the use of proton pump inhibitors

质子泵抑制剂长期使用的潜在安全性问题作者：汤玉茗来源：《上海医药》2013年第21期摘要随着质子泵抑制剂的广泛应用，其长期使用的潜在安全性问题也逐渐引起人们的关注。

本文介绍与质子泵抑制剂长期使用相关的风险。

关键词质子泵抑制剂难辨梭状芽胞杆菌氯吡格雷中图分类号：R975.2； R975.6 文献标识码：A 文章编号：1006-1533（2013）21-0012-04 The potential safety issues related to long-term use of proton pump inhibitorsTang Yuming*（Department of Gastroenterology， Ruijin Hospital， School of Medicine， Shanghai Jiao Tong University， Shanghai 200025， China）Abstract With the extensive application of proton pump inhibitors in clinic， great attention should be paid to the potential safety issues related to long-term use of proton pump inhibitors. This review describes the risks associated with long-term use of proton pump inhibitors.Key wordS proton pump inhibitors； Clostridium difficile； clopidogrel自20世纪80年代奥美拉唑上市后，各种质子泵抑制剂便以高效、低毒的特性迅速成为酸相关疾病治疗的主要用药。

不过，经过20多年的临床广泛应用，质子泵抑制剂的潜在安全性问题也逐渐浮现并受到国内、外学者的重视，其中主要包括质子泵抑制剂与矿物质和维生素的吸收、与难辨梭状芽胞杆菌相关性腹泻（Clostridium difficile-associated diarrhea， CDAD）、与肺部感染、与氯吡格雷的相互作用以及与萎缩性胃炎、胃息肉、胃癌和类癌的关系等问题。

某综合医院住院患者质子泵抑制药使用情况分析杨平;王利;刘凌云;陈静【摘要】目的：了解住院患者质子泵抑制药的使用情况。

方法：以药品说明书等为依据，分析某综合医院2015年9月质子泵抑制药临床使用情况。

结果：9月份某院注射用质子泵抑制剂用量最多的是注射用泮托拉唑，质子泵抑制剂销售金额最高的科室为消化内科，年龄51~70岁的患者使用质子泵抑制剂最多，占42％，其中男性患者居多；不合理应用情况主要表现为用药指证不明确、遴选剂型不适宜、用药疗程偏长、重复用药。

结论：质子泵抑制药临床应用广泛，同时不合理用药也较多，医护人员应规范处方，减少不合理用药处方，达到患者用药安全、有效、经济，从而实现医疗质量的持续改进。

%Objective:To understand the use of proton pump inhibitors in hospitalized patients. Methods:Based on the drug instruction and so on,to analyze the clinical use of proton pump inhibitor in a comprehensive hospital in September 2015. Results:In September in a hospital pantoprazole injection is the largest amount of injection of proton pump inhibitors,digestion department is the highest sales amount of proton pump inhibitors,patients age from 51~70 use proton pump inhibitors most of all,42%,male patients are in the majority. Unreasonable applications mainly include unclear application of the drug use,ap-propriate selection of dosage form,longer treatment,repeated drug use. Conclusion:Proton pump inhibitors are widely used in clinical applications,at the same time,unreasonable application is alsomore,paramedics should regulate prescription,reduce irrationalprescriptions,to realize patient medication safely,effective,economic and continuous improvement of medical quality.【期刊名称】《临床医药实践》【年(卷),期】2016(025)004【总页数】3页(P286-287,306)【关键词】质子泵抑制药;用药指证;合理用药;用药疗程【作者】杨平;王利;刘凌云;陈静【作者单位】岳阳市一人民医院，湖南岳阳 414000;岳阳市一人民医院，湖南岳阳 414000;岳阳市一人民医院，湖南岳阳 414000;岳阳市一人民医院，湖南岳阳414000【正文语种】中文【中图分类】R95Abstract Objective：To understand the use of proton pump inhibitors in hospitalized patients. Methods：Based on the drug instruction and so on，to analyze the clinical use of proton pump inhibitor in a comprehensive ho spital in September 2015.Results：In September in a hospital pantoprazole injection is the largest amount of i njection of proton pump inhibitors，digestion department is the highest sales amount of proton pump inhibito rs，patients age from 51～70 use proton pump inhibitors most of all，42%，male patients are in the majority.Unreasonable applications mainly include unclear application of the drug use，appropriate selection of dosage form，longer treatment，repeated drug use.Conclusion：Proton pump inhibitors are widely used in clinical applications，at the same time，unreasonable application is also more，paramedics should regulate prescription，reduce irrational prescriptions，to realize patient medication safely，effective，economic and continuous improvement of medical quality.Key words proton pump inhibitors；medication indications；rational drug use；medication course of treatment质子泵抑制药(PPI)经过20多年的临床实践，已成为大多数胃酸分泌过多相关疾病治疗的首选用药，在预防和治疗急性胃黏膜病变及应激性溃疡方面也有很好的疗效，数亿的临床病例显示，其不良反应较轻，患者长期应用耐受性较好，是一个相对比较安全的药物。

