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奥扎格雷钠葡萄糖注射液

奥扎格雷钠葡萄糖注射液药品名称：【通用名称】奥扎格雷钠葡萄糖注射液【商品名称】丹仑【英文名称】 Sodium Ozagrel and Glucose Injection【汉语拼音】 Ao Zha Ge Lei Na Pu Tao Tang Zhu She Ye成份：本品主要成份是奥扎格雷钠，其化学名称为反式-3-[4（1H-咪唑-1-基甲基）苯基]-2-丙烯酸钠。

其结构式为：所属类别：化药及生物制品>> 神经系统药物>> 脑血管药化药及生物制品>> 血液系统药物>> 抗血小板药>> 血小板聚集抑制药性状：本品为无色或几乎无色的澄明液体。

适应症：本品为血栓素合成酶抑制剂。

用于治疗急性血栓性脑梗死和脑梗死所伴随的运动障碍。

规格：250ml：奥扎格雷钠80mg与葡萄糖12.5g用法用量：静脉滴注，一次250ml(一次一瓶)，一日1～2次，2周为一疗程。

静脉滴注，一次250ml(一次一瓶)，一日1～2次，2周为一疗程。

其它项详见说明书。

不良反应：血液：由于有出血的倾向，要仔细观察，出现异常立即停止给药。

肝肾：偶有GOT、GPT、BUN升高。

消化系统：偶有恶心、呕吐、腹泻、食欲不振、腹部胀满感。

过敏反应：偶见荨麻疹、皮疹等，发生时应停药。

循环系统：偶有室上性心律失常、血压下降，发现时应减量或终止给药。

其他：偶有头痛、发热、注射部位疼痛、休克及血小板减少等。

严重不良反应可出现出血性脑梗塞、硬膜外血肿、脑内出血、消化道出血、皮下出血等。

禁忌：以下患者禁用：1. 对本品过敏者；2. 脑出血或脑梗塞并出血者；3. 有严重心、肺、肝、肾功能不全者，如严重心律不齐；4. 有血液病或有出血倾向者；5. 严重高血压，收缩压超过26.6 kpa（即200 mmHg）以上者。

注意事项：1．限糖者慎用。

2．临用前需肉眼观察溶液澄清度，如观察到不溶性微粒析出时禁止使用。

拉努利苏拉特浓液（拉努利腺液浓液）说明书

17349 Lauryl sulfate Broth (Lauryl Tryptose Broth)Selective medium acc. to Mallmann and Darby (1941) for the presumptive testing for coliform and their selective enrichment in the examination of water, dairy products and foodstuffs. The difference to Cat. No. 61749 is that Tryptose is used instead of CaseinComposition:Ingredients Grams/LitreTryptose 20.0Lactose 5.0Dipotassium hydrogen phosphate 2.75Potassium dihydrogen phosphate 2.75Sodium lauryl sulfate 0.1Sodium chloride 5.0Final pH 6.8 +/- 0.2 at 25°CPrepared Broth becomes cloudy if stored at 2-8°C, but it should get cleared at room temperature. Store dehydrated powder, in a dry place, in tightly-sealed containers at 2-25°C.Directions:Dissolve 35.6 g in 1 litre distilled water. Distribute to convenient flasks or disspense 10 ml into each test-tubes containing inverted Durham tubes. Sterilize by autoclaving at 121°C for 15 minutes. Cool down slowly to prevent bubbles in Durham-tubes.Gas production from lactose fermentation is indicated by using inverted Durham tubes. Inoculate the tubes containing 10 ml of Lauryl sulfate Broth and the Durham tubes. Incubate at the wished temperature for 18-24 hours. In case of gas formation the Durham tubes rise or/and show bubbles. Turbidity of the medium accompanied by formation of gas within 48 hours is a positive presumtive test for the presence of E. coli and/or other coliform organisms.Principle and Interpretation:Tryptose provides the nitrogen, carbon compounds, vitamins and amino acids. Lactose is the fermentable sugar. Sodium lauryl sulphate inhibits organisms other than coliforms. Bile salts inhibit gram-positive bacteria especially bacilli and faecal Streptococci. Sodium chloride maintains the osmotic balance of the medium. Potassium phosphates control the pH during fermentation of lactose. Lactose-positive bacteria metabolize lactose with gas formation, within 24 hour or less is a presumptive evidence of the presence of coliform bacteria.After inoculation, incubate the tubes at 37°C for 24-48 hours. For every tube showing fermentation (primary fermentation), inoculate two tubes of Lauryl Tryptose Broth from the tube showing primary fermentation and incubate these tubes at 37°C and 44°C respectively. If there is fermentation in the tube incubated at 44°C after 8 to 24 hours, perform indole test by adding Kovac‘s reagent (Cat. No. 60983). A positive indole test in a broth tube showing gas production at 44°C indicates the presence of Escherichia coli. If no fermentation occurs in the tube incubated at 37°C after 24 hours, the primary fermentation is assumed to be due to organisms other than coliforms.Cultural characteristics after 18-24 hours at 35°C.Organisms (ATCC) Growth Gasformation Indole test (44°C)Enterobacter aerogenes (13048) +++ + - Escherichia coli (25922 and 11775) +++ + + Salmonella typhimurium (14028) +++ - - Staphylococcus aureus (25923) - - - Enterococcus faecalis (29212) - - -References:1. A.E. Greenberg, R.R.Trussell, L.S. Clesceri (Eds.), Standard Methods for the Examination of Waterand Wastewater, 16th ed., APHA Washington, D.C. (1985)2.M. Speck (Ed.), Compendium of Methods for the Microbiological Examination of Foods, 2nd ed.,APHA, Washington, D.C. (1984)3.J. Cowls, Am. Water Werks Association, 30, 979. (1938)4.International Organization for Standardization (ISO) , Draft ISO/DIS 4831 (1991)5.W.L. Mallmann, C.W. Darby, Am. J. Pbl. Health 31, 127 (1941)Precautions and DisclaimerThis product is for R&D use only, not for drug, household, or other uses. Please consult the Material Safety Data Sheet for information regarding hazards and safe handling practices.The vibrant M, Millipore, and Sigma-Aldrich are trademarks of Merck KGaA, Darmstadt, Germany orits affiliates. Detailed information on trademarks is available via publicly accessible resources.。

曼月乐使用说明之欧阳数创编

说明书如下:【曼月乐药品名称】商品名：曼月乐通用名：左炔诺孕酮宫内节育系统【曼月乐成份】曼月乐主要成分为左炔诺孕酮。

【曼月乐药物分类】其它避孕药和用品【曼月乐性状】曼月乐为白色至类白色筒状物，架在T状体上，外罩不透明的套管。

T 状体的一端上有一小环，小环上系有取出尾丝，另一端为两臂。

曼月乐应无异物。

【曼月乐药理作用】左炔诺孕酮是一种孕激素，在妇科学上有多种用途：如用作口服避孕药与激素替代治疗中的孕激素成分，或单独用于避孕的仅含有孕激素的避孕药及皮下埋植剂。

左炔诺孕酮也可通过宫内释放系统在宫腔内给药。

这样，由于激素直接释放进入靶器官，就可以使用很低的日剂量。

左炔诺孕酮宫内节育系统在宫腔内主要发挥局部孕激素作用。

子宫内膜的高左炔诺孕酮浓度抑制了雌激素受体在子宫内膜的合成，使子宫内膜对血循环中的雌二醇失去敏感性，从而发挥强力的内膜增生拮抗作用。

使用左炔诺孕酮宫内节育系统期间，可以观察到内膜的形态学变化和微弱的局部异物反应。

宫颈粘液变为粘稠阻止了精子通过宫颈管。

子宫和输卵管的局部内环境抑制了精子的活动与功能，防止了受精。

在某些妇女中，排卵亦受到抑制。

对其避孕效果的研究主要是将左炔诺孕酮宫内节育系统与各种含铜宫内节育器进行比较。

迄今左炔诺孕酮宫内节育系统的使用达13000妇女1年，总的妊娠率为0.16/100妇女年。

使用左炔诺孕酮宫内节育系统不影响以后的生育力。

约有80%希望妊娠的妇女在取出系统后12个月内受孕。

月经类型是左炔诺孕酮直接作用于子宫内膜的结果，而并不反映卵巢的周期。

出血类型不同的妇女在卵泡发育、排卵或雌二醇和孕酮产生方面并无明显的不同。

在对抗子宫内膜增生的过程中，使用的最初几个月可能出现点滴出血的初始性增加。

然后，在左炔诺孕酮宫内节育系统使用期间，由于对子宫内膜很强的抑制作用，使月经出血持续时间及出血量减少。

月经血量减少常发展为月经过少或闭经。

即使左炔诺孕酮宫内节育系统的使用者出现闭经，卵巢功能仍是正常的，雌二醇水平也能维持原状。

奥氮平片说明书

核准日期：2007年01月11日修改日期：(1) 5mg: 2007年01月24日 (2) 10mg: 2014年01月06日2007年04月11日2015年12月01日2014年01月06日2018年05月14日2015年12月01日2018年05月14日奥氮平片说明书请仔细阅读说明书并在医师指导下使用警告患有痴呆相关精神病的老年患者死亡率增加:与安慰剂相比，使用不典型抗精神病药时，患有痴呆相关精神病的老年患者有死亡率增加的风险。

对在患有痴呆相关精神病的老年患者中进行的17项安慰剂对照临床研究（平均众数治疗时间为10周）的分析发现，药物治疗组患者死亡的危险性为安慰剂对照组的1.6～1.7倍。

