波立维说明书

合集下载

硫酸氢氯吡格雷片(波立维)国外说明书

核准日期：硫酸氢氯吡格雷片说明书请仔细阅读说明书并在医师指导下使用【药品名称】通用名：硫酸氢氯吡格雷片英文名：Clopidogrel Hyd rogen Sulphate Tablets汉语拼音：Liusuanqinglubigelei Pian本品主要成份为：硫酸氢氯吡格雷化学名称为：：甲基(+)-(s)-α-邻氯苯基-6，7-二氢噻吩[3，2-C]吡啶-5(4H)-乙酸酯硫酸氢盐，其结构式为：分子式：C16H16ClNO2S·H2SO4分子量：419.9【性状】硫酸氢氯吡格雷片75mg 薄膜衣片剂呈粉红色，圆形双凸，薄膜包衣，一面刻有《75》，另一面刻有《1171》字样。

【适应症】氯吡咯雷用于以下患者的预防动脉粥样硬化血栓形成事件：·心肌梗死患者（从几天到小于35 天）、缺血性卒中患者（从7 天到小于6 个月）或确诊外周动脉性疾病的患者。

·急性冠脉综合征的患者-非ST 段抬高性急性冠脉综合征（包括不稳定性心绞痛或非Q波心肌梗死），包括经皮冠状动脉介入术后置入支架的患者，与阿司匹林合用。

-用于ST 段抬高性急性冠脉综合征患者，与阿司匹林联合，可合并在溶栓治疗中使用。

【规格】75 mg【用法用量】成人和老年人硫酸氢氯吡格雷片的推荐剂量为每天75mg，与或不与食物同服。

对于急性冠脉综合征的患者：-非ST 段抬高性急性冠脉综合征（不稳定性心绞痛或非Q波心肌梗死）患者，应以单次负荷量氯吡格雷300 mg开始，然后以75 mg每日1 次连续服药（合用阿司匹林75 mg-325 mg/日）。

由于服用较高剂量的阿司匹林有较高的出血危险性，故推荐阿司匹林的剂量不应超过100 mg。

最佳疗程尚未正式确定。

临床试验资料支持用药12个月，用药3个月后表现出最大效果。

-ST段抬高性急性心肌梗死：应以负荷量氯吡格雷开始，然后以75 mg每日1次，合用阿司匹林，可合用或不合用溶栓剂。

对于年龄超过75岁的患者，不使用氯吡格雷负荷剂量。

波立维说明书

药品商品名称波立维药品正式名称硫酸氢氯吡格雷药品英文名称Plavix药品规格75mg*7粒/盒基本药理血小板聚集抑制剂，通过选择性抑制二磷酸腺苷（ADP）与血小板结合及继发由ADP介导的糖蛋白复合物活化。

临床用途适用于有过近期发作的中风、心肌梗塞和确诊外周动脉硬化的患者，波立维（氯吡格雷）可减少动脉粥样硬化性事件的发生（如心肌梗塞，中风和血管性死亡）。

给药途径及用量推荐剂量每日75mg，对老年患者和肾病患者不需调整剂量[用法用量]：推荐剂量为每天75mg，与或不与食物同服。

对于老年患者和肾病患者不需调整剂量。

[不良反应]：出血，波立维（氯吡格雷）严重出血事件的发生率分别为1.4% 胃肠道：如腹痛，消化不良，胃炎和便秘皮疹和其它皮肤病中枢和周围神经系统：头痛、眩晕、头昏和感觉异常肝脏和胆道疾病禁忌证对药品或本品任一成分过敏严重的肝脏损伤活动性病理性出血，如消化性溃疡或颅内出血注意事项：氯吡格雷延长出血时间，对于有伤口（特别是在胃肠道和眼内）易出血的病人应慎用。

病人应知服用波立维止血时间可能比往常长，同时病人应向医生报告异常出血情况，手术前和服用其它新药前病人应告知医生他们在服用波立维。

由于患有肾脏损伤病人使用氯吡格雷的经验极有限，因此这些病人应慎用波立维（氯吡格雷）。

严重肝病的病人可能有出血倾向，这类病人使用本药的经验极有限，应慎用波立维。

由于服用华法令也有出血倾向，所以服用时不推荐同时使用华法令。

对于同时服用易出现胃肠道伤口的药物（如非甾体消炎药）的病人应慎用波立维未见服用本药后对驾驶或心理学检测产生影响不建议孕妇及哺乳期妇女服用此药。

在儿科使用的安全性和有效性还未明确。

我有一位家属患有“冠心病”伴高血压，去年做了支架手术，现在常期靠药物来维持，当然也包括波立维，不过波立维的价钱挺贵的，一般都要20多块钱一颗。

【批准文号】国药准字H20056410【中文名称】硫酸氢氯吡格雷片【产品英文名称】Clopidogrel Sulfate Tablets【生产企业】杭州赛诺菲安万特民生制药有限公司【功效主治】预防和治疗因血小板高聚集状态引起的心、脑及其它动脉的循环障碍疾病。

国产波立维信息

病人应知服用波立维止血时间可能比往常长，同时病人应向医生报告异常出血情况，手术前和服用其它新药前病人应告知医生他们在服用波立维。

由于患有肾脏损伤病人使用氯吡格雷的经验极有限，因此这些病人应慎用波立维（氯吡格雷）。

严重肝病的病人可能有出血倾向，这类病人使用本药的经验极有限，应慎用波立维。

由于服用华法令也有出血倾向，所以服用时不推荐同时使用华法令。

在儿科使用的安全性和有效性还未明确。

药品商品名称波立维药品正式名称硫酸氢氯吡格雷药品英文名称 Plavix药品规格 75mg*7粒/盒基本药理血小板聚集抑制剂，通过选择性抑制二磷酸腺苷（ADP）与血小板结合及继发由ADP介导的糖蛋白复合物活化。

给药途径及用量推荐剂量每日75mg，对老年患者和肾病患者不需调整剂量[用法用量]：推荐剂量为每天75mg，与或不与食物同服。

对于老年患者和肾病患者不需调整剂量。

波立维说明书

波立维说明书
一、波立维说明书二、波立维的用法用量三、波立维的注意事项
波立维说明书1、波立维的功能主治
氯吡格雷用于以下患者的预防动脉粥样硬化血栓形成事件; --心肌梗死患者(从几天到小于35天)、缺血性卒中患者(从7天到小于6个月)或确诊外周动脉性疾病的患者。

