Invokana(canagliflozin)作为治疗2型糖尿病的新一代药物 2013年3月29日，美国食品药品管理局(FDA)与杨森制药宣布，Invokana(canagliflozin)已获准用于治疗成人2型糖尿病。Invokana将会联合饮食与运动治疗，以改善血糖控制。 Invokana是一类名为钠葡萄糖协同转运子2抑制剂的新型药物中的一种。该药通过阻断肾脏葡萄糖重吸收、增加葡萄糖排泄而发挥降低血糖的作用。 Invokana的安全性和有效性在9项临床试验、超过10,285例2型糖尿病患者中得到了评估。这些试验中的患者显示出糖化血红蛋白A1c水平和空腹血糖水平的改善。Invokana单独治疗和联合其他2型糖尿病治疗(包括二甲双胍、磺酰脲类、吡格列酮和胰岛素)的方案均已得到了研究。 来自3期研究的结果显示，Invokana通常耐受性良好。接受Invokana治疗的患者中最常见的不良事件为生殖器霉菌(真菌)感染、尿路感染和排尿增多。这些特定的不良事件通常为轻至中度，很少导致停药。女性使用Invokana与外阴阴道念珠菌病风险增加有关。 由于Invokana有利尿作用，使用该药可导致血管内容量下降，进而引起直立性或体位性低血压。后者可能导致头晕或昏厥，而且在治疗的头3个月内最常见。不得使用Invokana治疗1型糖尿病，也不得用于合并糖尿病酮症酸中毒的患者、正在接受透析的患者，以及患有严重肾功能损害或终末期肾病的患者。 FDA正在要求开展5项关于Invokana的上市后研究：1项心血管结局试验，1项用于监测恶性肿瘤、严重胰腺炎、严重超敏反应、光敏反应、肝功能异常和不良妊娠结局的强化药物警戒计划，1项骨骼安全性研究，以及2项儿科研究(包括1项药代学与药效学研究和1项安全性与有效性研究)。 推荐的初始剂量为100 mg每日1次，第一餐前服用。之后可将剂量增加至300 mg/d。 Invokana (Canagliflozin Tablets) Pharmacological Class: Sodium-glucose co-transporter 2 (SGLT2) inhibitor. Active Ingredient(s): Canagliflozin 100mg, 300mg; tablets. Company Janssen Pharmaceuticals, Inc. Indication(s): Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). Limitation of use: not for treatment of type 1 diabetes or diabetic ketoacidosis. Pharmacology: Canagliflozin inhibits the sodium-glucose co-transporter 2, which reduces reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Clinical Trials: Canagliflozin has been studied as monotherapy, in combination with metformin, sulfonylurea, metformin and sulfonylurea, metformin and a thiazolidinedione (eg, pioglitazone), and in combination with insulin (with or without other antihyperglycemic agents). The efficacy of canagliflozin was compared to a dipeptidyl peptidase‑4 (DPP‑4) inhibitor (sitagliptin) and a sulfonylurea (glimepiride). Canagliflozin was also evaluated in adults 55–80 years of age and patients with moderate renal impairment. In patients with T2DM, treatment with canagliflozin produced clinically and statistically significant improvements in HbA1c compared to placebo. A total of 584 patients with T2DM inadequately controlled on diet and exercise participated in a 26‑week, double-blind, placebo-controlled study to evaluate the efficacy and safety of canagliflozin monotherapy. Patients taking other antihyperglycemic agents (N=281) discontinued the agent and underwent an 8-week washout followed by a 2‑week, single-blind, placebo run-in period. Patients not taking oral antihyperglycemic agents (N=303) entered the 2‑week, single-blind, placebo run-in period directly. After the placebo run-in period, patients were randomized to canagliflozin 100mg, canagliflozin 300mg, or placebo, given once daily for 26 weeks. At the end of treatment, both canagliflozin doses resulted in a statistically significant improvement in HbA1c (P <0.001 for both doses) vs. placebo. Also, both doses resulted in a greater proportion of patients achieving an HbA1c <7%, in significant reduction in fasting plasma glucose, in improved postprandial glucose, and in percent body weight reduction compared to placebo. Statistically