在一项典型的10周对照临床研究中，药物治疗组的死亡率为4.5%，安慰剂对照组为2.6%。

虽然死亡原因各异，但是大多数死于心血管病（如心衰、猝死）或感染（如肺炎）。

奥氮平未被批准用于治疗痴呆相关的精神病（见【注意事项】）。

【药品名称】通用名称：奥氮平片商品名称：欧兰宁英文名称：Olanzapine Tablets汉语拼音：Aodanping Pian【成份】本品主要成份为奥氮平。

化学名称：2-甲基-4-（4-甲基-1-哌嗪基）-10H-噻吩并[2,3-b][1,5]苯二氮杂䓬。

化学结构式：分子式：C17H20N4S分子量：312.43【性状】本品为白色或类白色圆形双凸薄膜包衣片。

【适应症】奥氮平用于治疗精神分裂症。

初始治疗有效的患者，奥氮平在维持治疗期间能够保持其临床效果。

奥氮平用于治疗中、重度躁狂发作。

对奥氮平治疗有效的躁狂发作患者，奥氮平可用于预防双相情感障碍的复发。

【规格】（1）5mg（2）10mg【用法用量】成人精神分裂症奥氮平的建议起始剂量为10mg/天。

每日一次。

躁狂发作单独用药时起始剂量为每日15mg，合并治疗时每日10mg。

预防双相情感障碍复发推荐起始剂量为10mg/日。

对于使用奥氮平治疗躁狂发作的患者，预防复发的持续治疗剂量同前。

阿格列汀英文说明书

____________________________________________________________________________________________________________________________________ HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use KAZANO safely and effectively. See full prescribing information for KAZANO. KAZANO (alogliptin and metformin HCl) tablets for oral administration Initial U.S. Approval: 2013 WARNING: LACTIC ACIDOSIS See full prescribing information for complete boxed warning ∙ Lactic acidosis can occur due to metformin accumulation.The risk increases with conditions such as sepsis,dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute congestive heart failure. (5.1) ∙ Symptoms include malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap and elevated blood lactate. (5.1) ∙ If acidosis is suspected, discontinue KAZANO and hospitalize the patient immediately. (5.1) ---------------------------INDICATIONS AND USAGE-------------------------- KAZANO is a dipeptidyl-peptidase-4 (DPP-4) inhibitor and abiguanide combination product indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. (1.1) Important Limitation of Use: Not for treatment of type 1 diabetes or diabetic ketoacidosis. (1.2)-----------------------DOSAGE AND ADMINISTRATION---------------------∙Individualize the starting dose of KAZANO based on the patient’s current regimen. (2.1) ∙KAZANO should be taken twice daily with food. (2.1) ∙ May adjust the dosing based on effectiveness and tolerability, while not exceeding the maximum recommended daily dose of 25 mg alogliptin and 2000 mg metformin HCl. (2.1) ---------------------DOSAGE FORMS AND STRENGTHS--------------------Tablets: 12.5 mg alogliptin and 500 mg metformin HCl, 12.5 mg alogliptin and 1000 mg metformin HCl. (3) ----------------------------CONTRAINDICATIONS-------------------------------∙Renal impairment. (4, 5.5) ∙Metabolic acidosis, including diabetic ketoacidosis. (4, 5.1) ∙History of a serious hypersensitivity reaction to alogliptin ormetformin, components of KAZANO, such as anaphylaxis, angioedema or severe cutaneous adverse reactions. (4) -----------------------WARNINGS AND PRECAUTIONS---------------------- ∙ Lactic acidosis: Warn against excessive alcohol intake. KAZANOis not recommended in hepatic impairment and is contraindicated in renal impairment. Ensure normal renal function before initiating and at least annually thereafter. (5.1) ∙ Acute pancreatitis: There have been postmarketing reports of acutepancreatitis. If pancreatitis is suspected, promptly discontinue KAZANO. (5.2) ∙ Hypersensitivity: There have been postmarketing reports of serious hypersensitivity reactions in patients treated with alogliptin such as anaphylaxis, angioedema and severe cutaneous adverse reactions. In such cases, promptly discontinue KAZANO, assess for otherpotential causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes. (5.3) ∙ Hepatic effects: Postmarketing reports of hepatic failure, sometimesfatal. Causality cannot be excluded. If liver injury is detected, promptly interrupt KAZANO and assess patient for probable cause, then treat cause if possible, to resolution or stabilization. Do notrestart KAZANO if liver injury is confirmed and no alternative etiology can be found. (5.4) ∙ Temporarily discontinue in patients undergoing radiologic studies with intravascular administration of iodinated contrast materials or any surgical procedures necessitating restricted intake of food and fluids. (5.5) ∙ Vitamin B12 deficiency: Metformin may lower Vitamin B12 levels.Monitor hematologic parameters annually. (5.8) ∙ Hypoglycemia: When used with an insulin secretagogue (e.g.,sulfonylurea) or with insulin, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia. (5.9) ∙ Macrovascular outcomes: There have been no clinical studiesestablishing conclusive evidence of macrovascular risk reduction with KAZANO or any other antidiabetic drug. (5.10) -----------------------------ADVERSE REACTIONS------------------------------Common adverse reactions reported in ≥4% of patients treated with coadministration of alogliptin with metformin were: upper respiratory tract infection, nasopharyngitis, diarrhea, hypertension, headache, back pain and urinary tract infection. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-877-TAKEDA-7 or FDA at 1-800-FDA-1088 or /medwatch.------------------------------DRUG INTERACTIONS-------------------------------Cationic drugs eliminated by renal tubular secretion: Use with caution. (7.2)-----------------------USE IN SPECIFIC POPULATIONS---------------------- ∙ Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women. (8.1) ∙ Pediatrics: Safety and effectiveness of KAZANO in patients below the age of 18 have not been established. (8.4) ∙ Geriatric Use: Caution should be used when prescribing KAZANO to elderly patients because reduced renal functions are associated with increasing age. (8.5) See 17 for PATIENT COUNSELING INFORMATION and Medication Guide Revised: 01/2013FULL PRESCRIBING INFORMATION: CONTENTS*WARNING: LACTIC ACIDOSIS 1 INDICATIONS AND USAGE 1.1 Monotherapy and Combination Therapy1.2 Limitation of Use2 DOSAGE AND ADMINISTRATION 2.1 Recommendations for All Patients3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Lactic Acidosis5.2 Pancreatitis 5.3 Hypersensitivity Reactions 5.4 Hepatic Effects5.5 Monitoring of Renal Function5.6 Hypoxic States5.8 Vitamin B12 Levels 5.9 Use with Medications Known to Cause Hypoglycemia5.10 Macrovascular Outcomes 6 ADVERSE REACTIONS6.1 Clinical Studies Experience 6.2 Laboratory Abnormalities 6.3 Postmarketing Experience 7 DRUG INTERACTIONS7.1 Carbonic Anhydrase Inhibitors7.2 Cationic Drugs7.3 The Use of Metformin with Other Drugs 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy8.3 Nursing Mothers 8.4 Pediatric Use8.5 Geriatric Use11 DESCRIPTION 14 CLINICAL STUDIES12 CLINICAL PHARMACOLOGY 16 HOW SUPPLIED/STORAGE AND HANDLING12.1 Mechanism of Action 17 PATIENT COUNSELING INFORMATION12.2 Pharmacodynamics 17.1 Instructions12.3 Pharmacokinetics* Sections or subsections omitted from the full prescribing information 13 NONCLINICAL TOXICOLOGYare not listed13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility____________________________________________________________________________________________________________________________________FULL PRESCRIBING INFORMATIONWARNING: LACTIC ACIDOSIS∙Lactic acidosis is a rare, but serious complication that can occurdue to metformin accumulation. The risk increases withconditions such as sepsis, dehydration, excess alcohol intake,hepatic impairment, renal impairment, and acute congestive heartfailure [see Warnings and Precautions (5.1)].∙The onset is often subtle, accompanied only by nonspecificsymptoms such as malaise, myalgias, respiratory distress,increasing somnolence, and nonspecific abdominal distress.Laboratory abnormalities include low pH, increased anion gapand elevated blood lactate. [see Warnings and Precautions (5.1)] ∙If acidosis is suspected, KAZANO (alogliptin and metformin HCl)should be discontinued and the patient hospitalized immediately.[see Warnings and Precautions (5.1)]1 1 INDICATIONS AND USAGE2 1.1 Monotherapy and Combination Therapy3 KAZANO is indicated as an adjunct to diet and exercise to improve glycemic control in4 adults with type 2 diabetes mellitus in multiple clinical settings when treatment with both5 alogliptin and metformin is appropriate [see Clinical Studies (14)].6 1.2 Limitation of Use7 KAZANO should not be used in patients with type 1 diabetes mellitus or for the8 treatment of diabetic ketoacidosis, as it would not be effective in these settings.9 2 DOSAGE AND ADMINISTRATION10 2.1 Recommendations for All Patients11 ∙Health care providers should individualize the starting dose of KAZANO based on12 the patient’s current regimen.13 ∙KAZANO should be taken twice daily with food with gradual dose escalation to14 reduce the gastrointestinal (GI) side effects due to metformin. KAZANO tablets must15 not be split before swallowing.16 ∙Dosing may be adjusted based on effectiveness and tolerability while not exceeding17 the maximum recommended daily dose of 25 mg alogliptin and 2000 mg metformin18 HCl.19 ∙The following doses are available:20 12.5 mg alogliptin and 500 mg metformin HCl21 12.5 mg alogliptin and 1000 mg metformin HCl22 3 DOSAGE FORMS AND STRENGTHS23 ∙12.5 mg/500 mg tablets are pale yellow, oblong, film-coated tablets with “12.5/500”24 debossed on one side and “322M” debossed on the other side25 ∙12.5 mg/1000 mg tablets are pale yellow, oblong, film-coated tablets with26 “12.5/1000” debossed on one side and “322M” debossed on the other side27 4 CONTRAINDICATIONS28 KAZANO is contraindicated in patients with:29 ∙Renal impairment (e.g., serum creatinine levels ≥1.5 mg/dL for men, ≥1.4 mg/dL for30 women or abnormal creatinine clearance) which may also result from conditions31 such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia32 [see Warnings and