Vescap二十碳五烯酸乙酯说明书

Ziska Pharmaceuticals Ltd.（齐斯卡制药有限公司）

简介

Vescap 是二十碳五烯酸 （EPA） 的乙酯，适应症：

作为最大耐受他汀类药物治疗的辅助手段，以降低甘油三酯 （TG） 水平升高 （≥ 150 mg/dL） 和

• 确诊的心血管疾病或

• 糖尿病和 2 个或更多心血管疾病的其他危险因素。

作为饮食的辅助手段，以降低重度 （≥500 mg/dL） 高甘油三酯血症成年患者的 TG 水平。

使用限制：Vescap对严重高甘油三酯血症患者胰腺炎风险的影响尚未确定。

药理学

研究表明，EPA可减少肝脏极低密度脂蛋白甘油三酯（VLDL-TG）的合成和/或分泌，并增强循环VLDL颗粒的TG清除率。潜在的作用机制包括增加β氧化;抑制酰基辅酶A：1,2-二酰基甘油酰基转移酶（DGAT）;肝脏脂肪生成减少;并增加血浆脂蛋白脂肪酶活性。

使用二十碳五烯酸乙基减少心血管事件的作用机制尚不完全清楚，但可能是多因素的。在 EPA 治疗后，观察到颈动脉斑块标本的 EPA 脂质成分增加，循环 EPA/花生四烯酸比率增加。EPA在某些离体条件下抑制血小板聚集。然而，个体发现的直接临床意义尚不清楚。

剂量与给药

在开始治疗前评估血脂水平。确定甘油三酯水平升高的其他原因，并酌情进行管理。

患者在接受二十碳五烯醇乙基药物之前应进行适当的营养摄入和身体活动，治疗期间应继续进行。

二十碳五醇乙基的日剂量为每天 4 克，作为 -

• 每日两次，每次 4 粒 0.5 克胶囊，随餐服用，或

• 每日两次，每次 2 粒 1 克胶囊，随餐服用。

建议患者吞服整个胶囊。请勿掰开、压碎、溶解或咀嚼二十碳五烯酸乙酯。

儿科使用：儿科患者的安全性和有效性尚未确定。

老年使用：在二十碳五醇乙酯对照良好的临床研究中，45%的患者年龄在65岁及以上。在这些患者和年轻组之间没有观察到安全性或有效性的总体差异。其他报告的临床经验尚未确定老年患者和年轻患者之间的反应差异。

肝功能损害：在肝功能损害患者中，丙氨酸氨基转移酶 （ALT） 和天冬氨酸氨基转移酶 （AST） 水平应在乙基二十碳五戊治疗期间定期监测。

* 遵医嘱服药'

互动

抗凝剂和抗血小板药物增加出血风险：一些已发表的 omega-3 脂肪酸研究表明，出血时间延长。监测接受 Vescap 和伴随抗凝剂和/或抗血小板药物治疗的患者出血情况。

禁忌

对于已知对二十碳五醇乙基或其任何成分过敏（例如过敏反应）的患者，这是禁忌的。

副作用

心血管结局试验中的常见不良反应（发生率≥3%，比安慰剂高≥1%）：肌肉骨骼疼痛、外周水肿、便秘、痛风和心房颤动。

高甘油三酯血症试验中的常见不良反应（发生率≥比安慰剂高 1%）：关节痛和口咽痛。

怀孕和哺乳期

哺乳：已发表的病例报告和药物警戒数据库中关于孕妇使用二十碳五戊乙酯的可用数据不足以确定与药物相关的重大出生缺陷、流产或不良母体或胎儿结局的风险。

哺乳期：已发表的研究在母乳中检测到 omega-3 脂肪酸，包括 EPA。哺乳期妇女口服 omega-3 脂肪酸补充剂后，母乳中 omega-3 脂肪酸含量升高。没有关于omega-3脂肪酸乙酯对母乳喂养婴儿或产奶量影响的数据。母乳喂养对发育和健康的益处应与母亲对二十碳五戊乙酯的临床需求以及二十碳五烯乙酯或潜在的母体疾病对母乳喂养儿童的任何潜在不利影响一起考虑。

注意事项和警告

心房颤动/扑动：在一项双盲、安慰剂对照试验中，Vescap 与心房颤动或需要住院治疗的心房颤动风险增加有关。在既往有心房颤动或心房扑动病史的患者中，心房颤动的发生率更高。

鱼类过敏患者过敏反应的可能性：Vescap 含有从鱼油中获得的 omega-3 脂肪酸二十碳五烯酸 （EPA） 的乙酯。目前尚不清楚对鱼类和/或贝类过敏的患者是否对 Vescap 过敏反应的风险增加。告知已知对鱼类和/或贝类过敏的患者过敏反应的可能性，并建议他们停用 Vescap，并在出现任何反应时就医。

出血：在一项双盲、安慰剂对照试验中，Vescap 与出血风险增加有关。同时接受抗血栓药物（如阿司匹林、氯吡格雷或华法林）的患者出血发生率更高。

治疗类

其他抗心绞痛和抗缺血药物

Indications

Vescap is an ethyl ester of eicosapentaenoic acid (EPA) indicated:

As an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated triglyceride (TG) levels (≥ 150 mg/dL) and

• Established cardiovascular disease or

• Diabetes mellitus and 2 or more additional risk factors for cardiovascular disease.

