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Description
Curator's Comment:: 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

TargetsConditions

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

959299200000
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

959299200000
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

959299200000
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
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 Sat Jun 26 18:17:58 UTC 2021
Edited
by admin
on Sat Jun 26 18:17:58 UTC 2021
Record UNII
1XU104G55N
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
COLESEVELAM
EMA EPAR   INN   VANDF   WHO-DD  
INN  
Official Name English
COLESEVELAM [INN]
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
Common Name English
COLESEVELAM [EMA EPAR]
Common Name English
COLESEVELAM [WHO-DD]
Common Name English
COLESEVELAM [VANDF]
Common Name English
ALLYLAMINE POLYMER WITH 1-CHLORO-2,3-EPOXYPROPANE, (6-(ALLYLAMINO)HEXYL)TRIMETHYLAMMONIUM CHLORIDE AND N-ALLYLDECYLAMINE
Common Name English
Classification Tree Code System Code
NDF-RT N0000180292
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
NDF-RT N0000175365
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
NCI_THESAURUS C98148
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
WHO-VATC QC10AC04
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
LIVERTOX 235
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
WHO-ATC C10AC04
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
Code System Code Type Description
MESH
C107058
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
PRIMARY
PUBCHEM
56843207
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
PRIMARY
DRUG CENTRAL
4405
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
PRIMARY
WIKIPEDIA
COLESEVELAM
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
PRIMARY
HSDB
7925
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
PRIMARY
CAS
182815-43-6
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
PRIMARY
RXCUI
141626
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
PRIMARY RxNorm
DRUG BANK
DB00930
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
PRIMARY
NCI_THESAURUS
C78056
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
PRIMARY
INN
7621
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
PRIMARY
EVMPD
SUB01423MIG
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
PRIMARY
LACTMED
Colesevelam
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
PRIMARY
FDA UNII
1XU104G55N
Created by admin on Sat Jun 26 18:17:58 UTC 2021 , Edited by admin on Sat Jun 26 18:17:58 UTC 2021
PRIMARY
Display Structure of COLESEVELAM
Related Record Type Details
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY

Structural Modifications

Modification Type Location Site Location Type Residue Modified Extent Fragment Name Fragment Approval
AMINO_ACID_SUBSTITUTION EPICHLOROHYDRIN 08OOR508C0