Precautions (5.5)].33 ∙Acute or chronic metabolic acidosis, including diabetic ketoacidosis. Diabetic34 ketoacidosis should be treated with insulin.35 ∙History of a serious hypersensitivity reaction to alogliptin or metformin, components36 of KAZANO, such as anaphylaxis, angioedema or severe cutaneous adverse37 reactions.38 5 WARNINGS AND PRECAUTIONS39 5.1 Lactic Acidosis40 Lactic acidosis is a rare, but serious, metabolic complication that can occur due to41 metformin accumulation during treatment with KAZANO and is fatal in approximately42 50% of cases. Lactic acidosis may also occur in association with a number of43 pathophysiologic conditions, including diabetes mellitus, and whenever there is44 significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by45 elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances46 with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin47 is implicated as the cause of lactic acidosis, metformin plasma levels >5 mcg/mL are48 generally found.49 The reported incidence of lactic acidosis in patients receiving metformin HCl is very low50 (approximately 0.03 cases/1000 patient years, with approximately 0.015 fatal51 cases/1000 patient years). In more than 20,000 patient years exposure to metformin in52 clinical trials, there were no reports of lactic acidosis. Reported cases have occurred53 primarily in diabetic patients with significant renal impairment, including both intrinsic54 renal disease and renal hypoperfusion, often in the setting of multiple concomitant55 medical/surgical problems and multiple concomitant medications. Patients with56 congestive heart failure requiring pharmacologic management, particularly when57 accompanied by hypoperfusion and hypoxemia due to unstable or acute failure, are at58 increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of59 renal dysfunction and the patient’s age. The risk of lactic acidosis may, therefore, be60 significantly decreased by regular monitoring of renal function in patients taking61 metformin. In particular, treatment of the elderly should be accompanied by careful62 monitoring of renal function. Metformin treatment should not be initiated in any patients63 unless measurement of creatinine clearance demonstrates that renal function is not64 reduced, as these patients are more susceptible to developing lactic acidosis. In65 addition, metformin should be promptly withheld in the presence of any condition66 associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function67 may significantly limit the ability to clear lactate, metformin should generally be avoided68 in patients with clinical or laboratory evidence of hepatic impairment. Patients should be69 cautioned against excessive alcohol intake when taking metformin, because alcohol70 potentiates the effects of metformin on lactate metabolism. In addition, metformin71 should be temporarily discontinued prior to any intravascular radiocontrast study and for72 any surgical procedure necessitating restricted intake of food or fluids. Use of73 topiramate, a carbonic anhydrase inhibitor, in epilepsy and migraine prophylaxis may74 frequently cause dose-dependent metabolic acidosis (In controlled trials, 32% and 67%75 for adjunctive treatment in adults and pediatric patents, respectively, and 15 to 25% for76 monotherapy of epilepsy, with decrease in serum bicarbonate to less than 20 mEq/L;77 3% and 11% for adjunctive treatment in adults and pediatric patents, respectively, and 178 to 7% for monotherapy of epilepsy, with decrease in serum bicarbonate to less than 1779 mEq/L) and may exacerbate the risk of metformin-induced lactic acidosis [see Drug80 Interactions (7.1) and Clinical Pharmacology (12.3)].81 The onset of lactic acidosis often is subtle, and accompanied only by nonspecific82 symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and83 nonspecific abdominal distress. There may be associated hypothermia, hypotension,84 and resistant bradyarrhythmias with more marked acidosis.85 Patients should be educated to promptly report these symptoms should they occur. If86 present, KAZANO should be withdrawn until lactic acidosis is ruled out. Serum87 electrolytes, ketones, blood glucose, blood pH, lactate levels, and blood metformin88 levels may be useful. Once a patient is stabilized on any dose level of metformin,89 gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to90 recur. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or91 other serious disease.92 Levels of fasting venous plasma lactate above the upper limit of normal but less than93 5 mmol/L in patients taking metformin do not necessarily indicate impending lactic94 acidosis and may be explainable by other mechanisms, such as poorly controlled95 diabetes or obesity, vigorous physical activity, or technical problems in sample handling.96 Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis97 lacking evidence of ketoacidosis (ketonuria and ketonemia).98 Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a99 patient with lactic acidosis who is taking metformin, the drug should be discontinued 100 immediately and general supportive measures promptly instituted. Because metformin 101 is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic102 conditions), prompt hemodialysis is recommended to correct the acidosis and remove 103 the accumulated metformin. Such management often results in prompt reversal of104 symptoms and recovery [see Contraindications (4)].105106 5.2 Pancreatitis107 There have been postmarketing reports of acute pancreatitis in patients taking108 alogliptin. After initiation of KAZANO, patients should be observed carefully for signs 109 and symptoms of pancreatitis. If pancreatitis is suspected, alogliptin should promptly be 110 discontinued and appropriate management should be initiated. It is unknown whether 111 patients with a history of pancreatitis are at increased risk for the development of112 pancreatitis while using KAZANO.113 5.3 Hypersensitivity Reactions114 There have been postmarketing reports of serious hypersensitivity reactions in patients 115 treated with alogliptin. These reactions include anaphylaxis, angioedema, and severe 116 cutaneous adverse reactions including Stevens-Johnson syndrome. If a serious117 hypersensitivity reaction is suspected, discontinue KAZANO, assess for other potential 118 causes for the event, and institute alternative treatment for diabetes [see Adverse119 Reactions (6.3)]. Use caution in patients with a history of angioedema to another DPP-4 120 inhibitor because it is unknown whether such patients will be predisposed to121 angioedema with KAZANO.122 5.4 Hepatic Effects123 There have been postmarketing reports of fatal and non-fatal hepatic failure in patients 124 taking alogliptin, although the reports contain insufficient information necessary to125 establish the probable cause [see Adverse Reactions (6.3)]. In randomized controlled 126 studies, serum alanine aminotransferase (ALT) elevations greater than three times the 127 upper limit of normal (ULN) were observed: 1.3% in alogliptin-treated patients and 1.5% 128 in all comparator-treated patients.129 Patients with type 2 diabetes may have fatty liver disease which may cause liver test 130 abnormalities, and they may also have other forms of liver disease, many of which can 131 be treated or managed. Therefore, obtaining a liver test panel and assessing the patient 132 before initiating KAZANO therapy is recommended. Because impaired hepatic function 133 has been associated with some cases of lactic acidosis with use of metformin, KAZANO 134 should generally be avoided in patients with clinical or laboratory evidence of hepatic 135 disease.136 Measure liver tests promptly in patients who report symptoms that may indicate liver 137 injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or138 jaundice. In this clinical context, if the patient is found to have clinically significant liver 139 enzyme elevations and if abnormal liver tests persist or worsen, KAZANO should be 140 interrupted and investigation done to establish the probable cause. KAZANO should 141 not be restarted in these patients without another explanation for the liver test142 abnormalities.143144145 5.5 Monitoring of Renal Function146 Metformin is substantially excreted by the kidney, and the risk of metformin147 accumulation and lactic acidosis increases with the degree of impairment. Therefore, 148 KAZANO is contraindicated in patients with renal impairment.149 Before initiation of KAZANO therapy and at least annually thereafter, renal function150 should be assessed and verified as normal. In patients in whom development of renal 151 dysfunction is anticipated, renal function should be assessed more frequently and152 KAZANO discontinued if evidence of renal impairment is present. Metformin treatment 153 should not be initiated in patients ≥80 years of age unless measurement of creatinine 154 clearance demonstrates that renal function is not reduced, as these patients are more 155 susceptible to developing lactic acidosis.156 Use of concomitant medications that may affect renal function or metformin157 disposition158 Concomitant medication(s) that may affect renal function or result in significant159 hemodynamic change or may interfere with the disposition of metformin, such as160 cationic drugs that are eliminated by renal tubular secretion [see Drug Interactions161 (7.2)], should be used with caution.162 Radiological studies and surgical procedures:163 Radiologic studies involving the use of intravascular iodinated contrast materials (for 164 example, intravenous urogram, intravenous cholangiography, angiography, and165 computed tomography) can lead to acute alteration of renal function and have been166 associated with lactic acidosis in patients receiving metformin. Therefore, in patients in 167 whom any such study is planned, KAZANO should be temporarily discontinued at the 168 time of or prior to the procedure, and withheld for 48 hours subsequent to the procedure 169 and reinstituted only after renal function has been re-evaluated and found to be normal. 