英文药名：NESINA (alogliptin tabs) 中文药名：阿格列汀片 生产厂家：武田制药北美公司 药品简介 NESINA (阿格列汀 alogliptin)片，使口服使用 美国初次批准：2013 一般描述 NESINA片含活性成分alogliptin，是一种选择性，口服生物利用的二肽肽酶-4(DPP-4)酶活性的抑制剂。 化学上，alogliptin被制备为苯甲酸盐，被鉴定为 2-({6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl}methyl)benzonitrile monobenzoate。分子式C18H21N5O2•C7H6O2和分子量461.51道尔顿。结构式为： Alogliptin苯甲酸盐是白色至淡白色，结晶粉含一个不对称碳在氨基哌啶部分。溶于二甲基亚砜，微溶于水和甲醇及乙醇，和极微溶于辛醇和乙酸异丙酯。 每片NESINA片含34 mg，17 mg，或8.5 mg alogliptin苯甲酸盐分别等同于25 mg，12.5 mg，或6.25 mg， alogliptin和以下无活性成分：甘露醇，微晶纤维素，羟丙基纤维素，交联羧甲基纤维素钠，和硬脂酸镁。此外，包膜衣含以下无活性成分：羟丙甲纤维素，二氧化钛，三氧化二铁(红或黄色)，和聚乙二醇，和被印刷油墨标记(灰F1)。 作用机制 小肠对进餐反应释放肠促胰岛素激素[incretin hormones]例如胰高血糖素-样肽-1(GLP-1)和葡萄糖依赖性促胰岛素多肽[glucose-dependent insulinotropic polypeptide(GIP)]的增加的浓度。这些激素引起胰腺β细胞以葡萄糖依赖方式释放胰岛素，但是这些激素在几分钟内被二肽肽酶-4(DPP-4)失活。GLP-1还减低从胰腺α细胞分泌一改血糖素[glucagon]，减低肝脏葡萄糖生成。在2型糖尿病患者中，GLP-1浓度被减低但保留胰岛素对GLP-1反应。Alogliptin是一种DPP-4抑制剂减慢肠促胰岛素激素的失活，从而在2型糖尿病患者中增加其血流浓度和以葡萄糖依赖方式减低空腹和餐后葡萄糖浓度。在体外在接近治疗性暴露浓度Alogliptin选择性结合至和抑制DPP-4 但不抑制DPP-8或DPP-9 活性。 适应证和用途 NESINA是一种二肽肽酶-4(DPP-4)抑制剂适用为辅助饮食和远动改善血糖控制2型糖尿病成年。 使用的限制：不是为治疗1型糖尿病或糖尿病酮症酸中毒。 剂量和给药方法 （1）正常肾功能或轻度肾受损患者推荐剂量是25mg每天1次。 （2）可有或无食物服用。 （3）调整剂量如中度或严重肾受损或肾病终末期(ESRD). 剂型和规格 片：25mg，12.5mg和6.25mg 禁忌证 对含alogliptin产品，例如 过敏性反应，血管水肿或严重皮肤不良反应的严重超敏性反应史。 警告和注意事项 （1）急性胰腺炎：有上市后急性胰腺炎报告。如怀疑胰腺炎，立即终止NESINA。 （2） 超敏性：在用NESINA治疗患者中有严重超敏性反应上市后报告例如过敏性反应，血管水肿和严重皮肤不良反应。在这类病例中立即终止NESINA，评估其他潜在原因，开始适当监视和治疗，和开始对糖尿病另外治疗。 （3） 肝脏影响：肝衰竭上市后报告，有时致命性。不能排除因果关系。如检测到肝损伤，立即中断NESINA和评估患者可能的原因，如可能然后治疗原因，解决或稳定化。如确认肝损伤和不能找到另外病因不要重新开始NESINA。 （4） 低血糖：当使用胰岛素促分泌素(如磺酰脲类)或胰岛素与NESINA联合治疗，可能需要较低剂量胰岛素促分泌素或胰岛素以减低低血糖风险。 （5）大血管结局：尚无临床研究确定用NESINA或任何其他降糖药大血管风险减低的结论性证据。 不良反应 常见不良反应(报道用NESINA 25mg治疗患者 ≥4%和比接受安慰剂患者更频)是：鼻咽炎，头痛，和上呼吸道感染。 NESINA(ALOGLIPTIN BENZOATE)TABLET ORAL Pharmacological Class: Dipeptidyl peptidase-4 (DPP-4) inhibitor. Active Ingredient(s): Alogliptin 6.25mg, 12.5mg, 25mg; tabs. Company Takeda Pharmaceuticals North America, Inc. Indication(s): As adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). Limitations of use: not for treatment of type 1 diabetes or diabetic ketoacidosis. Pharmacology: Alogliptin acts by slowing the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner. Clinical Trials: Nesina has been studied as monotherapy and in combination with metformin, a sulfonylurea, a thiazolidinedione (either alone or in combination with metformin or a sulfonylurea), and insulin (either alone or in combination with metformin). A total of 8,673 patients with T2DM were randomized in 10 double-blind, placebo- or active-controlled clinical studies conducted to evaluate the effects of Nesina on glycemic control. Three of the ten studies evaluated Nesina in 1,768 patients with T2DM that had inadequate glycemic control on diet and exercise. All three studies had a 4-week, single-blind, placebo run-in period followed by a 26-week randomized treatment period. In the first study, 329 patients were randomized to Nesina 12.5mg, Nesina 25mg, or placebo once daily. The Nesina 25mg treatment group demonstrated statistically significant improvements compared to placebo from baseline in A1C (−0.6% vs. 0%) and fasting plasma glucose (FPG; −16mg/dL vs. 11mg/dL; P<0.01 for both) at Week 26. In the second study, 655 patients were randomized to Nesina 25mg, pioglitazone 30mg, Nesina 12.5mg + pioglitazone 30mg, or Nesina 25mg + pioglitazone 30mg once daily. Coadministration of Nesina 25mg + pioglitazone 30mg resulted in statistically significant improvements from baseline in A1C (−1.7%) and FPG (−50mg/dL) compared to Nesina 25mg alone (−1.0% and −26mg/dL, respectively) and pioglitazone 30mg alone (−1.2% and −37mg/dL, respectively; P<0.01 compared to individual component regimens) at Week 26. In the third study, 784 patients were randomized to placebo, metformin HCl 500mg or metformin HCl 1000mg twice daily, Nesina 12.5mg twice daily or Nesina 25mg daily; Nesina 