As an adjunct to diet to reduce TG levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia.

Limitations of use: The effect of Vescap on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined.

Pharmacology

Studies suggest that EPA reduces hepatic very low-density lipoprotein triglycerides (VLDL-TG) synthesis and/or secretion and enhances TG clearance from circulating VLDL particles. Potential mechanisms of action include increased β-oxidation; inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase (DGAT); decreased lipogenesis in the liver; and increased plasma lipoprotein lipase activity.

The mechanisms of action contributing to reduction of cardiovascular events with Icosapent Ethyl are not completely understood but are likely multi-factorial. Increased EPA lipid composition from carotid plaque specimens and increased circulating EPA/arachidonic acid ratio have been observed following EPA treatment. EPA inhibits platelet aggregation under some ex vivo conditions. However, the direct clinical meaning of individual findings is not clear.

Dosage & Administration

Assess lipid levels before initiating therapy. Identify other causes of high triglyceride levels and manage as appropriate.

Patients should engage in appropriate nutritional intake and physical activity before receiving Icosapent Ethyl, which should continue during treatment.

The daily dose of Icosapent Ethyl is 4 grams per day taken as either-

• Four 0.5 gram capsules twice daily with food or

• Two 1 gram capsules twice daily with food.

Advise patients to swallow capsules whole. Do not break open, crush, dissolve, or chew Icosapent Ethyl.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: Of the total number of patients in well-controlled clinical studies of Icosapent Ethyl, 45% were 65 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger groups. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Hepatic Impairment: In patients with hepatic impairment, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels should be monitored periodically during therapy with Icosapent Ethyl.

* চিকিৎসকের পরামর্শ মোতাবেক ঔষধ সেবন করুন'

Interaction

Increased Bleeding Risk with Anticoagulants and Antiplatelet Agents: Some published studies with omega-3 fatty acids have demonstrated prolongation of bleeding time. Monitor patients receiving Vescap and concomitant anticoagulants and/or antiplatelet agents for bleeding.

Contraindications

This is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to Icosapent Ethyl or any of its components.

Side Effects

Common adverse reactions in the cardiovascular outcomes trial (incidence ≥3% and ≥1% more frequent than placebo): musculoskeletal pain, peripheral edema, constipation, gout, and atrial fibrillation.

Common adverse reactions in the hypertriglyceridemia trials (incidence ≥1% more frequent than placebo): arthralgia and oropharyngeal pain.

Pregnancy & Lactation

Lactation: The available data from published case reports and the pharmacovigilance database on the use of Icosapent Ethyl in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes.

Lactation: Published studies have detected omega-3 fatty acids, including EPA, in human milk. Lactating women receiving oral omega-3 fatty acids for supplementation have resulted in higher levels of omega-3 fatty acids in human milk. There are no data on the effects of omega-3 fatty acid ethyl esters on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Icosapent Ethyl and any potential adverse effects on the breastfed child from Icosapent Ethyl or from the underlying maternal condition.

Precautions & Warnings

Atrial Fibrillation/Flutter: Vescap was associated with an increased risk of atrial fibrillation or atrial flutter requiring hospitalization in a double-blind, placebo-controlled trial. The incidence of atrial fibrillation was greater in patients with a previous history of atrial fibrillation or atrial flutter.

Potential for Allergic Reactions in Patients with Fish Allergy: Vescap contains ethyl esters of the omega-3 fatty acid, eicosapentaenoic acid (EPA), obtained from the oil of fish. It is not known whether patients with allergies to fish and/or shellfish are at increased risk of an allergic reaction to Vescap. Inform patients with known hypersensitivity to fish and/or shellfish about the potential for allergic reactions and advise them to discontinue Vescap and seek medical attention if any reactions occur.

Bleeding: Vescap was associated with an increased risk of bleeding in a double-blind, placebo-controlled trial. The incidence of bleeding was greater in patients receiving concomitant antithrombotic medications, such as aspirin, clopidogrel, or warfarin.

Therapeutic Class

Other Anti-anginal & Anti-ischaemic drugs