Gupta Eric K, Ito Matthew K
University of the Pacific Thomas J. Long School of Pharmacy and Health Sciences, Stockton, California, USA.
Heart Dis. 2002 Mar-Apr;4(2):124-37. doi: 10.1097/00132580-200203000-00010.
Advicor (lovastatin and extended-release niacin) is the first cholesterol-lowering combination product to become available for the management of hyperlipidemia. Lovastatin significantly lowers low-density lipoprotein cholesterol, whereas niacin significantly lowers triglycerides and lipoprotein (a) and markedly increases high-density lipoprotein cholesterol. These effects are ideal for managing a variety of lipid disorders, including metabolic syndrome. Lovastatin and niacin reduce coronary heart disease mortality in primary and secondary prevention patients, respectively. The extended-release niacin component uses a unique technology to minimize adverse effects (e.g., flushing and hepatotoxicity) while retaining the same lipid-altering effects as immediate-release niacin. The combination product appears to be well tolerated, with discontinuation due to adverse effects other than flushing occurring in a similar percent of patients as for lovastatin in clinical trials. Approximately 9% of patients discontinued the combination product due to flush. No confined cases of myopathy or hepatotoxicity have been reported with this product. Once-daily dosing provides ease of administration that should improve compliance and result in a greater proportion of patients meeting their low-density lipoprotein cholesterol goals. The nomenclature surrounding niacin products used to treat dyslipidemias is confusing. While only two types of niacin formulations exist (immediate-release formulations and formulations which dissolve more slowly than immediate-release formulations), government regulations allow for slowly dissolved niacin formulations to be divided into two types of niacin products; those that are available over-the-counter (OTC) and those that are available by prescription only. Over-the-counter slowly dissolved niacin preparations are not classified as OTC per se, but are considered "nutritional supplements". For this reason, they fall under the jurisdiction of the Federal Trade Commission and do not fall under the umbrella of the FDA branch that controls dyslipidemic products (Endocrine and Metabolic Division of the Center for Drug Evaluation and Research). The slowly dissolved niacin nutritional supplements have not been reviewed by the FDA for safety nor efficacy in the treatment of dyslipidemia nor are they required to meet generic drug rules (even though various brands are available). These brands are described on their labels as "sustained-release", "timed-release", and "slow-release" for example. Only two slowly absorbed niacin products have been approved by the FDA for the treatment of dyslipidemia; they are Niaspan (Kos Pharmaceuticals, Inc., Miami, FL) and Advicor (Kos Pharmaceuticals, Inc., Miami, FL). The term "extended-release" has been given to these two products to simplify the terminology and differentiate the products from immediate-release niacin. In this review, we will use "extended-release" to refer to the FDA approved slowly dissolving niacin preparation and "sustained-release" to refer to the nutritional supplements (not FDA approved).
Advicor（洛伐他汀与缓释烟酸）是首个可用于治疗高脂血症的降胆固醇复方产品。洛伐他汀能显著降低低密度脂蛋白胆固醇，而烟酸能显著降低甘油三酯和脂蛋白(a)，并显著提高高密度脂蛋白胆固醇。这些作用对于治疗包括代谢综合征在内的多种脂质紊乱非常理想。洛伐他汀和烟酸分别降低了一级和二级预防患者的冠心病死亡率。缓释烟酸成分采用独特技术，在保留与速释烟酸相同的脂质调节作用的同时，将不良反应（如潮红和肝毒性）降至最低。该复方产品耐受性良好，在临床试验中，因除潮红以外的不良反应而停药的患者比例与使用洛伐他汀的患者相似。约9%的患者因潮红而停用该复方产品。尚未有该产品引起局限性肌病或肝毒性的报告。每日一次给药便于服用，应能提高依从性，并使更多患者达到其低密度脂蛋白胆固醇目标。用于治疗血脂异常的烟酸产品的命名令人困惑。虽然仅存在两种类型的烟酸制剂（速释制剂和比速释制剂溶解更慢的制剂），但政府法规允许将溶解缓慢的烟酸制剂分为两种类型的烟酸产品；即非处方药（OTC）和仅凭处方可用的产品。非处方的溶解缓慢的烟酸制剂本身并不归类为非处方药，而是被视为“营养补充剂”。因此，它们属于联邦贸易委员会的管辖范围，不属于控制血脂异常产品的FDA部门（药物评价和研究中心内分泌与代谢科）的管辖范围。FDA尚未对溶解缓慢的烟酸营养补充剂在治疗血脂异常方面的安全性和有效性进行审查，它们也无需符合仿制药规则（尽管有各种品牌）。例如，这些品牌在其标签上被描述为“缓释”、“定时释放”和“长效释放”。FDA仅批准了两种吸收缓慢的烟酸产品用于治疗血脂异常；它们是Niaspan（Kos制药公司，迈阿密，佛罗里达州）和Advicor（Kos制药公司，迈阿密，佛罗里达州）。“缓释”一词已赋予这两种产品，以简化术语并将这些产品与速释烟酸区分开来。在本综述中，我们将使用“缓释”来指代FDA批准的溶解缓慢的烟酸制剂，使用“长效释放”来指代营养补充剂（未获FDA批准）。