妊娠期和哺乳期使用质子泵抑制剂的安全性评价妊娠妇女是胃食管反流病的高发人群。

质子泵抑制剂是目前治疗反流症状和食管炎最有效的药物。

然而质子泵抑制剂在妊娠期的应用并没有H2受体拮抗剂普遍，安全性资料非常有限。

本文结合近年来可靠的临床研究数据，认为质子泵抑制剂在妊娠期的应用相对安全，不应被过度限制。

同时，质子泵抑制剂在哺乳期胃食管反流病中的使用资料更加有限，考虑到其可能分泌入乳汁，在哺乳期不建议使用。

[Abstract] Pregnant women are high-risk group of gastro-esophageal reflux disease. Proton pump inhibitors are currently the most effective drugs for reflux symptoms and esophagitis. However，the use of proton pump inhibitors during pregnancy is not as common as that of H2 receptor antagonists，and safety data are very limited. This article，combined with reliable clinical research data in recent years，believes that the use of proton pump inhibitors during pregnancy is relatively safe and should not be excessively limited. At the same time，the use of proton pump inhibitors in the treatment of gastro-esophageal reflux disease during breastfeeding is even more limited. Considering that it may be secreted into breast milk，the proton pump inhibitor is not recommended during lactation.[Key words] Gastro-esophageal reflux disease；Proton pump inhibitor；Pregnancy；Lactation；Safety胃食管反流病（gastro-esophageal reflux disease，GERD）是指胃內容物反流入食管引起的反流相关症状和（或）并发症的一种疾病[1]，表现为一过性或频发的反酸、胃灼热等。

关于质⼦泵抑制剂（PPI），这些内容不可不知你对PPI了解多少呢？来源：医学界消化频道作者：糖果天天质⼦泵抑制剂（(proton pump inhibitor，PPI）为苯并咪唑类衍⽣物，能迅速穿过胃壁细胞膜，聚积在强酸性分泌⼩管中，转化为次磺酰胺类化合物，后者与H+K-—ATP酶a亚基中半胱氨酸残基上的巯基作⽤，形成共价结合的⼆硫键，使H+K-—ATP酶失活，从⽽抑制其泌酸活性。

PPI是治疗酸相关疾病的⾸选药物，其问世在消化系统疾病的治疗中具有⾥程碑式的意义。

全球⾸个质⼦泵抑制剂奥美拉唑（洛赛克）1987年在瑞典上市，继⽽兰索拉唑、泮托拉唑、雷贝拉唑、埃索美拉唑相继问世。

PPI较H2受体阻滞剂抑酸作⽤更强⼤、更持久。

PPI的应⽤使许多消化性溃疡患者免于⼿术。

同样，PPI治疗反流性⾷管炎（RE）的愈合率及对反流症状的缓解率也显著⾼于H2RA。

此外，PPI治疗胃泌素瘤所致的难治性及多发性溃疡、⾮类固醇类抗炎药相关性溃疡和应激性溃疡也发挥了较好的疗效。

在上消化道出⾎、急性胰腺炎的治疗中也具有显著疗效。

但是如同科学是把双刃剑⼀样，PPI同样也是把双刃剑。

⽬前关于PPI应⽤的不良反应⽇益凸显，这些相关风险也需要得到⼴⼤医务⼯作者的认识。

关于PPI与抗⾎⼩板药物氯吡格雷的研究由来已久，美国FDA曾于2009年1⽉26⽇和11⽉27⽇两次发出警戒，其观点鲜明，要⾼度警惕可抑制或诱导CYP2C19的药物，或经CYP2C19代谢的药物对氯吡格雷抗⾎⼩板作⽤的影响。