--急性冠脉综合症的患者 -非ST段抬高性急性冠脉综合症(包括不稳定性心绞痛或非Q波心肌梗死),包括经皮冠状动脉介入术后置入支架的患者与阿司匹林合用。

-用于ST段抬高性急性冠脉综合症患者,与阿司匹林联合,可合并在溶栓治疗中使用。

2、波立维的禁忌
2.1、对药品或本品任一成份过敏。

2.2、严重的肝脏损伤。

2.3、活动性病理性出血,如消化性溃疡或颅内出血。

2.4、哺乳(参见妊娠和哺乳)。

3、波立维的药物相互作用
阿斯匹林:本品增加阿斯匹林对胶原引起的血小板聚集的抑制效果,长期合并用药的安全性无进一步的研究资料。

肝素:健康志愿者研究表明,本品与肝素无相互作用。

但合并用药时应小心。

非甾体抗炎药(NSAIDs):健康志愿者同时服用本品和萘普生,胃肠潜血损失增加,故本品与NSAIDs合用时应小心。

法华令:无合并用药的安全性研究。

4、波立维的药理作用。

波立维说明书

说明书【药品名称】硫酸氢氯吡格雷片【商品名】波立维【英文商品名】PLAVIX【英文名】Clopidogrel Hydrogen Sulfate Tablets【汉语拼音】Liusuanlubigelei Pian【成份】本品的主要成份为氯吡格雷。

【性状】本品为粉红色圆形薄膜衣片。

化学名称：甲基（+）-（S）-α-邻氯苯基-6，7-二氢噻吩[3，2-C]吡啶-5（4H）-乙酸酯硫酸氢盐分子式：C16H16ClNO2S·H2SO4 分子量：419.9【适应证】本品适用于有过近期发作的中风，心肌梗死和确诊外周动脉疾病的患者，该药可减少动脉粥样硬化性事件的发生（如心肌梗死，中风和血管性死亡）。

与阿司匹林联合，用于非ST段抬高性冠脉综合征（不稳定性心绞痛或非Q波心肌梗死）患者。

【规格】75mg【用法用量】波立维的推荐剂量为每天75mg，与或不与食物同服。

对于老年患者和肾病患者不需调整剂量。

非ST段抬高性急性冠脉综合征（不稳定性心绞痛或非Q波心肌梗塞死）患者，应以单次负荷量氯吡格雷300mg开始，然后以75mg每日一次连续服用（合用阿司匹林75mg-325mg/日）。

由于服用较高剂量的阿司匹林伴随有较高的出血危险性，故推荐阿司匹林的剂量不应超过100mg。

最佳疗程尚未正式确定。

临床实验资料支持用药12个月，用药3个月时的益处最大（参见药效学特征）。

儿童和未成年人：18岁以下受试者的安全性、有效性尚未建立。

【不良反应】临床研究经验：已在17500多例患者中对氯吡格雷的安全性进行了评价，其中9000例患者治疗不少于1年。

在CAPRIE研究中，与阿司匹林325mg/日相比，氯吡格雷75mg/日的耐受性较好。

在该研究中，氯吡格雷的总体耐受性与阿司匹林相似，与年龄、性别及种族无关。

在CAPRIE和CURE研究中观察到以下有临床意义的不良反应：出血性疾患：在CAPRIE研究，接受氯吡格雷或阿司匹林治疗的患者，出血事件的总体发生率均为9.3%。

硫酸氢氯吡格雷片说明书(美国,FDA,英文)

