KOMBIGLYZE XR Rx
Generic Name and Formulations:
Saxagliptin, metformin HCl (ext-rel); 5mg/500mg, 5mg/1000mg, 2.5mg/1000mg; tabs.
Company:
AstraZeneca Pharmaceuticals
Indications for KOMBIGLYZE XR:
Adjunct to diet and exercise in type 2 diabetes when treatment with both saxagliptin and metformin is appropriate. Limitations of use: not for treating type 1 diabetes or diabetic ketoacidosis. Not studied in patients with history of pancreatitis.
Adult:
Take once daily with evening meal. Swallow whole. Individualize; titrate based on response. Max saxagliptin 5mg/day and metformin ext-rel 2000mg/day. Concomitant strong CYP3A4/5 inhibitors: max saxagliptin 2.5mg/day.
Children:
<18yrs: not established.
Pharmacological Class:
Dipeptidyl peptidase-4 (DPP4) inhibitor + biguanide.
Contraindications:
Renal impairment (serum creatinine ≥1.5mg/dL [men], ≥1.4mg/dL [women], or abnormal CrCl). Metabolic acidosis, diabetic ketoacidosis. History of serious hypersensitivity reactions (eg, anaphylaxis, angioedema, exfolitative skin conditions).
Warnings/Precautions:
Discontinue if lactic acidosis is suspected. Monitor for signs/symptoms of pancreatitis; discontinue if suspected. Confirm normal renal function before starting; monitor (esp. in patients ≥80yrs). Avoid in hepatic disease. Discontinue if shock, acute CHF or MI, sepsis, or hypoxemia occurs. Suspend therapy if dehydration occurs or before surgery. Monitor hepatic function, 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. Concomitant intravascular iodinated contrast agents (suspend during and for 48 hours after use). History of angioedema to other DPP4 inhibitors. Pregnancy (Cat.B), nursing mothers: not recommended; consider using insulin instead.
Interactions:
Saxagliptin potentiated by strong CYP3A4/5 inhibitors (eg, ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin). Cationic drugs eliminated by renal tubular secretion (eg, cimetidine, amiloride, digoxin, morphine, procainamide, quinidine, quinine, triamterene, trimethoprim, ranitidine, vancomycin): may increase metformin levels. Avoid excessive alcohol intake (potentiates effects of metformin on lactate). Diuretics, steroids, phenothiazines, phenytoin, sympathomimetics, calcium channel blockers, isoniazid, niacin, thyroid products, estrogens, oral contraceptives may cause hyperglycemia. May need lower dose of concomitant sulfonylurea or insulin to reduce risk of hypoglycemia. β-blockers may mask hypoglycemia.
Adverse Reactions:
Diarrhea, nausea, vomiting, URI, UTI, headache, nasopharyngitis, hypersensitivity reactions (discontinue if suspected); lactic acidosis (rare, ½ the cases are fatal).
How Supplied:
Tabs 5/500—30; 5/1000—30, 90, 500; 2.5/1000—60, 500
Kombiglyze缓释剂用于治疗2型糖尿病
2010年11月5日，阿斯利康公司与百时美-施贵宝公司宣布，美国食品药品管理局(FDA)已批准Kombiglyze缓释剂用于治疗成人2型糖尿病。Kombiglyze缓释剂是一种含有二肽基肽酶-IV抑制剂沙克列汀(Onglyza)和双胍类药物二甲双胍缓释剂的复方制剂，使用方法为一次1片、一天1次。生产商声明，使用Kombiglyze缓释剂可在糖化血红蛋白(HbA1c)、空腹血糖(FPG)和餐后血糖(PPG)水平方面强化血糖的控制。
在可以合理应用沙克列汀与二甲双胍的情况下，Kombiglyze 缓释剂可作为饮食和锻炼的一种辅助用药来改善成人2型糖尿病患者的血糖控制。该药禁用于1型糖尿病患者或糖尿病酮症酸中毒患者，目前尚未对其与胰岛素联用进行研究。
FDA批准Kombiglyze缓释剂是以3项II期临床试验以及生物等效性研究中的结果为依据的。这些临床研究旨在评估沙克列汀+二甲双胍(速释剂[IR])(单片用药)相对于安慰剂+甲福明二甲双胍IR的疗效与安全性。通过在健康成人受试者中比较Kombiglyze缓释剂与沙克列汀+二甲双胍缓释剂(单片用药)来确定生物等效性。
一项历时24周的临床试验纳入了1,306例首次接受治疗、单纯采用饮食和锻炼血糖控制不充分的成人2型糖尿病患者。接受Kombiglyze缓释剂治疗(Onglyza 5 mg+甲福明二甲双胍IR单片用药 [n=306，基线时HbA1c=9.4%])的患者HbA1c水平显著下降，为-2.5%，而安慰剂+二甲双胍IR治疗组(n = 313; 基线时HbA1c =9.4%)为-2.0%。此外，Kombiglyze缓释剂治疗组患者FPG 和 PPG水平的下降相对于安慰剂+甲福明二甲双胍IR治疗组有显著的统计学意义。沙克列汀5 mg+二甲双胍IR治疗组有≥5%的患者发生了不良反应，而且与采用二甲双胍IR单药治疗的患者相比，头痛(7.5% vs 5.2%)和鼻咽炎(6.9% vs 4.0%)更常见。
Kombiglyze缓释剂禁用于肾功能受损、糖尿病酮症酸中毒等代谢性酸中毒和对甲福明二甲双胍过敏的患者。与二甲双胍的包装说明书一致，Kombiglyze缓释剂的处方信息也包含一则黑框警告：乳酸中毒，这是一种罕见但较严重的代谢性并发症，可由治疗期间二甲双胍的积聚而引起。
采用碘造影剂进行放射性检查的患者应暂时停用Kombiglyze缓释剂。