170 KAZANO therapy should be temporarily suspended for any surgical procedure (except 171 minor procedures not associated with restricted intake of food and fluids) and should not 172 be restarted until the patient’s oral intake has resumed and renal function has been173 evaluated as normal.174 5.6 Hypoxic States175 Cardiovascular collapse (shock) from whatever cause, acute congestive heart failure, 176 acute myocardial infarction and other conditions characterized by hypoxemia have been 177 associated with lactic acidosis and may also cause prerenal azotemia. When such178 events occur in patients on KAZANO therapy, the drug should be promptly179 discontinued.180 5.7 Alcohol Intake181 Alcohol is known to potentiate the effect of metformin on lactate metabolism. Patients, 182 therefore, should be warned against excessive alcohol intake while receiving KAZANO. 183 5.8 Vitamin B12 Levels184 In controlled, 29-week clinical trials of immediate release metformin, a decrease to185 subnormal levels of previously normal serum Vitamin B12 levels, without clinical186 manifestations, was observed in approximately 7% of patients. Such decrease, possibly 187 due to interference with B12 absorption from the B12-intrinsic factor complex is,188 however, very rarely associated with anemia and appears to be rapidly reversible with 189 discontinuation of metformin or Vitamin B12 supplementation. Measurement of190 hematologic parameters on an annual basis is advised in patients on KAZANO and any 191 apparent abnormalities should be appropriately investigated and managed. Certain192 individuals (those with inadequate Vitamin B12 or calcium intake or absorption) appear 193 to be predisposed to developing subnormal Vitamin B12 levels. In these patients,194 routine serum Vitamin B12 measurements at two- to three-year intervals may be useful. 195 5.9 Use with Medications Known to Cause Hypoglycemia196 Alogliptin197 Insulin and insulin secretagogues, such as sulfonylureas, are known to cause198 hypoglycemia. Therefore, a lower dose of insulin or insulin secretagogue may be199 required to reduce the risk of hypoglycemia when used in combination with KAZANO. 200 Metformin hydrochloride201 Hypoglycemia does not occur in patients receiving metformin alone under usual202 circumstances of use, but could occur when caloric intake is deficient, when strenuous 203 exercise is not compensated by caloric supplementation, or during concomitant use with 204 other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol. Elderly, 205 debilitated, or malnourished patients and those with adrenal or pituitary insufficiency or 206 alcohol intoxication are particularly susceptible to hypoglycemic effects. Hypoglycemia 207 may be difficult to recognize in the elderly, and in people who are taking β-adrenergic 208 blocking drugs.209 5.10 Macrovascular Outcomes210 There have been no clinical studies establishing conclusive evidence of macrovascular 211 risk reduction with KAZANO or any other antidiabetic drug.REACTIONS212 6 ADVERSE213 6.1 Clinical Studies Experience214 Because clinical trials are conducted under widely varying conditions, adverse reaction 215 rates observed in the clinical trials of a drug cannot be directly compared to rates in the 216 clinical trials of another drug and may not reflect the rates observed in practice.217218Alogliptin and Metformin hydrochloride219 Over 2700 patients with type 2 diabetes have received alogliptin coadministered with 220 metformin in four large randomized, double-blind controlled clinical trials. The mean 221 exposure to KAZANO was 58 weeks with more than 1400 subjects treated for more 222 than one year. These included two 26-week placebo controlled studies, one 52-week 223 active control study and an interim analysis of a 104-week active control study. In the 224 KAZANO arm, the mean duration of diabetes was approximately 6 years, the mean 225 body mass index (BMI) was 31 kg/m 2 (56% of patients had a BMI ≥30 kg/m 2), and the 226 mean age was 55 years (18% of patients ≥65 years of age).227 In a pooled analysis of these four controlled clinical studies, the overall incidence of228 adverse reactions was 74% in patients treated with KAZANO compared to 76% treated 229 with placebo. Overall discontinuation of therapy due to adverse events was 6.2% with 230 KAZANO compared to 1.9% in placebo, 6.4% in metformin, and 5.0% in alogliptin. 231 Adverse reactions reported in ≥4% of patients treated with KAZANO and more 232 frequently than in patients who received alogliptin, metformin or placebo are 233 summarized in Table 1. 234Table 1. Adverse Reactions Reported in ≥4% of Patients Treated with KAZANO and More Frequently Than in Patients Receiving Either Alogliptin, Metformin or Placebo Number of Patients (%)KAZANO* Alogliptin † Metformin ‡ Placebo N =2794 N =222 N =1592 N =106 Upper respiratory tractinfection 224 (8.0) 6 (2.7) 105 (6.6) 3 (2.8) Nasopharyngitis 191 (6.8) 7 (3.2) 93 (5.8) 2 (1.9) Diarrhea 155 (5.5) 4 (1.8) 105 (6.6) 3 (2.8) Hypertension 154 (5.5) 5 (2.3) 96 (6.0) 6 (5.7) Headache 149 (5.3) 11 (5.0) 74 (4.6) 3 (2.8) Back pain119 (4.3)1 (0.5)72 (4.5)1 (0.9)Urinary tract infection 116 (4.2) 4 (1.8) 59 (3.7) 2 (1.9)*KAZANO – includes data pooled for patients receiving alogliptin 25 and 12.5 mg combined with variousdose of metformin†Alogliptin – includes data pooled for patients receiving alogliptin 25 and 12.5 mg ‡Metformin – includes data pooled for patients receiving various doses of metformin235Hypoglycemia236 In a 26-week, double-blind, active-controlled study, of alogliptin in combination with 237 metformin, the number of patients reporting hypoglycemia was 1.9% in the alogliptin 238 12.5 mg with metformin HCl 500 mg, 5.3% in the alogliptin 12.5 mg with metformin HCl239 1000 mg, 1.8% in the metformin HCl 500 mg, and 6.3% in the metformin HCl 1000 mg 240 treatment groups.241 In a 26-week placebo-controlled study of alogliptin 25 mg administered once daily as 242 add-on to metformin regimen, the number of patients reporting hypoglycemic events 243 was 0.9% in the alogliptin with metformin and 2.9% in the placebo treatment groups. 244 In a 52-week, active-controlled, double-blind study of alogliptin once daily as add-on 245 therapy to the combination of pioglitazone 30 mg and metformin compared to the246 titration of pioglitazone 30 mg to 45 mg and metformin, the number of patients reporting 247 hypoglycemia was 4.5% in the alogliptin 25 mg with pioglitazone 30 mg and metformin 248 group versus 1.5% in the pioglitazone 45 mg with metformin group.249 In an interim analysis conducted in a 104-week, double-blind, active controlled study, of 250 alogliptin 25 mg in combination with metformin, the number of patients reporting251 hypoglycemia was 1.4% in the alogliptin 25 mg with metformin group versus 23.8% in 252 the glipizide with metformin group.253 Alogliptin254 Approximately 8500 patients with type 2 diabetes have been treated with alogliptin in 14 255 randomized, double-blind, controlled clinical trials with approximately 2900 subjects256 randomized to placebo and approximately 2200 to an active comparator. The mean 257 exposure to alogliptin was 40 weeks with more than 2400 subjects treated for more than 258 one year. Among these patients, 63% had a history of hypertension, 51% had a history 259 of dyslipidemia, 25% had a history of myocardial infarction, 8% had a history of unstable 260 angina, and 7% had a history of congestive heart failure. The mean duration of diabetes 261 was 7 years, the mean body mass index (BMI) was 31 kg/m2 (51% of patients had a 262 BMI ≥30 kg/m2), and the mean age was 57 years (24% of patients ≥65 years of age). 263 Two placebo-controlled monotherapy trials of 12 and 26 weeks of duration were264 conducted in patients treated with alogliptin 12.5 mg daily, alogliptin 25 mg daily and 265 placebo. Four placebo-controlled add-on combination therapy trials of 26 weeks266 duration were also conducted: with metformin, with a sulfonylurea, with a267 thiazolidinedione, and with insulin.268 Five placebo-controlled trials of 16 weeks up through two years in duration were269 conducted in combination with metformin, in combination with pioglitazone and with270 pioglitazone added to a background of metformin therapy.271 Three active-controlled trials of 52 weeks in duration were conducted in patients treated 272 with pioglitazone and metformin, in combination with metformin and as monotherapy 273 compared to glipizide.274 In a pooled analysis of these 14 controlled clinical trials, the overall incidence of adverse 275 events was 66% in patients treated with alogliptin 25 mg compared to 62% with placebo 276 and 70% with active comparator. Overall discontinuation of therapy due to adverse277 events was 4.7% with alogliptin 25 mg compared to 4.5% with placebo or 6.2% with 278 active comparator.。

