【中文品名】盐酸考来维仑 【药效类别】降血脂药 【通用药名】COLESEVELAM HYDROCHLORIDE 【别　　名】Welchol 【化学名称】 1-Hexanaminium, N,N,N-trimethyl-6-(2-propenylamino)-, chloride, polymer with (chloromethyl)oxirane, 2-propen-1-amine and N-2-propenyl-1-decanamine, hydrochloride 【CA登记号】[182815-44-7] 【用　　途】本品可单独或与他汀类药物联合使用，用作原发性高胆固醇血症病人饮食和运动的辅助治疗，以降低其升高的低密度脂蛋白胆固醇〔LDL—C)水平。 美国Sankyo Pharma公司宣布Colesevelam（商品名WelChol）作为一种新的降低胆固醇的药物已在全美国投放市场，可供医师和病人选用。 WelChol不但可以单独使用降低LDL胆固醇，而且还是唯一的经FDA批准的可与他汀类药物联合使用的降脂药。对以胆固醇升高为主的高脂血症，当饮食和锻炼不能很好达到效果时， WelChol单独使用或与他汀类合用可有效的降低血浆胆固醇。 WelChol的一个优点是它与其他常用的降低胆固醇的药物不同，它不被吸收入血而散布全身。美国芝加哥临床研究中心主席Michael Davidson教授在评价这种新药时说：“对于血浆胆固醇较高而正在服用其他降脂药的病人来说，WelChol是他们的福音，因为它不被吸收的特性决定了它无全身副作用，这些副作用在其他降脂药中很常见。这使得已经服药很久的病人可以在加服WelChol的同时继续服用其他降脂药。” 此外，WelChol与其他药之间的交叉反应也很小。在药物交叉反应研究中，WelChol没有明显的影响地高辛、洛伐他汀、奎尼丁和华法令等药的吸收，而这些药却与其他降脂药之间却有显著的反应。尽管如此，病人还是应该在服用WelChol之前将他们正在服用的药物告诉他们的医生。 一项调查显示，尽管国家胆固醇教育计划（NCEP）中列出了降低胆固醇的指导方针，但仅有54％的患有高胆固醇血症的被调查者知晓他们的降脂目标。另一项称为血脂治疗评估计划（L-TAP）的研究指出，在患有高胆固醇血症的被调查者中，仅有38％接受降脂治疗的病人达到了NCEP要求的胆固醇降低的目标水平。为此，Sankyo Pharma的负责人William L. Bailey说：“L-TAP研究表明对于难以达到降脂目标水平的病人来说，的确需要在现有药物治疗之上找到更好的辅助药物。我们临床试验表明，在降低LDL-c方面WelChol是有效的和安全的。特别是当WelChol与他汀类药物（如洛伐他汀、辛伐他汀等）联合使用时，WelChol能够很好的达到降低胆固醇的作用，且这种效果是单用其中一种药物所达不到的。”美国贝勒医学院的Peter H. Jones教授指出：“WelChol与他汀类药物合用可显著改善病人的血脂水平，以达到NCEP的目标水平。此外如果病人不能耐受他汀类药物，单独使用WelChol也能有很不错的效果。 ” 【原产地英文商品名】WELCHOL POWDER 3.75g/packet 30Packets/box 【原产地英文药品名】COLESEVELAM HCL 【中文参考商品译名】WELCHOL粉剂 3.75克/袋 30袋/盒 【中文参考药品译名】盐酸考来维仑 【生产厂家中文参考译名】第一三共 【生产厂家英文名】DAIICHI SANKYO Welchol (colesevelam hydrochloride) Company: Daiichi Sankyo Approval Status: Approved January 2008 Treatment for: glycemic control in type 2 diabetes mellitus Areas: Endocrinology General Information Welchol contains colesevelam hydrochloride, a non-absorbed, polymeric, lipid-lowering and glucose-lowering agent. It works by binding bile acids, including the major bile acid in humans known as glycocholic acid. However, the exact mechanism by which Welchol improves glycemic control is unknown. Welchol is specifically indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Welchol is supplied as a 625 mg tablet designed for oral administration. The recommended initial dose of the drug is 6 tablets once daily or 3 tablets twice daily. Welchol should be taken with a meal and liquid. Clinical Results FDA Approval The FDA approval of Welchol for this indication was based on the results of three clinical trials. These double-blind, placebo-controlled add-on therapy trials enrolled a total of 1,018 subjects with baseline A1C 7.5-9.5%. The subjects received Welchol, in combination with metformin, sulfonylureas or insulin or placebo administered either as 3 tablets twice daily with lunch and dinner or as 6 tablets with dinner alone. Add-on Combination Therapy with Metformin: Welchol 3.8 g/day or placebo was added to background anti-diabetic therapy in a 26-week trial of 316 subjects already receiving treatment with metformin alone (N=159) or metformin in combination with other oral agents (N=157). The combination of Welchol plus metformin resulted in statistically significant placebo-corrected reductions in A1C with a -0.6 treatment difference (p<0.001) and FPG with a -14 treatment difference (p=0.10). The mean percent change in serum LDL-C levels with Welchol compared to placebo was -16% among statin users and statin non-users; the median percent change in serum TG levels with Welchol compared to placebo was -2% among statin users and 10% among statin non-users. The mean change in body weight was -0.5 kg for Welchol and -0.3 kg for placebo. Add-on Combination Therapy with Sulfonylurea: Welchol 3.8 g/day or placebo was added