2010年3⽉12⽇，美国FDA再次向医师、患者以及企业发出警告，要求在药品说明书中添加新的⿊框警告：抗⾎⼩板药氯吡格雷具有潜在的因减效⽽增加⼼⾎管事件的风险。

虽然⽬前PPI与氯吡格雷联⽤会增加⼼⾎管事件风险尚⽆最终定论，但美国⾷品与药物管理局（FDA）还是发出警惕两药联⽤风险的警告[奥美拉唑与埃索美拉避免与氯吡格雷联⽤]。

2009年《美国胃肠病学》杂志曾报道：PPI所致的医源性低胃酸症会增加患者肠道细菌的易感性；可增加医院获得性肺炎的发⽣率，减少维⽣素C、维⽣素B12和铁的吸收；影响钙的吸收可能增加⾻折风险。

氯吡格雷与奥美拉唑药物相互作用的应用分析一、案例背景知识简介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，是冠心病患者尤其是PCI 术后必不可少的抗血小板药物，其应用已经相当普遍。

对于老年冠心病患者，常常会合并有高血压，糖尿病等多种疾病，因此服用药物种类较多，临床药师应密切关注合并有多种疾病的老年冠心病患者可能存在的药物间的相互作用。

本病例通过探讨氯吡格雷与质子泵抑制剂之间的相互作用及处理对策，强调临床药师在临床中的积极作用，从药师的角度发现问题，解决问题，为患者制订出最大获益的个体化治疗方案。

二、病例内容简介患者，男性，79岁，主因反复心前区不适5个月余入院。

患者于2007年活动后出现心前区疼痛，体力活动时加重，休息后可缓解。

2009年10月于夜间睡眠时再次出现心前区疼痛，伴胸闷气短，向背部、咽喉部放射，约5分钟后自行缓解，此后患者反复于静息状态下出现上述症状。

今为进一步诊治以“冠心病、不稳定型心绞痛”于2010年3月16日收入心内科。

患者既往糖尿病10年，长期服用阿卡波糖，血糖控制满意。

有慢性胃炎病史20年，门诊胃镜（2009-10-26）提示胃食管反流、糜烂性胃炎，服用奥美拉唑肠溶片保护胃黏膜。

入院查体：体温36.3℃，脉搏71次/分，呼吸18次/分，血压144/74mmHg。

辅助检查：生化监测：ALT 23.6U/L，AST 22.1U/L，肌钙蛋白 T 0.020ng/ml，肌酐 101.8μmol/L，血清尿酸 463.3μmol/L，肌酸激酶 127.8U/L，钾3.74mmol/L，BNP 92.07pg/ml。

凝血检查：血浆活化部分凝血酶原时间测定33.0秒，血浆凝血酶原活动度测定120%，血浆纤维蛋白原测定3.23g/L，血浆D-二聚体测定2.66μg/ml ↑。

论著·社区用药指导CHINESE COMMUNITY DOCTORS质子泵抑制剂(PPIs)是现阶段效果最好、应用最为广泛的治疗酸相关性疾病药物，但随着用药范围扩大，不良反应及合理性问题逐渐引起相关部门关注。

国内外目前仅有个别适应证使用指南，尚无关乎合理性使用的系统性指南和规范性文献[1]。

本文依据循证医学材料、国内外相关文献等，对PPIs应用指导原则进行制定，并分析我院门诊此类药物处方的具体情况，旨在促进合理用药。

资料与方法2016年1-6月抽取我院门诊信息管理系统中使用PPIs的病历3720份，通过等距抽样法，采用逢十抽一的方式，对其中372份随机选择，将不完整病历和未归档病历自动剔除。

点评标准：依据《实用内科学》、药品说明书、《临床药物治疗学》及相应临床指南、文献，对我院临床应用PPIs的指导原则制定。

适应证：①预防性用药：对下列情况诱导的相关性溃疡预防：机体严重创伤；全身重度感染；高龄；有持续低血压或合并休克；机械通气＞3d，有多器官功能障碍综合征(MODS)并发；脏器移植术后；1年内有溃疡病史；凝血机能障碍；重大手术；重度黄疸；使用大剂量糖皮质激素；使用抗血小板药物；使用化疗药物。