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to usePLAVIX safely and effectively. See full prescribing information forPLAVIX.PLAVIX (clopidogrel bisulfate) tabletsInitial U.S. Approval: 1997WARNING: DIMINISHED EFFECTIVENESS IN POORMETABOLIZERSSee full prescribing information for complete boxed warning.• Effectiveness of Plavix depends on activation to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19. (5.1)• Poor metabolizers treated with Plavix at recommended doses exhibit higher cardiovascular event rates following acute coronary syndrome(ACS) or percutaneous coronary intervention (PCI) than patients withnormal CYP2C19 function. (12.5)• Tests are available to identify a patient's CYP2C19 genotype and can be used as an aid in determining therapeutic strategy. (12.5)• Consider alternative treatment or treatment strategies in patients identified as CYP2C19 poor metabolizers. (2.3, 5.1)----------------------------RECENT MAJOR CHANGES--------------------------BoxedWarning 03/2010 Dosage and Administration (2.3, 2.4) 08/2010 Warnings and Precautions (5.1, 5.2, 5.3) 08/2010----------------------------INDICATIONS AND USAGE---------------------------Plavix is a P2Y12 platelet inhibitor indicated for:• Acute coronary syndrome- For patients with non-ST-segment elevation ACS [unstable angina(UA)/non-ST-elevation myocardial infarction (NSTEMI)] includingpatients who are to be managed medically and those who are to bemanaged with coronary revascularization, Plavix has been shown todecrease the rate of a combined endpoint of cardiovascular death,myocardial infarction (MI), or stroke as well as the rate of a combinedendpoint of cardiovascular death, MI, stroke, or refractory ischemia.(1.1)- For patients with ST-elevation myocardial infarction (STEMI), Plavixhas been shown to reduce the rate of death from any cause and the rateof a combined endpoint of death, re-infarction, or stroke. The benefitfor patients who undergo primary PCI is unknown. (1.1)• Recent myocardial infarction (MI), recent stroke, or established peripheral arterial disease. Plavix has been shown to reduce the combined endpoint ofnew ischemic stroke (fatal or not), new MI (fatal or not), and othervascular death. (1.2)----------------------DOSAGE AND ADMINISTRATION----------------------• Acute coronary syndrome (2.1)- Non-ST-segment elevation ACS (UA/NSTEMI): 300 mg loading dosefollowed by 75 mg once daily, in combination with aspirin(75-325 mg once daily)- STEMI: 75 mg once daily, in combination with aspirin (75-325 mgonce daily), with or without a loading dose and with or withoutthrombolytics• Recent MI, recent stroke, or established peripheral arterial disease: 75 mg once daily (2.2)---------------------DOSAGE FORMS AND STRENGTHS---------------------Tablets: 75 mg, 300 mg (3)-------------------------------CONTRAINDICATIONS-----------------------------• Active pathological bleeding, such as peptic ulcer or intracranial hemorrhage (4.1)• Hypersensitivity to clopidogrel or any component of the product (4.2)-----------------------WARNINGS AND PRECAUTIONS------------------------ • Reduced effectiveness in impaired CYP2C19 function: Avoid concomitant use with drugs that are strong or moderate CYP2C19 inhibitors (e.g.,omeprazole). (5.1)• Bleeding: Plavix increases risk of bleeding. Discontinue 5 days prior to elective surgery. (5.2)• Discontinuation of Plavix: Premature discontinuation increases risk of cardiovascular events. (5.3)• Recent transient ischemic attack or stroke: Combination use of Plavix and aspirin in these patients was not shown to be more effective than Plavix alone, but was shown to increase major bleeding. (5.4)• Thrombotic thrombocytopenic purpura (TTP): TTP has been reported with Plavix, including fatal cases. (5.5)------------------------------ADVERSE REACTIONS------------------------------Bleeding, including life-threatening and fatal bleeding, is the most commonly reported adverse reaction. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership at 1-800-633-1610 or FDA at 1-800-FDA-1088 or /medwatch.------------------------------DRUG INTERACTIONS-------------------------------• Nonsteroidal anti-inflammatory drugs (NSAIDs): Combination use increases risk of gastrointestinal bleeding. (7.2)• Warfarin: Combination use increases risk of bleeding. (7.3)------------------------USE IN SPECIFIC POPULATIONS-----------------------Nursing mothers: Discontinue drug or nursing, taking into consideration importance of drug to mother. (8.3)See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.Revised: 2010FULL PRESCRIBING INFORMATION: CONTENTS*WARNING: DIMINISHED EFFECTIVENESS IN POOR METABOLIZERS1 INDICATIONS AND USAGE1.1 Acute Coronary Syndrome (ACS)1.2 Recent MI, Recent Stroke, or Established Peripheral ArterialDisease2 DOSAGE AND ADMINISTRATION2.1 Acute Coronary Syndrome2.2 Recent MI, Recent Stroke, or Established Peripheral ArterialDisease2.3 CYP2C19 Poor Metabolizers2.4 Use with Proton Pump Inhibitors (PPI)3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS4.1 Active Bleeding4.2 Hypersensitivity5 WARNINGS AND PRECAUTIONS5.1 Diminished Antiplatelet Activity Due to Impaired CYP2C19Function5.2 General Risk of Bleeding5.3 Discontinuation of Plavix5.4 Patients with Recent Transient Ischemic Attack (TIA) orStroke5.5 Thrombotic Thrombocytopenic Purpura (TTP)6 ADVERSE REACTIONS6.1 Clinical Studies Experience6.2 Postmarketing Experience7 DRUG INTERACTIONS7.1 CYP2C19 Inhibitors7.2 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)7.3 Warfarin (CYP2C9 Substrates)8 USE IN SPECIFIC POPULATIONS* Sections or subsections omitted from the full prescribing information are not listed.8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Renal Impairment8.7 Hepatic Impairment10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics12.5 Pharmacogenomics13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility14 CLINICAL STUDIES14.1 Acute Coronary Syndrome14.2 Recent Myocardial Infarction, Recent Stroke, or EstablishedPeripheral Arterial Disease14.3 Lack of Established Benefit of Plavix plus Aspirin in Patientswith Multiple Risk Factors or Established Vascular Disease16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION17.1 Benefits and Risks17.2 Bleeding17.3 Other Signs and Symptoms Requiring Medical Attention17.4 Invasive Procedures17.5 Concomitant Medications17.6 Medication GuideFULL PRESCRIBING INFORMATIONWARNING: DIMINISHED EFFECTIVENESS IN POOR METABOLIZERSThe effectiveness of Plavix is dependent on its activation to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19 [see Warnings and Precautions (5.1)]. Plavix at recommended doses forms less of that metabolite and has a smaller effect on platelet function in patients who are CYP2C19 poor metabolizers. Poor metabolizers with acute coronary syndrome or undergoing percutaneous coronary intervention treated with Plavix at recommended doses exhibit higher cardiovascular event rates than do patients with normal CYP2C19 function. Tests are available to identify a patient's CYP2C19 genotype; these tests can be used as an aid in determining therapeutic strategy [see Clinical Pharmacology (12.5)]. Consider alternative treatment or treatment strategies in patients identified as CYP2C19 poor metabolizers [see Dosage and Administration (2.3)].1 INDICATIONS AND USAGE1.1 Acute Coronary Syndrome (ACS)• For patients with non-ST-segment elevation ACS [unstable angina (UA)/non-ST-elevation myocardial infarction (NSTEMI)], including patients who are to be managed medically and those who are to be managed with coronary revascularization, Plavix has been shown todecrease the rate of a combined endpoint of cardiovascular death, myocardial infarction (MI), or stroke as well as the rate of a combined endpoint of cardiovascular death, MI, stroke, or refractory ischemia.• For patients with ST-elevation myocardial infarction (STEMI), Plavix has been shown to reduce the rate of death from any cause and the rate of a combined endpoint of death,re-infarction, or stroke. The benefit for patients who undergo primary percutaneous coronary intervention is unknown.The optimal duration of Plavix therapy in ACS is unknown.1.2 Recent MI, Recent Stroke, or Established Peripheral Arterial DiseaseFor patients with a history of recent myocardial infarction (MI), recent stroke, or established peripheral arterial disease, Plavix has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death.2 DOSAGE AND ADMINISTRATION2.1 Acute Coronary SyndromePlavix can be administered with or without food [see Clinical Pharmacology (12.3)].• For patients with non-ST-elevation ACS (UA/NSTEMI), initiate Plavix with a single 300 mg oral loading dose and then continue at 75 mg once daily. Initiate aspirin (75-325 mg once daily) and continue in combination with Plavix [see Clinical Studies (14.1)].