to background anti-diabetic therapy in a 26-week trial of 460 patients already treated with sulfonylurea alone (N=156) or sulfonylurea in combination with other oral agents (N=304). In combination with a sulfonylurea, Welchol resulted in statistically significant placebo corrected reductions in A1C and FPG. Welchol also reduced TC, LDL-C, Apo B, and non-HDL-C, but increased serum TG (Table 11). The mean percent change in serum LDLC levels with Welchol compared to placebo was -18% among statin users and -15% among statin non-users; the median percent increase in serum TG with Welchol compared to placebo was 29% among statin users and 9% among statin non-users. The mean change in body weight was 0.0 kg for Welchol and -0.4 kg for placebo. Add-on Combination Therapy with Insulin: Welchol 3.8 g/day or placebo was added to background anti-diabetic therapy in a 16-week trial of 287 patients already treated with insulin alone (N=116) or insulin in combination with oral agents (N=171). At baseline, the median daily insulin dose was 70 units in the Welchol group and 65 units in the placebo group. In combination with insulin, Welchol resulted in a statistically significant placebo-corrected reduction in A1C (Table 12). Welchol also reduced LDL-C and Apo B, but increased serum TG (Table 13). The mean percent change in serum LDL-C levels with Welchol compared to placebo was -13% among statin users and statin non-users; the median percent increase in serum TG levels with Welchol compared to placebo was 24% among statin users and 17% among statin non-users. The mean change in body weight was 0.6 kg for Welchol and 0.2 kg for placebo. Ongoing Study Commitments Daiichi Sankyp has agreed to study WelChol as monotherapy treatment for type 2 diabetes mellitus: Protocol Submission: by July 31, 2008 Study Start: by January 31, 2009 Final Report Submission: by July 31, 2011 Daiichi Sankyo has agreed to study WelChol in combination with thiazolidinediones as treatment for type 2 diabetes mellitus: Protocol Submission: by October 31, 2008 Study Start: by April 30, 2009 Final Report Submission: by October 31, 2011 Daiichi Sankyo has agreed to the following time lines for in Vivo Studies for an ARB, glimepiride, glipizide ER, and phenytoin: Protocol Submission: by June 30, 2008 Study Start: by September 30, 2008 Final Report Submission: by September 30, 2009 Side Effects Adverse events associated with the use of Welchol may include, but are not limited to, the following: Constipation Nasopharyngitis Dyspepsia Hypoglycemia Nausea Hypertension Mechanism of Action Colesevelam hydrochloride, the active pharmaceutical ingredient in Welchol, is a non-absorbed, lipid-lowering polymer that binds bile acids in the intestine, impeding their reabsorption. However, the exact mechanism by which Welchol improves glycemic control is unknown. Literature References Staels B, Kuipers F Bile acid sequestrants and the treatment of type 2 diabetes mellitus. Drugs 2007;67(10):1383-92 Zieve FJ, Kalin MF, Schwartz SL, Jones MR, Bailey WL Results of the glucose-lowering effect of WelChol study (GLOWS): a randomized, double-blind, placebo-controlled pilot study evaluating the effect of colesevelam hydrochloride on glycemic control in subjects with type 2 diabetes. Clinical therapeutics 2007 Jan;29(1):74-83 Zema MJ Colesevelam HCl and ezetimibe combination therapy provides effective lipid-lowering in difficult-to-treat patients with hypercholesterolemia. American Journal of Therapeutics 2005 Jul-Aug;12(4):306-10 Additional Information For additional information regarding Welchol or glycemic control, please visit the Welchol web page.