Invokana获准用于治疗2型糖尿病

圣路易斯(MD Consult)——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。

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ST LOUIS (MD Consult) - On March 29, 2013, the US Food and Drug Administration (FDA) and Janssen Pharmaceuticals announced the approval of Invokana (canagliflozin) for the treatment of type 2 diabetes in adults. Invokana is intended for use, along with diet and exercise, as a means to improve glycemic control.

Invokana is a member of a new class of drugs known as sodium-glucose co-transporter 2 inhibitors. It works by blocking the reabsorption of glucose by the kidney, increasing glucose excretion, and therby lowering blood glucose levels.

The safety and effectiveness of Invokana were evaluated in 9 clinical trials involving more than 10,285 patients with type 2 diabetes. Patients in these trials showed improvement in hemoglobin A1c levels and fasting plasma glucose levels. Invokana has been studied as a stand-alone therapy and in combination with other type 2 diabetes therapies including metformin, sulfonylurea, pioglitazone, and insulin.

Results from the phase 3 studies showed that Invokana was generally well tolerated. The most common adverse events in patients who received Invokana were genital mycotic (fungal) infections, urinary tract infections, and increased urination. These specific adverse events were generally mild to moderate and infrequently led to discontinuation. The use of Invokana in women is associated with an increased risk of vulvovaginal candidiasis.

Because Invokana promotes diuresis, it can cause a reduction in intravascular volume leading to orthostatic or postural hypotension. This may result in symptoms such as dizziness or fainting, and is most common during the first 3 months of therapy. Invokana should not be used for the treatment of type 1 diabetes, in patients with diabetic ketoacidosis, in persons undergoing dialysis, or in persons with severe renal impairment or end-stage renal disease.

The FDA is requiring 5 postmarketing studies for Invokana: a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes; a bone safety study; and 2 pediatric studies, including a pharmacokinetic and pharmacodynamic study and a safety and efficacy study.

The recommended starting dose is 100 mg once daily, taken before the first meal of the day. The dose can be increased to 300 mg once daily.