| PROMACTA(ELTROMBOPAG OLAMINE 中文药名 艾曲波帕)TABLET ORAL获美国FDA扩展使用幼儿罕见血液疾病 批准日期：2015年8月24日 公司：葛兰素史克公司 PROMACTA（艾曲波帕 eltrombopag）片剂，供用于口服用途 美国首次批准：2008 警告： 风险肝功能失代偿期慢性肝炎患者CSEE为完整的黑框警告完整的处方信息。 在治疗慢性丙型肝炎，PROMACTA与干扰素和利巴韦林合用可加重肝功能失代偿的风险。 目前的主要变化 适应证和用法，血小板减少慢性ITP患者的治疗 06/2015 适应证和用法，重型再生障碍性贫血的治疗 08/2014 用法与用量，慢性免疫（特发性）血小板减少 06/2015 剂量和给药方法，重症再生障碍性贫血 08/2014 作用机制 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，并启动信号级联诱导细胞增殖和分化的骨髓祖细胞。 适应症和用法 PROMACTA是用于治疗所表示的血小板生成素受体激动剂： •血小板减少症在成人和儿童患者6年以上有慢性免疫（特发性）血小板减少症（ITP）谁曾不充分响应糖皮质激素，免疫球蛋白，或脾切除术。 •血小板减少症患者的慢性丙型肝炎，以允许干扰素为基础的治疗的起始和维持。 •例重症再生障碍性贫血谁曾不充分反应免疫抑制治疗。 使用限制： •PROMACTA应仅用于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应仅用于治疗慢性丙型肝炎的血小板减少症的程度防止干扰素为基础的治疗开始或限制，以保持干扰素为基础的治疗的能力。 •安全性和有效性尚未确定结合使用而不干扰素治疗的慢性丙型肝炎感染的直接作用的抗病毒剂。 用法用量 •以空腹（前1小时或2餐后小时）。 •慢性ITP：每天大部分的成人和儿童患者6岁的年龄较大的一次启动PROMACTA在50毫克。减少患者的肝功能损害和/或东亚血统的患者初始剂量。调整以维持血小板计数大于或等于50×109/L。不要超过每日75毫克。 •慢性丙型肝炎相关性血小板减少症：每天对所有患者一旦启动PROMACTA在25毫克。调整来实现启动抗病毒治疗所需的目标血小板计数。不超过每日剂量100毫克。 •重型再生障碍性贫血：每天对大多数患者一旦启动PROMACTA在50毫克。减少患者的肝功能损害或东亚血统的患者初始剂量。调整以维持血小板计数大于50×10 9 /L。不要超过每天150毫克。 •肝损伤：减少患者withchronic ITP和肝功能损害的初始剂量。 剂型和规格 片剂：12.5毫克，25毫克，50毫克，75毫克和100毫克。 禁忌 无。 警告和注意事项 •肝毒性：之前和治疗期间监测肝功能。 •血栓/血栓栓塞性并发症：门静脉血栓形成有报道在慢性肝病患者接受PROMACTA。定期监测血小板计数。 不良反应 •在成年ITP患者中，最常见的不良反应（大于或等于5％和大于安慰剂）分别为：恶心，腹泻，上呼吸道感染，呕吐，ALT升高，肌肉痛，和泌尿道感染。 •在儿科患者年龄6岁及以上的ITP，最常见的不良反应（大于或等于10％和高于安慰剂）是上呼吸道感染，鼻咽炎，和鼻炎。 •在慢性丙型肝炎相关的血小板减少症中，最常见的不良反应（比安慰剂大于或等于10％和更高）分别为：贫血，发热，疲劳，头痛，恶心，腹泻，食欲降低，流感样疾病，乏力，失眠，咳嗽，皮肤瘙痒，寒战，肌肉痛，脱发和外周水肿。 （ •重症患者再生障碍性贫血，最常见的不良反应（大于或等于20％）为：恶心，疲劳，咳嗽，腹泻，和头痛。 药物相互作用 PROMACTA不能在4个小时的任何药物或含有多价阳离子如抗酸剂，钙丰富的食物，和矿物质补充剂产品内拍摄。 特殊人群中使用 •妊娠：根据动物实验数据，PROMACTA可能对胎儿造成伤害。 •哺乳母亲：应做出决定停止PROMACTA或哺乳，考虑到PROMACTA的重视母亲。 包装规格/储存与处理 包装 12.5mg*30片/瓶： NDC 0007-4643-13 本品含有干燥剂 25mg*30片/瓶： NDC 0007-4640-13 本品含有干燥剂 50mg*30片/瓶： NDC 0007-4641-13 本品含有干燥剂 75mg*30片/瓶： NDC 0007-4642-13 本品含有干燥剂 100mg*30/片瓶： NDC 0007-4646-13 本品含有干燥剂 储存 在储存在20°C至25°C（68°F至77°F）的室温;允许15°C至30°C（59°F至86°F），游览[见USP控制室温。如果存在的话，不要取出干燥剂。分装在原瓶。 Novartis gains FDA approval for Promacta® providing new option for children, ages 6 and older, with chronic ITP, a rare blood disorder •Promacta®(eltrombopag) significantly increased and sustained platelet counts in two studies, including the largest Phase III clinical trial in this patient population •Characterized by a low platelet count, ITP can affect up to 5 in 100,000 children each year and those with chronic ITP are at ongoing risk of significant bleeding •Promacta was approved to treat chronic ITP in adults in 2008, and remains the first and only oral TPO-receptor agonist that increases platelet production US Food and Drug Administration (FDA) has approved Promacta® (eltrombopag) for the treatment of children six years and older with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy. Promacta was approved by the FDA in 2008 for use in adult patients with the same condition. ITP affects as many as 5 in 100,000 children each year[2] and is characterized by a low platelet count[1]. Up to 30% of affected children experience persistent disease for more than 6 months and are diagnosed with chronic ITP[2],[5]. Pediatric patients with chronic ITP are at ongoing risk of significant bleeding. "Young patients with chronic ITP who have either an insufficient response to or side effects from standard therapies have limited treatment options, making this FDA approval of eltrombopag for children six years and older particularly important," said James B. Bussel, MD, a professor of pediatrics, of pediatrics in obstetrics and gynecology and of pediatrics in medicine at Weill Cornell Medical College, and lead study investigator of the PETIT study. "Through the eltrombopag studies, one of which is the largest randomized trial ever performed in children with chronic ITP, we discovered that Promacta - a treatment that can be taken once daily by mouth and shown to be well tolerated - can manage this disorder and help these young patients." The approval of Promacta was based on data from two double-blind, placebo-controlled trials, including the largest Phase III clinical trial in this patient population. Treatment with