阿司匹林制剂的国外专利介绍_顾茂健_图文_百度文库
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阿司匹林制剂的国外专利介绍_顾茂健
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有人说去痛片是国内叫法，阿司匹林片是国外叫法，具体...
有人说去痛片是国内叫法，阿司匹林片是国外...
病情描述（发病时间、主要症状、症状变化等）：有人说去痛片是国内叫法，阿司匹林片是国外叫法，具体区别是什么？
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职称：医师
专长：中医科
&&已帮助用户：76403
问题分析： 你好。去痛片是国内叫法，阿司匹林片是国外叫法的说法不对。两药成分不同。
去痛片每片含氨基比林150mg、非那西丁150mg、咖啡因50mg、苯巴比妥15mg。阿司匹林片主要成份是阿司匹林。意见建议：要在医院医生指导下使用。
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问阿司匹林和去痛片有区别吗
职称：医生会员
专长：高血压、糖尿病、心血管疾病
&&已帮助用户：5999
病情分析：去痛片或者说镇痛药有两种，一类是抑制其恶劣限速生物合成的非甾体类解热镇痛药，用于外周钝痛，另一类是作用于阿片受体的镇痛药，用于中枢镇痛。阿司匹林属于解热镇痛药，药理学为抑制前列腺素合成，用于外周的慢性钝痛。
意见建议：
问阿司匹林和去痛片有区别吗
职称：医生会员
专长：高血压、糖尿病、心血管疾病
&&已帮助用户：5999
病情分析：去痛片或者说镇痛药有两种，一类是抑制其恶劣限速生物合成的非甾体类解热镇痛药，用于外周钝痛，另一类是作用于阿片受体的镇痛药，用于中枢镇痛。阿司匹林属于解热镇痛药，药理学为抑制前列腺素合成，用于外周的慢性钝痛。
意见建议：
问牛皮癣药物选国内的好还是国外的好
职称：医师
专长：银屑病、牛皮癣、皮肤癣各类疑难病
&&已帮助用户：21874
病情分析： 治牛皮癣，我们要分型对待，对不同的临床类型，不同的皮疹特点，选择适合的药物，脓包型的牛皮癣是比较严重的，治疗的时候，是需要非常注意用药的选择的。意见建议：脓包型的牛皮癣在治疗上，需要有一个好的认识，这种疾病在治疗的时候，只是病情稳定维持时间长短而已，目前通过规律的治疗用药实现病情长时间的持续稳定就是一种比较理想的疗效。
问阿司匹林片与阿司匹林肠溶片有区别吗
职称：主治医师
专长：小儿感冒,小儿肺炎,腹泻病
&&已帮助用户：100940
您好，肠溶片简单的说就是为了减少乙酰水杨酸对胃的刺激，以及以便在肠子溶解吸收更全面，减少首关效应。阿司匹林肠溶片 一般用于预防血栓凝集
阿司匹林片是解热镇痛的，阿司匹林肠溶片是防止血栓的。
问医生您好！我是在国外我女儿在国内查出乳房纤维瘤，还...
职称：医生会员
专长：擅长妇科常见病，不孕不育等疾病
&&已帮助用户：182844
病情分析： 你好乳腺纤维腺瘤最有效的治疗手段就是手术.手术可以将腺瘤切除而使之治愈,但部分病例可于原手术部位复发或在乳房其他部位再生新的腺瘤.该病一经确诊,以局部（包括瘤周部分正常乳腺组织）切除来治疗.对少数巨纤维腺瘤,若局部切除后将致乳房严重变形,可作皮下乳腺切除加硅胶囊假体乳腺植入乳房一期成形术.切除的组织常规作病理检查,如有恶变,则按乳腺癌处理意见建议：建议饮食要定时,定量,少食多餐,宜清淡,多食蔬菜以及含维生素A,C,E,绿色蔬菜和水果.,忌辛燥刺激之品,如姜,蒜,韭菜,花椒,辣椒等;
问请问电灼伤的整形哪个医院最好国内国外都可以.
职称：药师
专长：多发性骨骺发育异常,儿童钙尔奇,二十八味补肾胶囊,妇炎康分散片,活血止痛膏,降脂通络软胶囊,三金片,生脉饮,半硫丸,金莲花胶囊
&&已帮助用户：38952
指导意见：可采用国际领先的超高频高科技皮肤整形微创技术治疗它发扬了外科手术激光冷冻擦皮术等的优点且弥补了它们的不足它是一种精细微创技术用超高频皮肤整形技术治疗修复瘢痕后根据瘢痕的种类不同术后均能达到明显好转修复后新生皮肤可较平展或接近正常皮肤.
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评价成功！阿司匹林的合理用药
阿司匹林的合理用药
作者：会菲的鱼 &东营市人民医院本文为投稿文章（），转载请务必注明作者和来源“医脉通”。阿司匹林预防用药国内外指南推荐：一、国内推荐—高血压指南二级预防&1.合并冠心病等心血管疾病，需应用小剂量（100mg/d）；&2.合并血栓症急性发作，通常急性期给予负荷剂量（300mg/d），而后应用小剂量（100mg/d）；&一级预防&1.高血压伴糖尿病、心血管高风险者（10年心血管总风险≥10%),可用小剂量（75-100mg/d）；&2.不能耐受者可应用氯吡格雷（75-100mg/d）代替；3.30岁以下和80岁以上者应权衡获益风险使用；&二、国内推荐—糖尿病指南二级预防心血管疾病史的糖尿病患者应常规使用，小剂量（75-150mg/d）；一级预防1.具有高危心血管风险：小剂量（75-150mg/d）；&2.具有中度心血管风险：权衡利弊使用；&3.具有心血管低风险：不推荐；&4.不推荐用于＜30岁糖尿病患者；禁用于＜21岁患者，因为会增加Reye综合征的风险；5.氯吡格雷(75mg/d)推荐用于存在CVD且有记录表明阿司匹林过敏的患者；&三、国内推荐—抗血小板共识有以下三项及以上危险因素者服用75-100mg/d：1.男性≥50岁或女性绝经期后&2.高血压&3.糖尿病&4.高胆固醇血症&5.肥胖&6.早发心脑血管病家族史&7.吸烟&四、国外推荐-ADA二级预防患有心肌梗死、血管搭桥术、脑卒中或短暂性脑缺血发作、外周血管病变、跛行或心绞痛病史之一者，服用剂量(75-162mg/d) ；一级预防1.具有高危心血管风险，推荐证据较弱。服用剂量(75-162mg/d) ；2.不推荐用于＜30岁糖尿病患者；禁用于＜21岁患者；3.氯吡格雷(75mg/d)推荐用于存在CVD且有记录表明阿司匹林过敏的患者；4.女性服用阿司匹林年龄由＞60岁改为≥50岁；五、国外推荐-USPSTP年龄50-69岁，10年心血管风险≥10%，无出血风险增加，建议低剂量阿司匹林预防心血管疾病；推荐最佳剂量81mg/d。阿司匹林预防用药剂量：对于年龄≥50岁无过高出血风险的患者，剂量范围：75-100mg/d；&阿司匹林出血风险：相关meta分析中，在5年间，阿司匹林的非致命性颅外严重出血的预测绝对发生率随Framingham危险评分的增加而增加：根据CAD风险分层，5年出血风险：CAD风险小于5%：出血风险为0.4%，CAD风险5%-10%：出血风险为1.0% ，CAD风险大于10%：出血风险为2.7%；&小结：心血管事件风险越大，使用阿司匹林获益越大；但需要评估出血风险；心血管事件获益超过出血风险时，推荐使用，剂量范围：75-100mg/d为宜。主要参考文献：1.中国2型糖尿病防治指南（2013年版）&2.中国高血压基层管理指南（2014年修订版）&3.中国高血压防治指南（2010年版）&4.抗血小板治疗专家共识（2013年版）&5.ADA糖尿病医学诊疗标准（2016年版）&6.USPSTP阿司匹林一级预防指南（2016年版）&
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【求助】复方埃索美拉唑镁阿司匹林国外说明书
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阿斯利康的缓释片说明见下：DESCRIPTIONThe active ingredients of VIMOVO are naproxen which is a NSAID and esomeprazole magnesium which is a Proton Pump Inhibitor (PPI).VIMOVO is available as an oval, yellow, multi-layer, delayed release tablet combining an enteric coated naproxen core and an immediate release esomeprazole magnesium layer surrounding the core. Each strength contains either 375 mg of naproxen and 20 mg of esomeprazole (present as 22.3 mg esomeprazole magnesium trihydrate) or 500 mg of naproxen and 20 mg of esomeprazole (present as 22.3 mg esomeprazole magnesium trihydrate) for oral administration. The inactive ingredients are carnauba wax, colloidal silicon dioxide, croscarmellose sodium, iron oxide yellow, glyceryl monostearate, hypromellose, iron oxide black, magnesium stearate, methacrylic acid copolymer dispersion, methylparaben, polysorbate 80, polydextrose, polyethylene glycol, povidone, propylene glycol, propylparaben, titanium dioxide, and triethyl citrate.The chemical name for naproxen is (S)-6-methoxy-alpha-methyl- 2-naphthaleneacetic acid. Naproxen has the following structure:Naproxen has a molecular weight of 230.26 and a molecular formula of C14H14O3.Naproxen is an odorless, white to off-white crystalline substance. It is lipid soluble, practically insoluble in water at low pH and freely soluble in water at high pH. The octanol/water partition coefficient of naproxen at pH 7.4 is 1.6 to 1.8.The chemical name for esomeprazole is bis(5-methoxy-2- [(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1 H -benzimidazole-1-yl) magnesium trihydrate. Esomeprazole is the S-isomer of omeprazole, which is a mixture of the S- and R-isomers. Its molecular formula is (C17H18N3O3S)2Mg x 3 H2O with molecular weight of 767.2 as a trihydrate and 713.1 on an anhydrous basis. The structural formula is:The magnesium salt is a white to slightly colored crystalline powder. It contains 3 moles of water of solvation and is slightly soluble in water.The stability of esomeprazole magnesium is a function of pH; it rapidly degrades in acidic media, but it has acceptable stability under alkaline conditions. At pH 6.8 (buffer), the half-life of the magnesium salt is about 19 hours at 25°C and about 8 hours at 37°C.CLINICAL PHARMACOLOGYMechanism of ActionVIMOVO consists of an immediate-release esomeprazole magnesium layer and an enteric-coated naproxen core. As a result, esomeprazole is released first in the stomach, prior to the dissolution of naproxen in the small intestine. The enteric coating prevents naproxen release at pH levels below 5.5.Naproxen is a NSAID with analgesic and antipyretic properties. The mechanism of action of the naproxen anion, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition.Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. Esomeprazole is protonated and converted in the acidic compartment of the parietal cell forming the active inhibitor, the achiral sulphenamide. By acting specifically on the proton pump, esomeprazole blocks the final step in acid production, thus reducing gastric acidity. This effect is dose-related up to a daily dose of 20 to 40 mg and leads to inhibition of gastric acid secretion.PharmacodynamicsAntisecretory ActivityThe effect of VIMOVO on intragastric pH was determined in 25 healthy volunteers in one study. Three VIMOVO combinations (naproxen 500 mg combined with either esomeprazole 10, 20, or 30 mg) were administered twice daily over 9 days. The results are shown in the following table:Table 3: Effect on Intragastric pH on Day 9 (N=25)Naproxen 500 mg combined with esomeprazole 10 mg20 mg30 mg% Time Gastric pH &4 LS Mean (SE)41.1 (3.0)71.5 (3.0)76.8 (3.0)Coefficient of variation55%18%16% Gastric pH was measured over a 24-hour periodSerum Gastrin EffectsThe effect of esomeprazole on serum gastrin concentrations was evaluated in approximately 2,700 patients in clinical trials up to 8 weeks and in over 1,300 patients for up to 6-12 months. The mean fasting gastrin level increased in a dose-related manner. This increase reached a plateau within two to three months of therapy and returned to baseline levels within four weeks after discontinuation of therapy.Enterochromaffin-like (ECL) Cell EffectsIn over 1,000 patients treated with esomeprazole (10, 20 or 40 mg/day) up to 6-12 months, the prevalence of ECL cell hyperplasia increased with time and dose. No patient developed ECL cell carcinoids, dysplasia, or neoplasia in the gastric mucosa.Endocrine EffectsEsomeprazole had no effect on thyroid function when given in oral doses of 20 or 40 mg for 4 weeks. Other effects of esomeprazole on the endocrine system were assessed using omeprazole studies. Omeprazole given in oral doses of 30 or 40 mg for 2 to 4 weeks had no effect on carbohydrate metabolism, circulating levels of parathyroid hormone, cortisol, estradiol, testosterone, prolactin, cholecystokinin or secretin.Effects on Gastrointestinal Microbial EcologyDecreased gastric acidity due to any means including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter and possibly Clostridium difficile in hospitalized patients.PharmacokineticsAbsorptionNaproxenAt steady state following administration of VIMOVO twice daily, peak plasma concentrations of naproxen are reached on average 3 hours following both the morning and the evening dose.Bioequivalence between VIMOVO and enteric-coated naproxen, based on both area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) of naproxen, has been demonstrated for both the 375 mg and 500 mg doses.Naproxen is absorbed from the gastrointestinal tract with an in vivo bioavailability of 95%.Steady-state levels of naproxen are reached in 4 to 5 days.EsomeprazoleFollowing administration of VIMOVO twice daily, esomeprazole is rapidly absorbed with peak plasma concentration reached within on average, 0.43 to 1.2 hours, following the morning and evening dose on both the first day of administration and at steady state. The peak plasma concentrations of esomeprazole are higher at steady state compared to on first day of dosing of VIMOVO.Figure 1 represents the pharmacokinetics of naproxen and esomeprazole following administration of VIMOVO 500 mg/20 mg.Figure 1: Mean plasma concentrations of naproxen and esomeprazole following single dose administration of VIMOVO (500mg/20 mg)Food effectAdministration of VIMOVO together with high-fat food in healthy volunteers does not affect the extent of absorption of naproxen but significantly prolongs tmax by 10 hours and decreases peak plasma concentration (Cmax) by about 12%.Administration of VIMOVO together with high-fat food in healthy volunteers delays tmax of esomeprazole by 1 hour and significantly reduces the extent of absorption, resulting in 52% and 75% reductions of area under the plasma concentration versus time curve (AUC) and peak plasma concentration (Cmax), respectively.Administration of VIMOVO 30 minutes before high-fat food intake in healthy volunteers does not affect the extent of absorption of naproxen but delays the absorption by about 4 hours and decreases peak plasma concentration (Cmax) by about 17%, but has no significant effect on the rate or extent of esomeprazole absorption compared to administration under fasted conditions [see Dosage and Administration (2) ].Administration of VIMOVO 60 minutes before high-fat food intake in healthy volunteers has no effect on the rate and extent of however, increases the esomeprazole AUC by 25% and Cmax by 50% compared to administration under fasted conditions. This increase in esomeprazole Cmax does not raise a safety issue since the approved dosing regimen of esomeprazole at 40 mg QD would result in higher Cmax [see Dosage and Administration (2) ].Therefore, VIMOVO should be taken at least 30 minutes before the meal.DistributionNaproxenNaproxen has a volume of distribution of 0.16 L/kg. At therapeutic levels naproxen is greater than 99% albumin-bound. At doses of naproxen greater than 500 mg/day there is less than proportional increase in plasma levels due to an increase in clearance caused by saturation of plasma protein binding at higher doses (average trough Css 36.5, 49.2 and 56.4 mg/L with 500, 1000 and 1500 mg daily doses of naproxen, respectively). The naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma [see Use in Specific Populations (8.3) ].EsomeprazoleThe apparent volume of distribution at steady state in healthy subjects is approximately 16L. Esomeprazole is 97% plasma protein bound.MetabolismNaproxenNaproxen is extensively metabolized in the liver by the cytochrome P450 system (CYP), CYP2C9 and CYP1A2, to 6-0-desmethyl naproxen. Neither the parent drug nor the metabolites induce metabolizing enzymes. Both naproxen and 6-0-desmethyl naproxen are further metabolized to their respective acylglucuronide conjugated metabolites. Consistent with the half-life of naproxen, the area under the plasma concentration time curve increases with repeated dosing of VIMOVO twice daily.EsomeprazoleEsomeprazole is extensively metabolized in the liver by the CYP enzyme system. The major part of the metabolism of esomeprazole is dependent on the polymorphic CYP2C19, responsible for the formation of the hydroxyl- and desmethyl metabolites of esomeprazole. The remaining part is dependent on another specific isoform CYP3A4, responsible for the formation of esomeprazole