Role of colesevelam in managing heterozygous familial hypercholesterolemia in adolescents and children

Abstract

BackgroundColesevelam hydrochloride is a synthetic, nonsystemically absorbed polymer that functions as a bile acid sequestrant for the treatment of hypercholesterolemia. Recently, colesevelam was investigated for the treatment of heterozygous familial hypercholesterolemia (HeFH) in the pediatric/adolescent population aged 10–17 years.ObjectiveThe purpose of this article is to review the disease state of HeFH in children and adolescents, review the pharmacologic mechanism of action, kinetics, and safety profile of colesevelam, analyze the results of a recent clinical trial of colesevelam in the pediatric/adolescent HeFH population, and discuss the role of colesevelam as a viable treatment option for HeFH.MethodsA literature search using Medline (1966–03 May 2010), PubMed (1950–03 May 2010), Science Direct (1994–03 May 2010), and International Pharmaceutical Abstracts (2004–2010) was performed using the search term colesevelam. English language, original research, and review articles were examined, and citations from these articles were also assessed. The manufacturer’s prescribing information and the Food and Drug Administration review of the new drug application for the powder formulation were also examined.ResultsA 32-week trial was performed investigating the efficacy of colesevelam as monotherapy or combination therapy with a stable statin regimen. Upon completion of the trial, significant benefits were found in regard to the treatment of HeFH and the lowering of low-density lipoprotein cholesterol, total cholesterol, and other secondary measures. Safety and tolerability were also examined throughout the duration of the clinical trial, with adverse drug reactions considered mild in severity.ConclusionColesevelam has been shown to reduce low-density lipoprotein cholesterol levels significantly in pediatric/adolescent patients with HeFH, while maintaining a mild side effect profile. Although further research would be beneficial for long-term effects in this population, colesevelam should be considered when developing a treatment regimen for HeFH in the pediatric/adolescent population.

Circulating bile acids concentration is predictive of coronary artery disease in human

“…The induction of an intestinal loss of BA after binding to BA sequestrants (colesevelam or cholestyramin) is a known pathway of cholesterol elimination through the gut, that can lower the concentration of LDL. 37 , 38 Decreasing the BA pool, triggers a reaction in the liver, that promotes the conversion of the intracellular cholesterol to BA synthesis: colesevelam and cholestyramine could increase the circulating concentration of cholic acid, whereas the total BA concentrations remain stable or decrease 39 , 40 . Despite encouraging studies, the ability of bile acids sequestrants to slow the progression of CAD remains uncertain 41 .…”

Young Fatal Case of Familial Hypercholesterolemia: A Case Report

“…. For more severe cases, combination therapy with a bile acid sequestrant [10], nicotinic acid, fi brates, low-density lipoprotein apheresis [8,11], or orthotopic liver transplantation [8] may be required. The workup should almost always include a cardiology evaluation to rule out early coronary artery disease.…”

An Unusual Case of Multiple Tendinous Xanthomas Involving the Extremities and the Ears

“…Treatment is focused on decreasing LDL levels through the use of statin medications, or ezetimibe, combined with dietary modification and counseling regarding the risks of alcohol, smoking, and sedentary lifestyle [ 12 ]. For more severe cases, combination therapy with a bile acid sequestrant [ 13 ], nicotinic acid, fibrates, low-density lipoprotein apheresis [ 2 , 14 ], or orthotopic liver transplantation [ 2 ] may be required. However, very large tendinous xanthomas, or those that impede joint function, will typically require surgical removal with possible skin grafting [ 15 ].…”