Liptruzet复方片获准用于治疗高脂血症

圣路易斯(MD Consult)——2013年5月3日，默克公司宣布美国食品与药品管理局(FDA)已批准Liptruzet(依折麦布和阿托伐他汀)用于单纯饮食治疗未能控制低密度脂蛋白胆固醇(LDL-C)水平达标的原发性或混合性高脂血症患者。该药物将作为饮食治疗的辅助，用于降低LDL-C水平。这一药物的适应证还包括降低总胆固醇、载脂蛋白B、甘油三酯和非高密度脂蛋白胆固醇水平，以及升高高密度脂蛋白胆固醇水平。尚不明确Liptruzet对心血管发病率和病死率的影响是否大于阿托伐他汀。

每日1次Liptruzet通过抑制胆固醇在消化道的吸收(通过依折麦布)和胆固醇在肝脏的产生(通过阿托伐他汀)而双管齐下。每片Liptruzet片剂含依折麦布10 mg和阿托伐他汀10、20、40或80 mg。

在一项多中心、双盲、安慰剂对照的临床试验中，628例高脂血症患者接受最长达12周的治疗，结果显示最小剂量(10/10 mg)Liptruzet治疗使LDL-C降低了53%(平均基线LDL-C为177 mg/dl)，10/20 mg剂量的Liptruzet使LDL-C降低54%(平均基线LDL-C为184 mg/dl)，10/40 mg剂量的Liptruzet使LDL-C降低56%(平均基线LDL-C为184 mg/dl)，最大剂量(10/80 mg) Liptruzet使LDL-C降低61%(平均基线LDL-C为183 mg/dl)。来自其他研究的数据显示，Liptruzet降低LDL-C水平的效果优于单用阿托伐他汀。

在一项关于Liptruzet的临床试验中，报告的最常见不良反应(无论原因如何)包括丙氨酸氨基转移酶水平升高、天冬氨酸氨基转移酶水平升高和肌肉骨骼疼痛。因此，应避免对有活动性肝病或无法解释的持续性肝脏转氨酶升高患者处方Liptruzet。Liptruzet说明书中也包含关于发生肌病和横纹肌溶解的警告和指导。

建议的Liptruzet起始剂量为10/10 mg或 10/20 mg每日1次，对于需要更大幅度降低LDL-C的患者，也可给予10/40 mg每日1次。该药可在一天中的任何时间使用，不受进餐时间影响。

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ST LOUIS (MD Consult) - On May 3, 2013, Merck announced that the US Food and Drug Administration (FDA) has approved Liptruzet (ezetimibe and atorvastatin) for the treatment of elevated low-density lipoprotein cholesterol (LDL-C) levels in patients with primary or mixed hyperlipidemia as adjunctive therapy to diet when diet alone is not adequate in achieving treatment goals. Use of the drug is also indicated for the reduction of elevated total cholesterol, apolipoprotein B, triglyceride, and non-high-density lipoprotein cholesterol levels, as well as to increase high-density lipoprotein cholesterol levels. No incremental benefit of Liptruzet on cardiovascular morbidity and mortality over and above that demonstrated for atorvastatin has been established.

Once-daily Liptruzet treats 2 sources of cholesterol by inhibiting both the absorption of cholesterol in the digestive tract (through ezetimibe) and the production of cholesterol in the liver (through atorvastatin). The Liptruzet tablet contains 10 mg of ezetimibe combined with either 10, 20, 40, or 80 mg of atorvastatin.

In a multicenter, double-blind, placebo-controlled clinical study in which 628 patients with hyperlipidemia were treated for up to 12 weeks, Liptruzet (coadministered as ezetimibe and atorvastatin) provided LDL-C reductions of 53% at the lowest dose (10/10 mg; mean baseline LDL-C, 177 mg/dL), 54% at the 10/20-mg dose (mean baseline LDL-C, 184 mg/dL), 56% at the 10/40-mg dose (mean baseline LDL-C, 184 mg/dL) and 61% at the maximum dose (10/80 mg; mean baseline LDL-C, 183 mg/dL). Data from additional studies demonstrated the superiority of Liptruzet over atorvastatin alone in reducing LDL-C levels.

In a clinical trial of Liptruzet, the most commonly reported adverse effects, regardless of cause, included increased alanine transaminase levels, increased aspartate transaminase levels, and musculoskeletal pain.

Liptruzet should not be prescribed for persons with active liver disease or unexplained persistent elevations in hepatic transaminases. The Litruzet label also carries warnings and guidance about the occurrence of myopathy and rhabdomyolysis.

The recommended starting dose of Liptruzet is 10/10 mg or 10/20 mg taken once daily, or 10/40 mg once-daily for patients who require a larger reduction in LDL-C levels. The drug may be taken at any time of day, with or without food.