每日一片的口服固定剂量Qtern(dapagliflozin/saxagliptin)，用于治疗2型糖尿病新药获FDA批准
近日，美国食品和药物管理局（FDA）批准每日一次口服固定剂量药物Qtern用于成年2型糖尿病患者的疾病控制。该药物由5mg的DPP-4抑制剂沙格列汀（saxagliptin）和10mg的SGLT2抑制剂达格列净（dapagliflozin）组成。
批准日期：2017年3月1日 公司：阿斯利康
QTERN®（达格列嗪/沙格列汀 dapagliflozin/saxagliptin）片剂，用于口服
美国最初批准：2017年
作用机制
QTERN结合了两种抗高血糖药物，以改善2型糖尿病患者的血糖控制：dapagliflozin，一种钠 - 葡萄糖协同转运蛋白2（SGLT-2）抑制剂和沙克列汀，一种二肽基肽酶-4（DPP-4）抑制剂。
达格列
在近端肾小管中表达的钠-葡萄糖协同转运蛋白2（SGLT-2）负责过滤葡萄糖从管状腔中的大部分再吸收。Dapagliflozin是一种抑制剂
SGLT-2。通过抑制SGLT-2，达格列嗪减少过滤葡萄糖的重吸收并降低葡萄糖的肾阈值，从而增加尿糖排泄。
沙格列汀
增加的肠促胰岛素激素如胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性促胰岛素多肽（GIP）的浓度响应于进餐从小肠释放到血流中。这些激素以胰糖依赖性方式引起胰岛β细胞的胰岛素释放，但在几分钟内被DPP-4酶灭活。 GLP-1还降低胰腺α细胞的胰高血糖素分泌，减少肝葡萄糖的产生。在2型糖尿病患者中，GLP-1的浓度降低但胰岛素对GLP-1的反应得以保留。沙格列汀是一种竞争性DPP-4抑制剂，可减缓肠促胰岛素激素的失活，从而增加其血流浓度，减少空腹和餐后葡萄糖浓度以葡萄糖依赖方式治疗2型糖尿病患者。
适应症和用法
QTERN是一种钠 - 葡萄糖协同转运蛋白2（SGLT-2）抑制剂和一种二肽基肽酶-4(DPP-4)抑制剂组合产品，作为饮食和运动的辅助手段，用于改善2型糖尿病（T2DM）成人的血糖控制dapagliflozin或已用dapagliflozin和沙格列汀治疗的人控制不足。
使用限制：
剂量和给药
QTERN的推荐剂量是每天早上一次口服10mg达格列嗪/5mg沙格列汀片剂
有或没有食物。
剂量形式和强度
片剂：10mg达格列嗪/5mg沙格列汀。
禁忌症
QTERN禁用于以下患者：
警告和注意事项
胰腺炎：如果怀疑胰腺炎，请立即停止使用QTERN。
心力衰竭：考虑已知已知心力衰竭危险因素的患者的QTERN风险和益处。监测患者的体征和症状。
低血压：在开始QTERN之前，评估老年人，肾功能不全或收缩压低的患者以及袢利尿剂患者的容量状态并纠正血容量不足。监测治疗期间的体征和症状。
酮症酸中毒：评估出现酮症酸中毒代谢性酸中毒症状和体征的患者，无论血糖水平如何。如果怀疑，停止QTERN，立即评估和治疗。在开始QTERN之前，考虑酮症酸中毒的风险因素。 QTERN患者可能需要在已知易患酮症酸中毒的临床情况中进行监测并暂时停止治疗。
急性肾损伤和肾功能损害：考虑在口服摄入减少或液体流失减少的情况下暂时停药。如果发生急性肾损伤，请停药并及时治疗。在治疗期间监测肾功能。
尿脓毒症和肾盂肾炎：评估尿路感染的体征和症状，如果需要，及时治疗。
低血糖：考虑降低胰岛素促分泌素或胰岛素的剂量，以降低发生QTERN时发生低血糖的风险。
过敏反应（如荨麻疹，面部水肿）：有严重的上市后报告
用沙克列汀治疗的超敏反应，如过敏反应，血管神经性水肿和剥脱性皮肤病。
及时停止使用QTERN，评估其他潜在原因，进行适当的监测和治疗，并为糖尿病开展替代治疗。
生殖器真菌感染：如果有指示，监测和治疗。
LDL-C增加：按照标准护理监测和治疗。
膀胱癌：在dapagliflozin的临床研究中观察到膀胱癌的不平衡。QTERN不应用于患有活动性膀胱癌的患者，并应在有膀胱癌史的患者中谨慎使用。
关节痛：服用DPP-4抑制剂的患者有严重和致残性关节痛。考虑可能导致严重的关节疼痛并在适当时停用药物。
大疱性类天疱疮：有大疱性类天疱疮的上市后报告需要住院治疗DPP-4抑制剂。告诉患者报告水疱或糜烂的发展。如果怀疑是大疱性类天疱疮，
停止QTERN。
宏观血管结果：目前还没有临床研究证实QTERN可以提供大血管风险减少的确凿证据。
不良反应
在用10mg达格列嗪和5mg沙格列汀治疗的受试者中，≥5％报告的不良反应是：上呼吸道感染，尿路感染和血脂异常。
药物相互作用
强CYP3A4/5抑制剂（例如，酮康唑）：不要与强细胞色素P450 3A4/5抑制剂共同施用QTERN。
用于特定人群
怀孕：告知女性胎儿的潜在风险，特别是在孕中期和孕晚期。
哺乳期：母乳喂养时不建议使用QTERN。
老年医学：与体积减少和肾功能减退相关的不良反应发生率更高。
肾功能损害：与血管内容量和肾功能降低相关的不良反应发生率较高。
如何提供/存储和处理
如何提供
口服使用的QTERN（dapagliflozin和saxagliptin）片剂如下列所示：
10毫克/5毫克
瓶：30片 03106780-30
瓶：90片 03106780-90
瓶：500片 03106780-50
存储和处理
储存在20°C至25°C（68°F至77°F）; 允许偏移15°C至30°C（59°F至86°F）[见USP
受控室温]。
完整资料附件：
file:///C:/Users/Administrator/AppData/Local/Microsoft/Windows/Temporary%20Internet%20Files/Content.IE5/7MUINVY8/20180629_423c489c-085b-4320-b892-7868ebd6dc6b.pdf
IMPORTANT SAFETY INFORMATION for QTERN®(dapagliflozin and saxagliptin)
Contraindications
Prior serious hypersensitivity reaction to QTERN or its components
Moderate to severe renal impairment (eGFR <45 mL/min/1.73 m2), end-stage renal disease, or patients on dialysis
Warning and Precautions
Pancreatitis: There have been postmarketing reports of acute pancreatitis in patients taking saxagliptin, and in the SAVOR cardiovascular outcomes trial. Observe for pancreatitis. If pancreatitis is suspected, discontinue QTERN
Heart Failure: In the SAVOR cardiovascular outcomes trial, more patients treated with saxagliptin were hospitalized for heart failure compared to placebo. Patients with a prior history of heart failure or renal impairment had a higher risk for hospitalization for heart failure. Consider the risks and benefits of QTERN in patients who have known risk factors for heart failure. Monitor for signs and symptoms. If heart failure develops, consider discontinuation of QTERN.
Hypotension: Dapagliflozin causes intravascular volume contraction, and symptomatic hypotension can occur. Assess and correct volume status before initiating QTERN in patients with impaired renal function, elderly patients, or patients on loop diuretics. Do not initiate QTERN in patients with an eGFR <60 mL/min/1.73 m2. Monitor for hypotension
