英文药名: Welchol(Colesevelam Tablets)

中文药名: 考来维仑

生产厂家: Genzyme Corporation

药品简介

盐酸考来维仑是三共公司开发的一个非吸收性聚合物类降脂药物，它可与肠道中的胆酸结合并显著减少后者的再吸收。由于胆酸的耗竭会提高胆固醇转化为胆酸的平衡，故能用来降低胆固醇浓度。盐酸考来维仑的这种作用机制与考来烯胺（cholestyramine／Questran等）和考来替泊（ colestipol/Colestid）等已有药物相似，但因其对胆酸的结合亲和力更强，所以可以更低剂量使用，胃肠道副反应减少，药物相互作用潜力亦更低。
盐酸考来维仑被批准用作饮食和运动疗法的辅助疗法，单用或再并用一种他汀类药物降低原发性高血胆固醇症患者的高水平低密度脂蛋白胆固醇（LDL－C）。在临床研究中，盐酸考来维仑显现可以降低LDL－C浓度15％～18％，提高高密度脂蛋白胆固醇（HDL－C）浓度3％。受试患者的甘油三酯浓度稍有上升，然与安慰剂治疗者相比没有统计学显著差异性。盐酸考来维仑尚未与考来烯胺和考来替泊进行对照研究，但其对脂质构成作用的类型和程度似仍和此两药相似。
胆酸螫合剂、包括盐酸考来维仑对脂质浓度的作用强度均不如他汀类药物，故单用此类药物治疗高血胆固醇症患者大多会逐渐转向单用他汀类药物或再并用一种他汀类药物。在并用阿伐他汀、洛伐他汀或辛伐他汀的临床研究中，盐酸考来维仑显现可使患者的LDL－C浓度较单用他汀类药物再额外最高降低16％。这些研究发现,阿伐他汀80mg／天剂量与阿伐他汀10mg／天加盐酸考来维仑3.8g／天两方案所致患者LDL－C浓度降低值在统计学显著范围内没有差异。研究还发现，阿伐他汀和辛伐他汀即使在它们剂量低至10mg／天时亦能显著降低甘油三酯。但若并用盐酸考来维仑，则阿伐他汀的这一作用几乎完全抵消，然辛伐他汀降低甘油三酯的效应却仅受到很小影响。盐酸考来维仑并用辛找他汀似更有益。
盐酸考来维仑的最常见副反应包括肠胃气胀（12％）、便秘（11％）、消化不良（8％）、感染（l％）和头痛（6％）等，其中胃肠道副应、尤是便秘发生率明显小于考来烯胺和考来替泊、上述三个胆酸鳌合剂的胃肠道副反应都大于他汀类药物，然因它们不被吸收，故系统副反应发生率却小于他汀类药物。盐酸考来维仑禁忌用于肠梗阻患者并应谨慎给药于吞咽困难、吞烟机能障碍、严重胃肠道功能障碍或已施行主要胃肠道手术者。
考来烯胺和考来替泊会减少脂溶性维生素A、D．E、K的吸收，但盐酸考来维仑却无此不良作用。考来烯胺和考来替泊因也能与其它药物结合，故它们通常宜于使用其它药物前1小时或4小时后给药。然盐酸考来维仑却在药物相互作用研究中显现，其并不明显影响地高辛、洛伐他汀、美托洛尔（meto-prolol／LOpressor）、奎尼T、丙戌酸（valproicacid／DePakene等）或华法林的生物利用度。盐酸考来维仑似亦不会降低缓释维拉帕米（veraPamil／Calan SR）的血药峰值和生物利用度，尽管后者的个体生物利用度变化很大。
盐酸考来维仑为片剂，每片含药625mg。盐酸考来维仑的推荐初始剂量每天2次、每次3片或每天1次6片。盐酸考来维仑的最大治疗效应约出现于开始给药的2周时，其最大治疗剂量推荐为每天7片。盐酸考来维仑与他汀类药物合用时可以同服，且其推荐剂量方案不变。
圣路易斯(MD Consult)——2009年10月7日，日本第一制药三共公司宣布，美国食品药物管理局(FDA)已批准增加降胆固醇药考来维仑(Welchol)的一个新适应证。这项新批准令使得考来维仑可作为10~17岁、患杂合子家族性高胆固醇血症(heFH)男孩及月经初潮后女孩饮食和运动疗法外的辅助治疗药，以降低其升高的低密度脂蛋白胆固醇(LDL-C)水平。可在这类患者对充分的饮食疗法试验无效后单独应用考来维仑，亦可联用一种他汀类药物。
FDA同时还批准了考来维仑口服混悬液，这使得现有片剂有了替代剂型。口服混悬液可作为成人2型糖尿病患者饮食和运动疗法外的辅助治疗药以改善血糖控制，还可作为成人原发性高脂血症患者饮食和运动疗法外的辅助治疗药以降低其升高的LDL-C水平，以上两种情况均可单独应用考来维仑口服混悬液或联用羟甲基戊二酰辅酶A还原酶抑制剂(他汀类药物)。口服混悬液亦适用于10~17岁、患heFH男孩及月经初潮后女孩饮食控制和运动疗法外的辅助治疗，以降低其升高的LDL-C水平，在认为其对饮食疗法无效后应用，既可单独用药，亦可与他汀类药物联合应用。考来维仑口服混悬液的推荐剂量为1日1包(规格：3.75 g/包)。
批准考来维仑用于治疗儿科heFH患者是基于一项历时8周、多中心、随机、安慰剂对照临床研究的数据。该研究旨在评价考来维仑单药(1.875 g/d 或3.75 g/d，片剂)或与他汀类药物联用的疗效。研究所纳入的男孩及月经初潮后女孩的年龄介于10~17岁，他们先前未接受过治疗或一直接受稳定剂量的他汀类药物治疗。