• For patients with STEMI, the recommended dose of Plavix is 75 mg once daily orally, administered in combination with aspirin (75-325 mg once daily), with or withoutthrombolytics. Plavix may be initiated with or without a loading dose [see Clinical Studies(14.1)].2.2 Recent MI, Recent Stroke, or Established Peripheral Arterial DiseaseThe recommended daily dose of Plavix is 75 mg once daily orally, with or without food [see Clinical Pharmacology (12.3)].2.3 CYP2C19 Poor MetabolizersCYP2C19 poor metabolizer status is associated with diminished antiplatelet response to clopidogrel. Although a higher dose regimen in poor metabolizers increases antiplatelet response [see Clinical Pharmacology (12.5)], an appropriate dose regimen for this patient population has not been established.2.4 Use with Proton Pump Inhibitors (PPI)Omeprazole, a moderate CYP2C19 inhibitor, reduces the pharmacological activity of Plavix. Avoid using omeprazole concomitantly or 12 hours apart with Plavix. Consider using another acid-reducing agent with less CYP2C19 inhibitory activity. A higher dose regimen of clopidogrel concomitantly administered with omeprazole increases antiplatelet response; an appropriate dose regimen has not been established [see Warnings and Precautions (5.1), Drug Interactions (7.1) and Clinical Pharmacology (12.5)].3 DOSAGE FORMS AND STRENGTHS• 75 mg tablets: Pink, round, biconvex, film-coated tablets debossed with “75” on one side and “1171” on the other• 300 mg tablets: Pink, oblong, film-coated tablets debossed with “300” on one side and “1332” on the other4 CONTRAINDICATIONS4.1 Active BleedingPlavix is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage.4.2 HypersensitivityPlavix is contraindicated in patients with hypersensitivity (e.g., anaphylaxis) to clopidogrel or any component of the product [see Adverse Reactions (6.2)].5 WARNINGS AND PRECAUTIONS5.1 Diminished Antiplatelet Activity Due to Impaired CYP2C19 FunctionClopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by genetic variations in CYP2C19 [see Boxed Warning] and by concomitant medications that interfere with CYP2C19. Avoid concomitant use of Plavix and strong or moderate CYP2C19 inhibitors.Omeprazole, a moderate CYP2C19 inhibitor, has been shown to reduce the pharmacological activity of Plavix if given concomitantly or if given 12 hours apart. Consider using anotheracid-reducing agent with less CYP2C19 inhibitory activity. Pantoprazole, a weak CYP2C19 inhibitor, had less effect on the pharmacological activity of Plavix than omeprazole [see Drug Interactions (7.1) and Dosage and Administration (2.4)].5.2 General Risk of BleedingThienopyridines, including Plavix, increase the risk of bleeding. If a patient is to undergo surgery and an antiplatelet effect is not desired, discontinue Plavix five days prior to surgery. In patients who stopped therapy more than five days prior to CABG the rates of major bleeding were similar (event rate 4.4% Plavix + aspirin; 5.3% placebo + aspirin). In patients who remained on therapy within five days of CABG, the major bleeding rate was 9.6% for Plavix + aspirin, and 6.3% for placebo + aspirin.Thienopyridines inhibit platelet aggregation for the lifetime of the platelet (7-10 days), so withholding a dose will not be useful in managing a bleeding event or the risk of bleeding associated with an invasive procedure. Because the half-life of clopidogrel’s active metabolite is short, it may be possible to restore hemostasis by administering exogenous platelets; however, platelet transfusions within 4 hours of the loading dose or 2 hours of the maintenance dose may be less effective.5.3 Discontinuation of PlavixAvoid lapses in therapy, and if Plavix must be temporarily discontinued, restart as soon as possible. Premature discontinuation of Plavix may increase the risk of cardiovascular events. 5.4 Patients with Recent Transient Ischemic Attack (TIA) or StrokeIn patients with recent TIA or stroke who are at high risk for recurrent ischemic events, the combination of aspirin and Plavix has not been shown to be more effective than Plavix alone, but the combination has been shown to increase major bleeding.5.5 Thrombotic Thrombocytopenic Purpura (TTP)TTP, sometimes fatal, has been reported following use of Plavix, sometimes after a short exposure (<2 weeks). TTP is a serious condition that requires urgent treatment including plasmapheresis (plasma exchange). It is characterized by thrombocytopenia, microangiopathic hemolytic anemia (schistocytes [fragmented RBCs] seen on peripheral smear), neurological findings, renal dysfunction, and fever [see Adverse Reactions (6.2)].6 ADVERSE REACTIONSThe following serious adverse reactions are discussed below and elsewhere in the labeling: • Bleeding [see Warnings and Precautions (5.2)]• Thrombotic thrombocytopenic purpura [see Warnings and Precautions (5.5)]6.1 Clinical Studies ExperienceBecause clinical trials are conducted under widely varying conditions and durations of follow up, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.Plavix has been evaluated for safety in more than 54,000 patients, including over 21,000 patientstreated for 1 year or more. The clinically important adverse reactions observed in trialscomparing Plavix plus aspirin to placebo plus aspirin and trials comparing Plavix alone to aspirinalone are discussed below.BleedingCUREIn CURE, Plavix use with aspirin was associated with an increase in major bleeding (primarilygastrointestinal and at puncture sites) compared to placebo with aspirin (see Table 1). Theincidence of intracranial hemorrhage (0.1%) and fatal bleeding (0.2%) were the same in bothgroups. Other bleeding events that were reported more frequently in the clopidogrel group wereepistaxis, hematuria, and bruise.The overall incidence of bleeding is described in Table 1.Table 1: CURE Incidence of Bleeding Complications (% patients)PlaceboEvent Plavix(+ aspirin)* (+ aspirin)*(n=6259)(n=6303)§Major bleeding † 3.7 ‡ 2.7Life-threatening bleeding 2.2 1.8Fatal 0.2 0.25 g/dL hemoglobin drop 0.9 0.9Requiring surgical intervention 0.7 0.7strokes 0.1 0.1HemorrhagicRequiringinotropes 0.5 0.5Requiring transfusion (≥4 units) 1.2 1.0Other major bleeding 1.6 1.0disabling 0.4 0.3SignificantlyIntraocular bleeding with 0.05 0.03significant loss of visionRequiring 2-3 units of blood 1.3 0.9Minor bleeding ¶ 5.1 2.4* Other standard therapies were used as appropriate.† Life-threatening and other major bleeding.‡ Major bleeding event rate for Plavix + aspirin was dose-dependent on aspirin: <100 mg = 2.6%;100-200 mg = 3.5%; >200 mg = 4.9%Major bleeding event rates for Plavix + aspirin by age were: <65 years = 2.5%, ≥65 to <75 years= 4.1%, ≥75 years = 5.9%§ Major bleeding event rate for placebo + aspirin was dose-dependent on aspirin: <100 mg = 2.0%;100-200 mg = 2.3%; >200 mg = 4.0%Major bleeding event rates for placebo + aspirin by age were: <65 years = 2.1%, ≥65 to <75 years =3.1%, ≥75 years = 3.6%¶ Led to interruption of study medication.Ninety-two percent (92%) of the patients in the CURE study received heparin or low molecularweight heparin (LMWH), and the rate of bleeding in these patients was similar to the overallresults.COMMITIn COMMIT, similar rates of major bleeding were observed in the Plavix and placebo groups, both of which also received aspirin (see Table 2).Table 2: Incidence of Bleeding Events in COMMIT (% patients)Type of bleeding Plavix(+ aspirin)(n=22961)Placebo(+ aspirin)(n=22891)p-valueMajor* noncerebral or cerebral bleeding** Major noncerebralFatalHemorrhagic strokeFatal 0.60.40.20.20.20.50.30.20.20.20.590.480.900.910.81Other noncerebral bleeding (non-major) 3.6 3.1 0.005 Any noncerebral bleeding 3.9 3.4 0.004* Major bleeds were cerebral bleeds or non-cerebral bleeds thought to have caused death or that required transfusion.** The relative rate of major noncerebral or cerebral bleeding was independent of age. Event rates for Plavix + aspirin by age were: <60 years = 0.3%, ≥60 to <70 years = 0.7%, ≥70 years = 0.8%. Event rates for placebo + aspirin by age were: <60 years = 0.4%, ≥60 to <70 years = 0.6%, ≥70 years = 0.7%.CAPRIE (Plavix vs. Aspirin)In CAPRIE, gastrointestinal hemorrhage occurred at a rate of 2.0% in those taking Plavix vs.2.7% in those taking aspirin; bleeding requiring hospitalization occurred in 0.7% and 1.1%, respectively. The incidence of intracranial hemorrhage was 0.4% for Plavix compared to 0.5%for aspirin.Other bleeding events that were reported more frequently in the Plavix group were epistaxis and hematoma.Other Adverse EventsIn CURE and CHARISMA, which compared Plavix plus aspirin to aspirin alone, there was no differencein the rate of adverse events (other than bleeding) between Plavix and placebo.In CAPRIE, which compared Plavix to aspirin, pruritus was more frequently reported in those taking Plavix. No other difference in the rate of adverse events (other than bleeding) was reported.6.2 Postmarketing ExperienceThe following adverse reactions have been identified during post-approval use of Plavix.Because these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.