sulphone, the main metabolite in plasma. The major metabolites of esomeprazole have no effect on gastric acid secretion.The area under the plasma esomeprazole concentration-time curve increases with repeated administration of VIMOVO. This increase is dose-dependent and results in a non-linear dose-AUC relationship after repeated administration. An increased absorption of esomeprazole with repeated administration of VIMOVO probably also contributes to the time-and dose-dependency.ExcretionNaproxenFollowing administration of VIMOVO twice daily, the mean elimination half-life for naproxen is approximately 15 hours following the evening dose, with no change with repeated dosing.The clearance of naproxen is 0.13 mL/min/kg. Approximately 95% of the naproxen from any dose is excreted in the urine, primarily as naproxen (&1%), 6-0-desmethyl naproxen (&1%) or their conjugates (66% to 92%). Small amounts, 3% or less of the administered dose, are excreted in the feces. In patients with renal failure, metabolites may accumulate [see Warnings and Precautions (5.6, 5.7) ].EsomeprazoleFollowing administration of VIMOVO twice daily, the mean elimination half-life of esomeprazole is approximately 1 hour following both the morning and evening dose on day 1, with a slightly longer elimination half-life at steady state (1.2-1.5 hours).Almost 80% of an oral dose of esomeprazole is excreted as metabolites in the urine, the remainder in the feces. Less than 1% of the parent drug is found in the urine.Special PopulationsGeriatric PatientsThere is no specific data on the pharmacokinetics of VIMOVO in patients over age 65.Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly, although the unbound fraction is &1% of the total naproxen concentration. Unbound trough naproxen concentrations in elderly subjects have been reported to range from 0.12% to 0.19% of total naproxen concentration, compared with 0.05% to 0.075% in younger subjects. The clinical significance of this finding is unclear, although it is possible that the increase in free naproxen concentration could be associated with an increase in the rate of adverse events per a given dosage in some elderly patients [see Adverse Reactions (6) and Use in Specific Populations (8.5) ].The AUC and Cmax values of esomeprazole were slightly higher (25% and 18%, respectively) in the elderly as compared to younger subjects at steady state. Dosage adjustment for the esomeprazole component based on age is not necessary.RacePharmacokinetic differences due to race have not been studied for naproxen.Approximately 3% of Caucasians and 15 to 20% of Asians lack a functional CYP2C19 enzyme and are called poor metabolizers. In these individuals the metabolism of esomeprazole is probably mainly catalyzed by CYP3A4. After repeated once-daily administration of 40 mg esomeprazole, the mean area under the plasma concentration-time curve was approximately 100% higher in poor metabolizers than in subjects having a functional CYP2C19 enzyme (extensive metabolizers).Hepatic InsufficiencyThe pharmacokinetics of VIMOVO or naproxen have not been determined in subjects with hepatic impairment.Chronic alcoholic liver disease and probably also other forms of cirrhosis reduce the total plasma concentration of naproxen, but the plasma concentration of unbound naproxen is increased. The implication of this finding for the naproxen component of VIMOVO dosing is unknown but it is prudent to use the lowest effective dose.The AUCs of esomeprazole in patients with severe hepatic insufficiency (Child Pugh Class C) have been shown to be 2-3 times higher than in patients with normal liver function. For this reason, it has been recommended that esomeprazole doses not exceed 20 mg daily in patients with severe hepatic impairment. However, there is no dose adjustment necessary for patients with Child Pugh Class A and B for the esomeprazole component of VIMOVO. There is no VIMOVO dosage form that contains less than 20 mg esomeprazole for twice daily dosing.Renal InsufficiencyThe pharmacokinetics of VIMOVO or naproxen have not been determined in subjects with renal impairment.Given that naproxen, its metabolites and conjugates are primarily excreted by the kidney, the potential exists for naproxen metabolites to accumulate in the presence of renal insufficiency. Elimination of naproxen is decreased in patients with severe renal impairment. Naproxen-containing products, including VIMOVO, is not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance &30 ml/min) [see Dosage and Administration (2), Warnings and Precautions (5.6, 5.7), and Use in Specific Populations (8.7) ].No studies have been performed with esomeprazole in patients with decreased renal function. Since the kidney is responsible for the excretion of the metabolites of esomeprazole but not for the elimination of the parent compound, the metabolism of esomeprazole is not expected to be changed in patients with impaired renal function.GenderThe AUC and Cmax values of esomeprazole were slightly higher (13%) in females than in males at steady state. Dosage adjustment for the esomeprazole component based on gender is not necessary.NONCLINICAL TOXICOLOGYCarcinogenesis, Mutagenesis, Impairment of FertilityNaproxenA 2-year study was performed in rats to evaluate the carcinogenic potential of naproxen at rat doses of 8, 16, and 24 mg/kg/day (50, 100, and 150 mg/m2). The maximum dose used was 0.28 times the highest recommended human dose. No evidence of tumorigenicity was found.EsomeprazoleThe carcinogenic potential of esomeprazole was assessed using omeprazole studies. In two 24-month oral carcinogenicity studies in rats, omeprazole at daily doses of 1.7, 3.4, 13.8, 44 and 140.8 mg/kg/day (about 0.7 to 57 times the human dose of 20 mg/day expressed on a body surface area basis) produced gastric ECL cell carcinoids in a dose-related manner in both
