英文药名: Janumet(Sitagliptin/Metformin Tablets) 中文药名: 西他列汀二甲双胍复方片 生产厂家: 默克制药公司 药品介绍 Janumet(西他列汀+二甲双胍 )-二肽基肽酶组合- 4抑制剂+双胍类 2007年4月2日，默克制药公司宣布FDA已经批准西他列汀和二甲双胍的复方片剂规格每片含西他列汀/二甲双胍50mg/1000mg，商品名Janumet上市用于治疗Ⅱ型糖尿病。Janumet中的有效成分Janu via为新型二肽基肽酶-4抑制剂（DPP- 4inhibitor）具有独特的作用机制，可用作单一治疗药物，也可用作其它两种口服降糖药（二甲双胍或噻唑烷二酮）的辅助药物。 Janumet这种药物含有西他列汀和盐酸二甲双胍两种成分，可以解决Ⅱ型糖尿病患者3个关键的病症，即胰岛素缺乏、胰岛素流失和葡萄糖过剩，从而有效降低患者的血糖水平。 与单独服用盐酸二甲双胍药物相比，Janumet可以更有效降低Ⅱ型糖尿病患者体重增加和发生低血糖的风险。 去年4月，美国食品和药物管理局批准Janumet在美国上市。到目前为止，这种药物已在全球50多个国家和地区获得上市批准。 糖尿病分为Ⅰ型糖尿病、Ⅱ型糖尿病和妊娠期糖尿病。Ⅰ型糖尿病患者体内只能产生少量或不能产生胰岛素；Ⅱ型糖尿病又称成年发病型糖尿病，特点是胰岛素抵抗，即自体能够产生胰岛素，但细胞无法对它作出反应；妊娠期糖尿病是指妇女妊娠怀孕期间患上糖尿病。 美国默克公司的糖尿病复方新药Janumet(Sitagliptin/Metformin Tablets) 于7月22日获准在欧盟27个成员国上市。 　　 这种药物含有西他列汀和盐酸二甲双胍两种成分，可以解决Ⅱ型糖尿病患者3个关键的病症，即胰岛素缺乏、胰岛素流失和葡萄糖过剩，从而有效降低患者的血糖水平。与单独服用盐酸二甲双胍药物相比，Janumet可以更有效降低Ⅱ型糖尿病患者体重增加和发生低血糖的风险。 　　 --------------------------------------------------- 【原产地英文商品名】JANUMET 50/1000MG 【原产地英文药品名】SITAGLIPTIN PHOSPHATE/METFORMIN HCL 【中文参考商品译名】JANUMET 50/1000毫克 【中文参考药品译名】 注：以下产品不同规格和不同价格，采购以电话咨询为准！ ·JANUMET 50/500毫克x60片 ·JANUMET 50/1000毫克x60片 ·JANUMET 50/500毫克x720片 ·JANUMET 50/1000毫克x60片 ·JANUMET 50/1000毫克x180片 ·JANUMET 50/1000毫克x720片 【中文参考药品译名】二甲双胍的复方制剂 【中文参考化合物名称】DPP-4抑制剂 【生产厂家中文参考译名:美国默克 【生产厂家英文名】Merck & Co., Inc JANUMET® (sitagliptin/metformin HCl) Tablets Merck & Co., Inc. Selected Important Risk Information About JANUMET®(sitagliptin and metformin HCl) tabletsWARNING: LACTIC ACIDOSIS Lactic acidosis is a rare but serious complication that can occur because of 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, JANUMET should be discontinued and the patient hospitalized immediately [see Warnings and Precautions]. JANUMET is contraindicated in patients with renal impairment (serum creatinine levels greater than or equal to 1.5 mg/dL for men and greater than or equal to 1.4 mg/dL for women or abnormal creatinine clearance); hypersensitivity to metformin hydrochloride; acute or chronic metabolic acidosis, including diabetic ketoacidosis; or history of a serious hypersensitivity reaction to JANUMET or sitagliptin (one of the components of JANUMET), such as anaphylaxis or angioedema. Temporarily discontinue JANUMET in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function. Avoid use in patients with hepatic disease. Temporarily discontinue for intercurrent serious conditions, infection, or surgery. There have been postmarketing reports of worsening renal function, including acute renal failure, sometimes requiring dialysis. Before initiation of JANUMET and at least annually thereafter, renal function should be assessed and verified as normal. In patients in whom development of renal dysfunction is anticipated, particularly in elderly patients, renal function should be assessed more frequently and JANUMET discontinued if evidence of renal impairment is present. When lactic acidosis occurs, it is fatal in approximately 50% of cases. The reported incidence of lactic acidosis in patients receiving metformin is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). Reported cases have occurred primarily in diabetic patients with significant renal impairment, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient’s age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin treatment should not be initiated in patients ≥80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. There have been postmarketing reports of acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, in patients taking JANUMET. After initiating JANUMET, observe patients carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue JANUMET and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while taking JANUMET. Alcohol is known to potentiate the effect of metformin on lactate metabolism. Patients, therefore, should be warned against excessive alcohol intake, acute or chronic, when receiving JANUMET. Intravascular contrast studies with iodinated materials can lead to acute alteration of renal function and have been