②治疗性用药：慢性胃炎；根除幽门螺杆菌；卓-艾综合征；消化性溃疡；胃食管反流性咽炎/慢性咳嗽；胃食管反流病；急性胰腺炎；上消化道出血。

用法用量：现阶段，我院门诊PPIs共5种，即雷贝拉唑、奥美拉唑、埃索美拉唑、泮托拉唑、兰索拉唑，见表1。

结果372份病历中，男176份(47.3%)，女196份(52.7%)。

0～18岁4份，18～65岁283份，＞65岁85份。

合理病历212份(56.9%)，其余160例(43.0%)不合理病历。

不合理病历分类包括药物相互作用、给药途径、重复用药、无使用指征、超常用药、疗程偏长，见表2。

讨论结合上述研究结果，得出我院门诊在使用PPIs上尚存在不甚合理的状况，若针对性防控，一些问题可以避免，现分析如下。

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.。

质子泵抑制剂的处方和审核要点2019年重庆市执业药师继续教育【最新版】目录一、质子泵抑制剂的概述二、质子泵抑制剂的适应证三、质子泵抑制剂的用法用量四、质子泵抑制剂的注意事项五、质子泵抑制剂的药物相互作用六、结语正文一、质子泵抑制剂的概述质子泵抑制剂（Proton Pump Inhibitors，PPIs）是一类抑制胃酸分泌的药物，具有抑酸作用强、特异性高、持续时间长等特点。

它们通过阻断胃酸分泌的最后通道，即胃壁细胞内的质子泵驱动细胞内 H+的交换，从而达到抑制胃酸分泌的目的。

与传统的胃酸抑制药物相比，PPIs 的作用位点不同，具有不同的特点，如夜间抑酸作用好、起效快、抑酸作用强、时间长、服用方便等。

二、质子泵抑制剂的适应证质子泵抑制剂被广泛应用于治疗消化性溃疡、胃食管反流病、上消化道出血和卓 - 艾综合征（又称胃泌素瘤）等酸相关性疾病及应激性溃疡的临床治疗和预防。

三、质子泵抑制剂的用法用量根据《质子泵抑制剂审方规则专家共识》，质子泵抑制剂的用法用量如下：1.慢性胃炎或功能性消化不良患者：以胃黏膜糜烂和/或以上腹痛、反酸、烧灼感等为主要症状的慢性胃炎患者；以上腹痛、灼烧感为主要症状的功能性消化不良患者。

所有 PPIs 口服制剂均可使用（常规用量，口服，每天 1 次）。

2.急性胰腺炎患者：所有 PPIs 注射剂均可使用（常规用量，静脉滴注，每天 2 次）。

3.胃食管反流病患者：伴有咽喉症状的胃食管反流病患者，特别是酸反流患者。

所有 PPIs 口服制剂均可使用（常规用量，口服，每天 2 次）。

四、质子泵抑制剂的注意事项1.质子泵抑制剂使用过程中可能出现不良反应，如头痛、恶心、呕吐、腹泻等，一般在用药过程中逐渐减轻或消失。

2.长期使用质子泵抑制剂可能会影响肠道菌群平衡，降低肠道菌群丰度和多样性，但口腔和上消化道共生菌的丰度显著增加。

3.质子泵抑制剂可能增加肠道感染或其他感染的风险。

五、质子泵抑制剂的药物相互作用质子泵抑制剂与其他药物的相互作用较少，但仍需注意以下情况：1.与氯吡格雷合用可能降低氯吡格雷的疗效。

关于质子泵抑制剂在咽喉疾病治疗中的应用分析工作单位：江西省吉安市青原区人民医院【摘要】：目的：分析质子泵抑制剂在咽喉疾病治疗中的应用价值。

方法：选取2019年1月-2021年12月120咽喉反流患者，随机分组。

对照组采取常规治疗方案，观察组则加入质子泵抑制剂治疗。

比较两组疗效以及症状缓解时间的差异，并比较两组治疗前后反流症状指数评分量表（RSI评分）和反流体征评分量表（RFS评分）的变化。

结果：观察组总有效率高于对照组（P＜0.05）；观察组咽部不适、声音嘶哑、反酸等症状缓解时间短于对照组（P＜0.05）；观察组RSI评分、RFS评分变化幅度高于对照组（P＜0.05）。

