Colesevelam hydrochloride: a non-absorbed, polymeric cholesterol-lowering agent

Colesevelam hydrochloride (formerly known as Cholestagel((R)) and re-named WelCholtrade mark, GelTex Pharmaceuticals, Inc. and Sankyo Parke-Davis) is a new, polymeric, high potency, water-absorbing hydrogel. It has been shown to be a safe and effective cholesterol-lowering agent with a non-systemic mechanism of action, good tolerability and minimal side effects. To date, the lipid-lowering activity of colesevelam has been evaluated in approximately 1400 subjects. Colesevelam reduces low density lipoprotein (LDL)-cholesterol levels, in a dose-dependent manner, by as much as 20% (median) in patients with hypercholesterolaemia. Dosing regimen evaluations indicate that colesevelam is effective at both once per day and twice daily dosing and that concurrent administration of colesevelam with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), specifically lovastatin, does not alter the absorption of the statin. Combination therapy with HMG-CoA reductase inhibitors, including lovastatin, simvastatin and atorvastatin, produces an additional reduction (8 - 16%) in LDL-cholesterol levels above that seen with the statin alone. The overall incidence of adverse effects with colesevelam alone and in combination with statins is comparable with that seen with placebo. Colesevelam lacks the constipating effect seen with typical bile acid sequestrants, a trait that would be expected to improve compliance with lipid-lowering therapy. Colesevelam, recently approved by the US FDA, represents a valuable non-absorbed alternative in the armamentarium against hypercholesterolaemia, both for monotherapy and combination therapy, as an adjunct to diet and exercise.