12.5mg + metformin HCl 500mg or metformin HCl 1000mg twice daily. Both coadministration arms resulted in statistically significant improvements in A1C and FPG when compared to their respective individual alogliptin and metformin component regimens. Coadministration treatment arms also showed improvements in 2-hour postprandial glucose compared to Nesina or metformin alone. For information on studies conducted in add-on combination therapy: see full labeling. Legal Classification: Rx Adults: 25mg once daily. Renal impairment: moderate (CrCl ≥30–<60mL/min): 12.5mg once daily; severe (CrCl ≥15–<30mL/min) or ESRD (CrCl <15mL/min or need hemodialysis): 6.25mg once daily. Children: Not established. Warnings/Precautions: Monitor for signs/symptoms of pancreatitis; discontinue if suspected. History of angioedema with other DPP-4 inhibitors. Discontinue if serious hypersensitivity reaction is suspected. Hepatic impairment. Obtain liver function tests before starting therapy; interrupt and evaluate if liver enzymes elevated or abnormal tests persist; do not restart if liver injury is confirmed and no other etiology can be found. Monitor renal function prior to therapy and periodically thereafter. Pregnancy (Category B). Nursing mothers. Interaction(s) Concomitant sulfonylurea or insulin: may need lower dose of sulfonylurea or insulin to reduce risk of hypoglycemia. Adverse Reaction(s) Nasopharyngitis, headache, upper respiratory tract infection. How Supplied: 6.25mg—30, 90; 12.5mg, 25mg—30, 90, 500 LAST UPDATED: 8/2/2013 WARNING: LACTIC ACIDOSIS—for KAZANO Lactic acidosis is a rare, but serious complication that 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. The onset is often subtle,accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate. If acidosis is suspected, KAZANO should be discontinued and the patient hospitalized immediately. NESINA, KAZANO, and OSENI are contraindicated in NESINA, KAZANO, and OSENI are contraindicated in patients with a history of serious hypersensitivity reaction to any of the components of these products, such as anaphylaxis, angioedema, or severe cutaneous adverse reactions. KAZANO is contraindicated in patients with renal impairment (e.g., serum creatinine levels =1.5 mg/dL for men, =1.4 mg/dL for women or abnormal creatinine clearance), which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarctions, and septicemia. KAZANO is contraindicated in patients with acute or chronic metabolic acidosis, including diabetic ketoacidosis. Do not initiate OSENI in patients with established NYHA Class III or IV heart failure. Warnings and Precautions—for KAZANO Lactic acidosis: Warn against excessive alcohol intake. KAZANO is not recommended in hepatic impairment and is contraindicated in renal impairment. Ensure normal renal function before initiating and at least annually thereafter. Temporarily discontinue in patients undergoing radiologic studies with intravascular iodinated contrast materials or any surgical procedures necessitating restricted intake of food and fluids. Lactic acidosis due to metformin accumulation during therapy is fatal in approximately 50% of cases. The risk increases in patients with renal impairment, congestive heart failure requiring drug treatment, and with increasing age. Vitamin B12 deficiency: Metformin may lower Vitamin B12 levels. Monitor hematologic parameters annually. Warnings and Precautions—for OSENI Congestive heart failure: Fluid retention may occur and can exacerbate or lead to congestive heart failure. Combination use with insulin and use in congestive heart failure NYHA Class I and II may increase risk. Monitor patients for signs and symptoms. Edema: Dose-related edema may occur. Use with caution in patients with edema. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a3768c7e-aa4c-44d3-bc53-43bb7346c0b0