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Nonabsorbed Polymer Approved for Reducing High Cholesterol Levels

Jane L. Miller

Colesevelam hydrochloride (Welchol, GelTex), a polymer that binds bile acids in the intestine, has been cleared for marketing by FDA. Sankyo Parke Davis will market colesevelam for the treatment of primary hypercholesterolemia. The drug should be used as an adjunct to diet and exercise and can be given alone or in combination with a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor.

Colesevelam binds bile acids in the intestine, thereby reducing their reabsorption. As the bile acid pool contracts, more cholesterol is converted to bile acids. This increases the demand for cholesterol in hepatic cells and increases the activity of HMG-CoA reductase and the number of hepatic low-density-lipoprotein (LDL) receptors. More LDL cholesterol is cleared from the blood, resulting in a reduction of serum LDL cholesterol concentrations. Colesevelam is not absorbed after oral administration. In clinical trials, colesevelam reduced serum concentrations of total cholesterol, LDL cholesterol, and apolipoprotein B and raised concentrations of high-density-lipoprotein cholesterol when given alone or in combination with an HMG-CoA reductase inhibitor. In two studies, the mean reduction in LDL cholesterol with colesevelam alone was 15-18%. 

In studies of colesevelam in combination with atorvastatin, simvastatin, or lovastatin, reductions in LDL cholesterol with the combination regimen were greater than reductions achieved with the HMG-CoA reductase inhibitor alone. After four weeks, mean reductions were 38% for atorvastatin 10 mg/day, 48% for atorvastatin 10 mg plus colesevelam 3.8 g, and 53% for atorvastatin 80 mg and, in a separate study, 22% for lovastatin 10 mg/day and 34% for lovastatin 10 mg plus colesevelam 2.3 g. After six weeks of therapy, LDL cholesterol was reduced 26% by simvastatin 10 mg/day, 42% by simvastatin 10 mg plus colesevelam 3.8 g, 34% by simvastatin 20 mg, and 42% by simvastatin 20 mg plus colesevelam 2.3 g. In all three studies, changes in LDL cholesterol were negligible (0-4%) in placebo-treated patients. 

Adverse event profiles for placebo and colesevelam treatment groups were similar. 

In drug interaction studies, colesevelam did not alter the bioavailability of digoxin, lovastatin, metoprolol, quinidine, valproic acid, or warfarin. The bioavailability of extended-release verapamil was reduced, but the clinical relevance of these observations is unclear. Other drugs have not been studied. 

Colesevelam should be taken with a liquid at mealtime. If it is the sole lipid-lowering agent, ingestion of six or seven 625-mg tablets daily (approximately 3.8-4.4 g) in one dose or two divided doses is recommended. When used in combination with an HMG-CoA reductase inhibitor, ingestion of four to six tablets per day (approximately 2.5-3.8 g) in one or two doses is recommended. The two lipid-lowering agents can be taken at the same time or at different times. 

Welchol will be supplied in bottles of 180. Click here to access the package labeling (PDF).