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近日，新型抗血小板药物vorapaxar已获FDA批准上市，用于降低有心肌梗死或外周动脉疾病史患者的心梗、卒中、心血管死亡以及需要冠脉血运重建术风险。
Vorapaxar是一种可抑制血小板凝血酶活性的蛋白酶活化受体-1（PAR-1）拮抗剂，也是这类药物中首个获批的药物。默沙东将以商品名Zontivity上市该药物，剂型为片剂。
批准日期：2014年5月8日；公司：默沙东
ZONTIVITY(沃拉帕沙[vorapaxar])片2.08 mg*,为口服使用[*等同于2.5mg硫酸vorapaxar]
美国初次批准：2014
作用机制
Vorapaxar是一种表达在血小板上蛋白酶激活受体-1(PAR-1)的可逆性拮抗剂，但其长半衰期使它有效地不逆转。在体外研究中Vorapaxar抑制凝血酶-诱导和凝血酶受体激动剂肽(TRAP)-诱导的血小板聚集。Vorapaxar不抑制通过二磷酸腺苷(ADP)，胶原或一个血栓素模拟物诱导血小板聚集和在体外[ex vivo]不影响凝血参数。PAR-1受体也在广泛各种细胞类型上表达，包括内皮细胞，神经元，和平滑肌细胞，但未曾在这些类型细胞中评估药效动力学作用。
适应证和用途
ZONTIVITY是一种蛋白酶激活受体-1(PAR-1)拮抗剂适用为心肌梗死(MI)或有外周动脉疾病(PAD)史患者中血栓性心血管事件的减低。ZONTIVITY曾显示减低心血管死亡，MI，中风，和紧急冠状动脉血运重建的组合终点发生率。
剂量和给药方法
⑴ 口服一片ZONTIVITY每天1次。
⑵按其适应证或标准医护与阿司匹林[aspirin]和/或氯吡格雷[clopidogrel]使用。用其他抗血小板药物临床经验有限或用ZONTIVITY作为唯一的抗血小板药物。
剂型和规格
片：2.08mg vorapaxar。
禁忌证
⑴ 中风，TIA，或ICH史。
⑵ 活动性病理性出血。
警告或无注意事项
⑴ 像其他抗血小板药物，ZONTIVITY增加出血风险。
⑵ 避免使用强CYP3A抑制剂或诱导剂。
不良反应
出血，包括危及生命和致命性出血，是最常见报道的不良反应。
包装规格 [注：以下美国上市产品，不同规格和不同价格，采购者以咨询为准]
ZONTIVITY TAB 2.08MG 30 VORAPAXAR SULFATE MERCK SHARP & DOHME 00006-0351-31
ZONTIVITY TAB 2.08MG 90 VORAPAXAR SULFATE MERCK SHARP & DOHME 00006-0351-54
ZONTIVITY TB 2.08MG UD 100 VORAPAXAR SULFATE MERCK SHARP & DOHME 00006-0351-48
ZONTIVITY TAB 2.08MG 30 VORAPAXAR SULFATE ARALEZ PHARMACEUTICALS US 70347-0208-30
ZONTIVITY TAB 2.08MG 30 VORAPAXAR SULFATE SPS/ARALEZ PHARMACEUTICAL 70347-0208-30
ZONTIVITY TAB 2.08MG 90 VORAPAXAR SULFATE SPS/ARALEZ PHARMACEUTICAL 70347-0208-90
ZONTIVITY TAB 2.08MG 90 VORAPAXAR SULFATE ARALEZ PHARMACEUTICALS US 70347-0208-90
ZONTIVITY® (vorapaxar) has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke, and urgent coronary revascularization
Indications and Usage
ZONTIVITY is a protease-activated receptor-1 (PAR-1) antagonist indicated for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD). ZONTIVITY has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke, and urgent coronary revascularization.
Important Safety Information
Warning: Bleeding Risk
•Do not use ZONTIVITY in patients with a history of stroke, transient ischemic attack (TIA), or intracranial hemorrhage (ICH), or with active pathological bleeding
•Antiplatelet agents, including ZONTIVITY, increase the risk of bleeding, including ICH and fatal bleeding
ZONTIVITY is contraindicated in patients with a history of stroke, TIA, or ICH and in patients with active pathological bleeding. Discontinue ZONTIVITY in patients who experience a stroke, TIA, or ICH.
ZONTIVITY increases the risk of bleeding (which may include ICH and fatal bleeding) in proportion to the patient’s underlying bleeding risk. Consider the underlying risk of bleeding before initiating ZONTIVITY. General risk factors for bleeding include older age, low body weight, reduced renal or hepatic function, and history of bleeding disorders.
Use of certain concomitant medications (eg, anticoagulants, fibrinolytic therapy, chronic nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors) also increases the risk of bleeding.
Avoid concomitant use of warfarin or other anticoagulants due to the risk of bleeding. Avoid concomitant use of strong CYP3A inhibitors or inducers due to their effect on ZONTIVITY exposure.
Withholding ZONTIVITY for a brief period will not be useful in managing an acute bleeding event due to its long half-life. There is no known treatment to reverse the antiplatelet effect of ZONTIVITY.
ZONTIVITY is not recommended in patients with severe hepatic impairment.
Bleeding, including life-threatening and fatal bleeding, is the most commonly reported adverse reaction with ZONTIVITY.
•Any GUSTO bleeding (severe/moderate/mild) occurred in 27.7% of patients taking ZONTIVITY and in 19.8% of patients taking placebo (HR 1.52: 95% CI [1.43-1.61]) -GUSTO moderate or severe bleeding, 3.7% vs 2.4%, HR 1.55 (1.30-1.86)
-GUSTO severe bleeding, 1.3% vs 1.0%, HR 1.24 (0.92-1.66)
•Clinically significant bleeding (bleeding requiring medical attention including ICH, or overt signs of hemorrhage with a drop in Hgb ≥3 g/dL or when Hgb is not available, an absolute drop in Hct ≥9%) over 3 years occurred in 15.5% of patients taking ZONTIVITY and in 10.9% of patients taking placebo (HR 1.47: 95% CI [1.35-1.60])
To report SUSPECTED ADVERSE EVENTS, contact Aralez Pharmaceuticals at 1-866-207-6592 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. |