the incidence of this effect was markedly higher in female rats, which had higher blood levels of omeprazole. Gastric carcinoids seldom occur in the untreated rat. In addition, ECL cell hyperplasia was present in all treated groups of both sexes. In one of these studies, female rats were treated with 13.8 mg omeprazole/kg/day (about 5.6 times the human dose on a body surface area basis) for 1 year, then followed for an additional year without the drug. No carcinoids were seen in these rats. An increased incidence of treatment-related ECL cell hyperplasia was observed at the end of 1 year (94% treated vs 10% controls). By the second year the difference between treated and control rats was much smaller (46% vs 26%) but still showed more hyperplasia in the treated group. Gastric adenocarcinoma was seen in one rat (2%). No similar tumor was seen in male or female rats treated for 2 years. For this strain of rat no similar tumor has been noted historically, but a finding involving only one tumor is difficult to interpret. A 78-week mouse carcinogenicity study of omeprazole did not show increased tumor occurrence, but the study was not conclusive.Esomeprazole was negative in the Ames mutation test, in the in vivo rat bone marrow cell chromosome aberration test, and the in vivo mouse micronucleus test. Esomeprazole, however, was positive in the in vitro human lymphocyte chromosome aberration test. Omeprazole was positive in the in vitro human lymphocyte chromosome aberration test, the in vivo mouse bone marrow cell chromosome aberration test, and the in vivo mouse micronucleus test.The potential effects of esomeprazole on fertility and reproductive performance were assessed using omeprazole studies. Omeprazole at oral doses up to 138 mg/kg/day in rats (about 56 times the human dose on a body surface area basis) was found to have no effect on reproductive performance of parental animals.Animal Toxicology and/or PharmacologyNaproxenReproductive studies have been performed in rats at 20 mg/kg/day (125 mg/m2/day, 0.23 times the maximum recommended human dose), rabbits at 20 mg/kg/day (220 mg/m2/day, 0.27 times the maximum recommended human dose), and mice at 170 mg/kg/day (510 mg/m2/day, 0.28 times the maximum recommended human dose) with no evidence of impaired fertility or harm to the fetus due to the drug. However, animal reproduction studies are not always predictive of human response.EsomeprazoleReproductive studies have been performed in rats at oral doses up to 280 mg/kg/day (about 57 times the human dose on a body surface area basis) and in rabbits at oral doses up to 86 mg/kg/day (about 35 times the human dose on a body surface area basis) and have revealed no evidence of impaired fertility or harm to the fetus due to esomeprazole.Reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 56 times the human dose on a body surface area basis) and in rabbits at doses up to 69 mg/kg/day (about 56 times the human dose on a body surface area basis) did not disclose any evidence for a teratogenic potential of omeprazole. In rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (about 5.5 to 56 times the human dose on a body surface area basis) produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at 13.8 to 138.0 mg/kg/day (about 5.6 to 56 times the human doses on a body surface area basis).CLINICAL STUDIESTwo randomized, multi-center, double-blind trials (Study 1 and Study 2) compared the incidence of gastric ulcer formation in 428 patients taking VIMOVO and 426 patients taking enteric-coated naproxen. Subjects were at least 18 years of age with a medical condition expected to require daily NSAID therapy for at least 6 months, and, if less than 50 years old, with a documented history of gastric or duodenal ulcer within the past 5 years. The majority of patients were female (67%), white (86%). The majority of patients were 50-69 years of age (83%). Approximately one quarter were on low-dose aspirin.Studies 1 and 2 showed that VIMOVO given as 500 mg/20 mg twice daily statistically significantly reduced the 6-month cumulative incidence of gastric ulcers compared to enteric-coated naproxen 500 mg twice daily (see Table 4).Approximately a quarter of the patients in Studies 1 and 2 were taking concurrent low-dose aspirin (≤ 325 mg daily). The results for this subgroup analysis in patients who used aspirin were consistent with the overall findings of the study.The results at one month, three months, and six months are presented in Table 4.Table 4 — Cumulative Observed Incidence of Gastric Ulcers at 1, 3 and 6 MonthsStudy 1Study 2VIMOVON=218 number (%)EC-naproxenN=216 number (%)VIMOVON=210 number (%)EC-naproxenN=210 number (%)0-1 Month3 (1.4)28 (13.0)4 (1.9)21 (10.0)0-3 Months4 (1.8)42 (19.4)10 (4.8)37 (17.6)0-6 Months 9 (4.1)50 (23.1)15 (7.1)51 (24.3) For both Studies, p & 0.001 for treatment comparisons of cumulative GU incidence at six months.In these trials, patients receiving VIMOVO had a mean duration of therapy of 152 days compared to 124 days in patients receiving enteric-coated naproxen alone. A higher proportion of patients taking EC-naproxen (12%) discontinued the study due to upper GI adverse events (including duodenal ulcers) compared to VIMOVO (4%) in both trials [see Adverse Reactions (6) ].The efficacy of VIMOVO in treating the signs and symptoms of osteoarthritis was established in two 12-week randomized, double-blind, placebo-controlled trials in patients with osteoarthritis (OA) of the knee. In these two trials, patients were allowed to remain on low-dose aspirin for cardioprophylaxis. VIMOVO was given as 500 mg/20 mg twice daily. In each trial, patients receiving VIMOVO had significantly better results compared to patients receiving placebo as measured by change from baseline of the WOMAC pain subscale and the WOMAC physical function subscale and a Patient Global Assessment Score.Based on studies with enteric-coated naproxen, improvement in patients treated for rheumatoid arthritis was demonstrated by a reduction in joint swelling, a reduction in duration of morning stiffness, a reduction in disease activity as assessed by both the investigator and patient, and by increased mobility as demonstrated by a reduction in walking time. In patients with osteoarthritis, the therapeutic action of naproxen has been shown by a reduction in joint pain or tenderness, an increase in range of motion in knee joints, increased mobility as demonstrated by a reduction in walking time, and improvement in capacity to perform activities of daily living impaired by the disease. In patients with ankylosing spondylitis, naproxen has been shown to decrease night pain, morning stiffness and pain at rest.
