DescriptionCurator's Comment: description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT00754039 | https://www.ncbi.nlm.nih.gov/pubmed/9145384 | https://www.ncbi.nlm.nih.gov/pubmed/19783712
Curator's Comment: description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT00754039 | https://www.ncbi.nlm.nih.gov/pubmed/9145384 | https://www.ncbi.nlm.nih.gov/pubmed/19783712
Colesevelam (trade name Welchol) a non-absorbed, polymeric, lipid-lowering agent intended for oral administration. Colesevelam is poly(allylamine hydrochloride) cross-linked with epichlorohydrin and alkylated with 1-bromodecane and (6-bromohexyl)-trimethylammonium bromide. Colesevelam hydrochloride is a hydrophilic, water-insoluble polymer that is not hydrolyzed by digestive enzymes and is not absorbed. Colesevelam is part of a class of drugs known as bile acid sequestrants. Colesevelam hydrochloride, the active pharmaceutical ingredient in Welchol, is a non-absorbed, lipid-lowering polymer that binds bile acids in the intestine, impeding their reabsorption. As the bile acid pool becomes depleted, the hepatic enzyme, cholesterol 7-α-hydroxylase, is upregulated, which increases the conversion of cholesterol to bile acids. This causes an increased demand for cholesterol in the liver cells, resulting in the dual effect of increasing transcription and activity of the cholesterol biosynthetic enzyme, HMG-CoA reductase, and increasing the number of hepatic LDL receptors. These compensatory effects result in increased clearance of LDL-C from the blood, resulting in decreased serum LDL-C levels. Colesevelam is indicated as an adjunct to diet and exercise to reduce elevated low-density lipoprotein cholesterol (LDL-C) in patients with primary hyperlipidemia as monotherapy and to improve glycemic control in adults with type 2 diabetes mellitus, including in combination with a statin. The expanded use of colesevelam in adults with type 2 diabetes mellitus is an example of drug repositioning.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: bile acid reabsorption |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | WELCHOL Approved UseWELCHOL is a bile acid sequestrant indicated as an adjunct to diet and exercise to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia as monotherapy or in combination with a hydroxymethyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor (statin) (1.1). reduce LDL-C levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia as monotherapy or in combination with a statin after failing an adequate trial of diet therapy. improve glycemic control in adults with type 2 diabetes mellitus (1.2). Important Limitations of Use (1.3): Do not use for glycemic control in type 1 diabetes or for treating diabetic ketoacidosis. WELCHOL has not been studied in type 2 diabetes in combination with a dipeptidyl peptidase 4 inhibitor. WELCHOL has not been studied in Fredrickson Type I, III, IV, and V dyslipidemias. WELCHOL has not been studied in children younger than 10 years of age or in pre-menarchal girls. 1.1 Primary Hyperlipidemia WELCHOL is indicated as an adjunct to diet and exercise to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia (Fredrickson Type IIa) as monotherapy or in combination with a hydroxymethyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor (statin). WELCHOL is indicated as monotherapy or in combination with a statin to reduce LDL-C levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: a. LDL-C remains ≥ 190 mg/dL or b. LDL-C remains ≥ 160 mg/dL and there is a positive family history of premature cardiovascular disease or two or more other CVD risk factors are present in the pediatric patient. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and non-pharmacological interventions alone has been inadequate [See Clinical Studies (14.1) Launch Date2000 |
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Primary | WELCHOL Approved UseWELCHOL is a bile acid sequestrant indicated as an adjunct to diet and exercise to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia as monotherapy or in combination with a hydroxymethyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor (statin) (1.1). reduce LDL-C levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia as monotherapy or in combination with a statin after failing an adequate trial of diet therapy. improve glycemic control in adults with type 2 diabetes mellitus (1.2). Important Limitations of Use (1.3): Do not use for glycemic control in type 1 diabetes or for treating diabetic ketoacidosis. WELCHOL has not been studied in type 2 diabetes in combination with a dipeptidyl peptidase 4 inhibitor. WELCHOL has not been studied in Fredrickson Type I, III, IV, and V dyslipidemias. WELCHOL has not been studied in children younger than 10 years of age or in pre-menarchal girls. 1.1 Primary Hyperlipidemia WELCHOL is indicated as an adjunct to diet and exercise to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia (Fredrickson Type IIa) as monotherapy or in combination with a hydroxymethyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor (statin). WELCHOL is indicated as monotherapy or in combination with a statin to reduce LDL-C levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: a. LDL-C remains ≥ 190 mg/dL or b. LDL-C remains ≥ 160 mg/dL and there is a positive family history of premature cardiovascular disease or two or more other CVD risk factors are present in the pediatric patient. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and non-pharmacological interventions alone has been inadequate [See Clinical Studies (14.1) Launch Date2000 |