• Blood and lymphatic system disorders: Agranulocytosis, aplastic anemia/pancytopenia, thrombotic thrombocytopenic purpura (TTP)• Eye disorders: Eye (conjunctival, ocular, retinal) bleeding• Gastrointestinal disorders: Gastrointestinal and retroperitoneal hemorrhage with fatal outcome, colitis (including ulcerative or lymphocytic colitis), pancreatitis, stomatitis,gastric/duodenal ulcer, diarrhea• General disorders and administration site condition: Fever, hemorrhage of operative wound• Hepato-biliary disorders: Acute liver failure, hepatitis (non-infectious), abnormal liver function test• Immune system disorders: Hypersensitivity reactions, anaphylactoid reactions, serum sickness• Musculoskeletal, connective tissue and bone disorders: Musculoskeletal bleeding, myalgia, arthralgia, arthritis• Nervous system disorders: Taste disorders, fatal intracranial bleeding, headache• Psychiatric disorders: Confusion, hallucinations• Respiratory, thoracic and mediastinal disorders: Bronchospasm, interstitial pneumonitis, respiratory tract bleeding• Renal and urinary disorders: Increased creatinine levels• Skin and subcutaneous tissue disorders: Maculopapular or erythematous rash, urticaria, bullous dermatitis, eczema, toxic epidermal necrolysis, Stevens-Johnson syndrome,angioedema, erythema multiforme, skin bleeding, lichen planus, generalized pruritus • Vascular disorders: Vasculitis, hypotension7 DRUG INTERACTIONS7.1 CYP2C19 InhibitorsClopidogrel is metabolized to its active metabolite in part by CYP2C19. Concomitant use of drugs that inhibit the activity of this enzyme results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition [see Warnings and Precautions (5.1) and Dosage and Administration (2.4)].Proton Pump Inhibitors (PPI)A study was conducted with Plavix (300 mg loading dose followed by 75 mg/day) administered with a high dose (80 mg/day) of omeprazole. As shown in Table 3 below, with concomitant dosing of omeprazole, exposure (C max and AUC) to the clopidogrel active metabolite and platelet inhibition were substantially reduced. Similar reductions in exposure to the clopidogrel active metabolite and platelet inhibition were observed when Plavix and omeprazole were administered 12 hours apart (data not shown).There are no adequate studies of a lower dose of omeprazole or a higher dose of Plavix in comparison with the approved dose of Plavix.A study was conducted using Plavix (300 mg loading dose followed by 75 mg/day) and a high dose (80 mg/day) of pantoprazole, a PPI with less CYP2C19 inhibitory activity than omeprazole. The plasma concentrations of the clopidogrel active metabolite and the degree of platelet inhibition were less than observed with Plavix alone but were greater than observed when omeprazole 80 mg was co-administered with 300 mg loading dose followed by 75 mg/day of Plavix (Table 3).Table 3: Comparison of Clopidogrel Active Metabolite Exposure and Platelet Inhibition with and without Proton Pump Inhibitors, Omeprazole and Pantoprazole% Change from Plavix (300 mg/75 mg) alone Plavix plus C max (ng/mL) AUC Platelet Inhibition† (%)Day 1 Day 5 Day 1 Day 5** Day 1 Day 5 Omeprazole* 80 mg ↓46% ↓42% ↓45% ↓40% ↓39% ↓21% Pantoprazole 80 mg ↓24% ↓28% ↓20% ↓14% ↓15% ↓11% †Inhibition of platelet aggregation with 5 mcM ADP*Similar results seen when Plavix and omeprazole were administered 12 hours apart.**AUC at Day 5 is AUC0-247.2 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)Coadministration of Plavix and NSAIDs increases the risk of gastrointestinal bleeding.7.3 Warfarin (CYP2C9 Substrates)Although the administration of clopidogrel 75 mg per day did not modify the pharmacokinetics of S-warfarin (a CYP2C9 substrate) or INR in patients receiving long-term warfarin therapy, coadministration of Plavix with warfarin increases the risk of bleeding because of independent effects on hemostasis.However, at high concentrations in vitr o, clopidogrel inhibits CYP2C9.8 USE IN SPECIFIC POPULATIONS8.1 PregnancyPregnancy Category BReproduction studies performed in rats and rabbits at doses up to 500 and 300 mg/kg/day, respectively (65 and 78 times the recommended daily human dose, respectively, on a mg/m2 basis), revealed no evidence of impaired fertility or fetotoxicity due to clopidogrel. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of a human response, Plavix should be used during pregnancy only if clearly needed.8.3 Nursing MothersStudies in rats have shown that clopidogrel and/or its metabolites are excreted in the milk. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from clopidogrel, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.8.4 Pediatric UseSafety and effectiveness in the pediatric population have not been established.8.5 Geriatric UseOf the total number of subjects in the CAPRIE and CURE controlled clinical studies, approximately 50% of patients treated with Plavix were 65 years of age and older, and 15% were 75 years and older. In COMMIT, approximately 58% of the patients treated with Plavix were 60 years and older, 26% of whom were 70 years and older.The observed risk of bleeding events with Plavix plus aspirin versus placebo plus aspirin by age category is provided in Table 1 and Table 2 for the CURE and COMMIT trials, respectively [see Adverse Reactions (6.1)]. No dosage adjustment is necessary in elderly patients.8.6 Renal ImpairmentExperience is limited in patients with severe and moderate renal impairment [see Clinical Pharmacology (12.2)].8.7 Hepatic ImpairmentNo dosage adjustment is necessary in patients with hepatic impairment [see Clinical Pharmacology (12.2)].10 OVERDOSAGEPlatelet inhibition by Plavix is irreversible and will last for the life of the platelet. Overdose following clopidogrel administration may result in bleeding complications. A single oral dose of clopidogrel at 1500 or 2000 mg/kg was lethal to mice and to rats and at 3000 mg/kg to baboons. Symptoms of acute toxicity were vomiting, prostration, difficult breathing, and gastrointestinal hemorrhage in animals.Based on biological plausibility, platelet transfusion may restore clotting ability.11 DESCRIPTIONPlavix (clopidogrel bisulfate) is a thienopyridine class inhibitor of P2Y12 ADP platelet receptors. Chemically it is methyl (+)-(S)-α-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)acetate sulfate (1:1). The empirical formula of clopidogrel bisulfate is C16H16ClNO2S•H2SO4 and its molecular weight is 419.9.The structural formula is as follows:Clopidogrel bisulfate is a white to off-white powder. It is practically insoluble in water at neutral pH but freely soluble at pH 1. It also dissolves freely in methanol, dissolves sparingly in methylene chloride, and is practically insoluble in ethyl ether. It has a specific optical rotation of about +56°.Plavix for oral administration is provided as either pink, round, biconvex, debossed, film-coated tablets containing 97.875 mg of clopidogrel bisulfate which is the molar equivalent of 75 mg of clopidogrel base or pink, oblong, debossed film-coated tablets containing 391.5 mg of clopidogrel bisulfate which is the molar equivalent of 300 mg of clopidogrel base.Each tablet contains hydrogenated castor oil, hydroxypropylcellulose, mannitol, microcrystalline cellulose and polyethylene glycol 6000 as inactive ingredients. The pink film coating contains ferric oxide, hypromellose 2910, lactose monohydrate, titanium dioxide and triacetin. The tablets are polished with Carnauba wax.12 CLINICAL PHARMACOLOGY12.1 Mechanism of ActionClopidogrel 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.12.2 PharmacodynamicsClopidogrel must be metabolized by CYP450 enzymes to produce the active metabolite that inhibits platelet aggregation. The active metabolite of clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet P2Y12 receptor and the subsequentADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. This action is irreversible. Consequently, platelets exposed to clopidogrel’s active metabolite are affected for the remainder of their lifespan (about 7 to 10 days). Platelet aggregation induced by agonists other than ADP is also inhibited by blocking the amplification of platelet activation by released ADP.Dose-dependent inhibition of platelet aggregation can be seen 2 hours after single oral doses of Plavix. Repeated doses of 75 mg Plavix per day inhibit ADP-induced platelet aggregation on the first day, and inhibition reaches steady state between Day 3 and Day 7. At steady state, the average inhibition level observed with a dose of 75 mg Plavix per day was between 40% and 60%. Platelet aggregation and bleeding time gradually return to baseline values after treatment is discontinued, generally in about 5 days.Geriatric PatientsElderly (≥75 years) and young healthy subjects had similar effects on platelet aggregation. Renally-Impaired PatientsAfter repeated doses of 75 mg Plavix per day, patients with severe renal impairment (creatinine clearance from 5 to 15 mL/min) and moderate renal impairment (creatinine clearance from 30 to 60 mL/min) showed low (25%) inhibition of ADP-induced platelet aggregation.。

