英文药名：JANUMET XR（SITAGLIPTIN; METFORMIN HYDROCHLORIDE）   中文药名：西格列汀/二甲双胍复方缓释片 　　  　　 生产厂家：美国默沙东制药有限公司 药品介绍： 近日，默克公司宣布美国食品药品管理局(FDA)已经批准Janumet XR(西他列汀/二甲双胍缓释片)用于治疗2型糖尿病。Janumet XR适合作为饮食和运动疗法的辅助用药，用于同时适宜采用西他列汀和缓释型二甲双胍治疗的2型糖尿病患者，以改善其血糖控制。 Janumet XR以糖尿病的3个重要缺陷为靶点：胰岛β细胞引起的胰岛素缺乏、胰岛素抵抗以及肝脏葡萄糖生成过量。 FDA批准Janumet XR是基于一项临床生物等效性研究的结果，该研究显示应用Janumet XR与相应剂量的这两种药物——西他列汀和缓释二甲双胍联用的效果相当。缓释二甲双胍与速释二甲双胍等效。 据默克公司称，西他列汀与二甲双胍联合用药所能使血红蛋白A1c(HbA1c)水平降低的程度大于西他列汀或二甲双胍单独用药。在一项对1，091例通过饮食和运动疗法未能充分控制血糖的2型糖尿病患者进行的随机、双盲、安慰剂对照的析因研究中，在24周时，速释型二甲双胍与西他列汀联合用药、每日2次治疗组的HbA1c水平相对于安慰剂对照组降低。西他列汀100 mg、每日1次+速释型二甲双胍2000 mg、每日1次治疗组(n=178)基线时的平均HbA1c水平为8.8%，安慰剂调整的平均降幅为2.1%(P<0.001)。该研究的其他小组安慰剂调整的平均HbA1c降幅分别为1.6%(西他列汀100 mg、每日1次+速释型二甲双胍1000 mg、每日1次治疗组，n=183)、1.3%(速释型二甲双胍2000 mg、每日1次治疗组，n=177)，1.0%(速释型二甲双胍1000 mg、每日1次治疗组，n=178)及0.8%(西他列汀治疗组，n=175)(所有治疗组vs. 安慰剂组：P<0.001)。在24周时，初始治疗方案为西他列汀100 mg、每日1次+速释型二甲双胍2000 mg、每日1次的患者中有66%达到美国糖尿病学会(ADA)设定的目标血红蛋白A1c水平<7%，而采用速释型二甲双胍2000 mg、每日1次单药治疗组中有38%的患者达到此目标。在该研究的其他小组中，西他列汀100 mg、每日1次+速释型二甲双胍1000 mg、每日1次联合治疗组有43%、速释型二甲双胍1000 mg、每日1次治疗组有23%、西他列汀治疗组有20%的患者达到了ADA设定的血红蛋白A1c<7%的目标水平。 Janumet XR的说明书中包含一个有关乳酸酸中毒的黑框警告，该药禁用于有肾功能损害的患者。 目前已收到有关服用西他列汀联合(或不联合)二甲双胍的患者发生肾功能恶化的上市后报告，其中包括急性肾衰竭，有时甚至需要透析治疗。在开始Janumet治疗前及此后至少每年应进行一次肾功能评估，以确认其正常。 此外，上市后报告还涉及急性胰腺炎，其中包括服用西他列汀联合(或不联合)二甲双胍的患者发生致死性和非致死性出血性或坏死性胰腺炎。在开始Janumet XR治疗后，应该对患者密切监测胰腺炎的症状和体征。若疑似胰腺炎，则应立即停用Jamumet XR，并开始适当的处置。有胰腺炎病史的患者在接受Janumet XR治疗的过程中发生胰腺炎的风险是否会增加，尚不清楚。 市售的Janumet XR有100 mg西他列汀/1000 mg二甲双胍缓释片、50mg西他列汀/500mg二甲双胍缓释片以及50 mg西他列汀/1000 mg二甲双胍缓释片。Janumet XR的用法为每日1次，最好在晚餐后服用。应告知患者Janumet XR片在吞服前不得切割、压碎或咀嚼。 Janumet XR的剂量应根据患者当前的治疗方案、有效性和耐受性采取个体化原则，同时不要超过西他列汀和二甲双胍的每日最大推荐剂量(分别为100 mg和2000 mg)。初始联合治疗或联合治疗的维持用药也应采取个体化原则，并由医务人员判断决定。 对于已经开始二甲双胍治疗的患者，Janumet XR的每日总推荐开始剂量为西他列汀100 mg，二甲双胍仍遵循之前的处方剂量. Indication: Janumet XR (sitagliptin and metformin HCl extended-release) tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with sitagliptin and metformin is appropriate. Janumet XR is not indicated for type 1 diabetes or diabetic ketoacidosis, and it has not been studied in patients with a history of pancreatitis. Tablets should be swallowed whole and not split, crushed, or chewed. The maximum daily dose is 100 mg sitagliptin/2000 mg metformin extended release. Dosage Form: Tablets (sitagliptin/metformin HCl extended release): 100 mg/1000 mg, 50 mg/500 mg, and 50 mg/1000 mg JANUMET XR Rx Generic Name and Formulations: Sitagliptin, metformin (as HCl) ext-rel; 50mg/500mg, 50mg/1000mg, 100mg/1000mg; tabs. Company: Merck & Co., Inc. Indications for JANUMET XR: Adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes when treatment with both sitagliptin and metformin extended-release is appropriate. Limitations of use: not for treating type 1 diabetes or diabetic ketoacidosis. Not studied in patients with history of pancreatitis. Adult: Individualize. Swallow whole. Take once daily with a meal, preferably in the evening. Not currently treated with metformin: initially 100mg/1000mg daily. Previously on metformin alone: initially 100mg daily of sitagliptin plus metformin dose. Previously on metformin 850mg twice daily or 1000mg twice daily: start with two 50mg/1000mg tablets taken together once daily. Previously on Janumet: switch on a mg/mg basis. Max 100mg sitagliptin/2000mg metformin per day. Children: <18yrs: not established. Pharmacological Class: Dipeptidyl peptidase-4 inhibitor + biguanide. Contraindications: Renal impairment (Scr ≥1.5mg/dL [men], ≥1.4mg/dL [women], or abnormal CrCl). Metabolic acidosis, diabetic ketoacidosis. Warnings/Precautions: Confirm normal renal function before starting and monitor (esp. in elderly). Discontinue if lactic acidosis, renal impairment, shock, acute MI or CHF, sepsis, hypoxemia, pancreatitis, or hypersensitivity reactions occur. Avoid if clinical or lab evidence of hepatic disease. 