奥美拉唑说明书

_______________________________________________________________________________________________________________________________________ _______________________________________________________________________________________________________________________________________ HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to useOmeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets safely and effectively. See full prescribing information for Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets. Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets Initial U.S. Approval: 2006----------------------------INDICATIONS AND USAGE--------------------------- Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is a proton pump inhibitor indicated for: • Treatment of duodenal ulcer (1.1) • Treatment of gastric ulcer (1.2) • Treatment of gastroesophageal reflux disease (GERD) (1.3) • Maintenance of healing of erosive esophagitis (1.4)----------------------DOSAGE AND ADMINISTRATION----------------------- • Short-Term Treatment of Active Duodenal Ulcer: 20 mg once daily for 4 weeks (some patients may require an additional 4 weeks of therapy (14.1)) (2.2) • Gastric Ulcer: 40 mg once daily for 4-8 weeks (2.3) • Gastroesophageal Reflux Disease (GERD) (2.4) -Symptomatic GERD (with no esophageal erosions): 20 mg once daily for up to 4 weeks- Erosive Esophagitis: 20 mg once daily for 4-8 weeks • Maintenance of Healing of Erosive Esophagitis: 20 mg once daily (2.5) ---------------------DOSAGE FORMS AND STRENGTHS---------------------- • Tablets 20 mg omeprazole, 750 mg sodium bicarbonate, and 343 mg magnesium hydroxide (3) • Tablets 40 mg omeprazole, 750 mg sodium bicarbonate, and 343 mg magnesium hydroxide (3) -------------------------------CONTRAINDICATIONS----------------------------- • Known hypersensitivity to Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets or any components in the formulation (4) • Patients who cannot take magnesium (4)-----------------------WARNINGS AND PRECAUTIONS-----------------------• Concomitant Gastric Malignancy: Symptomatic response to therapy withOmeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets does not preclude the presence of gastric malignancy (5.1)• Atrophic Gastritis: Has been observed in gastric corpus biopsies from patients treated long-term with omeprazole (5.2) • Buffer Content: Sodium content should be taken into consideration when administering to patients on a sodium-restricted diet or at risk of developing congestive heart failure (CHF). (5.3)• Buffer Content: Magnesium content increases risk of hypermagnesemia andmagnesium toxicity in the elderly and in patients with renal impairment or renal disease (5.3) • Buffer Content: Use with caution in patients with Bartter’s syndrome, hypokalemia, respiratory alkalosis, and problems with acid-base balance because of its sodium bicarbonate content; long-term administration of bicarbonate with calcium or milk can cause milk-alkali syndrome (5.3) ------------------------------ADVERSE REACTIONS------------------------------- Most common adverse reactions (incidence ≥ 2%) are:Headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence (6)To report SUSPECTED ADVERSE REACTIONS, contact Santarus Inc. at 1-888-778-0887 or FDA at 1-800-FDA-1088 or /medwatch . ------------------------------DRUG INTERACTIONS------------------------------- • Drugs metabolized by cytochrome P450 (e.g., diazepam, warfarin,phenytoin, cyclosporine, disulfiram, benzodiazepines): Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets can prolong their elimination. Monitor to determine the need for possible dose adjustments when taken with Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets (7) • Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time (7) • Drugs for which gastric pH can affect bioavailability (e.g., ketoconazole,ampicillin esters, iron salts): Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets may interfere with absorption due to inhibition of gastric acid secretion (7) • Voriconazole: May increase plasma levels of omeprazole (7) • Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets mayreduce plasma levels of atazanavir and nelfinavir (7) • Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets mayincrease serum levels of tacrolimus, voriconazole, saquinavir, and clarithromycin (7) -----------------------USE IN SPECIFIC POPULATIONS----------------------- • Pregnancy: Based upon animal data, may cause fetal harm (8.1) • The safety and effectiveness of Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets in pediatric patients less than 18 years of age have not been established. (8.4) • Hepatic Impairment: Consider dose reduction, particularly for maintenance of healing of erosive esophagitis (8.6)See 17 for PATIENT COUNSELING INFORMATION.Revised: 12/2009 FULL PRESCRIBING INFORMATION: CONTENTS*1 INDICATIONS AND USAGE1.1 Duodenal Ulcer 1.2 Gastric Ulcer1.3 Treatment of Gastroesophageal Reflux Disease (GERD)1.4 Maintenance of Healing of Erosive Esophagitis 2 DOSAGE AND ADMINISTRATION2.1 Instructions for Use 2.2 Short-Term Treatment of Active Duodenal Ulcer 2.3 Gastric Ulcer2.4 Gastroesophageal Reflux Disease (GERD) 2.5 Maintenance of Healing of Erosive Esophagitis 3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Concomitant Gastric Malignancy 5.2 Atrophic Gastritis5.3 Buffer Content 6 ADVERSE REACTIONS6.1 Clinical Trials Experience 6.2 Post-marketing Experience 7 DRUG INTERACTIONS 8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy 8.3 Nursing Mothers8.4 Pediatric Use 8.5 Geriatric Use 8.6 Hepatic Impairment 8.7 Renal Impairment 8.8 Asian Population 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 13.2 Animal Toxicology and/or Pharmacology 14 CLINICAL STUDIES 14.1 Duodenal Ulcer Disease 14.2 Gastric Ulcer 14.3 Gastroesophageal Reflux Disease (GERD) 14.4 Long Term Maintenance Treatment of Erosive Esophagitis 15 REFERENCES 16 HOW SUPPLIED/STORAGE AND HANDLING 17PATIENT COUNSELING INFORMATION * Sections or subsections omitted from the full prescribing information are not listed.FULL PRESCRIBING INFORMATION:1 INDICATIONS AND USAGE1.1 Duodenal UlcerOmeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is indicated for short-term treatment of active duodenal ulcer. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy. [See Clinical Studies (14.1)]1.2 Gastric UlcerOmeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is indicated for short-term treatment (4-8 weeks) of active benign gastric ulcer. [See Clinical Studies (14.2)]1.3 Treatment of Gastroesophageal Reflux Disease (GERD)Symptomatic GERDOmeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is indicated for the treatment of heartburn and other symptoms associated with GERD. [See Clinical Studies (14.3)]Erosive EsophagitisOmeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is indicated for the short-term treatment (4-8 weeks) of erosive esophagitis that has been diagnosed by endoscopy.The efficacy of Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets used for longer than 8 weeks in these patients has not been established. If a patient does not respond to 8 weeks of treatment, it may be helpful to give up to an additional 4 weeks of treatment. If there is recurrence of erosive esophagitis or GERD symptoms (e.g., heartburn), additional 4-8 week courses of omeprazole may be considered. [See Clinical Studies (14.3)]1.4 Maintenance of Healing of Erosive EsophagitisOmeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is indicated to maintain healing of erosive esophagitis. Controlled studies do not extend beyond 12 months. [See Clinical Studies (14.4)]2 DOSAGE AND ADMINISTRATION2.1 Instructions for UseOmeprazole / Sodium Bicarbonate / Magnesium Hydroxide is available as tablets in 20 mg and 40 mg strengths of omeprazole for oral administration in adult patients 18 years and older.All recommended doses throughout the labeling are based upon omeprazole. Since both the 20 mg and 40 mg tablets contain the same amount of sodium bicarbonate (750 mg) and magnesium hydroxide (343 mg), two 20 mg tablets are not equivalent to one 40 mg tablet;therefore, two 20 mg tablets should not be substituted for one 40 mg tablet.Because Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets contain magnesium hydroxide, the tablets should not be substituted for ZEGERID products (e.g., ZEGERID Powder for Oral Suspension or ZEGERID Capsules).Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets should be taken on an empty stomach with water at least one hour before a meal.Do not use other liquids.2.2 Short-Term Treatment of Active Duodenal UlcerThe recommended adult oral dose of Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is 20 mg once daily. Most patients heal within 4 weeks. Some patients may require an additional 4 weeks of therapy.2.3 Benign Gastric UlcerThe recommended adult oral dose of Omeprazole / Sodium Bicarbonate /Magnesium Hydroxide Tablets is 40 mg once daily for 4-8 weeks.2.4 Gastroesophageal Reflux Disease (GERD)The recommended adult oral dose for the treatment of patients withsymptomatic GERD and no esophageal erosions is 20 mg once daily for up to 4 weeks. The recommended adult oral dose for the treatment of patients with erosive esophagitis is 20 mg once daily for 4-8 weeks.2.5 Maintenance of Healing of Erosive EsophagitisThe recommended adult oral dose of Omeprazole / Sodium Bicarbonate /Magnesium Hydroxide Tablets is 20 mg once daily. 3 DOSAGE FORMS AND STRENGTHSOmeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets, 20 mg, are white oval-shaped tablets. One side of each tablet is embossed with “ZM 20.” Each tablet contains 20 mg omeprazole and 750 mg sodium bicarbonate plus 343 mg magnesium hydroxide.Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets, 40 mg, are white oval-shaped tablets. One side of each tablet is embossed with “ZM 40.” Each tablet contains 40 mg omeprazole and 750 mg sodium bicarbonate plus 343 mg magnesium hydroxide.4 CONTRAINDICATIONSOmeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is contraindicated in patients with known hypersensitivity to any components of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial nephritis, and urticaria.Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets is contraindicated in patients who cannot take magnesium. [See Warnings and Precautions (5.3)]5 WARNINGS AND PRECAUTIONS5.1 Concomitant Gastric MalignancySymptomatic response to therapy with omeprazole does not preclude the presence of gastric malignancy.5.2 Atrophic GastritisAtrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with omeprazole.5.3 Buffer ContentEach 20 mg and 40 mg Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablet contains 750 mg (9 mEq) of sodium bicarbonate (equivalent to 209 mg of Na+) and 343 mg (12 mEq) of magnesium hydroxide (equivalent to 143 mg of Mg2+).Sodium BicarbonateBecause Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets contains sodium bicarbonate, it should be used with caution in patients with Bartter’s syndrome, hypokalemia, hypocalcemia, respiratory and metabolic alkalosis, and problems with acid-base balance. Long-term administration of bicarbonate with calcium or milk can cause milk-alkali syndrome.The sodium content of this product should be taken into consideration when administering to patients on a sodium-restricted diet or at risk of developing congestive heart failure (CHF).Chronic use of sodium bicarbonate may lead to systemic alkalosis and increased sodium intake can produce edema and weight increase.Magnesium HydroxideBecause Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets contains magnesium hydroxide, it should be used with caution in elderly and in patients with renal impairment or renal disease due to increased risk of developing hypermagnesemia and magnesium toxicity.Magnesium hydroxide should not be used in patients with renal failure unless serum magnesium levels are being closely monitored.Hypermagnesemia has been reported in infants whose mothers were using magnesium-containing antacid products chronically in high doses.6 ADVERSE REACTIONS6.1 Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, 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 clinical practice.In the U.S clinical trial population, of 465 patients, the adverse reactions summarized in Table 1 were reported to occur in 1% or more of patients on therapy with omeprazole. Numbers in parentheses indicate percentages of the adverse reactions considered by investigators as possibly, probably, or definitely related to the drug.Table 1: Adverse Reactions Occurring in 1% or More of Patients on Omeprazole Therapy from U.S. Studies Omeprazole Placebo Ranitidine(n = 465) (n = 64) (n = 195) Headache 6.9 (2.4) 6.3 7.7 (2.6) Diarrhea 3.0 (1.9) 3.1 2.1 (0.5) Abdominal Pain 2.4 (0.4) 3.1 2.1 Nausea 2.2 (0.9) 3.1 4.1 (0.5) URI 1.9 1.6 2.6 Dizziness 1.5 (0.6) 0.0 2.6 (1.0) Vomiting 1.5 (0.4) 4.7 1.5 (0.5) Rash 1.5 (1.1) 0.0 0.0 Constipation 1.1 (0.9) 0.0 0.0Cough 1.1 0.0 1.5 Asthenia 1.1 (0.2) 1.6 (1.6) 1.5 (1.0) Back Pain 1.1 0.0 0.5 The international clinical trials were double-blind and open-label in design. Table 2: Incidence of Adverse Reactions ≥ 1% Causal Relationship Not Assessed from International Studies Omeprazole Placebo (n = 2631) (n = 120) Body as a whole, site unspecified Abdominal Pain 5.2 3.3Asthenia 1.3 0.8Digestive System Constipation 1.5 0.8Diarrhea 3.7 2.5Flatulence 2.7 5.8Nausea 4.0 6.7Vomiting 3.2 10.0Acid Regurgitation 1.9 3.3Nervous System / Psychiatric Headache 2.9 2.5The most common adverse reactions reported (i.e., with an incidence rate ≥ 2%) from omeprazole-treated patients enrolled in these studies includedheadache (6.9%), abdominal pain (5.2%), nausea (4.0%), diarrhea (3.7%), vomiting (3.2%), and flatulence (2.7%). Additional adverse reactions that were reported with an incidence of ≥ 1% included acid regurgitation (1.9%), upper respiratory infection (1.9%), constipation (1.5%), dizziness (1.5%), rash (1.5%), asthenia (1.3%), back pain (1.1%), and cough (1.1%). The clinical trial safety profile in patients greater than 65 years of age was similar