波立维-氯吡格雷Clopidogrel说明书

1
Reference ID: 3792973
FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: DIMINISHED EFFECTIVENESS IN POOR METABOLIZERS 1 INDICATIONS AND USAGE 1.1 Acute Coronary Syndrome (ACS)
5 WARNINGS AND PRECAUTIONS 5.1 Diminished Antiplatelet Activity Due to Impaired CYP2C19
Function
5.2 General Risk of Bleeding
5.3 Discontinuation of Plavix
HIGHLIGHTS OF INFORMATION These highlights do not include all the information needed to use PLAVIX safely and effectively. See full prescribing information for PLAVIX. PLAVIX (clopidogrel bisulfate) tablets Initial U.S. Approval: 1997 WARNING: DIMINISHED EFFECTIVENESS IN POOR
5.4 Patients with Recent Transient Ischemic Attack (TIA) or
Stroke
5.5 Thrombotic Thrombocytopenic Purpura (TTP)
5.6 Cross-Reactivity among Thienopyridines

波立维

委托企业
赛诺菲圣德拉堡集团公司
包装企业
赛诺菲（杭州）制药有限公司
药代动力学
吸收
每天单次和多次口服75mg，氯吡格雷吸收迅速。原型化合物的氯吡格雷平均血浆浓度在给药后大约45分钟达到高峰（单次口服75mg后大约为2.2-2.5ng/ml）。根据尿液中氯吡格雷代谢物排泄量计算，至少有50%药物被吸收。
分布
体外试验显示，氯吡格雷及其主要循环代谢物（无活性）与人血浆蛋白呈可逆性结合（分别为98%和94%），在很广的浓度范围内为非饱和状态。
由于活性代谢物通过CYP450酶形成，部分CYP450酶是多态性的或受其他药物抑制，因此不是所有患者都将获得充分的血小板抑制。
氯吡格雷75 mg，每日一次重复给药，从第一天开始明显抑制 ADP诱导的血小板聚集，抑制作用逐步增强并在3-7天达到稳态。在稳态时，每天服用氯吡格雷75 mg的平均抑制水平为40%-60％，一般在中止治疗后5天内血小板聚集和出血时间逐渐回到基线水平。
非甾体抗炎药（NSAIDs）：在健康志愿者进行的临床试验中，氯吡格雷与萘普生合用使胃肠道隐性出血增加。
药物过量
氯吡格雷的过量使用可能会引起出血时间的延长以及出血并发症。如果发现出血应该进行适当的处理。
尚未发现针对氯吡格雷药理活性的解毒剂。如果需要迅速纠正延长的出血时间，输注血小板可逆转氯吡格雷的作用。
在对符合条件（心肌梗死、缺血性卒中和外周动脉性疾病）的亚组分析显示，由于外周动脉性疾病（尤其是那些同时有心肌梗死病史的患者，RRR=23.7% ；CI ：8.9-36.
药理毒理
药效学特性
药物治疗分类：血小板聚集抑制剂，不包括肝素，ATC编号;BO1AC-04
氯吡格雷是前体药物，其代谢产物之一是血小板聚集抑制剂。氯吡格雷必须通过CPY450酶代谢，生成能抑制血小板聚集的活性代谢物。氯吡格雷的活性代谢产物选择性的抑制二磷酸腺苷（ADP）与其血小板P2Y12受体的结合及继发的ADP介导的糖蛋白GPIIb/IIIa复合物的活化，因此抑制血小板聚集。由于结合不可逆，暴露于氯吡格雷的血小板的剩余寿命（大约为7-10天）受到影响，而血小板正常功能的恢复速率同血小板的更新一致。通过阻断释放的ADP诱导的血小板活化聚集途径也可抑制除ADP以外的其他激动剂诱导的血小板聚集。

