New Drug Reviews

Colesevelam (WelChol) for Reduction of LDL Cholesterol


Am Fam Physician. 2005 Jul 15;72(2):321-324.


Colesevelam (WelChol) is a nonabsorbed binder of bile acids in the intestine, and thereby impedes the reabsorption of this source of endogenously produced cholesterol. It can be used alone or in combination with a statin for the reduction of elevated low-density lipoprotein (LDL) cholesterol levels in patients with primary hypercholesterolemia.1

View/Print Table

NameStarting dosageDose formApproximate monthly cost*

Colesevelam (WelChol)

4 to 6 tablets daily with a statin or 6 to 7 tablets daily alone; may be divided and taken twice daily

625-mg tablet

$161 (6 tablets per day)

*—Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2004.

NameStarting dosageDose formApproximate monthly cost*

Colesevelam (WelChol)

4 to 6 tablets daily with a statin or 6 to 7 tablets daily alone; may be divided and taken twice daily

625-mg tablet

$161 (6 tablets per day)

*—Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2004.


The risk of systemic toxicity is low because colesevelam is not absorbed. Doses in excess of 4.5 g per day have not been tested. Colesevelam is pregnancy category B based on animal studies; there are no studies on the absorption of vitamins and other nutrients in pregnant women taking colesevelam. Colesevelam is contraindicated in persons with bowel obstruction and in those who have shown hypersensitivity to any of the drug’s components.1 In studies2,3 of the pharmacokinetics of colesevelam, there were no significant effects on absorption of the following concurrently administered drugs: digoxin, warfarin (Coumadin), sustained-release verapamil (Calan), metoprolol (Toprol XL), quinidine, valproic acid (Depakene), and lovastatin (Mevacor).


Side effects are infrequent and rarely result in discontinuation. In one trial,4 researchers randomized patients to receive placebo or colesevelam (2.3 g, 3.0 g, 3.8 g, or 4.5 g) daily for 24 weeks; no significant differences were found in adverse events or discontinuation rates among groups, and compliance rates were between 88 and 92 percent for all groups. In three separate trials,57 researchers examined the administration of colesevelam alone or in combination with a statin medication. The frequency of side effects did not differ among groups in any of these trials.


Colesevelam has been studied in several short-term trials, alone and in combination with statins. In two double-blind, placebo-controlled trials4,8 with 650 patients with hypercholesterolemia, colesevelam alone lowered LDL cholesterol levels in a dose-dependent manner over six to 24 weeks, with a median LDL cholesterol reduction of 20 percent at a daily dose of 4.5 g. The mean total cholesterol levels also decreased compared with placebo in a dose-dependent manner by 10 percent from baseline with 4.5 g of colesevelam daily. High-density lipoprotein (HDL) cholesterol levels increased by 3 percent over baseline. Triglyceride levels increased by approximately 9 percent over baseline in the colesevelam group, but this was statistically similar to the 5 percent rise in triglyceride levels in the placebo group.

In three double-blind studies57 lasting from four to six weeks, researchers gave patients with hypercholesterolemia colesevelam (2.3 to 3.8 g daily) alone or in combination with a statin (atorvastatin [Lipitor],5 lovastatin [Altocor],6 or simvastatin [Zocor]7) at varied doses. Reductions in LDL cholesterol levels with combination therapy (32 to 48 percent) were significantly superior to colesevelam or statins alone (7 to 16 percent and 22 to 34 percent, respectively). Combination therapy also decreased total cholesterol levels 6 to 10 percent more than statins alone, but did not impact HDL or triglyceride levels, whereas atorvastatin alone decreased triglyceride levels.5 High-dose atorvastatin (80 mg daily) lowered LDL cholesterol levels by 53 percent; a similar result was found with 10 mg of atorvastatin daily plus colesevelam.