to that in patients 65 years of age or less. 6.2 Post-marketing ExperienceThe following adverse reactions have been identified during post-approvaluse of omeprazole. Because these reactions are voluntarily reported from a population of uncertain size, it is not always possible to reliably estimatetheir actual frequency or establish a causal relationship to drug exposure. Body As a Whole: Hypersensitivity reactions including anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial nephritis, urticaria (see also Skin below); fever; pain; fatigue; malaise Cardiovascular: Chest pain or angina, tachycardia, bradycardia,palpitations, elevated blood pressure, peripheral edemaEndocrine: Gynecomastia Gastrointestinal : Pancreatitis (some fatal), anorexia, irritable colon, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, stomatitis, abdominal swelling, dry mouth. During treatment with omeprazole, gastric fundic gland polyps have been noted rarely. These polyps are benign and appear to be reversible when treatment is discontinued. Gastroduodenal carcinoids have been reported in patients with Zollinger-Ellison syndrome on long-term treatment with omeprazole. This finding is believed to be a manifestation of the underlying condition, which is known to be associated with such tumors. Hepatic: Liver disease including hepatic failure (some fatal), liver necrosis (some fatal), hepatic encephalopathy, hepatocellular disease, cholestatic disease, mixed hepatitis, jaundice, and elevations of liver function tests (ALT, AST, GGT, alkaline phosphatase, and bilirubin) Metabolic/Nutritional: Hypoglycemia, hyponatremia, weight gainMusculoskeletal: Muscle weakness, myalgia, muscle cramps, joint pain, leg painNervous System/Psychiatric: Psychiatric and sleep disturbances including depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, apathy, somnolence, anxiety, and dream abnormalities; tremors, paresthesia, vertigoRespiratory: Epistaxis, pharyngeal pain Skin: Severe generalized skin reactions including toxic epidermal necrolysis (some fatal). Stevens-Johnson syndrome, and erythema multiforme; photosensitivity; urticaria; rash; skin inflammation; pruritus; petechiae; purpura; alopecia; dry skin; hyperhidrosis Special Senses: Tinnitus, taste perversionOcular: Optic atrophy, anterior ischemic optic neuropathy, optic neuritis, dry eye syndrome, ocular irritation, blurred vision, double vision Urogenital: Interstitial nephritis, hematuria, proteinuria, elevated serum creatinine, microscopic pyuria, urinary tract infection, glycosuria, urinary frequency, testicular pain Hematologic: Agranulocytosis (some fatal), hemolytic anemia, pancytopenia, neutropenia, anemia, thromobocytopenia, leukopenia,leucocytosis 7 DRUG INTERACTIONSDrugs metabolized by cytochrome P450 (CYP) Omeprazole can prolong the elimination of diazepam, warfarin and phenytoin, drugs that are metabolized by oxidation in the liver. There have been reports of increased INR and prothrombin time in patients receivingproton pump inhibitors, including omeprazole, and warfarinconcomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin may need to be monitored for increases in INR and prothrombin time.Although in normal subjects no interaction with theophylline or propranolol was found, there have been clinical reports of interaction with other drugs metabolized via the cytochrome P450 system (e.g., cyclosporine, disulfiram, benzodiazepines). Patients should be monitored to determine if it is necessary to adjust the dosage of these drugs when taken concomitantly with Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets. Drugs for which gastric pH can affect bioavailability Because of its inhibition of gastric acid secretion, it is theoreticallypossible that omeprazole may interfere with absorption of drugs where gastric pH is an important determinant of their bioavailability (e.g., ketoconazole, ampicillin esters, and iron salts). In the clinical efficacy trials antacids were used concomitantly with the administration ofomeprazole. Concomitant administration of omeprazole and voriconazole (a combinedinhibitor of CYP2C19 and CYP3A4) resulted in more than doubling of the omeprazole exposure. Dose adjustment of omeprazole is not normally required.. When voriconazole (400 mg every 12 hours for one day, then 200 mg for 6 days) was given with omeprazole (40 mg once daily for 7 days) to healthy subjects, it significantly increased the steady-state Cmax and AUC0-24 of omeprazole, an average of 2 times (90% CI: 1.8, 2.6) and4 times (90% CI: 3.3, 4.4) respectively as compared to when omeprazole was given without voriconazole. Antiretroviral Agents Concomitant use of atazanavir and proton pump inhibitors is not recommended. Co-administration of atazanavir with proton pump inhibitors is expected to substantially decrease atazanavir plasma concentrations and thereby reduce its therapeutic effect. Omeprazole has been reported to interact with some antiretroviral drugs. The clinical importance and the mechanisms behind these interactions are not always known. Increased gastric pH during omeprazole treatment may change the absorption of the antiretroviral drug. Other possible interaction mechanisms are via CYP2C19. For some antiretroviral drugs, such as atazanavir and nelfinavir, decreased serum levels have been reported when given together with omeprazole. Following multiple doses of nelfinavir (1250 mg, twice daily) and omeprazole (40 mg, daily), AUC was decreased by 36% and 92%, Cmax by 37% and 89% and Cmin by 39% and 75% respectively for nelfinavir and M8. Following multiple doses of atazanavir (400 mg, daily) and omeprazole (40 mg, daily, 2 hours before atazanavir), AUC was decreased by 94%, Cmax by 96%, and Cmin by 95%. Concomitant administration with omeprazole and drugs such as atazanavir and nelfinavir is therefore not recommended. For otherantiretroviral drugs, such as saquinavir, elevated serum levels have beenreported with an increase in AUC by 82%, in Cmax by 75% and in Cminby 106% following multiple dosing of saquinavir/ritonavir (1000/100 mg)twice daily for 15 days with omeprazole 40 mg daily co-administered days11 to 15. Dose reduction of saquinavir should be considered from thesafety perspective for individual patients. There are also someantiretroviral drugs of which unchanged serum levels have been reportedwhen given with omeprazole.AntimicrobialsOmeprazole 40 mg daily was given in combination with clarithromycin500 mg every 8 hours to healthy adult male subjects. The steady stateplasma concentrations of omeprazole were increased (Cmax, AUC0-24,and T1/2 increases of 30%, 89% and 34% respectively) by the concomitantadministration of clarithromycin. The observed increases in omeprazoleplasma concentration were associated with the following pharmacologicaleffects. The mean 24-hour gastric pH value was 5.2 when omeprazole wasadministered alone and 5.7 when co-administered with clarithromycin.The plasma levels of clarithromycin and 14-hydroxyclarithromycin wereincreased by the concomitant administration of omeprazole. Forclarithromycin, the mean Cmax was 10% greater, the mean Cmin was 27%greater, and the mean AUC0-8 was 15% greater when clarithromycin wasadministered with omeprazole than when clarithromycin was administeredalone. Similar results were seen for 14-hydroxyclarithromycin, the meanCmax was 45% greater, the mean Cmin was 57% greater, and the meanAUC0-8 was 45% greater. Clarithromycin concentrations in the gastrictissue and mucus were also increased by concomitant administration ofomeprazole.Table 3: Clarithromycin Tissue Concentrations2 hours after Dose1Tissue Clarithromycin Clarithromycin+OmeprazoleAntrum 10.48 ± 2.01 (n = 5) 19.96 ± 4.71 (n = 5)Fundus 20.81 ± 7.64 (n= 5) 24.25 ± 6.37 (n = 5)Mucus 4.15 ± 7.74 (n = 4) 39.29 ± 32.79 (n = 4)Mean ± (µg/g)TacrolimusConcomitant administration of omeprazole and tacrolimus may increasethe serum levels of tacrolimus.8 USE IN SPECIFIC POPULATIONS8.1 PregnancyPregnancy Category CThere are no adequate and well-controlled studies on the use ofomeprazole in pregnant women. The vast majority of reported experiencewith omeprazole during human pregnancy is first trimester exposure andthe duration of use is rarely specified, e.g., intermittent versus chronic. Anexpert review of published data on experiences with omeprazole useduring pregnancy by TERIS – the Teratogen Information System –concluded that therapeutic doses during pregnancy are unlikely to pose asubstantial teratogenic risk (the quantity and quality of data were assessedas fair).1Three epidemiological studies compared the frequency of congenitalabnormalities among infants born to women who used omeprazole duringpregnancy to the frequency of abnormalities among infants of womenexposed to H2-receptor antagonists or other controls. A population-basedprospective cohort epidemiological study from the Swedish Medical BirthRegistry, covering approximately 99% of pregnancies, reported on 955infants (824 exposed during the first trimester with 39 of these exposedbeyond first trimester, and 131 exposed after the first trimester) whosemothers used omeprazole during pregnancy.2 In utero exposure toomeprazole was not associated with increased risk of any malformation(odds ratio 0.82, 95% CI 0.50-1.34), low birth weight or low Apgar score.The number of infants born with ventricular septal defects and the numberof stillborn infants was slightly higher in the omeprazole exposed infantsthan the expected number in the normal population. The author concludedthat both effects may be random.A retrospective cohort study reported on 689 pregnant women exposed toeither H2-blockers or omeprazole in the first trimester (134 exposed toomeprazole).3 The overall malformation rate was 4.4% (95% CI 3.6-5.3)and the malformation rate for first trimester exposure to omeprazole was3.6% (95% CI 1.5-8.1). The relative risk of malformations associated withfirst trimester exposure to omeprazole compared with nonexposed womenwas 0.9 (95% CI 0.3-2.2). The study could effectively rule out a relative risk greater than 2.5 for all malformations. Rates of preterm delivery or growth retardation did not differ between the groups.A controlled prospective observational study followed 113 women exposed to omeprazole during pregnancy (89% first trimester exposures).4 The reported rates of major congenital malformations was 4% for the omeprazole group, 2% for controls exposed to nonteratogens, and 2.8% in disease-paired controls (background incidence of major malformations 1-5%). Rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight did not differ between the groups. The sample size in this study has 80% power to detect a 5-fold increase in the rate of major malformation.Several studies have reported no apparent adverse short term effects on the infant when single dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia.Hypermagnesemia has been reported in infants whose mothers were using magnesium-containing antacid products chronically in high doses. Reproduction studies conducted with omeprazole in rats at oral doses up to 28 times the human dose of 40 mg/day (based on body surface area) and in rabbits at doses up to 28 times the human dose (based on body surface area) did not show any evidence of teratogenicity. In pregnant rabbits, omeprazole at doses about 2.8 to 28 times the human dose of 40 mg /day (based on body surface area) produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy loss. In rats treated with omeprazole at doses about 2.8 to 28 times the human dose (based on body surface area), dose-related embryo/fetal toxicity and postnatal developmental toxicity occurred in offspring. [See Nonclinical Toxicology (13.2)]There are no adequate and well-controlled studies in pregnant women. Because animal studies and studies in humans cannot rule out the possibility of harm, Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets should be used during pregnancy only if the potential benefit to pregnant women justifies the potential risk to the fetus.8.3 Nursing MothersOmeprazole concentrations have been measured in breast milk of a woman following oral administration of 20 mg. The peak concentration of omeprazole in breast milk was less than 7% of the peak serum concentration. The concentration will correspond to 0.004 mg of omeprazole in 200 mL of milk. Because omeprazole is excreted in human milk, because of the potential for serious adverse reactions in nursing infants from omeprazole, and because of the potential for tumorigenicity shown for omeprazole in rat carcinogenicity studies, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. In addition, sodium bicarbonate and magnesium hydroxide should be used with caution in nursing mothers.8.4 Pediatric UseThe safety and effectiveness of Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets in pediatric patients less than 18 years of age have not been established.8.5 Geriatric UseOmeprazole was administered to over 2000 elderly individuals (≥ 65 years of age) in clinical trials in the U.S. and Europe. There were no differences in safety and effectiveness between the elderly and younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.Pharmacokinetic studies with buffered omeprazole have shown the elimination rate was somewhat decreased in the elderly and bioavailability was increased. The plasma clearance of omeprazole was 250 mL/min (about half that of young subjects). The plasma half-life averaged one hour, about twice that in nonelderly, healthy subjects taking Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets. However, no dosage adjustment is necessary in the elderly. [See Clinical Pharmacology (12.3)] 8.6 Hepatic ImpairmentConsider dose reduction, particularly for maintenance of healing of erosive esophagitis. [See Clinical Pharmacology (12.3)]8.7 Renal ImpairmentNo dose reduction is necessary. However, Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets contains magnesium hydroxide (143 mg of Mg2+); therefore, magnesium levels should be closely monitored when using this product in patients with renal impairment. [See Clinical Pharmacology (12.3)]。