associated with lactic acidosis in patients receiving metformin. Therefore, in patients in whom any such study is planned, JANUMET should be temporarily discontinued at the time of or before the procedure, withheld for 48 hours subsequent to the procedure, and reinstituted only after renal function has been re-evaluated and found to be normal. There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with JANUMET or any other antidiabetic drug. Use With Medications Known to Cause Hypoglycemia Sitagliptin When sitagliptin was used in combination with a sulfonylurea or insulin, medications known to cause hypoglycemia, the incidence of hypoglycemia was increased over that of placebo used in combination with a sulfonylurea or insulin. Therefore, patients also receiving insulin or an insulin secretagogue (eg, sulfonylurea) may require a lower dose of insulin or the insulin secretagogue to reduce the risk of hypoglycemia. The incidence (and rate) of hypoglycemia based on all reports of symptomatic hypoglycemia were: 16.4% (0.82 episodes/patient-year) for sitagliptin 100 mg in combination with metformin and glimepiride, 0.9% (0.02 episodes/patient-year) for placebo in combination with metformin and glimepiride, 8.2% (0.61 episodes/patient-year) for placebo in combination with metformin and insulin, and 15.3% (0.98 episodes/patient-year) for sitagliptin in combination with metformin and insulin. Adverse reactions with sitagliptin in combination with metformin and rosiglitazone through Week 18 were: upper respiratory tract infection (sitagliptin, 5.5%; placebo, 5.2%) and nasopharyngitis (6.1%, 4.1%). Through Week 54 they were: upper respiratory tract infection (sitagliptin, 15.5%; placebo, 6.2%), nasopharyngitis (11.0%, 9.3%), peripheral edema (8.3%, 5.2%), and headache (5.5%, 4.1%). Metformin hydrochloride Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use but could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol. Elderly, debilitated, or malnourished patients and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects. There have been postmarketing reports of serious hypersensitivity reactions in patients treated with sitagliptin, one of the components of JANUMET, such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Onset of these reactions occurred within the first 3 months after initiation of treatment with sitagliptin, with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, discontinue JANUMET, assess for other potential causes for the event, and institute alternative treatment for diabetes. Angioedema has also been reported with other dipeptidyl peptidase-4 (DPP-4) inhibitors. Use caution in a patient with a history of angioedema to another DPP-4 inhibitor because it is unknown whether such patients will be predisposed to angioedema with JANUMET. There have been postmarketing reports of severe and disabling arthralgia in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from 1 day to years. Patients experienced relief of symptoms upon discontinuation of the medication. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible cause for severe joint pain and discontinue drug if appropriate. In clinical studies, the most common adverse reactions reported, regardless of investigator assessment of causality, in ≥5% of patients treated with either sitagliptin in combination with metformin or placebo were as follows: diarrhea (7.5% vs 4.0%), upper respiratory tract infection (6.2% vs 5.1%), and headache (5.9% vs 2.8%). In patients treated with sitagliptin in combination with metformin and sulfonylurea or placebo in combination with metformin and sulfonylurea: hypoglycemia (16.4% vs 0.9%) and headache (6.9% vs 2.7%). In patients treated with sitagliptin in combination with metformin and insulin or placebo in combination with metformin and insulin: hypoglycemia (15.3% vs 8.2%). Other adverse events with an incidence of ≥5% included nasopharyngitis for sitagliptin monotherapy and diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache for metformin therapy. Generic Name for JANUMET 50mg/500mg Sitagliptin 50mg, metformin (as HCl) 500mg; tabs. Legal Classification: Rx Pharmacological Class for JANUMET 50mg/500mg Dipeptidyl peptidase-4 inhibitor + biguanide. Manufacturer of JANUMET 50mg/500mg Merck & Co., Inc. Indications for JANUMET 50mg/500mg Adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes who are not adequately controlled on metformin or sitagliptin alone or in patients already being treated with the combination of sitagliptin and metformin. Adult dose for JANUMET 50mg/500mg Individualize. Take twice daily with meals. Previously on metformin alone: initially 50mg twice daily of sitagliptin plus metformin dose. Previously on metformin 850mg twice daily: start with 50mg/1000mg twice daily. Previously on sitagliptin alone: initially 50mg/500mg twice daily; may increase to 50mg/1000mg twice daily. Previously on sitagliptin and metformin: switch on a mg/mg basis. Max 100mg sitagliptin/2000mg metformin per day. Children's dosing for JANUMET 50mg/500mg <18yrs: not recommended. Also: JANUMET 50mg/1000mg Contraindications for JANUMET 50mg/500mg Renal disease or dysfunction. Metabolic acidosis, ketoacidosis. Concomitant intravascular iodinated contrast agents (suspend during and for 48 hours after use). Type 1 diabetes. Precautions for JANUMET 50mg/500mg Confirm normal renal function before starting and monitor (esp. in elderly). Avoid if clinical or lab evidence of hepatic disease. Discontinue if lactic acidosis, ketoacidosis, renal impairment, shock, acute MI, acute CHF, sepsis, or hypoxemia occurs. May need to suspend therapy during periods of stress or if dehydration occurs or before surgery. Monitor hematology (esp. serum Vit. B12 in susceptible patients). Elderly, debilitated, malnourished, deficient caloric intake, adrenal or pituitary insufficiency, or alcohol intoxication: increased risk of hypoglycemia. Pregnancy (Cat.B). Nursing mothers. Interactions for JANUMET 50mg/500mg Cationic drugs eliminated by renal tubular secretion (eg, amiloride, digoxin, morphine, procainamide, quinine, quinidine, ranitidine, triamterene, trimethoprim, vancomycin), furosemide, nifedipine, cimetidine: may increase metformin levels. Avoid excessive alcohol intake (potentiates effects of metformin on lactate). Monitor digoxin. Diuretics, steroids, estrogens, oral contraceptives, phenothiazines, phenytoin, thyroid products, nicotinic acid, sympathomimetics, calcium channel blockers, isoniazid, others that may cause hyperglycemia. β-blockers may mask hypoglycemia. Adverse Reactions for JANUMET 50mg/500mg Nasopharyngitis, GI disturbances, asthenia, headache; lactic acidosis (rare, half of the cases are fatal). How is JANUMET 50mg/500mg supplied? Tabs—60, 180, 1000 Related Disease: Diabetes mellitus~hyperglycemic agents Related Resources JANUMET tablets contain 2 prescription medicines: sitagliptin (JANUVIA®) and metformin. Once-daily prescription JANUMET XR tablets contain sitagliptin (the medicine in JANUVIA®) and extended-release metformin. JANUMET or JANUMET XR can be used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. Your doctor will determine whether JANUMET or JANUMET XR is right for you. JANUMET or JANUMET XR should not be used in patients with type 1 diabetes or with diabetic ketoacidosis (increased ketones in the blood or urine). If you have had pancreatitis (inflammation of the pancreas), it is not known if you have a higher chance of getting it while taking JANUMET or JANUMET XR. Selected Risk Information About JANUMET and JANUMET XR Metformin, one of the ingredients in JANUMET and JANUMET XR, can cause a rare but serious side effect called lactic acidosis (a buildup of lactic acid in the blood), which can cause death. Lactic acidosis is a medical emergency that must be treated in a hospital. Stop taking JANUMET or JANUMET XR and call your doctor right away if you get any of