Colesevelam has not been compared with ezetimibe (Zetia), another nonabsorbed cholesterol-lowering drug. Most important, there have been no studies examining the effect of colesevelam on patient-oriented outcomes such as mortality, myocardial infarction, or stroke risk.


A one-month supply of colesevelam at a dosage of six tablets daily will cost patients approximately $161. The monthly cost of ezetimibe is $78, atorvastatin 20 mg is $108, lovastatin 20 mg is $37–71, and ezetimibe 10 mg/simvastatin 20 mg (Vytorin) is $86.


Each solid tablet contains 625 mg of colesevelam. The recommended starting dose is four to six tablets daily with a statin or six to seven tablets daily alone. Colesevelam should be taken with a meal and a liquid. The dose may be divided and taken twice per day, though this would be much less convenient than many other lipid-lowering medications that are dosed daily.

Bottom Line

Colesevelam lowers LDL cholesterol levels a small amount (7 to 16 percent) when used alone and provides additional cholesterol lowering when added to statin therapy. It has a slightly beneficial effect on HDL cholesterol levels, has no effect on triglyceride levels, and is well tolerated. However, given the high price, more convenient treatment alternatives, and the lack of long-term studies or information regarding patient-oriented outcomes, colesevelam should be considered only in those who cannot take statins or in those who have not reached lipid profile goals despite lifestyle modification and maximum statin dosages.

The Author

LEE RADOSH, M.D., is a faculty associate in the Family Medicine Residency at the Reading Hospital and Medical Center, Reading, Pa., and is adjunct clinical professor at the Temple University School of Medicine, Philadelphia, and at Penn State College of Medicine, Hershey, Pa.


show all references

1. WelChol tablets (colesevelam hydrochloride) Sankyo. Physicians’ desk reference (electronic version). Thomson MICROMEDEX, Greenwood Village, Colo. (Edition expires March, 2005.)...

2. Donovan JM, Kisicki JC, Stiles MR, Tracewell WG, Burke SK. Effect of colesevelam on lovastatin pharmacokinetics. Ann Pharmacother. 2002;36:392–7.

3. Heller DP, Burke SK, Davidson DM, Donovan JM. Absorption of colesevelam hydrochloride in healthy volunteers. Ann Pharmacother. 2002;36:398–403.

4. Insull W Jr, Toth P, Mullican W, Hunninghake D, Burke S, Donovan JM, et al. Effectiveness of colesevelam hydrochloride in decreasing LDL cholesterol in patients with primary hypercholesterolemia: a 24-week randomized controlled trial. Mayo Clin Proc. 2001;76:971–82.

5. Hunninghake D, Insull W Jr, Toth P, Davidson D, Donovan JM, Burke SK. Coadministration of colesevelam hydrochloride with atorvastatin lowers LDL cholesterol additively. Atherosclerosis. 2001;158:407–16.

6. Davidson MH, Toth P, Weiss S, McKenny J, Hunninghake D, Isaacsohn J, et al. Low-dose combination therapy with colesevelam hydrochloride and lovastatin effectively decreases low-density lipoprotein cholesterol in patients with primary hypercholesterolemia. Clin Cardiol. 2001;24:467–74.

7. Knapp HH, Schrott H, Ma P, Knopp R, Chin B, Gaziano JM, et al. Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia. Am J Med. 2001;110:352–60.

8. Davidson MH, Dillon MA, Gordon B, Jones P, Samuels J, Weiss S, et al. Colesevelam hydrochloride (cholestagel): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects. Arch Intern Med. 1999;159:1893–900.

STEPS drug updates cover Safety, Tolerability, Effectiveness, Price, and Simplicity. Each update provides an independent review of a new medication by authors who have no financial association with the drug manufacturer.

The series coordinator is Allen F. Shaughnessy, Pharm.D., Tufts University Family Medicine Residency Program, Boston, Mass.



Copyright © 2005 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions

More in AFP

Editor's Collections

Related Content


Jan 2022

Access the latest issue of American Family Physician

Read the Issue

Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article