WELCHOL

Generic Name for WELCHOL

Colesevelam HCl 625mg; tabs.

Legal Classification:

Rx

Pharmacological Class for WELCHOL

Bile acid sequestrant.

Manufacturer of WELCHOL

Daiichi Sankyo

Indications for WELCHOL

Adjunct to diet and exercise in type 2 diabetes in combination with metformin, sulfonylureas, or insulin.

Adult dose for WELCHOL

Take with a meal and liquid. 3 tabs twice daily or 6 tabs once daily. Susp: one 1.875g pkt twice daily or one 3.75g pkt once daily. Empty contents into a glass or cup, add 4–8oz of water, fruit juice, or diet soft drinks; stir and drink. Do not take susp in its dry form.

Children's dosing for WELCHOL

Not recommended.

Also:

Contraindications for WELCHOL

History of bowel obstruction. Serum TG>500mg/dL. History of hypertriglyceridemia-induced pancreatitis.

Warnings/Precautions for WELCHOL

Not for treating type 1 diabetes or diabetic ketoacidosis. TG levels >300mg/dL. Monitor lipids, TG, and non-HDL-C levels prior to therapy and periodically thereafter. Susceptibility to Vit. A, D, E, or K deficiencies. Risk of bowel obstruction (eg, gastroparesis, other GI motility disorders, or a history of major GI surgery). Dysphagia or swallowing disorders (esp. w/tab form). Pregnancy (Cat.B). Nursing mothers.

Interactions for WELCHOL

Monitor drugs with a narrow therapeutic index, glyburide, levothyroxine, oral contraceptives containing ethinyl estradiol and norethindrone, phenytoin, warfarin; give at least 4 hours prior to colesevelam.

Adverse Reactions for WELCHOL

Constipation, dyspepsia, nausea.

How is WELCHOL supplied?

Tabs—180; Susp 1.875g—60 (single-dose pkt); 3.75g—30 (single-dose pkt)

Welchol™ (colesevelam HCl) Receives FDA Approval to Reduce Blood Glucose inAdults with Type 2 Diabetes

First and only medication approved to reduceboth A1C and LDL cholesterol
Parsippany, NJ · January 22, 2008 /PRNewswire/ — Daiichi Sankyo, Inc., announced that the United States Food and Drug Administration (FDA) has approved Welchol™ (colesevelam HCl) to improve glycemic control (measured as hemoglobin A1C) in adults with type 2 diabetes mellitus in combination with metformin, sulfonylureas, or insulin, either alone or in combination with other anti-diabetic agents. Welchol is now the first and only medication approved to reduce both glucose levels and low density lipoprotein cholesterol levels (LDL-C). The ADA estimates that 20.8 million people in the United States have diabetes with more than 90 percent of these people having type 2 diabetes.1 Forty percent of patients with type 2 diabetes also have high LDL-cholesterol.2 Welchol is a new option that addresses both these chronic health conditions and provides physicians with a unique therapeutic approach for treating patients with type 2 diabetes.