吉诺通使用手册(英语版)

Package leaflet: Information for the userGeloMyrtol® forte300 mg, gastro-resistant capsules, softActive substance:Myrtol standardized to at least 75 mg limonene, 75 mg cineole and 20 mg alpha-pinene.Read all of this package leaflet carefully because it contains important information for you.This medicinal product is available without prescription. However, you still need to takeGeloMyrtol® forte carefully to get the best results from it.- Keep this leaflet. You may need to read it again.- Ask your pharmacist if you need more information or advice.- You must contact a doctor if your symptoms worsen or do not improve after 10 days.- If any of the side effects affects gets serious or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.In this leaflet:1. What GeloMyrtol® forte is and what it is used for2. Before you take GeloMyrtol® forte3. How to take GeloMyrtol® forte4. Possible side effects5. How to store GeloMyrtol® forte6. Further informationGeloMyrtol® forte is available in packs of 20, 50 and 100 gastro-resistant capsules, soft.1. What GeloMyrtol® forte is and what it is used forEffect: GeloMyrtol® forte is a herbal medicine. It liquefies mucus and promotes its transport, makes mucus easier to cough up and reduces inflammation.Used to treatacute and chronic bronchitis and inflammation of paranasal sinuses (sinusitis)2. Before you take GeloMyrtol® forteDo not take GeloMyrtol® forte:- if you have an inflammatory disorder of the stomach, gut or bile duct region, or if you have a severe liver disorder;- if you are known to be allergic (hypersensitive) to eucalyptus oil, sweet orange oil, myrtle oil, lemon oil or cineole (the main constituent of eucalyptus oil), or to any of the other ingredients.Take special care with GeloMyrtol® forte:- if your symptoms should persist or get worse, or if you develop shortness of breath or fever, or if you start coughing up mucus containing blood or pus-like matter, you should consult a doctor immediately.- if you suffer from bronchial asthma, whooping cough or other respiratory diseases accompanied by manifest hypersensitivity of the respiratory system, always consult your doctor before you take GeloMyrtol® forte.Taking other medicinesInform your doctor or pharmacist if you take/apply other medicines or did so recently even if it is/was a non-prescription product.Pregnancy and breast feedingBefore you take any medicine ask your doctor or pharmacist.- Pregnancy:Animal studies do not indicate direct or indirect harmful effects on the foetus. Caution is basicallyadvised when taking it during pregnancy.- Breast feeding:Due to the liposoluble properties of the active ingredient it can be assumed that its constituents are also present in the breast milk at minor concentrations. So far there has been no indication of any risk when using GeloMyrtol® forte during the time of breast feedingDriving and using machinesNo special precautions are required.3. How to take GeloMyrtol® forteAlways take GeloMyrtol® forte exactly as directed in this leaflet. You should check with your doctor or pharmacist if you are not sure.Unless otherwise prescribed by your doctor, the usual dose is:Adults, juveniles and children from the age of 12 with acute inflammatory symptoms should take 1 gastro-resistant soft capsule 3 – 4 times a day. Patients with chronic symptoms should take 1 gastro-resistant capsule 2 or 3 times a day. This dose is also recommended for a long-term treatment.For children the following doses of GeloMyrtol® forte are recommended:Age group Under 6(approx. 13 – 19 kg)From 6 to 10 years(approx. 20 – 29 kg)From 10 to under 12years(approx. 30 – 43 kg)Acute symptoms 1 x 1gastro-resistant capsule2 x 1gastro-resistant capsule2 –3 x 1gastro-resistant capsuleChronic symptoms 1 x 1gastro-resistant capsule1 –2 x 1gastro-resistant capsule2 x 1gastro-resistant capsuleDirections for useGeloMyrtol® forte capsules should be taken 30 minutes before a meal, with plenty of cold liquid. The last dose of the day can be taken before bedtime.Duration of treatmentThe duration of GeloMyrtol® forte treatment depends on the medical condition. For chronic respiratory diseases a long-term treatment is possible.If you take more GeloMyrtol® forte than you shouldPlease inform your doctor. He/she can then decide on any measures that may be required. The side effects listed below may occur in a more exaggerated form.If you forget to take GeloMyrtol® forteDo not take a double dose to make up for a forgotten dose. Continue taking GeloMyrtol® forte at your next scheduled time, as prescribed by your doctor or as described in the dosage instructions.4. Possible side effectsLike all medicines GeloMyrtol® forte can cause side effects, although not everybody gets them. The frequency of occurrence of side effects is based on the following categories:Very common: more than one men in 10 Common: 1 to 10 men in 100Uncommon: 1 to 10 men in 1,000 Rare: 1 to 10 men in 10,000Very rare: less than 1 men in 10,000Not known: Frequency not assessable based on the data availablePotential side effects:In uncommon cases, gastrointestinal complaints may occur, in the stomach/upper abdomen region, for example, in rare cases nausea, vomiting or diarrhoea. There have been rare reports of hypersensitive reactions (e.g. rash, itching facial swelling, shortness of breath and circulatory problems). In very rare cases kidney stones or gallstones present may become dislodged.Inform your doctor or pharmacist if one of the listed side effects affects you considerably or you notice side effects not indicated in this leaflet.5. How to store GeloMyrtol® forteKeep out of the reach and sight of children.Do not use GeloMyrtol® forte after the expiry date which is stated on the blister pack and outer carton. The expiry date refers to the last day of the month.Storage conditions:Store in the original package, in order to protect it from moisture. Do not store above 25°C.6. Further informationWhat GeloMyrtol® forte contains:The active substance is:1 gastro-resistant soft capsule contains 300 mg Myrtol standardized to at least 75 mg limonene, 75 mg cineole and 20 mg alpha-pinene.Other ingredients are:refined rapeseed oil; gelatin; glycerol 85%; sorbitol liquid 70% (non-crystallising); hypromellose acetate succinate; triethyl citrate; sodium laurilsulfate; talc; dextrin; glycyrrhizic acid, ammonium saltHow GeloMyrtol® forte looks like and contents of the pack:GeloMyrtol® forte are long, uncoloured, naturally cloudy soft capsules.The following pack sizes are available:Pack of 20 gastro-resistant capsules, softPack of 50 gastro-resistant capsules, softPack of 100 gastro-resistant capsules, softMarketing authorisation holder and manufacturerG. POHL-BOSKAMP GmbH & Co. KG Tel.: +49 (0)48 26 59 0Kieler Strasse 11 Fax: +49 (0)48 26 59 10925551 Hohenlockstedt E-mail: i nfo@pohl-boskamp.deGermany Internet:www.pohl-boskamp.deLatest revision of these instructions in January 2009。

拉孚尔氨素沸液说明书

LAURYL SULPHATE BROTH Product Number L 3785Product DescriptionLauryl Sulfate Broth is used for the detection of coliform organisms in water, dairy products and other foods. It is recommended by the American Public Health Association (APHA) for the detection of coliforms in water, effluent or sewage and for the detection of coliforms in food. This medium is designed to get rich growth and a substantial amount of gas from small inocula of coliform organisms. This formulation is also recommended by the ISO Committee for the detection of coliforms.Tryptose provides essential growth substances, such as nitrogen and carbon compounds, sulfate, and trace ingredients. The potassium phosphates provide the buffering system, while sodium chloride maintains osmotic equilibrium. Sodium lauryl sulfate inhibits organisms other than coliforms.ComponentsItem g/LTryptose 20.00 Lactose 5.00Sodium Chloride 5.00 Dipotassium Phosphate 2.75 Monopotassium Phosphate 2.75Sodium Lauryl Sulfate 0.10Final pH (at 25 °C) 6.8 ± 0.2Precautions and DisclaimerFor laboratory use only. Not for drug, household or other uses.Preparation InstructionsSuspend 35.6 grams of Lauryl Sulfate Broth in1000 mls of distilled water. Distribute into tubes containing inverted Durham's tubes. Sterilize by autoclaving at 15 lbs. pressure (121 °C) for 15 minutes. Storage/StabilityStore the dehydrated medium at 24 °C and the prepared medium at 2-8 °C. ProcedureFor inoculum of 1 ml or less, use single strength medium. For inocula of 10 mls or more, double strength or proportionate medium should be prepared. After inoculation, incubate the tubes at 35 °C for 24 to 48 hours. For every tube showing fermentation, inoculate two tubes of Lauryl Sulfate Broth and incubate these tubes at 35 °C and 44 °C. If there is fermentation in the tube incubated at 44 °C after 8 to 24 hours, perform an indole test. A positive indole test indicates the presence of Escherichia coli. If there is not fermentation in the tube incubated at 37 °C, then fermentation is due to organisms other than coliforms. Product ProfileAppearance Light yellow colored,homogeneous, free flowingpowder.Color and Clarity Light yellow colored, clearsolution without anyprecipitate.Cultural Response Cultural chacteristicsobserved after 18-24 hoursat 35 °C.Organisms (ATCC) Growth Enterobacter aerogenes (13048) Luxuriant Escherichia coli (25922) Luxuriant Salmonella typhimurium (14028) Luxuriant Staphylococcus aureus (25923) Inhibited Enterococcus faecalis (29212) InhibitedGas Indole (44°C) Enterobacter aerogenes+ - Escherichia coli + + Salmonella typhimurium- - Staphylococcus aureus- - Enterococcus faecalis- -References1. Standard Methods for the Examination of Waterand Wastewater. (1985). Greenberg, A., et al., eds.16th Edition. APHA. Washington, D.C.2. International Organization for Standardization(ISO), (1991). Draft ISO/DIS 4831. 3. Compendium of Methods for the MicrobiologicalExamination of Foods, (1984). Speck, M. ed. 2nd Edition. APHA, Inc. Washington, D.C. American Type Culture Collection, Manassas Va., U.S.ASigma brand products are sold through Sigma-Aldrich, Inc.Sigma-Aldrich, Inc. warrants that its products conform to the information contained in this and other Sigma-Aldrich publications. Purchaser must determine the suitability of the product(s) for their particular use. Additional terms and conditions may apply. Please see reverse side ofthe invoice or packing slip.。

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核准日期： 2013.06.03修改日期：2013.08.01醋酸加尼瑞克注射液说明书请仔细阅读说明书并在医师指导下使用.【药品名称】通用名称：醋酸加尼瑞克注射液商品名称： ORGALUTRAN®英文名称：Ganirelix Injection汉语拼音：Cusuan Jia’niruike Zhusheye【成份】本品活性成份为：醋酸加尼瑞克活性成份加尼瑞克（INN）是一种合成十肽，对天然生成的促性腺激素释放激素（GnRH）具有高的拮抗活性。

通过替代天然GnRH的第l、2、3、6、8、10位点上的氨基酸而形成以下肽分子式。

化学名称：N-乙酰-3-(2-萘)-D-丙氨酰-4-氯-D-苯丙氨酰-3-(3-吡啶)-D-丙氨酰-L-丝氨酰-L-酪氨酰-N6-[双(乙氨)亚甲基]-D-赖氨酰-L-亮氨酰-N6-[双(乙氨)亚甲基]-L-赖氨酰-L-脯氨酰-D-丙氨酰胺醋酸盐化学结构式：分子式： C80H113N18O13Cl.2CH3COOH分子量：1690.42本品其他组份为：冰醋酸，甘露醇，注射用水，用氢氧化钠和醋酸调节pH 值。

