Colesevelam

Description

Colesevelam hydrochloride was launched as Welchol (formerly known as Cholestagel) in the US for the reduction of elevated levels of serum LDL cholesterol and accordingly, the decrease of the risk of vascular disease in patients with primary hypercholesterolemia. This orally administered cationic hydrogel is a non-absorbable, water-insoluble polymer of an hexanaminium chloride with N-(2-propenyl) decanamine, 2-propen-1-amine hydrochloride and chloromethyloxirane. It acts as a powerful bile acid sequestering agent, this binding and blockage of bile acids having the end result of compelling the removal of LDL cholesterol from the blood stream into the liver. In animals fed with a cholesterol-rich diet for several weeks, colesevelam demonstrated a good maintenance of low serum cholesterol levels, this activity being significantly greater when compared with cholestyramine. In several placebo-controlled studies, this agent decreased total cholesterol levels by 6 to 10% and LDL cholesterol levels by 9 to 20%. Combination therapy with the co-administration of a HMG-CoA reductase inhibitor (or statin) and colesevelam produced an additional reduction of 8-16% in LDL-cholesterol levels above that obtained with the statin alone. Due to its unique water-absorbing hydrogel formulation, this polymer is not absorbed at all from the GI tract, and thus, it is said to have a lower rate of side-effects (as the constipating effect) than the previously marketed bile acid sequestrants. Colesevelam hydrochloride may be used as a monotherapy or as a dual therapy with statins.

Originator

GelTex (US)

Uses

antibacterial

Uses

Colesevelam Hydrochloride is used to reduce elevated low-density lipoprotein (LDL) cholesterol in patients with primary hyperlipidemia as well as to improve glycemic control in patients with type 2 diabetes.

Definition

ChEBI: The hydrochloride of colesevelam. It is used as an orally administered bile acid sequestrant to reduce the amount of cholesterol and certain fatty substances in the blood.

brand name

Welchol (Sankyo).

General Description

Colesevelam (Welchol) is one of themore recent additions to the class of bile acid-sequesteringagents. Its structure is rather novel, and at first glance, it appearsto look like the previous examples of cholestyramineand colestipol. It does not possess the chloride ions, however,and, strictly speaking, is not an anion-exchange resin.This compound has good selectivity for both the trihydroxyand dihydroxy bile acids. The selectivity for these hydroxylatedderivatives lends some insight into the reduced side effectscolesevelam possesses, compared with cholestyramineand colestipol. Unlike the older agents, colesevelam doesnot have a high incidence of causing constipation. This resultsfrom the compound’s ability to “pick up” water as a resultof its affinity for hydroxyl system (i.e., hydrogen bondingwith either the bile acid or water). In turn, this yieldssofter, gel-like materials that are easier to excrete.

Drug interactions

Potentially hazardous interactions with other drugs
Antidiabetic agents: absorption of glipizide, glibenclamide and glimepiride reduced, administer at least 4 hours before colesevelam; metformin extended release exposure increased, monitor carefully.
Ciclosporin: may reduce absorption of ciclosporin.
Olmesartan: absorption of olmesartan reduced, administer at least 4 hours before colesevelam.

Metabolism

Not absorbed.