1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。

给药途径及用量推荐剂量每日75mg，对老年患者和肾病患者不需调整剂量[用法用量]：推荐剂量为每天75mg，与或不与食物同服。

对于老年患者和肾病患者不需调整剂量。

[不良反应]：出血，波立维（氯吡格雷）严重出血事件的发生率分别为% 胃肠道：如腹痛，消化不良，胃炎和便秘皮疹和其它皮肤病中枢和周围神经系统：头痛、眩晕、头昏和感觉异常肝脏和胆道疾病禁忌证对药品或本品任一成分过敏严重的肝脏损伤活动性病理性出血，如消化性溃疡或颅内出血注意事项：氯吡格雷延长出血时间，对于有伤口（特别是在胃肠道和眼内）易出血的病人应慎用。

病人应知服用波立维止血时间可能比往常长，同时病人应向医生报告异常出血情况，手术前和服用其它新药前病人应告知医生他们在服用波立维。

由于患有肾脏损伤病人使用氯吡格雷的经验极有限，因此这些病人应慎用波立维（氯吡格雷）。

严重肝病的病人可能有出血倾向，这类病人使用本药的经验极有限，应慎用波立维。

由于服用华法令也有出血倾向，所以服用时不推荐同时使用华法令。

在儿科使用的安全性和有效性还未明确。

【批准文号】国药准字H【中文名称】硫酸氢氯吡格雷片【产品英文名称】Clopidogrel Sulfate Tablets【生产企业】【功效主治】预防和治疗因血小板高聚集状态引起的心、脑及其它动脉的循环障碍疾病。

【化学成分】本品主要成分是硫酸氯吡格雷。

化学名为：S（+）-2-（2-氯苯基）-2-（4,5,6,7-四氢噻吩【3,2-c】并吡啶-5）乙酸甲酯硫酸氢【药理作用】本品为血小板聚集抑制剂，能选择性地抑制ADP与血小板受体的结合，随后抑制激活ADP与糖蛋白GPⅡb/Ⅲa复合物，从而抑制血小板的聚集。

本品也可抑制非ADP引起的血小板聚集，不影响磷酸二酯酶的活性。

本品通过不可逆地改变血小板ADP受体，使血小板的寿命受到影响。

【药物相互作用】阿斯匹林：本品增加阿斯匹林对胶原引起的血小板聚集的抑制效果，长期合并用药的安全性无进一步的研究资料。

肝素：健康志愿者研究表明，本品与肝素无相互作用。

但合并用药时应小心。

非甾体抗炎药（NSAIDs）：健康志愿者同时服用本品和萘普生，胃肠潜血损失增加，故本品与NSAIDs 合用时应小心。

法华令：无合并用药的安全性研究。

【不良反应】偶见胃肠道反应（如、、或），皮疹，皮肤粘膜出血。

罕见和。

【禁忌症】1 对本品成分过敏者禁用。

2 近期有活动性出血者（如或等）禁用。

【产品规格】75mg（按氯吡格雷计）【用法用量】口服，可与食物同服也可单独服用。

每日一次，每次二片。

【贮藏方法】避光，密封保存。

【注意事项】1 使用本品的病人需时应告知外科。

2 肝脏损伤、有患者慎用。

3 肾功能不全患者使用本品时不需要调整剂量。

药品名称货品编码规格生产厂家网上价【波立维】硫酸氢氯吡格雷片75mg*7片杭州赛诺菲安万特民生制药有限公司￥143>>导购热线:400-066-5560【硫酸氢氯吡格雷片适应症】适用于有过近期发作的中风，心肌梗死和确诊外周动脉疾病的患者，该药可减少动脉粥洋硬化事件的发生（如心肌梗死，中风和血管性死亡）。

与阿司匹林联合，用于非ST段抬高性急性冠脉综合症（不稳定性心绞痛或非Q波心肌梗死）患者。

【其它】3年。

【通用名拼音】BLW【不良反应】出血，波立维（氯吡格雷）严重出血事件的发生率分别为% 胃肠道：如腹痛，消化不良，胃炎和便秘皮疹和其它皮肤病中枢和周围神经系统：头痛、眩晕、头昏和感觉异常肝脏和胆道疾病。

【注意事项】1.患有急性心肌梗死的病人，在急性心肌梗死最初几天不推荐进行氯吡格雷治疗。

由于缺少相关数据，不主动推荐使用氯吡格雷治疗不稳定型心绞痛、PTCA（有支架）、CABG和急性缺血性中风（短于7天）。

2.与其它一些抗血小板药同时使用，氯吡格雷对那些由于创伤、手术或其它病理原因而可能引起出血增多的病人，应慎用。

病人择期手术，且无需抗血小板治疗，术前一周停止使用氯吡格雷。

氯吡格雷延长出血时间，对于有伤口（特别是在胃肠道和眼内）易出血的病人应慎用。

3.病人应知服用氯吡格雷止血时间可能比往常长，同时病人应向医生报告异常出血情况，手术前和服用其它新药前病人应告知医生他们在服用氯吡格雷。

由于患有肾脏损伤病人使用氯吡格雷的经验极有限，因此这些病人应慎用氯吡格雷。

4.严重肝病的病人可能有出血倾向，这类病人使用本药的经验极有限，应慎和氯吡格雷。

由于服用华法令也有出血倾向，所以服用本药时不推荐同时使用华法令。

由于同时服用阿司匹林，非甾体解热镇痛药，肝素和血栓溶解剂可增加出血的危险，所以不建议同时服用（[见药物相互作用]）。

5.对于同时服用易出现胃肠道损伤的药物（如非甾体解热镇痛药）的病人应慎用氯吡格雷（见[药物相互作用]）。

未见属用本药后对驾驶或心理学检测产生影响。

【主要成份】氯吡格雷；其化学名称为：消旋-a-（6，7-二氯噻吩并[3，4-c]哌啶-5（4H）-乙酸乙酯硫酸氢盐。

【药理毒理】1.药效学特性氯吡格雷是一种血小板聚集抑制剂，选择性地抑制二磷酸腺苷（ADP）与它的血小板受体的结合及继发的ADP介导的糖蛋白GPIIb/IIIa复合物的活化，因此可抑制血小板聚集。