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icesp 阿斯利康的缓释片说明见下：DESCRIPTIONThe active ingredients of VIMOVO are naproxen which is a NSAID and esomeprazole magnesium which is a Proton Pump Inhibitor (PPI).VIMOVO is available as an oval, yellow, multi-layer, delayed release tablet combining an enteric coated naproxen core and an immediate release esomeprazole magnesium layer surrounding the core. Each strength contains either 375 mg of naproxen and 20 mg of esomeprazole (present as 22.3 mg esomeprazole magnesium trihydrate) or 500 mg of naproxen and 20 mg of esomeprazole (present as 22.3 mg esomeprazole magnesium trihydrate) for oral administration. The inactive ingredients are carnauba wax, colloidal silicon dioxide, croscarmellose sodium, iron oxide yellow, glyceryl monostearate, hypromellose, iron oxide black, magnesium stearate, methacrylic acid copolymer dispersion, methylparaben, polysorbate 80, polydextrose, polyethylene glycol, povidone, propylene glycol, propylparaben, titanium dioxide, and triethyl citrate.The chemical name for naproxen is (S)-6-methoxy-alpha-methyl- 2-naphthaleneacetic acid. Naproxen has the following structure:Naproxen has a molecular weight of 230.26 and a molecular formula of C14H14O3.Naproxen is an odorless, white to off-white crystalline substance. It is lipid soluble, practically insoluble in water at low pH and freely soluble in water at high pH. The octanol/water partition coefficient of naproxen at pH 7.4 is 1.6 to 1.8.The chemical name for esomeprazole is bis(5-methoxy-2- [(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1 H -benzimidazole-1-yl) magnesium trihydrate. Esomeprazole is the S-isomer of omeprazole, which is a mixture of the S- and R-isomers. Its molecular formula is (C17H18N3O3S)2Mg x 3 H2O with molecular weight of 767.2 as a trihydrate and 713.1 on an anhydrous basis. The structural formula is:The magnesium salt is a white to slightly colored crystalline powder. It contains 3 moles of water of solvation and is slightly soluble in water.The stability of esomeprazole magnesium is a function of pH; it rapidly degrades in acidic media, but it has acceptable stability under alkaline conditions. At pH 6.8 (buffer), the half-life of the magnesium salt is about 19 hours at 25°C and about 8 hours at 37°C.CLINICAL PHARMACOLOGYMechanism of ActionVIMOVO consists of an immediate-release esomeprazole magnesium layer and an enteric-coated naproxen core. As a result, esomeprazole is released first in the stomach, prior to the dissolution of naproxen in the small intestine. The enteric coating prevents naproxen release at pH levels below 5.5.Naproxen is a NSAID with analgesic and antipyretic properties. The mechanism of action of the naproxen anion, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition.Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. Esomeprazole is protonated and converted in the acidic compartment of the parietal cell forming the active inhibitor, the achiral sulphenamide. By acting specifically on the proton pump, esomeprazole blocks the final step in acid production, thus reducing gastric acidity. This effect is dose-related up to a daily dose of 20 to 40 mg and leads to inhibition of gastric acid secretion.PharmacodynamicsAntisecretory ActivityThe effect of VIMOVO on intragastric pH was determined in 25 healthy volunteers in one study. Three VIMOVO combinations (naproxen 500 mg combined with either esomeprazole 10, 20, or 30 mg) were administered twice daily over 9 days. The results are shown in the following table:Table 3: Effect on Intragastric pH on Day 9 (N=25)Naproxen 500 mg combined with esomeprazole 10 mg20 mg30 mg% Time Gastric pH &4 LS Mean (SE)41.1 (3.0)71.5 (3.0)76.8 (3.0)Coefficient of variation55%18%16% Gastric pH was measured over a 24-hour periodSerum Gastrin EffectsThe effect of esomeprazole on serum gastrin concentrations was evaluated in approximately 2,700 patients in clinical trials up to 8 weeks and in over 1,300 patients for up to 6-12 months. The mean fasting gastrin level increased in a dose-related manner. This increase reached a plateau within two to three months of therapy and returned to baseline levels within four weeks after discontinuation of therapy.Enterochromaffin-like (ECL) Cell EffectsIn over 1,000 patients treated with esomeprazole (10, 20 or 40 mg/day) up to 6-12 months, the prevalence of ECL cell hyperplasia increased with time and dose. No patient developed ECL cell carcinoids, dysplasia, or neoplasia in the gastric mucosa.Endocrine EffectsEsomeprazole had no effect on thyroid function when given in oral doses of 20 or 40 mg for 4 weeks. Other effects of esomeprazole on the endocrine system were assessed using omeprazole studies. Omeprazole given in oral doses of 30 or 40 mg for 2 to 4 weeks had no effect on carbohydrate metabolism, circulating levels of parathyroid hormone, cortisol, estradiol, testosterone, prolactin, cholecystokinin or secretin.Effects on Gastrointestinal Microbial EcologyDecreased gastric acidity due to any means including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter and possibly Clostridium difficile in hospitalized patients.PharmacokineticsAbsorptionNaproxenAt steady state following administration of VIMOVO twice daily, peak plasma concentrations of naproxen are reached on average 3 hours following both the morning and the evening dose.Bioequivalence between VIMOVO and enteric-coated naproxen, based on both area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) of naproxen, has been demonstrated for both the 375 mg and 500 mg doses.Naproxen is absorbed from the gastrointestinal tract with an in vivo bioavailability of 95%.Steady-state levels of naproxen are reached in 4 to 5 days.EsomeprazoleFollowing administration of VIMOVO twice daily, esomeprazole is rapidly absorbed with peak plasma concentration reached within on average, 0.43 to 1.2 hours, following the morning and evening dose on both the first day of administration and at steady state. The peak plasma concentrations of esomeprazole are higher at steady state compared to on first day of dosing of VIMOVO.Figure 1 represents the pharmacokinetics of naproxen and esomeprazole following administration of VIMOVO 500 mg/20 mg.Figure 1: Mean plasma concentrations of naproxen and esomeprazole following single dose administration of VIMOVO (500mg/20 mg)Food effectAdministration of VIMOVO together with high-fat food in healthy volunteers does not affect the extent of absorption of naproxen but significantly prolongs tmax by 10 hours and decreases peak plasma concentration (Cmax) by about 12%.Administration of VIMOVO together with high-fat food in healthy volunteers delays tmax of esomeprazole by 1 hour and significantly reduces the extent of absorption, resulting in 52% and 75% reductions of area under the plasma concentration versus time curve (AUC) and peak plasma concentration (Cmax), respectively.Administration of VIMOVO 30 minutes before high-fat food intake in healthy volunteers does not affect the extent of absorption of naproxen but delays the absorption by about 4 hours and decreases peak plasma concentration (Cmax) by about 17%, but has no significant effect on the rate or extent of esomeprazole absorption compared to administration under fasted conditions [see Dosage and Administration (2) ].Administration of VIMOVO 60 minutes before high-fat food intake in healthy volunteers has no effect on the rate and extent of however, increases the esomeprazole AUC by 25% and Cmax by 50% compared to administration under fasted conditions. This increase in esomeprazole Cmax does not raise a safety issue since the approved dosing regimen of esomeprazole at 40 mg QD would