Identification

Name
Colesevelam
Accession Number
DB00930  (APRD00883)
Type
Small Molecule
Groups
Approved
Description

Colesevelam is a bile acid sequestrant. Colesevelam is used with exercise and diet changes (restriction of cholesterol and fat intake) to reduce the amount of cholesterol and certain fatty substances in the blood. It works by binding bile acids in the intestine. Bile acids are made when cholesterol is broken down in the body. Removing these bile acids helps to lower blood cholesterol.

Synonyms
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Colesevelam hydrochlorideP4SG24WI5Q182815-44-7VTAKZNRDSPNOAU-UHFFFAOYSA-M
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CholestagelTablet, film coated625 mgOralGenzyme Europe Bv2004-03-10Not applicableEu
CholestagelTablet, film coated625 mgOralGenzyme Europe Bv2004-03-10Not applicableEu
CholestagelTablet, film coated625 mgOralGenzyme Europe Bv2004-03-10Not applicableEu
CholestagelTablet, film coated625 mgOralGenzyme Europe Bv2004-03-10Not applicableEu
Colesevelam hydrochlorideTablet, film coated625 mg/1OralOhm Laboratories, Inc.2018-05-23Not applicableUs
Colesevelam hydrochloridePowder, for suspension3.75 g/1OralOhm Laboratories, Inc.2018-07-17Not applicableUs
LodalisPowder, for suspension3.75 gOralValeant Canada Lp Valeant Canada S.E.C.2015-04-02Not applicableCanada
LodalisTablet625 mgOralValeant Canada Lp Valeant Canada S.E.C.2012-02-06Not applicableCanada
WelcholTablet, film coated625 mg/1OralDaiichi Sankyo, Inc.2000-09-01Not applicableUs
WelcholTablet, film coated625 mg/1OralCarilion Materials Management2000-09-01Not applicableUs65597 0701 18 nlmimage10 ad1dd6fe
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Colesevelam HCLTablet, film coated625 mg/1OralAscend Laboratories, LLC2018-10-06Not applicableUs
Colesevelam HydrochlorideTablet, coated625 mg/1OralAmerincan Health Packaging2018-07-15Not applicableUs
Colesevelam HydrochlorideTablet, coated625 mg/1OralImpax Generics2018-05-17Not applicableUs
Colesevelam HydrochloridePowder, for suspension3.75 g/1OralGlenmark Pharmaceuticals Inc.,Usa2018-07-17Not applicableUs
Colesevelam HydrochlorideTablet, coated625 mg/1OralAv Kare, