≥3X upper limit of normal (ULN) and are: progressive; or persistent for ≥4 weeks; or accompanied by increased direct bilirubin; or accompanied by clinical symptoms of liver injury or evidence of hepatic decompensation. Reinitiating treatment with PROMACTA is not recommended and should be considered only with close medical supervision and under exceptional circumstances where the potential benefit outweighs the risk. Additional Safety Information Regarding Risk of Hepatotoxicity: Reinitiating treatment with PROMACTA is not recommended. If the potential benefit for reinitiating treatment with PROMACTA is considered to outweigh the risk for hepatotoxicity, then cautiously reintroduce PROMACTA and measure serum liver tests weekly during the dose adjustment phase. If liver test abnormalities persist, worsen or recur, then permanently discontinue PROMACTA. Exercise caution when administering PROMACTA to patients with hepatic impairment (Child-Pugh Class A, B, C). Use a lower starting dose of PROMACTA in patients with any degree of hepatic impairment and monitor closely. Bone Marrow Reticulin Formation and Risk for Bone Marrow Fibrosis: PROMACTA may increase the risk for development or progression of reticulin fiber deposition within the bone marrow. In the extension study, 151 patients have had bone marrow biopsies evaluated for increased reticulin and collagen fiber deposition. Bone marrow biopsies taken after 1 year of therapy showed predominantly myelofibrosis (MF) Grade 1 or less in 140/151 (93%) of patients. There were 11/151 (7%) of patients with MF Grade 2. Four patients had collagen deposition reported. One patient with a preexisting MF Grade 1 developed a MF Grade 2 and subsequently discontinued treatment with PROMACTA. Clinical studies have not excluded a risk of bone marrow fibrosis with clinical consequences. If new or worsening blood morphological abnormalities or cytopenias occur, consider a bone marrow biopsy including staining for fibrosis. Thrombotic/Thromboembolic Complications in Chronic ITP Patients: Thrombotic/thromboembolic complications may result from increases in platelet counts with PROMACTA. Reported thrombotic/thromboembolic complications included both venous and arterial events and were observed at low and at normal platelet counts. Consider the potential for an increased risk of thromboembolism when administering PROMACTA to patients with known risk factors for thromboembolism. To minimize the risk for thrombotic/thromboembolic complications, do not use PROMACTA in an attempt to normalize platelet counts. Follow the dose adjustment guidelines to achieve and maintain a platelet count of ≥50 x 109/L as necessary to decrease the risk for bleeding. Thrombotic/Thromboembolic Complications in non-ITP Thrombocytopenic Patients With Chronic Liver Disease (CLD): In a controlled study in non-ITP thrombocytopenic patients with CLD undergoing elective invasive procedures (N=292), seven thrombotic complications (six patients) were reported within the group that received PROMACTA and three thrombotic complications (two patients) within the placebo group. All of the thrombotic complications reported in the group that received PROMACTA were of the portal venous system, with thrombotic complications occurring in five of the six patients at a platelet count above 200 x 109/L. Exercise caution when administering PROMACTA to patients with hepatic impairment (Child-Pugh Class A, B, C). PROMACTA is not indicated for the treatment of thrombocytopenia in patients with CLD. Hematologic Malignancies: Stimulation of the TPO receptor on the surface of hematopoietic cells by PROMACTA may increase the risk for hematologic malignancies. PROMACTA is not indicated for the treatment of thrombocytopenia due to causes of thrombocytopenia (eg, myelodysplasia or chemotherapy) other than chronic ITP. Laboratory Monitoring: Complete Blood Counts (CBCs): Obtain 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. Obtain CBCs (including platelet counts) weekly for at least 4 weeks following discontinuation of PROMACTA. Liver tests: Monitor serum liver tests (ALT, AST, and bilirubin) prior to initiation of PROMACTA, every 2 weeks during the dose adjustment phase, and monthly following establishment of a stable dose. If bilirubin is elevated, perform fractionation. If abnormal levels are detected, repeat the tests within 3 to 5 days. If the abnormalities are confirmed, monitor serum liver tests weekly until the abnormality(ies) resolve, stabilize, or return to baseline levels. Discontinue PROMACTA for the development of important liver test abnormalities. Cataracts: In the 3 controlled clinical studies, cataracts developed or worsened in 15 (7%) patients who received 50 mg PROMACTA daily and 8 (7%) placebo-group patients. In the extension study, cataracts developed or worsened in 4% of patients who underwent ocular examination prior to therapy with PROMACTA. Cataracts were observed in toxicology studies of eltrombopag in rodents. Perform a baseline ocular examination prior to administration of PROMACTA and, during therapy with PROMACTA, regularly monitor patients for signs and symptoms of cataracts.   新的研究显示:Promacta对丙型肝炎的血液并发症有效 据悉，总部在旧金山的Ligand制药公司表示，其药物Promacta治疗丙型肝炎血液相关的并发症的后期试验结果宣告成功。 Ligand说，其合作者葛兰素史克公司将在即将召开的医学会议上公布结果。这项研究是两个正在进行的涉及肝炎相关性血小板减少症患者的研究之一，该病可导致患者血液中血小板水平异常降低。 Promacta最初在2008年被批准用于一种称为慢性免疫性血小板减少性紫癜的罕见疾病的治疗，在该疾病中机体攻击自身的血小板。在美国和欧洲大约有140,000人受到这种在轻伤后可导致瘀伤和出血的疾病的影响。   FDA：Promacta对慢性肝病患者存在血栓风险 2010年5月12日，GlaxoSmithKline公司与美国食品药品监督管理局通告医生，Promacta(eltrombopag)在治疗因慢性肝病而产生血小板减少症时存在门静脉血栓的风险，该药物是一种血小板生成素受体拮抗剂，已经获得FDA批准用于治疗成年人的慢性免疫性(自发性)血小板减少性紫癜产生的血小板减少。 在ELEVATE研究中，随机、双盲、安慰剂对照、多国等各项临床试验表明与空白安慰剂组相比，患者门静脉血栓形成与服用eltrombopag不无相关。Eltrombopag组的6名患者(4%)和1名安慰剂组(1%)发生了门静脉系统血栓，6名患者中的5名发生静脉系统血栓时血小板数量在200,000/μL以上，GSK已经将该项安全性问题通告给了临床试验研究者以及相关管理机构。 特别提醒:医生需要注意以下几点： Promacta适用于治疗成年人的慢性免疫性(自发性)血小板减少性紫癜产生的血小板减少，而不能用于治疗由于慢性肝病患者的血小板减少。 Promacta能提高血小板数量，减少出血的风险，而不能将血小板数量提高到标准水平。 对于有血栓栓塞风险的患者要慎用Promacta 对于有肝病的患者要尤其慎用Promacta，对于中到重度的肝病患者使用较低的初始剂量(25mg，1次/天)，并且密切观察是否发生不良反应。