英文药名：Invokamet(canagliflozin and metformin hydrochloride Tablets)

中文药名：复方坎格列净/二甲双胍固定剂量片

生产厂家：扬森制药
药品介绍
2型糖尿病新药坎格列净/二甲双胍复方片商品名为Invokamet，本品将SGLT2阻滞剂canagliflozin与常用的糖尿病药二甲双胍（metformin）合二为一，服用单一片剂达到降低血糖和减轻体重的目标。

INVOKAMET Rx
Generic Name and Formulations:
Canagliflozin, metformin HCl 50mg/500mg, 50mg/1000mg, 150mg/500mg, 150mg/1000mg; tabs.

Company:
Janssen Pharmaceuticals, Inc.
Indications for INVOKAMET:
Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled on a regimen containing metformin or canagliflozin or who are already being treated with both canagliflozin and metformin. Limitations of use: not for treating type 1 diabetes or diabetic ketoacidosis.

Adult:
See full labeling. Individualize. Take twice daily with meals; increase dose gradually. Max daily dose: 300mg/2000mg. Moderate renal impairment (eGFR 45–<60mL/min/1.73m2): max canagliflozin 50mg twice daily. Concomitant UGT inducers in patients with eGFR ≥60mL/min/1.73m2: consider increase to canagliflozin 150mg twice daily; if eGFR 45–<60mL/min/1.73m2: consider other antihyperglycemics.

Children:
<18yrs: not established.

Pharmacological Class:
Sodium-glucose co-transporter 2 inhibitor + biguanide.

Contraindications:
Renal impairment (SCr ≥1.5mg/dL [men], ≥1.4mg/dL [women], or eGFR <45mL/min/1.73m2), ESRD, or on dialysis. Metabolic acidosis, diabetic ketoacidosis.

Warnings/Precautions:
Confirm normal renal function before starting and monitor thereafter (esp. in elderly). Discontinue if lactic acidosis, renal impairment, shock, acute MI or CHF, dehydration, sepsis, hypoxemia, pancreatitis, or hypersensitivity reactions occur. Avoid in hepatic disease. Discontinue prior to any intravascular radiocontrast study or surgery; withhold for 48hrs after procedure. Correct volume depletion before initiating. Monitor for symptomatic hypotension after starting therapy (esp. elderly, renal impairment, low systolic BP, on diuretics or drugs that interfere with the RAAS system [eg, ACEIs, ARBs]). Monitor serum K+ levels in patients predisposed to hyperkalemia. Elderly, debilitated, uncompensated strenuous exercise, malnourished or deficient caloric intake, adrenal or pituitary insufficiency, or alcohol intoxication: increased risk of hypoglycemia. Monitor for genital mycotic infections, hematology (esp. serum Vit. B12), increases in LDL-C; treat if occur. Pregnancy (Cat.C). Nursing mothers.

Interactions:
Cationic drugs eliminated by renal tubular secretion (eg, amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin); may increase metformin levels; monitor. Increased risk of lactic acidosis with topiramate, other carbonic anhydrase inhibitors (eg, zonisamide, acetazolamide, dichlorphenamide). Diuretics, steroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, sympathomimetics, nicotinic acid, CCBs, and isoniazid may cause hyperglycemia. Avoid excessive alcohol. Concomitant drugs that may affect renal function or metformin disposition; monitor and adjust dose. Antagonized by UGT inducers (eg, rifampin, phenytoin, phenobarbital, ritonavir): see Adults. Concomitant digoxin: monitor. Concomitant insulin or insulin secretagogue: consider a lower dose of insulin/insulin secretagogue to reduce risk of hypoglycemia. May cause false (+) urine glucose tests or unreliable measurements of 1, 5-AG assay; use alternative methods to monitor glycemic control.

Adverse Reactions:
Female genital mycotic infections, UTI, increased urination, GI upset, flatulence, asthenia, indigestion, abdominal discomfort, headache.

How Supplied:
Tabs—60
FDA批准坎格列净/二甲双胍固定剂量复方制剂上市
Invokamet (canagliflozin and metformin hydrochloride) Tablets (坎格列净/二甲双胍复方片)
2014年8月10日,FDA批准糖尿病复方药INVOKAMET（canagliflozin/二甲双胍），用于2型糖尿病成人患者的治疗。VOKANAMET是由固定剂量canagliflozin和速释二甲双胍（metformin）组成的复方单片，在单一片剂中结合了2种机制互补的降糖药，可同时提供Invokana（canagliflozin）及二甲双胍的临床属性。Invokana是获批的首个钠葡萄糖协同转运蛋白2（SGLT2）抑制剂，而二甲双胍常处方用于2型糖尿病的早期治疗。在美国，INVOKAMET是首个SGLT2抑制剂和二甲双胍固定剂量组合产品。
INVOKAMET适用于作为一种辅助药物，结合运动和饮食，用于改善2型糖尿病成人患者的血糖控制，包括：（1）服用canagliflozin或二甲双胍不能充分控制血糖水平的患者；（2）已经在接受canagliflozin+二甲双胍组合疗法的患者。INVOKAMET不适用于1型糖尿病和糖尿病酮症酸中毒的治疗。
VOKANAMET的获批，是基于在横跨不同糖尿病群体中开展的全面全球III期项目的数据。数据表明，INVOKAMET与相应剂量canagliflozin+二甲双胍组合疗法具有等效性。
此前，VOKANAMET已于2014年4月获欧盟批准，用于2型糖尿病成人患者的治疗，该药适用于：（1）最大耐受剂量二甲双胍仍不能充分控制血糖水平的患者；（2）最大耐受剂量二甲双胍联合其他降糖药（包括胰岛素）仍不能充分控制血糖水平的患者；（3）正在接受canagliflozin和二甲双胍组合疗法的患者。
INVOKANA（canagliflozin）于2013年获FDA和欧盟批准，该药为日服一次的口服糖尿病药物，属于选择性钠葡萄糖共转运体2（SGLT2）抑制剂的一类新药，通过阻断肾脏对血糖的重吸收及增加尿液中血糖的排泄，来降低机体血糖水平。与非糖尿病人群相比，2型糖尿病患者的肾脏能够重吸收大量的葡萄糖进入血液，这可能会推高血糖水平。
二甲双胍则是2型糖尿病治疗的一线药物，可单独或与其他药物（包括胰岛素）联合用药。在2型糖尿病患者中，肝脏产生过量的葡萄糖（glucose），从而提高血糖水平。二甲双胍可通过降低肝脏产生葡萄糖的量、增加肌肉对葡萄糖的敏感性、延缓肠道的葡萄糖吸收，降低机体的血糖水平。