Promacta significantly increased and sustained platelet counts among some pediatric patients with chronic ITP, and some patients taking concomitant ITP medications were able to reduce or discontinue their use of these medications, primarily corticosteroids. Promacta should be used only in those whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. "Today's FDA approval of Promacta for children with chronic ITP, a rare and potentially serious blood disorder, gives new hope to patients and their families," said Bruno Strigini, President, Novartis Oncology. "All patients are important, but when we can help children, we are especially gratified. This approval underscores our expertise in benign hematologic disease and our commitment to provide treatments for rare diseases." Promacta is a once-daily oral thrombopoietin (TPO) receptor agonist that works by inducing stimulation and differentiation of megakaryocytes (large cells, found especially in bone marrow) from bone marrow stem cells to increase platelet production. About the PETIT and PETIT2 Clinical Trials PETIT was a Phase II, multi-center, three-part study to investigate the efficacy, safety and tolerability of Promacta in pediatric patients with previously treated chronic ITP. Part 1 was an open label, dose finding study; Part 2 was double-blind and placebo-controlled, and Part 3 was an open-label extension. The primary endpoint, which was percentage of participants who achieved a platelet count >=50 Gi/L without rescue therapy at least once between Weeks 1 and 6, was met by 63% and 18% of Promacta and placebo patients, respectively (p=0.0043). The secondary efficacy endpoint analyses demonstrated clinically meaningful benefit in terms of decreased need for rescue treatment (14% of patients on Promacta compared to 59% of patients on placebo). PETIT2 was a Phase III, multi-center, two-part study to investigate the efficacy, safety and tolerability of Promacta in pediatric patients with previously treated chronic ITP. Part 1 was randomized, double-blind and placebo-controlled and Part 2 was an open-label extension. The primary endpoint, which was percentage of participants who achieved a platelet count >=50 Gi/L without rescue therapy for at least six out of eight weeks between Weeks 5 and 12 of Part 1 of the study, was met by 43% of patients treated with Promacta and 4% of patients treated with placebo (p=0.0011). This result was consistent across the age cohorts. The secondary efficacy endpoint analyses demonstrated clinically meaningful benefit in terms of decreased need for rescue treatment (18% of patients on Promacta compared to 22% of patients on placebo),and reduction or discontinuation of baseline ITP medications (50% or 5/10 patients in the open-label phase who were receiving other ITP therapy at baseline) over the randomized and Promacta-only treatment periods. In both studies, safety was consistent with the known safety profile of Promacta in chronic ITP in adults and the population under study. No new safety signals were detected. The most common adverse reactions in pediatric chronic ITP patients six years and older (greater than or equal to 10% and greater than placebo) were upper respiratory tract infection, nasopharyngitis and rhinitis. About Chronic ITP ITP is a blood disorder characterized by blood that does not clot as it should due to a low number of platelets. People who have ITP often have purple bruises or tiny red or purple dots on the skin. They also may have nosebleeds, bleeding from the gums during dental work, or other bleeding that's hard to stop. In most cases, an autoimmune response is thought to cause ITP in which a person's immune system attacks and destroys its own platelets. The two types of ITP are acute (temporary or short-term) and chronic (long-lasting). Acute ITP mainly occurs in children, often after a viral infection, and generally lasts less than 6 months. The platelet count returns to normal within 6 to 12 months and treatment may not be needed[1]. However, up to 30% of teenagers and children with ITP experience persistent disease for more than 6 