ITP新药新消息

1、ITP新药新消息奥赛康申报一罕见病药物 该品国内市场尚属空白 国家食药监总局（CFDA）网站显示，奥赛康申报临床的3.1类造血新药艾曲泊帕原料药和片剂获受理。 目前，艾曲泊帕原研药尚未进入中国市场，也无国内企业生产该产品。 根据临床研究结果，艾曲泊帕片可刺激巨核细胞的增殖与分化，用于治疗血小板减少性紫癜（ITP），该产品最早由英国葛兰素史克公司研发，并于2008年5月获FDA指定为治疗罕见病的药物，在当年11月获得加速批准用来治疗慢性ITP。资料显示，我国治疗血小板减少性紫癜药品种类有限，主要有羟基脲片、复方皂矾丸、血康胶囊等产品，艾曲泊帕片的国内市场尚属空白。目前申报该艾曲泊帕片的国内企业除

2、了奥赛康外，仅有南京华威医药，该公司于今年3月申报临床。奥赛康主要从事消化类、抗肿瘤类及其他药品的生产和销售，拳头产品为消化药“奥西康”（注射用奥美拉唑钠）。奥西康占公司营业收入和毛利的比例均超过50%。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

3、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。PROMACTAGeneric Name for PROMACTAEltrombopag (as olamin

4、e) 25mg, 50mg; tabs.Legal Classification:RxPharmacological Class for PROMACTAThrombopoietin receptor agonist.Manufacturer of PROMACTAGlaxoSmithKline PharmaceuticalsIndications for PROMACTAThrombocytopenia due to chronic immune (idiopathic) thrombocytopenic purpura (ITP) in adults who have had an ins

5、ufficient response to corticosteroids, immunoglobulins, or splenectomy.Adult dose for PROMACTATake 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. A

6、djust dose based on platelet count: see literature.Children's dosing for PROMACTANot recommended.Warnings/Precautions for PROMACTAMonitor CBC, platelet count, and peripheral blood smears for cytopenias and abnormal morphologies; discontinue if no increase in platelet count occurs after 4 weeks a

7、t 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 p

8、ersistent 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

9、.C). Nursing mothers: not recommended.Interactions for PROMACTADo 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, na

10、teglinide, 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 PROMACTANausea,

11、 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 PROMA

12、CTANote: Physicians, pharmacies, and patients must enroll in Promacta Cares program. Register pregnant patients taking eltrombopag by calling (888) 825-5249.How is PROMACTA supplied?Tabs30Related Disease:Thrombocytopenia PROMACTA is indicated for the treatment of thrombocytopenia in patients with ch

13、ronic 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. PRO

14、MACTA should not be used in an attempt to normalize platelet counts.Important Safety InformationBOXED WARNINGPROMACTA may cause hepatotoxicity. Patients receiving therapy with PROMACTA must have regular monitoring of serum liver tests (see Laboratory Monitoring). Discontinue PROMACTA if ALT levels i

15、ncrease 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 co

16、nsidered 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

17、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 administ

18、ering 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

19、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

20、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

21、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 res

22、ult 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 patien

23、ts 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

24、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 repo

25、rted 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 patie

26、nts 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

27、 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 (C

28、BCs): 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 PR

29、OMACTA.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

30、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, c

31、ataracts 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.