result in higher Cmax [see Dosage and Administration (2) ].Therefore, VIMOVO should be taken at least 30 minutes before the meal.DistributionNaproxenNaproxen has a volume of distribution of 0.16 L/kg. At therapeutic levels naproxen is greater than 99% albumin-bound. At doses of naproxen greater than 500 mg/day there is less than proportional increase in plasma levels due to an increase in clearance caused by saturation of plasma protein binding at higher doses (average trough Css 36.5, 49.2 and 56.4 mg/L with 500, 1000 and 1500 mg daily doses of naproxen, respectively). The naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma [see Use in Specific Populations (8.3) ].EsomeprazoleThe apparent volume of distribution at steady state in healthy subjects is approximately 16L. Esomeprazole is 97% plasma protein bound.MetabolismNaproxenNaproxen is extensively metabolized in the liver by the cytochrome P450 system (CYP), CYP2C9 and CYP1A2, to 6-0-desmethyl naproxen. Neither the parent drug nor the metabolites induce metabolizing enzymes. Both naproxen and 6-0-desmethyl naproxen are further metabolized to their respective acylglucuronide conjugated metabolites. Consistent with the half-life of naproxen, the area under the plasma concentration time curve increases with repeated dosing of VIMOVO twice daily.EsomeprazoleEsomeprazole is extensively metabolized in the liver by the CYP enzyme system. The major part of the metabolism of esomeprazole is dependent on the polymorphic CYP2C19, responsible for the formation of the hydroxyl- and desmethyl metabolites of esomeprazole. The remaining part is dependent on another specific isoform CYP3A4, responsible for the formation of esomeprazole sulphone, the main metabolite in plasma. The major metabolites of esomeprazole have no effect on gastric acid secretion.The area under the plasma esomeprazole concentration-time curve increases with repeated administration of VIMOVO. This increase is dose-dependent and results in a non-linear dose-AUC relationship after repeated administration. An increased absorption of esomeprazole with repeated administration of VIMOVO probably also contributes to the time-and dose-dependency.ExcretionNaproxenFollowing administration of VIMOVO twice daily, the mean elimination half-life for naproxen is approximately 15 hours following the evening dose, with no change with repeated dosing.The clearance of naproxen is 0.13 mL/min/kg. Approximately 95% of the naproxen from any dose is excreted in the urine, primarily as naproxen (&1%), 6-0-desmethyl naproxen (&1%) or their conjugates (66% to 92%). Small amounts, 3% or less of the administered dose, are excreted in the feces. In patients with renal failure, metabolites may accumulate [see Warnings and Precautions (5.6, 5.7) ].EsomeprazoleFollowing administration of VIMOVO twice daily, the mean elimination half-life of esomeprazole is approximately 1 hour following both the morning and evening dose on day 1, with a slightly longer elimination half-life at steady state (1.2-1.5 hours).Almost 80% of an oral dose of esomeprazole is excreted as metabolites in the urine, the remainder in the feces. Less than 1% of the parent drug is found in the urine.Special PopulationsGeriatric PatientsThere is no specific data on the pharmacokinetics of VIMOVO in patients over age 65.Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly, although the unbound fraction is &1% of the total naproxen concentration. Unbound trough naproxen concentrations in elderly subjects have been reported to range from 0.12% to 0.19% of total naproxen concentration, compared with 0.05% to 0.075% in younger subjects. The clinical significance of this finding is unclear, although it is possible that the increase in free naproxen concentration could be associated with an increase in the rate of adverse events per a given dosage in some elderly patients [see Adverse Reactions (6) and Use in Specific Populations (8.5) ].The AUC and Cmax values of esomeprazole were slightly higher (25% and 18%, respectively) in the elderly as compared to younger subjects at steady state. Dosage adjustment for the esomeprazole component based on age is not necessary.RacePharmacokinetic differences due to race have not been studied for naproxen.Approximately 3% of Caucasians and 15 to 20% of Asians lack a functional CYP2C19 enzyme and are called poor metabolizers. In these individuals the metabolism of esomeprazole is probably mainly catalyzed by CYP3A4. After repeated once-daily administration of 40 mg esomeprazole, the mean area under the plasma concentration-time curve was approximately 100% higher in poor metabolizers than in subjects having a functional CYP2C19 enzyme (extensive metabolizers).Hepatic InsufficiencyThe pharmacokinetics of VIMOVO or naproxen have not been determined in subjects with hepatic impairment.Chronic alcoholic liver disease and probably also other forms of cirrhosis reduce the total plasma concentration of naproxen, but the plasma concentration of unbound naproxen is increased. The implication of this finding for the naproxen component of VIMOVO dosing is unknown but it is prudent to use the lowest effective dose.The AUCs of esomeprazole in patients with severe hepatic insufficiency (Child Pugh Class C) have been shown to be 2-3 times higher than in patients with normal liver function. For this reason, it has been recommended that esomeprazole doses not exceed 20 mg daily in patients with severe hepatic impairment. However, there is no dose adjustment necessary for patients with Child Pugh Class A and B for the esomeprazole component of VIMOVO. There is no VIMOVO dosage form that contains less than 20 mg esomeprazole for twice daily dosing.Renal InsufficiencyThe pharmacokinetics of VIMOVO or naproxen have not been determined in subjects with renal impairment.Given that naproxen, its metabolites and conjugates are primarily excreted by the kidney, the potential exists for naproxen metabolites to accumulate in the presence of renal insufficiency. Elimination of naproxen is decreased in patients with severe renal impairment. Naproxen-containing products, including VIMOVO, is not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance &30 ml/min) [see Dosage and Administration (2), Warnings and Precautions (5.6, 5.7), and Use in Specific Populations (8.7) ].No studies have been performed with esomeprazole in patients with decreased renal function. Since the kidney is responsible for the excretion of the metabolites of esomeprazole but not for the elimination of the parent compound, the metabolism of esomeprazole is not expected to be changed in patients with impaired renal function.GenderThe AUC and Cmax values of esomeprazole were slightly higher (13%) in females than in males at steady state. Dosage adjustment for the esomeprazole component based on gender is not necessary.NONCLINICAL TOXICOLOGYCarcinogenesis, Mutagenesis, Impairment of FertilityNaproxenA 2-year study was performed in rats to evaluate the carcinogenic potential of naproxen at rat doses of 8, 16, and 24 mg/kg/day (50, 100, and 150 mg/m2). The maximum dose used was 0.28 times the highest recommended human dose. No evidence of tumorigenicity was found.EsomeprazoleThe carcinogenic potential of esomeprazole was assessed using omeprazole studies. In two 24-month oral carcinogenicity studies in rats, omeprazole at daily doses of 1.7, 3.4, 13.8, 44 and 140.8 mg/kg/day (about 0.7 to 57 times the human dose of 20 mg/day expressed on a body surface area basis) produced gastric ECL cell carcinoids in a dose-related manner in both