2.氯吡格雷必须经生物转化才能抑制血小板的聚集。

除ADP外，氯吡格雷还能阻断其它激动剂通过释放ADP引起血小板活性的增强，从而抑制其引起的血小板聚集。

氯吡格雷通过不可逆地修饰血小板ADP受体起作用。

暴露于氯吡格雷的血小板的寿命受到影响，而血小板正常功能的恢复速率同血小板的更新一致。

氯吡格雷75mg，每日一次重复给药，从第一天开始明显抑制ADP 诱导的血小板聚集，抑制作用逐步增强并在3－7天达到稳态。

3.在稳态时，每天服用氯吡格雷75mg的平均抑制水平为40％－60％，一般在中止治疗后5天内血小板聚集和出血时间逐渐回到基线水平。

4.毒理学研究：在大鼠和狒狒进行的临床前研究发现，最常见的反应为肝脏变化。

这些肝脏变化是由于药品对肝代谢酶影响的结果，给药剂量为人体服用75mg/天氯吡格雷获得暴露量的25倍。

人体接受治疗剂量的氯吡格雷对肝脏代谢酶没有作用。

大鼠和狒狒服用高剂量氯吡格雷，胃耐受性差（胃炎，胃溃疡和/或眩晕）。

以每天大至77mg/kg的剂量，小鼠服用78周，大鼠服用104周的氯吡格雷没有发现致癌的证据。

此剂量的血药浓度较人类的推荐剂量（每天75mg）大25倍。

经过一系列体内和体外试验证实氯吡格雷无基因毒性作用。

5.氯吡格雷对雌性大鼠和雄性大鼠的生育能力没有影响，对大鼠和兔子均无致畸作用。

哺乳大鼠服用氯吡格雷可轻微延缓幼仔的发育。

药代动力学研究表明氯吡格雷和/或其代谢物从乳汁中排泄。

因此，不排除氯吡格雷有直接（轻微毒性）或间接（味道不好）作用。

【药代动力学】1.多次口服氯吡格雷75mg以后，氯吡格雷吸收迅速。

母体化合物的血浆浓度很低，一般在用药2小时后低于定量限（L）。

根据尿液中氯吡格雷代谢物排泄量计算，至少有50%药物被吸收。

氯吡格雷主要由肝脏代谢。

主要代谢产物是羧酸盐衍生物，无抗血小板聚集作用，占血浆中药物相关化合物的85％。

多次口服氯吡格雷75mg以后，该代谢物的血药浓度约在服药后1小时达峰（约为3mg/l）。

2.氯吡格雷是一种前体药。

氯吡格雷经氧化生成2-氧基-氯吡格雷，继之水解形成活性代谢物（一种硫醇衍生物）。

氧化作用主要由细胞色素P450同功酶2B6和3A4调节，1A1、1A2和2C19也有一定的调节作用。

3.体外已经分离出这种活性硫醇代谢物，它可迅速、不可逆地与血小板受体结合，从而抑制血小板聚集。

但在血浆中未检测到此种代谢物。

在50-150mg的剂量范围内，氯吡格雷的主要循环代谢物的药代动力学为线性（血浆浓度与剂量成正比）。

4.体外试验显示，氯吡格雷及其主要循环代谢物与人血浆蛋白呈可逆性结合（分别为98％和94％），在很广的浓度范围内为非饱和状态。

人体口服14C标记的氯吡格雷以后，在5天内约50％由尿液排出，约46％由粪便排出。

一次和重复给药后，血浆中主要循环代谢产物的消除半衰期为8小时。

氯吡格雷75mg每日一次，重复给药后，严重肾损害病人（肌酐清除率5－15ml min）的主要循环代谢物的血浆浓度低于中度肾损害的病人（肌酐清除率30－60ml/min）和健康受试者。

与健康受试者相比，尽管对ADP诱导的血小板聚集的抑制较低（25％），但出血时间的延长与每天服用氯吡格雷75mg的健康志愿者相同。

而且，所有病人的临床耐受性良好。

健康志愿者及患有肝硬化（Child-Pugh class A或B）病人单剂量、多剂量服用氯吡格雷，对氯吡格雷药效学及药代动力学进行评价。

5.结果表明，氯吡格雷75mg每天一次连续给药10天，安全、耐受性好。

肝硬化病人单次服药及稳态氯吡格雷血药浓度峰值高于健康志愿者几倍。

然而，肝硬化组和健康志愿者组间血中主要循环代谢物浓度、对ADP诱导的血小板聚集的作用和出血时间均相当。

【使用说明】波利维的推荐剂量是每天75mg，与或不与食物同服。

对于老年患者不需调整剂量。

非ST段抬高性急性冠状综合征（不稳定性心绞痛或非Q波心肌梗死）患者，应以单次负荷量氯吡格雷300mg开始，然后以75mg 每日一次连续服药（合用阿司匹林75mg~325mg/日）。

由于服用较高剂量的阿司匹林伴随有较高的出血性危险，故推荐阿司匹林的剂量不应超过100mg。

最佳疗程尚未正式确定。

临床实验资料支持用药12个月，用药3个月时的益处最大（参见药效学特性）。

儿童和未成年人：18岁以下受试者的安全性、有效性尚未建立。

【禁忌事项】1、对药品或本品任一成份过敏。

2、严重的肝脏损伤3、活动性病理性出血，如消化性溃疡或颅内出血。

【药物相互作用】华法林：见注意事项。

GPIIb/IIIa抑制剂：见注意事项。

阿斯匹林(阿司匹林)：阿斯匹林不改变氯吡格雷对由ADP诱导的血小板聚集的抑制作用，但氯吡格雷增强阿斯匹林对胶原诱导的血小板聚集的作用。

然而，合用阿斯匹林500mg, 一天服用两次，使用一天，并不显著增长氯吡格雷引起的出血时间延长。