英文药名：Opsumit(Macitentan Tablets) 中文药名：美西特田片（又名为：马西替坦片） 生产厂家：Actelion公司 オプスミット錠10mg 治疗类别名称 内皮素受体拮抗剂 批准日期：2015年6月 商標名 Opsumit 10mg 一般名： マシテンタン　Macitentan（JAN） 化学名： N-［5-（4-Bromophenyl）-6-｛2-［（5-bromopyrimidin-2-yl）oxy］ethoxy｝pyrimidin-4-yl］-N '-propylsulfuric diamide 構造式： 分子式： C19H20Br2N6O4S 分子量： 588.27 性　状： 它是一种白色结晶粉末。非常易溶于二氯甲烷，二甲亚砜，N，易溶于N-二甲基甲和四氢呋喃，丙酮，乙腈和乙酸乙酯微溶，在甲醇和乙醇中微溶，在异丙醇中极微溶于，和几乎不溶于水。 条件批准 和药品风险管理计划在发展，妥善执行。 由于审判案件在日本是非常有限的 - ，上市后，直到一定数量的情况下的数据集成，通过实现对一切案件的使用效果调查，代理人掌握使用患者数据采集初期这种药物的安全性和有效性，采取措施以获得正确使用药物的背景信息。 药效药理 1. 血管收缩的抑制 美西特田抑制内皮素内皮剥离从大鼠切除的主动脉（ET）-1刺激诱导的收缩（ETA受体介导的）和上皮剥离气管角蝰毒素S6c中刺激引起的收缩（ETB受体介导的），即的pA 2值分别为7.6±0.2（ETA受体）和5.9±0.2（ETB受体） 2. 对疾病模型的作用 (1) 肺动脉高压模型 马西在野百合碱诱导肺动脉高压大鼠，降低了平均肺动脉压不影响心脏率，也能抑制肺肥大和右心室肥大。此外，提高成活率。 (2) 高血压模型 美西特田在Dahl盐敏感（达尔-S）高血压大鼠和乙酸脱氧皮质酮（DOCA）盐高血压大鼠，降低而不影响心脏速率的平均动脉压。 (3) 高血压模类型 马西在博莱霉素致肺纤维化大鼠，并抑制了右心室肥厚和肺羟脯氨酸含量。 3. 作用机序 美西特田指示针对ETA和ETB受体拮抗作用，对于@125 I-ET-1结合的IC 50值（平均值±标准误差）分别为0.49±0.07 nM的和391±49纳米。活性代谢物也显示了类似的拮抗作用和美西特田，其IC 50值分别为3.4±0.20 nM的和987±92纳米。 适应病症 用于治疗肺动脉高压 用法与用量 成人，每天口服一次，每次10毫克。 包装规格 片剂 10mg：30片（15片×2）PTP 制造商 Actelion公司（Actellion Pharmaceuticals Japan KK） 完整处方资料附件：http://www.info.pmda.go.jp/go/pack/2190035F1021_1_03/ 美西特田片（又名为：马西替坦片） 批准日期: 2013年10月18日 (美国), 2013年12月20日 (欧盟)，2015年3月26日（日本） Announcement of sale of "Opumit® tablet 10mg" for treatment of pulmonary arterial hypertension Nippon Shinyaku develops jointly with Actellion Pharmaceuticals Japan Co., Ltd. (Headquarters: Shibuya-ku, Tokyo; President: Satoru Tanaka, hereinafter "Actellion Japan") in Japan and acquired pulmonary artery We are pleased to inform you that we have started selling today for "Opumit® Tablets 10 mg" (generic name: Masitantan, hereinafter this drug) for treatment of pulmonary hypertension (PAH). This drug is classified as an endothelin receptor antagonist and in international joint Phase III clinical trial (SERAPHIN test) conducted abroad, administration of 10mg/once daily of this drug compared to placebo results in morbidity/mortality Reduced the risk of developing complex endpoint by 45% (p <0.0001). Also in domestic clinical trials, improvement of pulmonary vascular resistance, 6-minute walking distance and WHO function classification class was recognized. Currently, PAH therapeutic agents widely used in clinical practice in Japan are classified into three different mechanisms of action (PDE 5 inhibitors, IP receptor agonists, endothelin receptor antagonists), but each time this book With the release of the drug, Nippon Shinyaku has added PAH therapeutic agent of all three different mechanisms of action in addition to "Adsilca ® tablet 20 mg" which is already on sale and NS - 304 (common name: Serexipag) currently under development in addition to NS - 304 You will be aligned. This drug is sold by Actelion Japan and sales promotion activities are performed jointly by Nippon Shinyaku and Actelion Japan, but with the spread of drug treatment options for PAH, which is a refractory disease, patients and their families I hope to be a great gospel of the people, and I would like to cooperate with each other to ensure that this drug is delivered to the medical institution as soon as possible. Product Summary Product name: Opposit ® tablets 