the incidence of this effect was markedly higher in female rats, which had higher blood levels of omeprazole. Gastric carcinoids seldom occur in the untreated rat. In addition, ECL cell hyperplasia was present in all treated groups of both sexes. In one of these studies, female rats were treated with 13.8 mg omeprazole/kg/day (about 5.6 times the human dose on a body surface area basis) for 1 year, then followed for an additional year without the drug. No carcinoids were seen in these rats. An increased incidence of treatment-related ECL cell hyperplasia was observed at the end of 1 year (94% treated vs 10% controls). By the second year the difference between treated and control rats was much smaller (46% vs 26%) but still showed more hyperplasia in the treated group. Gastric adenocarcinoma was seen in one rat (2%). No similar tumor was seen in male or female rats treated for 2 years. For this strain of rat no similar tumor has been noted historically, but a finding involving only one tumor is difficult to interpret. A 78-week mouse carcinogenicity study of omeprazole did not show increased tumor occurrence, but the study was not conclusive.Esomeprazole was negative in the Ames mutation test, in the in vivo rat bone marrow cell chromosome aberration test, and the in vivo mouse micronucleus test. Esomeprazole, however, was positive in the in vitro human lymphocyte chromosome aberration test. Omeprazole was positive in the in vitro human lymphocyte chromosome aberration test, the in vivo mouse bone marrow cell chromosome aberration test, and the in vivo mouse micronucleus test.The potential effects of esomeprazole on fertility and reproductive performance were assessed using omeprazole studies. Omeprazole at oral doses up to 138 mg/kg/day in rats (about 56 times the human dose on a body surface area basis) was found to have no effect on reproductive performance of parental animals.Animal Toxicology and/or PharmacologyNaproxenReproductive studies have been performed in rats at 20 mg/kg/day (125 mg/m2/day, 0.23 times the maximum recommended human dose), rabbits at 20 mg/kg/day (220 mg/m2/day, 0.27 times the maximum recommended human dose), and mice at 170 mg/kg/day (510 mg/m2/day, 0.28 times the maximum recommended human dose) with no evidence of impaired fertility or harm to the fetus due to the drug. However, animal reproduction studies are not always predictive of human response.EsomeprazoleReproductive studies have been performed in rats at oral doses up to 280 mg/kg/day (about 57 times the human dose on a body surface area basis) and in rabbits at oral doses up to 86 mg/kg/day (about 35 times the human dose on a body surface area basis) and have revealed no evidence of impaired fertility or harm to the fetus due to esomeprazole.Reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 56 times the human dose on a body surface area basis) and in rabbits at doses up to 69 mg/kg/day (about 56 times the human dose on a body surface area basis) did not disclose any evidence for a teratogenic potential of omeprazole. In rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (about 5.5 to 56 times the human dose on a body surface area basis) produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at 13.8 to 138.0 mg/kg/day (about 5.6 to 56 times the human doses on a body surface area basis).CLINICAL STUDIESTwo randomized, multi-center, double-blind trials (Study 1 and Study 2) compared the incidence of gastric ulcer formation in 428 patients taking VIMOVO and 426 patients taking enteric-coated naproxen. Subjects were at least 18 years of age with a medical condition expected to require daily NSAID therapy for at least 6 months, and, if less than 50 years old, with a documented history of gastric or duodenal ulcer within the past 5 years. The majority of patients were female (67%), white (86%). The majority of patients were 50-69 years of age (83%). Approximately one quarter were on low-dose aspirin.Studies 1 and 2 showed that VIMOVO given as 500 mg/20 mg twice daily statistically significantly reduced the 6-month cumulative incidence of gastric ulcers compared to enteric-coated naproxen 500 mg twice daily (see Table 4).Approximately a quarter of the patients in Studies 1 and 2 were taking concurrent low-dose aspirin (≤ 325 mg daily). The results for this subgroup analysis in patients who used aspirin were consistent with the overall findings of the study.The results at one month, three months, and six months are presented in Table 4.Table 4 — Cumulative Observed Incidence of Gastric Ulcers at 1, 3 and 6 MonthsStudy 1Study 2VIMOVON=218 number (%)EC-naproxenN=216 number (%)VIMOVON=210 number (%)EC-naproxenN=210 number (%)0-1 Month3 (1.4)28 (13.0)4 (1.9)21 (10.0)0-3 Months4 (1.8)42 (19.4)10 (4.8)37 (17.6)0-6 Months 9 (4.1)50 (23.1)15 (7.1)51 (24.3) For both Studies, p & 0.001 for treatment comparisons of cumulative GU incidence at six months.In these trials, patients receiving VIMOVO had a mean duration of therapy of 152 days compared to 124 days in patients receiving enteric-coated naproxen alone. A higher proportion of patients taking EC-naproxen (12%) discontinued the study due to upper GI adverse events (including duodenal ulcers) compared to VIMOVO (4%) in both trials [see Adverse Reactions (6) ].The efficacy of VIMOVO in treating the signs and symptoms of osteoarthritis was established in two 12-week randomized, double-blind, placebo-controlled trials in patients with osteoarthritis (OA) of the knee. In these two trials, patients were allowed to remain on low-dose aspirin for cardioprophylaxis. VIMOVO was given as 500 mg/20 mg twice daily. In each trial, patients receiving VIMOVO had significantly better results compared to patients receiving placebo as measured by change from baseline of the WOMAC pain subscale and the WOMAC physical function subscale and a Patient Global Assessment Score.Based on studies with enteric-coated naproxen, improvement in patients treated for rheumatoid arthritis was demonstrated by a reduction in joint swelling, a reduction in duration of morning stiffness, a reduction in disease activity as assessed by both the investigator and patient, and by increased mobility as demonstrated by a reduction in walking time. In patients with osteoarthritis, the therapeutic action of naproxen has been shown by a reduction in joint pain or tenderness, an increase in range of motion in knee joints, increased mobility as demonstrated by a reduction in walking time, and improvement in capacity to perform activities of daily living impaired by the disease. In patients with ankylosing spondylitis, naproxen has been shown to decrease night pain, morning stiffness and pain at rest.谢谢你的回复，但是这个不是我说的复方。
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网址： 还有一个pdf 你看看是不是要找的？谢谢你！我想要的是阿司匹林+埃索美拉唑镁的复方制剂啊，你这个也不符合要求。
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Product Name in the RMS: Axanum 81 mg/20 mg Hartkapseln MR Number: DE/H/ Date of outcome: 29.07.2011 Type of application Level 1:Level 2:Level 3:Level 4:Level 5:Known Active SubstanceInitial ApplicationFull DossierChemical SubstancePrescription OnlyActive Substancesacetylsalicylic acid esomeprazole FormCapsule, hardStrength81mgMA Holder in the RMSAstra Zeneca GmbHTinsdaler Weg 18322880 WedelGermanyRMSGermanyDate of last change19.12.2011ATC-CodeA02B DRUGS FOR TREATMENT OF PEPTIC ULCERCMS CountryDomestic Product NameAustriaAxanum 81 mg/20 mg HartkapselnBelgium BulgariaAxanumCyprusAXANUM HARD CAPSCzech RepublicAxanumDenmark EstoniaAXANUMFinland France Greece HungaryAxanum 81mg/20mg kemény kapszulaItaly Latvia LithuaniaAxanum 81 mg/20 mg kietos kapsul?sLuxembourg Netherlands Norway Poland Portugal RomaniaAxanum 81mg / 20 mg capsuleSlovak RepublicAxanum 81 mg/20 mg tvrdé kapsulySlovenia SwedenAxanum好像只在这几个欧洲国家上市，所以暂时没找到英文的spc....
