|
部份中文普拉格雷处方资料（仅供参考）
药品名称：普拉格雷（prasugrel hydrochloride）
商品名为Efient
批准日期：欧盟EMEA 2009年2月25日，美国FDA2009年7月10日，公司：Daiichi Sankyo与Eli Lilly。
一般描述：
Effien含普拉格雷，为噻吩并吡啶类，是P2Y12 ADP受体介导血小板活化和集聚抑制剂。消旋普拉格雷盐酸盐化学名：5-[(1RS)-2-cyclopropyl-1-(2fluorophenyl) -2-oxoethyl]-4,5,6,7- tetrahydrothieno[3,2-c]pyridine-2-yl acetate hydrochloride。盐酸普拉格雷分子式：C20H20FNO3S?HCl，分子量：409.90。结构式：
适应证
Effient是P2Y12血小板抑制剂，适用于急性冠状动脉综合征患者用经皮冠状动脉介入疗法(PCI)减低血栓性心血管事件(包括支架血栓形成)：即不稳定性心绞痛或非-ST-升高心肌梗死(NSTEMI)；ST-升高心肌梗死(STEMI)用初期或延迟PCI处理患者。
剂量和用法
起始负荷量与或无食物单次口服60mg，继续每天1次10 mg；对< 60 kg患者每天1次5 mg；还应每天服用阿司匹林(75 mg至325 mg)。
禁忌证
1.活动性病理性出血。
2.既往短暂缺血发作或卒中。
不良反应
出血，包括危及生命和致死性出血，是报道的最常见不良反应。
黑框警告：出血风险：可引起明显、有时致死出血；急性病理性出血或短暂缺血发作或卒中患者因增加致死和颅内出血及效益不确定不要使用本品；不推荐≥ 75岁患者使用本品，除高危患者(糖尿病或既往心肌梗死[MI])外，此时作用似乎较大可考虑使用；很可能进行冠状动脉旁路手术(CABG)时不要开始用本品。有可能时任何手术前7天中断Effient。以下情况增加出血风险：
1.体重< 60 kg；
2.出血倾向；
3.同时使用增加出血风险药物。用本品时，任何低血压和近期进行冠状动脉血管造影、PCI、CABG或其它手术应怀疑出血。如可能处理出血，不停用。急性冠状动脉综合征后，特别是头几周后停用本品增加随后心血管事件风险。
新型血栓预防药物Effient(prasugrel，普拉格雷)用于预防接受经皮冠状动脉介入(PCI)治疗后的冠脉综合症患者的血栓形成。Effient帮助预防血小板凝聚成块，在接受PCI手术后使用阿司匹林与Effient已证明可降低冠脉综合症患者发生心血管事件的风险。
欧盟批准第一制药-三共公司与礼来公司联合开发的普拉格雷薄膜包衣片（prasugrel，Efient）上市，用于预防经皮冠状动脉介入治疗（PCI）急性冠状动脉综合征（ACS）患者的动脉粥样栓塞发生。本品剂量规格：普拉格雷5mg/片、10mg/片。
此次欧洲批准本品对医生和患者是个好消息，这是由于欧盟每年死于心脏病发作的患者多达70万例以上。ACS系可能威胁生命的严重疾病，本品可作为进行PCI的ACS患者重要的新治疗方法。
普拉格雷通过抑制血小板表面特异受体（P2Y12二磷酸腺苷），防止血小板凝聚（造成动脉阻塞、导致心脏病发作）来发挥作用。
一项大规模Ⅲ期临床研究显示，普拉格雷减少进行PCI的ACS患者重大心血管疾病的危险（按心血管疾病死亡、非致死性心脏病发作或非致死性休克的综合评判）优于氯吡格雷（clopidogrel，Plavix/Iscover）。
Drug Name: Efient (prasugrel)
Company: Eli Lilly
Approval Status: Approved July 2009
Treatment Area: prevention of thrombotic cardiovascular complications in acute coronary syndromes
General Information
Efient (prasugrel) works by reducing the tendency of platelets, the blood particles responsible for clotting, from sticking or clumping together. Prasugrel blocks a specific receptor on the platelet surface, P2Y12 adenosine diphosphate (ADP), and prevents platelets from clumping, which can result in clogged arteries and may lead to heart attack.
Efient is specifically indicated to reduce the rate of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome who are to be managed with percutaneous coronary intervention (PCI) as follows:Patients with unstable angina or non-ST-elevation myocardial
infarction (NSTEMI)Patients with ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI.