Pivotal data presented at the American Diabetes Association's (ADA) 67 Annual Scientific Sessions in Chicago in June, 2007 demonstrated that Welchol can lower both A1C and LDL-C levels in patients with type 2 diabetes who were uncontrolled on a metformin-based regimen. Patients in the study were randomly assigned to two groups. The addition of Welchol was compared to the addition of placebo in patients on a metformin-based regimen. The addition of Welchol (n=79) to pre-existing metformin monotherapy achieved a significant mean reduction in A1C levels of 0.47 percent relative to placebo (p<0.0024). Further, the total Welchol treatment group, when treated with either metformin monotherapy or metformin-combination therapy, achieved significantly greater reductions in A1C levels compared to placebo (mean reduction of 0.54%; p<0.001). The study further demonstrated that the total Welchol treatment group achieved significantly lower LDL-C levels compared to the placebo group (mean reduction of 15.9%; p<0.001).

In addition, two other pivotal studies showed similar results in A1C reductions when Welchol was added to either sulfonylurea-based therapy or insulin-based therapy. In patients with type 2 diabetes who were inadequately controlled on sulfonylurea-based therapy the addition of Welchol was shown to have significant reductions in A1C (mean reduction of 0.54%; p<0.001) vs. placebo at week 26. In patients inadequately controlled with insulin, alone or in combination with other anti-diabetic agents, the addition of Welchol was shown to have a significant mean reduction in A1C (mean reduction of 0.50%; p<0.0001) vs. placebo.

"Welchol now offers physicians a treatment option that addresses two major cardiovascular risk factors; elevated LDL cholesterol and blood glucose in patients with type 2 diabetes," said Ronald B. Goldberg, MD, an investigator in the insulin and metformin pivotal studies and Professor of Medicine at the Division of Diabetes and Metabolism and Associate Director of the Diabetes Research Institute at the University of Miami, Miller School of Medicine in Florida. "Cardiovascular risk factors are of great concern because patients with type 2 diabetes have a significantly increased risk of developing cardiovascular disease. Once clinical cardiovascular disease develops, these patients have a poorer prognosis than normoglycemic patients."

Since 2000, Welchol, a bile acid sequestrant, has been indicated, alone or in combination with a statin, for the reduction of elevated LDL-C in patients with primary hypercholesterolemia. It is different from most other cholesterol-lowering drugs on the market because it is non-systemic, meaning that the body does not absorb it and it is eliminated without traveling to the liver or kidneys. Therefore, Welchol is not expected to have drug interactions via the cytochrome P450 pathway. Systemic medications, which include statins, fibrates and cholesterol absorption inhibitors, are those that are absorbed from the intestine into the bloodstream and travel throughout the body, specifically to the liver and/or kidneys.

Additionally, Welchol has demonstrated beneficial effects on other lipid parameters such as HDL-C and APO-B. Welchol has also been studied in combination with fenofibrate in patients with mixed dyslipidemia (Fredrickson Type IIb), and provided additional LDL-C reductions in these patients when added to a stable fenofibrate regimen. Welchol is not indicated for use in combination with fenofibrate or in the treatment of mixed dyslipidemia or lipid parameters other than LDL-C.

"We are excited by the opportunity to help more patients with chronic conditions reach their recommended health goals," said Joseph P. Pieroni, President and CEO of Daiichi Sankyo, Inc. "This approval represents an important milestone for our growing U.S. organization and underscores our continued commitment to combating cardiovascular and metabolic diseases."

People with diabetes face significantly higher risk of developing cardiovascular disease.3 The ADA recommends that patients with type 2 diabetes target an A1C level of <7%.4 A1C is a common test for persistent hyperglycemia ("too much glucose in the blood"). Additionally, the National Cholesterol Education Program (NCEP) recommends that patients with type 2 diabetes keep their cholesterol levels in check and target an LDL-C goal of <100 mg/dL.5 Despite this recommendation, nearly 40 percent of patients with type 2 diabetes have LDL cholesterol levels greater than 130 mg/dL.6

It is estimated that half of all Americans have elevated blood cholesterol levels that can negatively impact their health and quality of life.7 According to the National Healthcare Quality Report, nearly 40 percent of adults with high cholesterol also have type 2 diabetes.8

IMPORTANT INFORMATION ABOUT WELCHOL
Welchol is indicated as an adjunct to diet and exercise to reduce elevated low-density lipoprotein cholesterol (LDL-C) in patients with primary hyperlipidemia (Fredrickson Type IIa) as monotherapy or in combination with an hydroxymethyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor. Welchol is also indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Welchol should not be used for the treatment of type 1 diabetes or for the treatment of diabetic ketoacidosis. It has not been studied in type 2 diabetes as monotherapy or in combination with a dipeptidyl peptidase 4 inhibitor and has not been extensively studied in combination with thiazolidinediones. Welchol has not been studied in Fredrickson Type I, III, IV, and V dyslipidemias. Welchol is contraindicated in individuals with bowel obstruction, those with serum triglyceride (TG) concentrations of >500 mg/dL, or with a history of hypertriglyceridemia-induced pancreatitis.

