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.
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.
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.
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.
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.