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Primary | WELCHOL Approved UseWELCHOL is a bile acid sequestrant indicated as an adjunct to diet and exercise to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia as monotherapy or in combination with a hydroxymethyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor (statin) (1.1). reduce LDL-C levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia as monotherapy or in combination with a statin after failing an adequate trial of diet therapy. improve glycemic control in adults with type 2 diabetes mellitus (1.2). Important Limitations of Use (1.3): Do not use for glycemic control in type 1 diabetes or for treating diabetic ketoacidosis. WELCHOL has not been studied in type 2 diabetes in combination with a dipeptidyl peptidase 4 inhibitor. WELCHOL has not been studied in Fredrickson Type I, III, IV, and V dyslipidemias. WELCHOL has not been studied in children younger than 10 years of age or in pre-menarchal girls. 1.1 Primary Hyperlipidemia WELCHOL is indicated as an adjunct to diet and exercise to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia (Fredrickson Type IIa) as monotherapy or in combination with a hydroxymethyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor (statin). WELCHOL is indicated as monotherapy or in combination with a statin to reduce LDL-C levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: a. LDL-C remains ≥ 190 mg/dL or b. LDL-C remains ≥ 160 mg/dL and there is a positive family history of premature cardiovascular disease or two or more other CVD risk factors are present in the pediatric patient. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and non-pharmacological interventions alone has been inadequate [See Clinical Studies (14.1) Launch Date2000 |
PubMed
Title | Date | PubMed |
---|---|---|
Colesevelam hydrochloride in clinical practice: a new approach in the treatment of hypercholesterolaemia. | 2008 Apr |
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Colesevelam HCl improves glycemic control and reduces LDL cholesterol in patients with inadequately controlled type 2 diabetes on sulfonylurea-based therapy. | 2008 Aug |
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Xanthomas associated with homozygous familial hypercholesterolemia. | 2009 Dec |
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A 50-week extension study on the safety and efficacy of colesevelam in adults with primary hypercholesterolemia. | 2010 |
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Treatment with high-dose simvastatin inhibits geranylgeranylation in AML blast cells in a subset of AML patients. | 2012 Mar |
Patents
Sample Use Guides
WELCHOL Tablets: The recommended dose is 6 tablets once
daily or 3 tablets twice daily. WELCHOL Tablets should be taken
with a meal and liquid
WELCHOL for Oral Suspension: The recommended dose is one
3.75 gram packet once daily or one 1.875 gram packet twice daily.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19783712
A clinically relevant dose level of each study drug was incubated for 1 hour with and without colesevelam (or choletyramine for the subset of 4 drugs) in the 3 dissolution test media. Dissolution baths (900 mL) were used to consistently maintain the pH, temperature (37C), and stirring speed (200 rpm). After the 1-hour incubation, preparations were filtered to remove resin and any bound drug. The amount of drug remaining in the filtrate was primarily quantified using UV-visible spectrophotometry.
Substance Class |
Polymer
Created
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admin
on
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on
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Record UNII |
P4SG24WI5Q
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Record Status |
Validated (UNII)
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C98148
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PRIMARY | Merck Index |
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |
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Structural Modifications
Modification Type | Location Site | Location Type | Residue Modified | Extent | Fragment Name | Fragment Approval |
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CROSSLINKER | EPICHLOROHYDRIN | 08OOR508C0 | ||||
MOIETY | Hydrochloric acid | QTT17582CB |