months and are diagnosed with chronic ITP. The goal of treatment in chronic ITP for children is to maintain a safe platelet count that stops or prevents bleeding. The most commonly available and used therapies-corticosteroids and intravenous immunoglobulin (IVIG)-are associated with side effects that are often difficult to tolerate in a pediatric setting. About Promacta Promacta is marketed under the brand name Promacta® in the US and Revolade® in most countries outside the US. Promacta is a prescription medicine used to treat adults and children 6 years of age and older with low blood platelet counts due to chronic immune (idiopathic) thrombocytopenia (ITP), when other medicines to treat ITP or surgery to remove the spleen have not worked well enough. Promacta is used to try to raise platelet counts in order to lower the risk for bleeding. Promacta should be used only in those whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. It is not known if Promacta is safe and effective in children younger than 6 years with ITP. Separate applications were submitted to the FDA and the European Medicines Agency (EMA) earlier this year to include chronic ITP patients one year and older. These applications include chemistry, manufacturing and control (CMC) data supporting the new powder for oral suspension formulation of Promacta. The safety and efficacy profile of Promacta has not yet been established in countries outside the US in pediatric patients with chronic ITP. For various reasons, including the uncertainty of clinical trials, there is no guarantee that Promacta will become commercially available for pediatric patients with chronic ITP anywhere else in the world. Information about clinical trials for chronic ITP can be obtained by healthcare professionals at www.clinicaltrials.gov(link is external) In addition to the approval of Promacta for chronic ITP in the US, it is approved to treat low blood platelet counts in people with chronic hepatitis C virus (HCV) infection before and during treatment with interferon. Promacta should only be used in people with chronic hepatitis C whose low blood platelet counts keep them from starting or continuing interferon-based therapy. It is not known if Promacta is safe and effective when used with other antiviral medicines that are approved to treat chronic hepatitis C. Promacta is a prescription medicine used to treat people with severe aplastic anemia (SAA) when other medicines to treat SAA have not worked well enough. Promacta is not used to make a patient's platelet count normal. Important Safety Information for Promacta® (eltrombopag) Promacta can cause serious side effects, including liver problems, abnormal liver function tests, high platelet counts and higher risk for blood clots, and new or worsened cataracts (a clouding of the lens in the eye). For patients who have chronic hepatitis C virus and take Promacta with interferon and ribavirin treatment, Promacta may increase the risk of liver problems. Patients should tell a healthcare provider right away if they have any of these signs and symptoms of liver problems including yellowing of the skin or the whites of the eyes (jaundice), unusual darkening of the urine, unusual tiredness, right upper stomach area pain, confusion, swelling of the stomach area (abdomen). A healthcare provider will order blood tests to check the liver before starting Promacta and during Promacta treatment. In some cases, treatment with Promacta may need to be stopped due to changes in liver function tests. The risk of getting a blood clot is increased if the platelet count is too high during treatment with Promacta. The risk of getting a blood clot may also be increased during treatment with Promacta if platelet counts are normal or low. Some forms of blood clots, such as clots that travel to the lungs or that cause heart attacks or strokes can cause severe problems or death. A healthcare provider will check blood platelet counts, and change the dose of Promacta or stop Promacta, if platelet counts get too high. Patients should tell a healthcare provider right away if