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Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
WELCHOL

Approved Use

WELCHOL 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 Date

9.5929919E11
Primary
WELCHOL

Approved Use

WELCHOL 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 Date

9.5929919E11
Primary
WELCHOL

Approved Use

WELCHOL 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 Date

9.5929919E11
PubMed

PubMed

TitleDatePubMed
Coadministration of colesevelam hydrochloride with atorvastatin lowers LDL cholesterol additively.
2001 Oct
Effects of colesevelam hydrochloride on low-density lipoprotein cholesterol and high-sensitivity C-reactive protein when added to statins in patients with hypercholesterolemia.
2006 Apr 15
Lipid-lowering effects of colesevelam HCl in combination with ezetimibe.
2006 Nov
Colesevelam hydrochloride in clinical practice: a new approach in the treatment of hypercholesterolaemia.
2008 Apr
Colesevelam HCl improves glycemic control and reduces LDL cholesterol in patients with inadequately controlled type 2 diabetes on sulfonylurea-based therapy.
2008 Aug
Modulating LDL cholesterol and glucose in patients with type 2 diabetes mellitus: targeting the bile acid pathway.
2008 Sep
Xanthomas associated with homozygous familial hypercholesterolemia.
2009 Dec
A 50-week extension study on the safety and efficacy of colesevelam in adults with primary hypercholesterolemia.
2010
Treatment with high-dose simvastatin inhibits geranylgeranylation in AML blast cells in a subset of AML patients.
2012 Mar
Patents

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
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 (37C), 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
by admin
on Thu Jul 06 15:10:52 UTC 2023
Edited
by admin
on Thu Jul 06 15:10:52 UTC 2023
Record UNII
P4SG24WI5Q
Record Status Validated (UNII)
Record Version
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Name Type Language
COLESEVELAM HYDROCHLORIDE
MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN  
Official Name English
COLESEVELAM HYDROCHLORIDE [VANDF]
Common Name English
CHOLESTAGEL
Brand Name English
Allylamine polymer with 1-chloro-2,3-epoxypropane, [6-(allylamino)hexyl]trimethylammonium chloride and N-allyldecylamine, hydrochloride
Common Name English
COLESEVELAM HYDROCHLORIDE [USAN]
Common Name English
NSC-760126
Code English
COLESEVELAM HCL
Common Name English
COLESEVELAM HYDROCHLORIDE [MART.]
Common Name English
COLESEVELAM HYDROCHLORIDE [MI]
Common Name English
2-PROPEN-1-AMINE POLYMER WITH (CHLOROMETHYL)OXIRANE, N,N,N-TRIMETHYL-6-(2-PROPENYLAMINO)-1-HEXANAMINIUM CHLORIDE, AND N-2-PROPENYL-1-DECANAMINE, HYDROCHLORIDE
Common Name English
COLESEVELAM HYDROCHLORIDE [ORANGE BOOK]
Common Name English
Colesevelam hydrochloride [WHO-DD]
Common Name English
WELCHOL
Brand Name English
GT-31-104HB
Code English
GT31-104HB
Code English
IW-3718
Code English
Classification Tree Code System Code
NCI_THESAURUS C98148
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
Code System Code Type Description
DRUG BANK
DBSALT000790
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
PRIMARY
NCI_THESAURUS
C28937
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
PRIMARY
CAS
182815-44-7
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
PRIMARY
SMS_ID
100000090574
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
PRIMARY
RXCUI
141625
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
PRIMARY RxNorm
NSC
760126
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
PRIMARY
CHEBI
59599
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
PRIMARY
EPA CompTox
DTXSID50921256
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
PRIMARY
USAN
II-11
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
PRIMARY
ChEMBL
CHEMBL1201473
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
PRIMARY
EVMPD
SUB01424MIG
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
PRIMARY
DAILYMED
P4SG24WI5Q
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
PRIMARY
FDA UNII
P4SG24WI5Q
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
PRIMARY
MERCK INDEX
M3727
Created by admin on Thu Jul 06 15:10:52 UTC 2023 , Edited by admin on Thu Jul 06 15:10:52 UTC 2023
PRIMARY Merck Index
Display Structure of COLESEVELAM HYDROCHLORIDE
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY

Structural Modifications

Modification Type Location Site Location Type Residue Modified Extent Fragment Name Fragment Approval
CROSSLINKER EPICHLOROHYDRIN 08OOR508C0
MOIETY Hydrochloric acid QTT17582CB