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其他语言的倒是有，，，，
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前2天也在看这个药，试着找了下， 好像现在还没有英文的，只有德文、瑞典文等等其它文字的
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blackmoore Product Name in the RMS: Axanum 81 mg/20 mg Hartkapseln MR Number: DE/H/ Date of outcome: 29.07.2011 Type of application Level 1:Level 2:Level 3:Level 4:Level 5:Known Active SubstanceInitial ApplicationFull DossierChemical SubstancePrescription OnlyActive Substancesacetylsalicylic acid esomeprazole FormCapsule, hardStrength81mgMA Holder in the RMSAstra Zeneca GmbHTinsdaler Weg 18322880 WedelGermanyRMSGermanyDate of last change19.12.2011ATC-CodeA02B DRUGS FOR TREATMENT OF PEPTIC ULCERCMS CountryDomestic Product NameAustriaAxanum 81 mg/20 mg HartkapselnBelgium BulgariaAxanumCyprusAXANUM HARD CAPSCzech RepublicAxanumDenmark EstoniaAXANUMFinland France Greece HungaryAxanum 81mg/20mg kemény kapszulaItaly Latvia LithuaniaAxanum 81 mg/20 mg kietos kapsul?sLuxembourg Netherlands Norway Poland Portugal RomaniaAxanum 81mg / 20 mg capsuleSlovak RepublicAxanum 81 mg/20 mg tvrdé kapsulySlovenia SwedenAxanum好像只在这几个欧洲国家上市，所以暂时没找到英文的spc....谢谢你，请问一下这个怎么是胶囊呢？我查到的说是片剂上市都嘛，还有这么多国家上市，首次批准的时间是多久呢？
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shangrui 前2天也在看这个药，试着找了下， 好像现在还没有英文的，只有德文、瑞典文等等其它文字的觉着这个复方有点立题不足的感觉。
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zxmcomeon 觉着这个复方有点立题不足的感觉。怎么立题不足？
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shangrui 怎么立题不足？复方的优势不突出，而且临床试验没有做复方与联合用药的比较，最关键是FDA没批。
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zxmcomeon 复方的优势不突出，而且临床试验没有做复方与联合用药的比较，最关键是FDA没批。如果单是从临床角度来看，个人感觉立题应该没有什么问题。服用阿司匹林的最大问题就是怕消化道出血，与质子泵抑制剂联用正好解决了这个问题，是符合目前相关临床药物治疗指南的。这个复方给医生和病人提供了一个氯吡格雷之外的选择。
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shangrui 如果单是从临床角度来看，个人感觉立题应该没有什么问题。服用阿司匹林的最大问题就是怕消化道出血，与质子泵抑制剂联用正好解决了这个问题，是符合目前相关临床药物治疗指南的。这个复方给医生和病人提供了一个氯吡格雷之外的选择。临床方面说说我的观点哈，这是一个预防而且需要长期使用的药，而质子泵抑制剂长期用药的安全性也是一个问题，觉着有点顾此失彼啊
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FDA rejects AstraZeneca's AxanumJune 1, 2010
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The FDA has declined to approve AstraZeneca's () Axanum, a combination of aspirin and esomeprazole, the main ingredient in the blockbuster drug Nexium. The drug is an experimental treatment for the prevention of ulcers. Additionally, the FDA issued a complete response letter for Nexium for reducing the risk of low-dose aspirin-associated peptic ulcers.It's a setback for AstraZeneca, which is attempting to extend Nexium's usage before the $5 billion-a-year drug goes off patent in 2014. But the drugmaker has had some success developing line-extension products: It recently received approval of , which was developed with Pozen. Vimovo contains naproxen and esomeprazole, and treats arthritis patients in danger of developing an ulcer. In a statement, AstraZeneca says it's evaluating the CRLs and will continue discussions with the FDA to determine next steps with respect to both the Axanum NDA as well as the Nexium sNDA.- take a look at - see this Bloomberg - read this
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llb1978 FDA rejects AstraZeneca's AxanumJune 1, 2010
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ToolsThe FDA has declined to approve AstraZeneca's () Axanum, a combination of aspirin and esomeprazole, the main ingredient in the blockbuster drug Nexium. The drug is an experimental treatment for the prevention of ulcers. Additionally, the FDA issued a complete response letter for Nexium for reducing the risk of low-dose aspirin-associated peptic ulcers.It's a setback for AstraZeneca, which is attempting to extend Nexium's usage before the $5 billion-a-year drug goes off patent in 2014. But the drugmaker has had some success developing line-extension products: It recently received approval of , which was developed with Pozen. Vimovo contains naproxen and esomeprazole, and treats arthritis patients in danger of developing an ulcer. In a statement, AstraZeneca says it's evaluating the CRLs and will continue discussions with the FDA to determine next steps with respect to both the Axanum NDA as well as the Nexium sNDA.- take a look at - see this Bloomberg - read this
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Subscribe: 谢谢斑竹的热心回复，其实我想知道的是FDA为啥没批准，原因是啥？
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hahaTOT edited on
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不过是德文的，有英文的给我一份呗
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英文的说明书
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英文说明书 比较详细
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为什么Ema中找不到Axanum相关信息？
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哇塞！太难得了有这么好的资料！多谢！
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