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, uncompensated strenuous exercise, malnourished or deficient caloric intake, adrenal or pituitary insufficiency, or alcohol intoxication: increased risk of hypoglycemia. History of angioedema to other DPP-4 inhibitors. Concomitant intravascular iodinated contrast agents (suspend during and for 48hrs after use). Pregnancy (Cat.B). Nursing mothers. Interactions: Caution with concomitant topiramate or other carbonic anhydrase inhibitors (eg, zonisamide, acetazolamide, dichlorphenamide); may induce metabolic acidosis. Cationic drugs eliminated by renal tubular secretion (eg, amiloride, digoxin, morphine, procainamide, quinine, quinidine, ranitidine, triamterene, trimethoprim, vancomycin); monitor. Avoid excessive alcohol intake (potentiates effects of metformin on lactate). Diuretics, steroids, estrogens, oral contraceptives, phenothiazines, phenytoin, thyroid products, nicotinic acid, sympathomimetics, calcium channel blockers, isoniazid, others may cause hyperglycemia. May need to lower dose of concomitant sulfonylurea or insulin to reduce risk of hypoglycemia. β-blockers may mask hypoglycemia. Adverse Reactions: Diarrhea, URTI, headache, nasopharyngitis, hypoglycemia, asthenia; lactic acidosis (rare, half of the cases are fatal). Metabolism: Sitagliptin: hepatic (CYP3A4, 2C8) Elimination: Renal (major), fecal. How Supplied: XR tabs 50mg/500mg, 50mg/1000mg—60, 180, 1000; 100mg/1000mg—30, 90, 1000 PRESCRIPTION REQUIRED IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs. SITAGLIPTIN/METFORMIN EXTENDED-RELEASE - ORAL (SYE-ta-GLIP-tin/met-FOR-min) COMMON BRAND NAME(S): Janumet XR WARNING: Metformin can rarely cause a serious (sometimes fatal) condition called lactic acidosis. Stop taking this product and get medical help right away if you develop symptoms of lactic acidosis, including: unusual tiredness, dizziness, severe drowsiness, feeling cold (especially in your arms and legs), muscle pain, fast/difficult breathing, slow/irregular heartbeat, stomach pain with nausea/vomiting/diarrhea. Lactic acidosis is more likely to occur in patients who have certain medical conditions, including kidney or liver disease, recent surgery, a serious infection, conditions that may cause a low level of oxygen in the blood or poor circulation (such as heart failure, recent heart attack, recent stroke), heavy alcohol use, a severe loss of body fluids (dehydration), or X-ray or scanning procedures that require an injectable iodinated contrast drug. Tell your doctor right away if any of these conditions occur or if you notice a big change in your overall health. You may need to stop taking this medication temporarily. Older adults are also at higher risk, especially those older than 80 years who have not had kidney tests. (See also Side Effects and Precautions sections.) USES: This combination medication is used with a proper diet and exercise program and possibly with other medications to control high blood sugar. It is used by patients with type 2 diabetes (non-insulin-dependent diabetes). This product contains 2 medications. Sitagliptin works by increasing levels of natural substances called incretins. Incretins help to control blood sugar by increasing insulin release, especially after a meal. They also decrease the amount of sugar your liver makes. Metformin works by helping to restore your body's proper response to the insulin you naturally produce. It also decreases the amount of sugar that your liver makes and that your stomach/intestines absorb. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems. Proper control of diabetes may also lessen your risk of a heart attack or stroke. This medication should not be used to treat people with type 1 diabetes (insulin-dependent diabetes). HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using sitagliptin/metformin and each time you get a refill. If you have any questions, ask your doctor or pharmacist. Take this medication by mouth as directed by your doctor, usually once daily with a meal, preferably in the evening. Swallow this medication whole. Do not crush, chew, or split the tablets. Doing so can release all of the drug at once, increasing the risk of side effects. Drink plenty of fluids while taking this medication unless otherwise directed by your doctor. The dosage is based on your medical condition and response to treatment. To reduce your risk of side effects (such as stomach upset), your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully. Take this medication regularly to get the most benefit from it. Remember to take it at the same time each day. Carefully follow the medication treatment plan, meal plan, and exercise program your doctor has recommended. Tell your doctor if your condition does not improve or if it worsens (such as if your blood sugar levels remain high or increase). SIDE EFFECTS: See also Warning section. Nausea, vomiting, stomach upset, diarrhea, headache, or a metallic taste in the mouth may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly. If stomach symptoms return later (after taking the same dose for several days or weeks), tell your doctor right away. Stomach symptoms that occur after the first days of your treatment may be signs of lactic acidosis. Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects. Tell your doctor right away if you have any serious side effects, including: change in the amount of urine. Stop taking this medication and tell your doctor right away if you have any very serious side effects, including: signs of pancreatitis (such as persistent nausea/vomiting, loss of appetite, severe stomach/abdominal pain). Although this medication by itself usually does not cause low blood sugar (hypoglycemia), low blood sugar may occur if this drug is prescribed with other diabetes medications. Talk with your doctor or pharmacist about whether the dose(s) of your other diabetes medication(s) needs to be lowered. Drinking large quantities of alcohol, not getting enough calories from food, or doing unusually heavy exercise may also lead to low blood sugar. Symptoms may include sudden sweating, shaking, fast heartbeat, hunger, blurred vision, dizziness, headache, or tingling hands/feet. It is a good habit to carry glucose tablets or gel to treat low blood sugar. If you don't have these reliable forms of glucose, rapidly raise your blood sugar by eating a quick source of sugar such as table sugar, honey, or candy, or drink fruit juice or non-diet soda. Tell your doctor immediately about the reaction. To help prevent low blood sugar, eat meals on a regular schedule, and do not skip meals. Check with your doctor or pharmacist to find out what you should do if you miss a meal. Symptoms of high blood sugar (hyperglycemia) include thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, and fruity breath odor. If these symptoms occur, tell your doctor immediately. Your doctor may need to adjust your diabetes medication(s). A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing. This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist. In the US - Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345. PRECAUTIONS: See also Warning section. Before taking this medication, tell your doctor or pharmacist if you are allergic to sitagliptin or metformin; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details. Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, severe breathing problems (such as obstructive lung disease, severe asthma), metabolic acidosis (such as diabetic ketoacidosis), liver disease, a disease of the pancreas (pancreatitis). Before having surgery or any X-ray/scanning procedure using injectable iodinated contrast material, tell your doctor or dentist that you are taking this medication and about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). You will need to temporarily stop this medication before the time of your surgery/procedure. Consult your doctor for further instructions. You may experience blurred vision, dizziness, or drowsiness due to extremely low or high blood sugar levels. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely. Limit alcohol while using this medication because it can increase your risk of lactic acidosis and developing low blood sugar. High fever, "water pills" (diuretics such as hydrochlorothiazide), too much sweating, diarrhea, or vomiting may cause loss of too much body water (dehydration) and increase your risk of lactic acidosis. Stop taking this medication and tell your doctor right away if you have prolonged diarrhea or vomiting. Be sure to drink enough fluids to prevent dehydration unless your doctor directs you otherwise. It may be harder to control your blood sugar when your body is stressed (such as due to fever, infection, injury, or surgery). Consult your doctor because this may require a change in your treatment plan, medications, or blood sugar testing. Older adults may be at greater risk for side effects such as low blood sugar or lactic acidosis. During pregnancy, this medication should be used only when clearly needed. Pregnancy may worsen diabetes. Discuss a plan with your doctor for managing your blood sugar while pregnant. Your doctor may change your diabetes treatment during your pregnancy. Discuss the risks and benefits of different treatments (such as diet, exercise, and medications including insulin). Metformin can cause changes in the menstrual cycle (promote ovulation) and increase the risk of becoming pregnant. Consult your doctor or pharmacist about the use of reliable birth control while using this medication. Metformin passes into breast milk. It is unknown if sitagliptin passes into breast milk. Consult your doctor before breast-feeding. DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval. Many drugs can affect your blood sugar levels, making it more difficult to control your blood sugar. Before you start, stop, or change any medication, talk with your doctor or pharmacist about how the medication may affect your blood sugar. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor about the results and of any symptoms of high or low blood sugar. (See also Side Effects section.) Your doctor may need to adjust your anti-diabetic medication, exercise program, or diet. OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Overdose can cause lactic acidosis. Symptoms of overdose may include: severe drowsiness, severe nausea/vomiting/diarrhea, rapid breathing, slow/irregular heartbeat. NOTES: Do not share this medication with others. Attend a diabetes education program to learn more about diabetes and the important aspects of its treatment, including meals/diet, exercise, personal hygiene, medications, and getting regular eye/foot/medical exams. Keep all medical appointments. Laboratory and/or medical tests (such as liver/kidney function, blood glucose, hemoglobin A1c, complete blood counts) should be performed before you start treatment, periodically to monitor your progress, or to check for side effects. Check your blood sugar levels regularly as directed. MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up. STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets. Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company. MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada). Information last revised March 2013. Copyright(c) 2013 First Databank, Inc.