Ketoacidosis has been reported in patients with type 1 and type 2 diabetes receiving dapagliflozin. Some cases were fatal. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue QTERN, eva luate and treat promptly. Before initiating QTERN, consider risk factors for ketoacidosis. Patients on QTERN may require monitoring and temporary discontinuation in situations known to predispose to ketoacidosis
Acute Kidney Injury and Impairment in Renal Function: Dapagliflozin causes intravascular volume contraction and renal impairment, with reports of acute kidney injury requiring hospitalization and dialysis. Consider temporarily discontinuing in settings of reduced oral intake or fluid losses. If acute kidney injury occurs, discontinue and promptly treat
Dapagliflozin increases serum creatinine and decreases eGFR. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Before initiating QTERN, eva luate renal function and monitor periodically. Discontinue QTERN in patients if eGFR falls persistently below 60 mL/min/1.73 m2
Urosepsis and Pyelonephritis: SGLT2 inhibitors increase the risk for urinary tract infections (UTIs) and serious UTIs have been reported with dapagliflozin. eva luate for signs and symptoms of UTIs and treat promptly
Hypoglycemia: QTERN can increase the risk of hypoglycemia when coadministered with insulin and insulin secretagogues. Consider lowering the dose of these agents when coadministered with QTERN
Hypersensitivity Reactions: Serious reactions have been reported in patients treated with saxagliptin, including anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with saxagliptin, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue QTERN. Use caution in patients with a history of angioedema to another DPP-4 inhibitor.
Genital Mycotic Infections: Dapagliflozin increases the risk of genital mycotic infections, particularly in patients with prior genital mycotic infections. Monitor and treat appropriately
Increases in Low-Density Lipoprotein Cholesterol (LDL-C) occur with dapagliflozin. Monitor LDL-C and treat per standard of care
Bladder Cancer: An imbalance in bladder cancers was observed in clinical trials. There were too few cases to determine whether the emergence of these events is related to dapagliflozin, and insufficient data to determine whether dapagliflozin has an effect on pre-existing bladder tumors. QTERN should not be used in patients with active bladder cancer. Use with caution in patients with a history of bladder cancer
Severe and Disabling Arthralgia has been reported in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from one day to years. Patients experienced relief of symptoms upon discontinuation. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider discontinuing drug if appropriate.
Bullous Pemphigoid: There have been postmarketing reports of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If suspected, discontinue QTERN
Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with QTERN
Adverse Reactions
Most common adverse reactions reported in ≥5% of patients treated with 10 mg dapagliflozin and 5 mg saxagliptin were upper respiratory tract infection (13.6%), urinary tract infection (5.7%), and dyslipidemia (5.1%).
Drug Interactions
Strong CYP3A4/5 inhibitors (eg, ketoconazole): Coadministration with QTERN significantly increases saxagliptin concentrations. Do not coadminister QTERN.
Use in Specific Populations
Pregnancy: Advise females of the potential risk to a fetus especially during the second and third trimesters
Lactation: QTERN is not recommended when breastfeeding
INDICATION AND LIMITATIONS OF USE for QTERN® (dapagliflozin and saxagliptin)
QTERN is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM) who have inadequate control with dapagliflozin or who are already treated with dapagliflozin and saxagliptin.
QTERN is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. QTERN should only be used in patients who tolerate 10 mg dapagliflozin.
Please see accompanying US Full Prescribing Information for QTERN.
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.