Efient is supplied as a 5 mg or 10 mg tablet for oral administration. The recommended initial dose of the drug is as a single 60 mg oral loading dose which may be continued at 10 mg orally once daily. Patients taking Effient should also take aspirin(75 mg to 325 mg) daily.
Dosing in Low Weight Patients Patients weighing < 60 kg have an increased exposure to the active metabolite of prasugrel and an increased risk of bleeding on a 10 mg once daily maintenance dose.
Consider lowering the maintenance dose to 5 mg in this population.
Clinical Results
FDA Approval
The FDA approval of Efient was based on the results of TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel). This multicenter, international, randomized, double-blind, parallel-group study enrolled 13,608 subjects with ACS (UA, NSTEMI, or STEMI) who were to be managed with PCI. The subjects were randomized to receive Effient(60 mg loading dose followed by 10 mg once daily) or clopidogrel(300 mg loading dose followed by 75 mg once daily), with administration and follow-up for a minimum of 6 months (actual median 14.5 months). Patients also received aspirin (75 mg to 325 mg once daily). The primary outcome measure was the composite of cardiovascular death, nonfatal MI, or nonfatal stroke in the UA/NSTEMI population. Success in this group allowed analysis of the same endpoint in the overall ACS and STEMI populations. Efient produced a statistically significant reduction in this primary endpoint of 19% when compared to Plavix (p=0.0004). This was observed as early as three days into treatment. In a subgroup of subjects with diabetes, prasugrel reduced each of the endpoints by 21% in subjects with STEMI (p=0.02) and 18% in subjects with unstable angina (p=0.002), compared to Plavix. In addition, prasugrel resulted in a 34% decline in urgent target vessel revascularization (p<0.001) and a 42% reduction in heart attack with subsequent death from cardiovascular causes (p=0.02). Prasugrel treated subjects also had a statistically significant increase in non-CABG (coronary artery bypass grafting) major bleeding compared to Plavix-treated subjects (2.4% vs. 1.8%, p=0.03).
Fatal bleeding was statistically more frequent among prasugrel-treated than clopidogrel-treated subjects (0.4% vs. 0.1%, p=0.002). Overall, prasugrel showed a higher clinical benefit over Plavix, with a significant 13% reduction in overall events (12.2 vs. 13.9, p=0.004).
Ongoing Study Commitments
Eli Lilly has agreed to conduct an open-label trial of ex vivo reversal of platelet inhibition by exogenous platelets as a function of time and plasma level of prasugrel active metabolite in 28 normal volunteers administered a single 60-mg loading dose of prasugrel plus aspirin 325 mg.
Final Protocol Submission: 09/2009
Trial Completion Date: 08/2011
Final Report Submission: 09/2011
Eli Lilly has agreed to gather baseline cancer history and cancer adverse event data from the ongoing trial TRILOGY, a 10,300-subject trial being conducted in patients with acute coronary syndrome who are being managed medically (without coronary revascularization).
Protocol Submission: 06/2008
Trial Completion Date: 12/2012
Final Report Submission: 01/2013
Eli Lilly has agreed to perform a clinical trial in the fasting and fed state, to compare the pharmacokinetics of single 60-mg doses of the marketed and new prasugrel formulations with respect to concentrations of the prasugrel active metabolite and effects on platelet inhibition.
Trial Completion Date: 08/2009
Final Report Submission: 12/2009
perform, in the presence and absence of a proton pump inhibitor, a clinical trial to compare the pharmacodynamics of single 60-mg doses of the marketed and new prasugrel formulations with respect to concentrations of the prasugrel active metabolite and effects on platelet inhibition.
Final Report Submission: 12/2009
Eli Lilly has commited to the collection of samples at baseline for genotyping CYP450 enzymes in TRILOGY subjects, to allow a comparison of effectiveness and bleeding in prasugrel and clopidogrel subgroups by metabolizer status.
Trial Completion Date: 12/2012
Final Report Submission: 01/2013
Side Effects
Adverse events associated with the use of Efient may include, but are not limited to, the following:
TIMI major or minor bleeding
Hypertension
Hypercholesterolemia/Hyperlipidemia
Headache
Back Pain
Dyspnea
Nausea
Dizziness
Mechanism of Action
Efient contains prasugrel, a thienopyridine class inhibitor of platelet activation and aggregation mediated by the P2Y12 ADP receptor. Prasugrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets.