【性状】本品为无色的澄明溶液。

【适应症】本品在接受辅助生殖技术（ART）控制性卵巢刺激（COS）方案的妇女中使用，用于预防过早出现促黄体激素（LH）峰。

【规格】0.5ml： 0.25mg（以加尼瑞克计）【用法用量】本品应由对治疗不孕症有丰富经验的专业医师开立处方。

剂量本品用于预防接受COS治疗过程中提早发生的LH峰。

接受COS治疗的患者一般在月经周期第2或第3天开始使用卵泡刺激素（FSH），依据卵巢反应（例如生长发育的卵泡数量和大小以及/或外周血循环中的雌二醇水平），及时给予本品（0.25 mg），每天一次，可有效预防早发LH峰的出现。

根据临床应用经验，一般在FSH用药后第5天或第6天开始使用本品，但开始给药的时间应根据患者的个体化卵巢反应而决定。

本品和FSH应大约同时给药，但这两种药物不得混合，而且要在不同部位注射。

FSH剂量调整应基于生长发育的卵泡数量和大小进行，而不是循环中的雌二醇水平（见【药理毒理】）。

为预防多卵泡发育导致的早发LH峰，本品应连续每日治疗，直至出现大小足够且数量充足的卵泡后给予人绒毛膜促性腺激素（hCG）诱导卵母细胞最后的成熟。

由于加尼瑞克的半衰期原因，本品两次注射的时间间隔以及本品最后一次注射和hCG注射的时间间隔不应超过30个小时，否则会出现早发的LH峰。

因此，本品早晨用药时，自进行FSH卵巢刺激的第5或第6天开始给予本品，持续整个FSH治疗过程至诱发排卵的当日（包括诱发排卵当日）；本品晚间用药时，自进行卵巢刺激的第5天开始给予本品，持续整个FSH治疗过程至诱发排卵的前一夜。

本品对黄体期支持的需要还未进行研究。

在临床试验中，根据生殖医学中心的经验给予黄体期支持。

肝脏或肾脏损害受试者：本品没有肝脏或肾脏损害受试者的使用经验，因此，不能给出特定的推荐剂量（见【禁忌】）。

给药方法本品应皮下注射，最好是在大腿部。

为防止皮下脂肪萎缩，应循环更换注射部位。

如果能对患者或其伴侣给予充分指导，并可获得专家建议，可以自行注射本品。

【不良反应】在包括1589名接受本品治疗的患者的临床试验中，下列不良反应及其发生率较为明显：全身和给药部位反应本品可能导致注射部位局部皮肤反应（主要表现为皮肤发红，伴或不伴肿胀）。

在临床研究的每个治疗周期中，根据患者报告，注射后一小时，至少出现一次中度或严重的局部皮肤反应的发生率在接受本品治疗的患者中为12%，而在接受促性腺激素释放激素（GnRH）激动剂治疗的患者中为25%。

局部反应通常在给药后4小时内消失。

0.3%的患者报告有不适感。

免疫系统紊乱上市后监测显示，在给予本品的患者中，有极少病例报告在给予初次剂量时即发生超敏反应（包括各种症状，如皮疹，面部肿胀，呼吸困难）。

神经系统紊乱头痛（0.4％）。

胃肠紊乱恶心（0.5％）。

报告的其他与辅助生殖技术控制性卵巢刺激治疗相关的不良反应有明显的盆腔疼痛，腹胀，卵巢过度刺激综合征（OHSS），异位妊娠及自然流产（见【注意事项】）。

【禁忌】对本品活性成份或其中任何辅料过敏者禁用。

对GnRH或任何其他GnRH类似物过敏者禁用。

中度或重度肾脏或肝脏功能损害者禁用。

怀孕或哺乳期者禁用。

【注意事项】对有过敏体征或症状的妇女应特别注意观察。

在上市后不良反应监测中，有在使用初次剂量时即出现超敏反应案例的报道（见【不良反应】）。

在缺少临床经验的情况下，不建议对有严重过敏情况的妇女给予本品治疗。

本品的包装材料含天然乳胶，可能导致过敏反应（见【包装】）。

在卵巢刺激期间或之后可能会发生OHSS。

必须考虑OHSS是促性腺激素刺激的内在风险。

OHSS应对症治疗，例如休息，静脉滴注电解质溶液或胶体和肝素。

由于接受辅助生殖，尤其是体外受精（IVF）的不孕妇女，经常有输卵管异常的情况，异位妊娠的发生率可能增加。

因此早期超声证实宫内孕是很重要的。

采用ART的先天性畸形发生率可能略高于自然怀孕，这被认为与父母的生物学特征（例如，产妇的年龄，精子特征）以及多胞胎的高发生率相关。

1000多个新生儿的临床试验证明，采用本品进行COS治疗后出生的婴儿的先天性畸形发生率与使用GnRH激动剂进行COS治疗所报告的发生率相似。

本品在体重超过90公斤的妇女中的安全性和有效性还没有确立。

尚未对本品进行驾驶和机器操作能力影响的研究。

本品没有进行药物相容性研究。

本品一定不能与其他药物混合使用。

使用前请检查注射器。

仅在注射器包装完好，且在溶液清澈，无微粒的情况下使用。

任何未使用的药物或者废弃的材料应该按照当地的要求处置。

【孕妇及哺乳期妇女用药】尚无孕妇使用加尼瑞克的临床数据。

动物实验中，在胚胎植入时暴露于加尼瑞克会导致胚胎再吸收（见【药理毒理】）。

这些数据与人的相关性还未知。

尚不清楚加尼瑞克是否通过母乳分泌。

怀孕和哺乳期间禁止使用本品（见【禁忌】）。

【儿童用药】不适用。

【老年用药】不适用。

【药物相互作用】尚未进行本品与其他药物相互作用的研究。

不能排除本品与常规药物，包括组胺释放药物相互作用的可能性。

【药物过量】在人体中药物过量可能导致药物作用时间的延长。

当药物过量时，应暂时停止本品的治疗。

尚无本品对于人体的急性毒性数据。

本品单剂量最高达12mg的皮下给药临床研究未显示有全身不良反应。

在对大鼠和猴子的急性毒性研究中，只有静脉注射加尼瑞克超过1mg/kg和3mg/kg后观察到非特异性毒性症状，如血压过低和心动过缓。

【临床试验】国外III期临床试验研究38607是以布舍瑞林长方案为对照，评估本品在接受控制性卵巢刺激的欧洲妇女中的安全性和有效性研究。

纳入意向治疗人群的受试者共701名（本品组463名，布舍瑞林组238名）。

主要入选标准为，年龄18-39岁，体重指数在18-29kg/m2之间，月经周期在24至35天的正常范围内。

本品组于FSH 治疗第6天开始皮下注射本品（0.25mg/天），直至接受hCG之日（包括该日）；布舍瑞林组于月经周期的第21-24天开始接受治疗（0.6mg/天，经鼻给药），14天后如达到降调节（E2≤ 50 pg/mL）则开始接受FSH治疗，直至接受hCG之日。

主要疗效指标为取卵当天获得的卵母细胞数。

以每启动周期计算，本品组受试者获得的卵母细胞平均数为8.7，布舍瑞林组为9.7，差异的97.5%置信区间下限为-1.8。

研究103001是以亮丙瑞林长方案为对照，评估本品在接受控制性卵巢刺激的北美妇女中的安全性和有效性研究。

纳入意向治疗人群的受试者共297名（本品组198名，亮丙瑞林组99名）。

主要入选标准与研究38607相同。

本品组于FSH治疗第6天开始皮下注射本品（0.25mg/天），直至接受hCG之日（包括该日）；亮丙瑞林组于月经周期的第21-24天开始接受皮下注射（1.0mg/天），14天后如达到降调节（E2≤ 50 pg/mL）则开始接受FSH治疗，直至接受hCG 之日。

主要疗效指标为取卵当天获得的卵母细胞数。

以每启动周期计算，本品组受试者获得的卵母细胞平均数为11.1，亮丙瑞林为13.5，差异的97.5%置信区间下限为-4.0。

研究38616是以曲普瑞林长方案为对照，评估本品在接受控制性卵巢刺激的欧洲和中东妇女中的安全性和有效性研究。

纳入意向治疗组的受试者共337名（本品组226名，曲普瑞林组111名）。

主要入选标准与研究38607相同。

本品组于FSH治疗第6天开始皮下注射本品（0.25mg/天），直至接受hCG之日（包括该日）；曲普瑞林组于月经周期的第21-24天开始接受皮下注射（0.1mg/天），14天后如达到降调节（E2≤ 50 pg/mL）则开始接受FSH治疗，直至接受hCG之日。

主要疗效指标为取卵当天获得的卵母细胞数。

以每启动周期计算，本品组受试者获得卵母细胞平均数为7.9，曲普瑞林为9.6，差异的97.5%置信区间下限为-2.4。

中国临床试验研究38651是以曲普瑞林长方案为对照，评估本品在接受控制性卵巢刺激的中国妇女中的安全性和有效性研究。

纳入意向治疗人群的受试者共233名（本品组113名，曲普瑞林组120名）。

主要入选标准为，年龄18-35岁，体重指数在18-29kg/m2之间，月经周期在24至35天的正常范围内。

本品组于FSH 治疗第6天开始皮下注射本品（0.25mg/天），直至接受hCG之日（包括该日）；曲普瑞林组于月经周期的第21-24天开始接受皮下注射（0.05mg/天），14天后如达到降调节（E2≤ 50 pg/mL）则开始接受FSH治疗，直至接受hCG之日。

主要疗效指标为达到注射hCG标准的第一天为止，所用FSH的药量。

本品组的FSH平均需求量分别为1272.0IU，显著低于曲普瑞林组的1415.6IU。

估计治疗差异为-145.0IU，95%置信区间为[-212.0; -77.9]。

【药理毒理】药理作用促性腺激素释放激素（GnRH）的脉冲式释放能够刺激LH和FSH的合成和分泌。

卵泡期中期和后期的LH脉冲频率大约是每小时1次。

这些脉冲体现在血清LH的瞬时上升。

在月经中期，GnRH的大量释放造成LH激增。

月经中期的LH激增能引起数个生理反应，包括：排卵、卵母细胞减数分裂恢复和黄体形成。

黄体形成造成血清黄体酮水平上升，同时雌二醇水平下降。

醋酸加尼瑞克是GnRH拮抗剂，可竞争性阻断垂体促性腺细胞上的GnRH受体，以及其后的转导通路。

它产生一种快速、可逆的促性腺激素分泌抑制作用。

醋酸加尼瑞克对脑垂体LH分泌的抑制作用强于对FSH的抑制作用。

醋酸加尼瑞克不能引起内源性促性腺激素的首次释放，这与拮抗作用一致。

醋酸加尼瑞克停药后48小时内，垂体LH和FSH水平可完全恢复。