结论：在常规治疗方案上加入质子泵抑制剂，有助于快速缓解咽喉反流相关症状，提高临床疗效，可在咽喉反流中推广应用。

【关键词】：质子泵抑制剂；咽喉疾病；临床疗效Analysis on the application of proton pump inhibitors in the treatment of throat diseasesName: Liu Jue JunPostcode: 343009Working unit: Qingyuan District People's Hospital, Ji' an City, Jiangxi Province[Abstract]: Objective: To analyze the application value of proton pump inhibitors in the treatment of throat diseases. Methods: 120 throat reflux patients from 01 / 2019 to 12 / 2021 were selected and randomized. The control group adopted the conventional treatmentregimen, while the observation group added the proton pump inhibitor therapy. The difference in efficacy and symptom relief time were compared, and the changes in the reflux symptom index score scale (RSI score) and the reflux sign score scale (RFS score) were compared between the two treatment groups. Results: The total response rate in the observation group was higher than the control group (P <0.05); the response time of pharyngeal discomfort, hoarseness, and acid refluxwas shorter than the control group (P <0.05); the change range of RSI score and RFS score in the observation group was higher than thecontrol group (P <0.05). Conclusion: Adding proton pump inhibitor to conventional treatment is helpful to relieve the symptoms of throat reflux, improve clinical effect, and can be used in throat reflux.[Key words]: proton pump inhibitor; throat disease; clinicalefficacy喉咽反流是指胃内容物反流至食管上括约肌以上部位，包括鼻咽、口咽、喉咽、喉、气管、鼻腔等部位，会造成黏膜损伤进而出现一系列症状和体征，如声嘶或发声障碍、咽喉疼痛、咽喉部异物感、咳嗽、呼吸困难、喉痉挛，以及声带后联合区域黏膜增生、肥厚等[1]。

氯吡格雷与质子泵抑制剂的相互作用摘要氯吡格雷能够降低冠心病患者再次发生心肌梗死的风险，故广泛用于急性冠脉综合征和经皮冠脉介入术后的患者。

临床相关指南建议，氯吡格雷应与质子泵抑制剂（proton pump inhibitor，PPI）合用以减少氯吡格雷的胃肠道不良反应。

但是，氯吡格雷需经肝脏细胞色素P450酶的同功酶CYP 2C19代谢才能转化为活性产物发挥作用，而PPI同样主要由CYP 2C19代谢。

药代动力学研究显示，氯吡格雷与奥美拉唑合用会发生药物相互作用、由此降低氯吡格雷的抗血小板作用，而泮托拉唑与氯吡格雷的相互作用不明显。

发表于2009年的系列回顾性病例对照研究表明，氯吡格雷与PPI合用会增加心血管不良事件的发生风险。

但这一研究结果并未得到前瞻性的随机、对照研究和荟萃分析的证实。

因此，目前仍需进行大规模的前瞻性的随机、对照试验来分析氯吡格雷和PPI合用与心血管不良事件风险间的相关性。

鉴于临床上有大量服用氯吡格雷的患者需合用PPI来降低胃肠道出血风险，建议现最好选用与氯吡格雷相互作用较小的泮托拉唑。

关键词质子泵抑制剂氯吡格雷药物相互作用Interaction of clopidogrel and proton pump inhibitorsJIANG Weiru*，ZHONG Liang（Department of Gastroenterology，Huashan Hospital，Fudan University，Shanghai 200040，China）Abstract Clopidogrel is considered as a standard medical treatment for acute coronary syndrome and patients having percutaneous coronary intervention in order to reduce the risk of new ischemic events. Combination of clopidogrel with proton pump inhibitor （PPI）is recommended by clinical guidelines in order to prevent gastrointestinal side effects. Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme 2C19 and PPI are extensively metabolized by the same isoenzyme as well. Pharmacodynamic studies showed that a potential clopidogrel-PPI interaction occurred，resulting in a significant decrease of the clopidogrel platelet antiaggregation effect in case of combination of clopidogrel with omeprazole，but not with pantoprazole. A series of retrospective case-control studies published in 2009 reported that combination of clopidogrel with PPI could increase the risk of adverse cardiovascular events. However，the result of this study has not been confirmed by prospectively randomized and controlled studies and meta-analysis. So，a large-scale prospectively randomized and controlled trial should be performed in order to analyze the risk of cardiovascular adverse events associated with the combination of clopidogrel with PPI. Since many patients taking clopidogrel need to take PPI to reduce the risk of gastrointestinal bleeding，combination of clopidogrel with pantoprazole possessing less drug interaction should be recommended.Key words proton pump inhibitors；clopidogrel；interaction急性冠脉综合征（acute coronary syndrome，ACS）和经皮冠状动脉介入治疗术（percutaneous coronary intervention，PCI）后的患者具有很高的再次发生心肌梗死的风险。