significant (P <0.001 for both doses) mean changes from baseline in systolic BP relative to placebo were ‑3.7 mmHg and ‑5.4 mmHg with canagliflozin 100mg and 300mg, respectively. For information on studies conducted in add-on combination therapy and in special populations: see full labeling. Legal Classification: Rx Adults: See full labeling. Take before first meal of the day. Initially 100mg once daily; if tolerated and with eGFR ≥60mL/min/1.73m2, and need additional glycemic control; may increase to 300mg once daily. Moderate renal impairment (eGFR 45–<60mL/min/1.73m2): 100mg once daily; if eGFR <45mL/min/1.73m2: do not initiate. Concomitant UGT inducers in patients with eGFR ≥60mL/min/1.73m2: consider increase to 300mg once daily; if eGFR 45–<60mL/min/1.73m2: consider other antihyperglycemics. Children: <18 years: not established. Contraindication(s): Severe renal impairment (eGFR <30mL/min/1.73m2), ESRD, or patients on dialysis. Warnings/Precautions: Correct volume depletion before starting therapy. Monitor for symptomatic hypotension in patients with renal impairment (eGFR <30mL/min/1.73m2), elderly, low systolic BP, concomitant diuretics or drugs that interfere with the renin-angiotensin-aldosterone system (eg, ACEIs, ARBs). Monitor renal function before and during therapy; more frequently if eGFR <60mL/min/1.73m2. Monitor K+ levels in patients with renal impairment and predisposed to hyperkalemia. Risk of genital mycotic infections; monitor and treat. Monitor LDL levels and treat per standard of care. Severe hepatic impairment: not recommended. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended. Interaction(s) Antagonized by UGT inducers (eg, rifampin, phenytoin, phenobarbital, ritonavir): see Adults dose. Concomitant digoxin: monitor. Concomitant insulin or insulin secretagogue: consider a lower dose of insulin/insulin secretagogue to reduce risk of hypoglycemia. Adverse Reaction(s) Female genital mycotic infections, urinary tract infection, increased urination; hypersensitivity reactions (discontinue if occurs). How Supplied: Tabs—30, 90, (10x10 blister cards), 500 LAST UPDATED: 5/6/2013 ------------------------------------------------ 产地国家：美国  原产地英文商品名: INVOKANA 100MG/tablets 30tablets/bottle 原产地英文药品名: CANAGLIFLOZIN 中文参考商品译名: Invokana片 100毫克/片 30片/瓶 中文参考药品译名: 卡格列净 生产厂家中文参考译名: 杨森 生产厂家英文名: JANSSEN ------------------------------------------------ 产地国家：美国  原产地英文商品名: INVOKANA 100MG/tablets 90tablets/bottle 原产地英文药品名: CANAGLIFLOZIN 中文参考商品译名: Invokana片 100毫克/片 90片/瓶 中文参考药品译名: 卡格列净 生产厂家中文参考译名: 杨森 生产厂家英文名: JANSSEN ------------------------------------------------ 产地国家：美国  原产地英文商品名: INVOKANA 300MG/tablets 30tablets/bottle 原产地英文药品名: CANAGLIFLOZIN 中文参考商品译名: Invokana片 300毫克/片 30片/瓶 中文参考药品译名: 卡格列净 生产厂家中文参考译名: 杨森 生产厂家英文名: JANSSEN ------------------------------------------------ 产地国家：美国  原产地英文商品名: INVOKANA 300MG/tablets 90tablets/bottle 原产地英文药品名: CANAGLIFLOZIN 中文参考商品译名: Invokana片 300毫克/片 90片/瓶 中文参考药品译名: 卡格列净 生产厂家中文参考译名: 杨森 生产厂家英文名: JANSSEN