10 mg Common name: Mashitan (Yahoo name: Macitentan) Approval number: Opposit® tablet 10 mg (approval number: 22700 AMX 00649000) Ingredients · Contents: Opposit® tablet 10 mg 1 tablet contains 10 mg of masit tan Indications: Pulmonary arterial pulmonary hypertension Dosage/Dosage: Usually, adults receive 10 mg as Masitanthang once daily. Manufacture and sale approval date: March 26, 2015 Drug price criterion Listing date: 20th May 2015 Release date: June 9, 2015 Packing: PTP 30 tablets (15 tablets×2) <Supplemental explanation> Pulmonary arterial pulmonary hypertension (PAH) PAH is a chronic and life-threatening disorder characterized by abnormally high arterial blood pressure between the patient's heart and lungs. Symptoms of PAH are nonspecific, varying from mild shortness of breath and fatigue in daily life, severe restrictions on right heart failure and physical activity, and ultimately shortening of life expectancy. PAH is a group in the classification of pulmonary hypertension (PH). This group has PAH caused by idiopathic PAH, inherited PAH, connective tissue disease, HIV infection and congenital heart disease etc. Pathophysiological understanding of PAH has greatly advanced in the last 10 years, treatment guidelines and development of new therapies are being carried out in parallel. Endothelin receptor antagonists (ERA), IP receptor agonists (prostacyclin derivatives), and PDE 5 inhibitors (phosphodiesterase-5 inhibitors) have been identified as drugs targeting three mechanisms established as pathogenesis of PAH There is. Treatment of PAH has changed from delaying based on symptoms of exercise tolerance 10 years ago, to delay the progress of disease today. Improved awareness of PAH and evidence-based guidelines based on randomized controlled trial results highlight the need for early treatment interventions, therapeutic goal-oriented treatment and combination therapy. About Opsmit® (Masitantan) This drug is an entirely new dual endothelin receptor antagonist (ERA), and it was found as a result of its unique drug discovery process that tackled efficacy and safety and targeted the development of ERA. About endothelin receptor antagonist (ERA) Endothelin, a body substance that acts to contract blood vessels, acts by binding to the endothelin receptor, and it exists in the body of patients with pulmonary hypertension. ERA is a drug that inhibits the binding of endothelin to endothelin receptors. There are two types of endothelin receptors, A and B, and there are mashitan, bosentan and ambrisentan that inhibit both A and B receptors, and A receptors. About IP Receptor Agonists IP receptor acts on vasodilation etc. by binding with prostacyclin (PGI 2). This is weakening in patients with pulmonary hypertension. IP receptor stimulants are drugs that enhance this function. About PDE5 inhibitor Enzyme called PDE5 is distributed in blood vessels of lungs and decomposes cyclic GMP (cGMP), an intracorporeal substance that expands blood vessels. PDE5 inhibitor is a drug that inhibits the degradation of cGMP by PDE5, enhances the function of cGMP and expands blood vessels in the lungs. About the SERAPHIN exam SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome: Endothelin Receptor Antagonist Test to Improve Clinical Outcome in PAH) is a PAH patient with a well-defined morbidity / mortality as the primary endpoint It is a large-scale, long-term randomized controlled trial in. This major Phase III trial is a completely new dual endothelin receptor antagonist found as a result of its own drug discovery process The effectiveness and safety of this drug until symptomatic PAH patients until the first morbidity event expression Of the time and the death of all reasons as the main endpoint. Global patient registrations were completed in December 2009 in a total of 742 patients. Patients were randomized to 1: 1: 1 to administer the two doses of this product (3 mg or 10 mg daily) or placebo. Patients were allowed to take PAH-based therapies either PDE-5 inhibitors or oral / inhaled prostanoids during the study period. This event-driven trial was conducted in 151 institutions in approximately 40 countries in North America, Latin America, Europe, Asia-Pacific, Africa and was completed in the first half of 2012 with confirmation of the event development of 287 patients. About the SERAPHIN test data Patients were randomized to placebo (n = 250), 3 mg of this drug (n = 250) or 10 mg of nicotine (n = 242). Major endpoint events occurred in 46.4%, 38.0% and 31.4% of patients in these groups, respectively. The hazard ratio of this drug 3 mg to placebo was 0.70 (97.5% confidence interval, 0.52 to 0.96; p = 0.0108) and the hazard ratio of 10 mg of this drug to placebo was 0.55 (97.5% confidence interval, 0.39 to 0.76; p < 0.0001). The deterioration of PAH was the main event item event that occurred most frequently. The efficacy of this drug in this evaluation item was recognized regardless of the basic treatment for PAH. About safety and tolerability profile Adverse events reported by SERAPHIN at frequencies> 3% were nasopharyngitis, headache, anemia, bronchitis, urinary tract infections, pharyngitis and influenza. Cited document 1. Pulido T et al. Macitentan and Morbidity and Mortality in Pulmonary Arterial Hypertension. N Engl J Med 2013; 369: 809-18. 2. Bolli MH et al. The Discovery of N- [5- (4-Bromophenyl) -6- [2 - [(5-bromo-2-pyrimidinyl) oxy] ethoxy] -4-pyrimidinyl] - N '- propylsulfamide (Macitentan), an Orally Active, Potent Dual Endothelin Receptor Antagonist. J Med Chem. 2012; 55: 7849-61. 3.Iglarz M. et al. Pharmacology of macitentan, an orally active tissue targeting dual endothelin receptor antagonist. J Pharmacol Exp Ther. 2008; 327 (3): 736-745. ------------------------------------------- 产地国家：日本 原产地英文商品名: OPSUMIT（オプスミット錠）10mg/Tablets 30Tablets/box 原产地英文药品名: MACITENTAN 中文参考商品译名: OPSUMIT（オプスミット錠）10毫克/片 30片/盒 中文参考药品译名: 马西替坦 生产厂家中文参考译名: ACTELION 生产厂家英文名: ACTELION ------------------------------------------- 产地国家：德国 原产地英文商品名: OPSUMIT 10mg/Tablets 30Tablets/盒 原产地英文药品名: MACITENTAN 中文参考商品译名: OPSUMIT 10毫克/片 30片/盒 中文参考药品译名: 马西替坦 生产厂家中文参考译名: ACTELION 生产厂家英文名: ACTELION ------------------------------------------- 产地国家：美国 原产地英文商品名: OPSUMIT 10mg/Tablets 30Tablets/瓶 原产地英文药品名: MACITENTAN 中文参考商品译名: OPSUMIT 10毫克/片 30片/瓶 中文参考药品译名: 马西替坦 生产厂家中文参考译名: Actelion Pharmaceuticals Ltd. 生产厂家英文名: Actelion Pharmaceuticals Ltd.