The effect of Welchol on cardiovascular morbidity and mortality has not been determined.

Welchol can increase serum TG concentrations particularly when used in combination with sulfonylureas or insulin. Caution should be exercised when treating patients with TG levels >300 mg/dL.

Welchol may decrease the absorption of fat-soluble vitamins A, D, E, and K. Patients on vitamin supplements should take their vitamins at least 4 hours prior to Welchol. Caution should be exercised when treating patients with a susceptibility to vitamin K or fat soluble vitamin deficiencies.

Caution should also be exercised when treating patients with gastroparesis, gastrointestinal motility disorders, major gastrointestinal tract surgery, and when treating patients with dysphagia and swallowing disorders.

Welchol reduces gastrointestinal absorption of some drugs. Drugs with a known interaction with colesevelam (glyburide,levothyroxine, and oral contraceptives [ethinyl estradiol, norethindrone]) should be administered at least 4 hours prior to Welchol. Drugs that have not been tested for interaction with colesevelam, especially those with a narrow therapeutic index, should also be administered at least 4 hours prior to Welchol. Alternatively, the physician should monitor drug levels of the co-administered drug.

Primary Hyperlipidemia: In clinical trials, the adverse reactions observed in ≥2% of patients — and more commonly with Welchol than placebo — regardless of investigator assessment of causality were constipation (11.0% vs. 7.0%), dyspepsia (8.3% vs. 3.5%), nausea (4.2% vs. 3.9%), accidental injury (3.7% vs. 2.7%), asthenia (3.6% vs. 1.9%), pharyngitis (3.2% vs. 1.9%), flu syndrome (3.2% vs. 3.1%), rhinitis (3.2% vs. 3.1%) and myalgia (2.1% vs. 0.4%).

Type 2 Diabetes: In clinical trials, the adverse reactions observed in ≥2% of patients — and more commonly with Welchol than placebo — regardless of investigator assessment of causality were constipation (8.7% vs. 2.0%), nasopharyngitis (4.1% vs. 3.6%) dyspepsia (3.9% vs. 1.4%), hypoglycemia (3.0% vs. 2.3%), nausea (3.0% vs. 1.4%) and hypertension (2.8% vs. 1.6%).

Post-marketing experience: Due to the voluntary nature of these reports it is not possible to reliably estimate frequency or establish a causal relationship. Increased seizure activity or decreased phenytoin levels have been reported in patients receiving phenytoin concomitantly with Welchol. Reduced International Normalized Ratio (INR) has been reported in patients receiving warfarin concomitantly with Welchol.

Welchol is Pregnancy Category B.

For more information on Welchol, call 877-4-DSPROD (877-431-7763), or go to the Welchol web site at www.Welchol.com.

About Daiichi Sankyo, Inc.
Daiichi Sankyo, Inc., headquartered in Parsippany, New Jersey, is the U.S. subsidiary of Daiichi Sankyo Co., Ltd., Japan's second largest pharmaceutical company and a global leader in pharmaceutical innovation since 1899. The company is dedicated to the discovery, development and commercialization of innovative medicines that improve the lives of patients throughout the world.

The primary focus of Daiichi Sankyo's research and development is cardiovascular disease, including therapies for dyslipidemia, hypertension, diabetes, and acute coronary syndrome. The company is also pursuing the discovery of new medicines in the areas of glucose metabolic disorders, infectious diseases, cancer, bone and joint diseases, and immune disorders. For more information, please visit www.dsus.com.

Please see package insert for full prescribing information.

注：以下产品不同规格和不同价格，购买时请以电话咨询为准！
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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
原产地英文化合物名称:
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
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

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原产地英文商品名:
WELCHOL TABLET 625mg/tab 180tabs/bottle
原产地英文药品名:
COLESEVELAM HCL
原产地英文化合物名称:
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
中文参考商品译名:
WELCHOL片剂 625毫克/片 180片/瓶
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