Literature References
Michelson AD, Frelinger AL 3rd, Braunwald E, Downey WE, Angiolillo DJ, Xenopoulos NP, Jakubowski JA, Li Y, Murphy SA, Qin J, McCabe CH, Antman EM, Wiviott SD; TRITON-TIMI 38 Investigators Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial. European Heart Journal 2009
Jul;30(14):1753-63
Montalescot G, Wiviott SD, Braunwald E, Murphy SA, Gibson CM, McCabe CH, Antman EM; TRITON-TIMI 38 investigators Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009 Feb 28;373(9665):723-31
Scott DM, Norwood RM, Parra D P2Y(12) inhibitors in cardiovascular disease: focus on prasugrel.The Annals of Pharmacotherapy 2009 Jan;43(1):64-76.
Braun OO, Johnell M, Varenhorst C, James S, Brandt JT, Jakubowski JA, Winters KJ, Wallentin L, Erlinge D, Siegbahn A Greater reduction of platelet activation markers and platelet-monocyte aggregates by prasugrel compared to clopidogrel in stable coronary artery disease.
Thrombosis and Haemostasis 2008 Oct;100(4):626-33
Wiviott SD, Trenk D, Frelinger AL, O'Donoghue M, Neumann FJ, Michelson AD, Angiolillo DJ, Hod H, Montalescot G, Miller DL, Jakubowski JA, Cairns R, Murphy SA, McCabe CH, Antman EM, Braunwald E; PRINCIPLE-TIMI 44 Investigators Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 trial.
Circulation 2007 Dec 18;116(25):2923-32
Jakubowski JA, Matsushima N, Asai F, Naganuma H, Brandt JT, Hirota T, Freestone S, Winters KJ A multiple dose study of prasugrel(CS-747), a novel thienopyridine P2Y12 inhibitor, compared with clopidogrel in healthy humans. British Journal of Clinical Pharmacology 2007 Apr;63(4):421-30Wiviott SD, Antman EM, Winters KJ, Weerakkody G, Murphy SA, Behounek BD, Carney RJ, Lazzam C, McKay RG, McCabe CH, Braunwald E; JUMBO-TIMI 26 Investigators Randomized comparison of prasugrel(CS-747, LY640315), a novel thienopyridine P2Y12 antagonist, with clopidogrel in percutaneous coronary intervention: results of the Joint Utilization of Medications to Block Platelets Optimally(JUMBO)-TIMI 26 trial. Circulation 2005 Jun 28;111(25):3366-73Additional InformationFor additional information regarding Efient or thrombotic cardiovascular events in patients with acute coronary syndrome managed with PCI, please visit the Efient web page.
-----------------------------------------------------
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: 西班牙
原产地英文商品名:
EFFIENT 5mg/tab 28tabs/box
原产地英文药品名:
PRASUGREL HYDROCHLORIDE
中文参考商品译名:
EFFIENT 5毫克/片 28片/盒
中文参考药品译名:
普拉格雷
生产厂家中文参考译名:
第一制药三共公司
生产厂家英文名:
DAIICHI SANKYO ESPAÑA
------------------------------------------------------
产地国家: 德国
原产地英文商品名:
EFFIENT 5mg/tab 28tabs/box
原产地英文药品名:
PRASUGREL HYDROCHLORIDE
中文参考商品译名:
EFFIENT 5毫克/片 28片/盒
中文参考药品译名:
普拉格雷
生产厂家中文参考译名:
礼来和CO
生产厂家英文名:
Lilly Deutschland GmbH
------------------------------------------------------
产地国家: 德国
原产地英文商品名:
EFIENT 10mg/tab 28tabs/box
原产地英文药品名:
PRASUGREL HYDROCHLORIDE
中文参考商品译名:
EFIENT 10毫克/片 28片/盒
中文参考药品译名:
盐酸普拉格雷
生产厂家中文参考译名:
礼来
生产厂家英文名:
Lilly Deutschland GmbH
------------------------------------------------------
产地国家: 德国
原产地英文商品名:
EFIENT 5mg/tab 28tabs/box
原产地英文药品名:
PRASUGREL HYDROCHLORIDE
中文参考商品译名:
EFIENT 5毫克/片 28片/盒
中文参考药品译名:
盐酸普拉格雷
生产厂家中文参考译名:
礼来
生产厂家英文名:
Lilly Deutschland GmbH
------------------------------------------------------
产地国家: 加拿大
原产地英文商品名:
EFIENT 5mg/tab 28tabs/box
原产地英文药品名:
PRASUGREL HYDROCHLORIDE
中文参考商品译名:
EFIENT 5毫克/片 28片/盒
中文参考药品译名:
盐酸普拉格雷
生产厂家中文参考译名:
礼来
生产厂家英文名:
Lilly Deutschland GmbH
|