the following symptoms of lactic acidosis: you feel very weak or tired; have unusual (not normal) muscle pain; have trouble breathing; have unusual onScreenDetectsleepiness or sleep longer than usual; have sudden stomach or intestinal problems with nausea and vomiting or diarrhea; feel cold, especially in your arms and legs; feel dizzy or lightheaded; or have a slow or irregular heartbeat. You have a higher chance of getting lactic acidosis if you have kidney problems, liver problems, or congestive heart failure that requires treatment with medicines; if you drink alcohol very often, drink a lot of alcohol in a short period of time, or get dehydrated (lose large amounts of body fluids); if you have certain x-ray tests with dyes or contrast agents that are injected into your body; or if you have surgery, a heart attack, severe infection, or stroke. Pancreatitis is another serious side effect that can happen in people taking JANUMET or JANUMET XR. Pancreatitis may be severe and lead to death. Before you start taking JANUMET or JANUMET XR, tell your doctor if you've ever had pancreatitis. Stop taking JANUMET or JANUMET XR and call your doctor right away if you have pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen through to your back. The pain may happen with or without vomiting. These may be symptoms of pancreatitis. Do not take JANUMET or JANUMET XR if you are allergic to any of the ingredients in JANUMET or JANUMET XR. Allergic reactions, which may be serious, including rash; hives; or swelling of the face, lips, tongue, and throat that may cause difficulty breathing or swallowing, can occur. If you have an allergic reaction, stop taking JANUMET or JANUMET XR and call your doctor right away. Do not take JANUMET or JANUMET XR if your kidneys are not working properly. Your doctor will do blood tests before and during your treatment to see how well your kidneys are working. Tell your doctor if you are going to get an injection of dye or contrast agent for an x-ray procedure; JANUMET or JANUMET XR will need to be stopped for a short time. If you take JANUMET or JANUMET XR with another medicine that can cause low blood sugar (hypoglycemia), such as a sulfonylurea or insulin, your risk of getting low blood sugar is higher. The dose of your sulfonylurea or insulin may need to be lowered. Signs and symptoms of low blood sugar may include headache, drowsiness, weakness, dizziness, confusion, irritability, hunger, fast heart beat, sweating, and feeling jittery. Kidney problems, sometimes requiring dialysis, have been reported. Some people who take medicines called DPP-4 inhibitors, one of the medicines in JANUMET and JANUMET XR, may develop joint pain that can be severe. Call your doctor if you have severe joint pain. Common side effects when taking JANUMET or JANUMET XR include stuffy or runny nose and sore throat, upper respiratory tract infection, diarrhea, nausea and vomiting, gas, upset stomach, indigestion, weakness, headache, and low blood sugar (hypoglycemia) when used in combination with certain medications, such as a sulfonylurea or insulin. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Please read the accompanying Medication Guide for JANUMET® (sitagliptin and metformin HCl) tablets or JANUMET® XR (sitagliptin and metformin HCl extended-release) tablets, including the information about lactic acidosis, and discuss it with your doctor. The physician Prescribing Information for JANUMET or JANUMET XR also is available https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=9467#section-5 Ⅱ型糖尿病新药Janumet获欧盟批准上市 美国默克公司的糖尿病复方新药Janumet(Sitagliptin/Metformin Tablets) 于7月22日获准在欧盟27个成员国上市。 这种药物含有西他列汀和盐酸二甲双胍两种成分，可以解决Ⅱ型糖尿病患者3个关键的病症，即胰岛素缺乏、胰岛素流失和葡萄糖过剩，从而有效降低患者的血糖水平。与单独服用盐酸二甲双胍药物相比，Janumet可以更有效降低Ⅱ型糖尿病患者体重增加和发生低血糖的风险。 去年4月，美国食品和药物管理局批准Janumet在美国上市。到目前为止，这种药物已在全球50多个国家和地区获得上市批准。 糖尿病分为Ⅰ型糖尿病、Ⅱ型糖尿病和妊娠期糖尿病。Ⅰ型糖尿病患者体内只能产生少量或不能产生胰岛素；Ⅱ型糖尿病又称成年发病型糖尿病，特点是胰岛素抵抗，即自体能够产生胰岛素，但细胞无法对它作出反应；妊娠期糖尿病是指妇女妊娠怀孕期间患上糖尿病.