they have signs and symptoms of a blood clot in the leg, such as swelling, pain, or tenderness in the leg. People with chronic liver disease may be at risk for a type of blood clot in the stomach area. Patients should tell a healthcare provider right away if they have stomach area pain that may be a symptom of this type of blood clot. New or worsened cataracts have happened in people taking Promacta. A healthcare provider will check the patient's eyes before and during treatment with Promacta. Patients should tell a healthcare provider about any changes in eyesight while taking Promacta. Patients should tell a healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Promacta may affect the way certain medicines work. Certain medicines may keep Promacta from working correctly. Patients should take Promacta at least 4 hours before or 4 hours after taking products such as antacids used to treat stomach ulcers or heartburn and multivitamins or products that contain iron, calcium, aluminum, magnesium, selenium, and zinc, which may be found in mineral supplements. Patients should ask a healthcare provider if they are not sure if the medicine is one that is listed above. Patients should avoid situations and medications that may increase the risk of bleeding while taking Promacta. The most common side effects of Promacta when used to treat chronic ITP in adults are: nausea; diarrhea; upper respiratory tract infection (symptoms may include runny nose, stuffy nose, and sneezing); vomiting; muscle aches; urinary tract infection (symptoms may include frequent or urgent need to urinate, low fever in some people, pain or burning with urination); pain or swelling (inflammation) in the throat or mouth (oropharyngeal pain and pharyngitis); abnormal liver function tests; back pain; flu-like symptoms (influenza), including fever, headache, tiredness, cough, sore throat, and body aches; skin tingling, itching, or burning; and rash. The most common side effects of Promacta in children 6 years and older when used to treat chronic ITP are: upper respiratory tract infections (symptoms may include runny nose, stuffy nose, and sneezing); pain or swelling (inflammation) in the nose and throat (nasopharyngitis); runny, stuffy nose (rhinitis); stomach (abdominal) pain; cough; pain or swelling (inflammation) in the throat or mouth; toothache; abnormal liver function tests; diarrhea; rash; vitamin D deficiency. The most common side effects when Promacta is used in combination with other medicines to treat chronic HCV are: low red blood cell count (anemia); fever; tiredness; headache; nausea; diarrhea; decreased appetite; flu-like symptoms (influenza), including fever, headache, tiredness, cough, sore throat, and body aches; feeling weak; trouble sleeping; cough; itching; chills; muscle aches; hair loss; and swelling in the ankles, feet, and legs. The most common side effects of Promacta when used to treat severe aplastic anemia are: nausea, feeling tired, cough, diarrhea, headache, pain in arms, legs, hands or feet, shortness of breath, fever, dizziness, pain in nose or throat, abdominal pain, bruising, muscle spasms, abnormal liver function tests, joint pain, and runny nose. Laboratory tests may show abnormal changes to the cells in bone marrow. Please see full Prescribing Information, including Boxed WARNING and Medication Guide, for Promacta®. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=616224ff-a925-4b38-9ca2-00fbf669380f http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/psd/2013-07/eltrombopag 美国FDA批准Promacta(Eltrombopag Tablets)血液疾病新适应证 8月26日，FDA已批准Promacta（eltrombopag，艾曲波帕）补充新药申请（sNDA），用于对免疫抑制疗法（IST）反应不足的重型再生障碍性贫血（SAA）患者血细胞减少症（cytopenia）的治疗。 此前，FDA已于今年2月授予Promacta治疗SAA的突破性疗法认定。Promacta sNDA的提交，是基于一项开放标签II期NIH研究的数据，该项研究在43例对IST响应不足的SAA患者中开展。 重型再生障碍性贫血（SAA）是一种罕见性疾病，患者骨髓无法制造足够的新的血细胞。目前，还没有药物获批用于对免疫抑制疗法（IST）无响应的SAA患者的治疗。对初始IST响应不足的SAA患者群体，约40%的患者会在疾病确诊5年内，死于感染或出血。： 目前，Eltrombopag（艾曲波帕）已获全球100多个国家批准，用于慢性免疫（特发性）血小板减少性紫癜（ITP）患者血小板减少症（thrombocytopenia）的治疗，同时已获43个国家批准用于慢性丙型肝炎（CHC）患者血小板减少症的治疗，以便启动并维持以干扰素为基础的肝病标准疗法。 该药在美国的商品名为Promacta，在欧洲及其他国家和地区的商品名为Revolade |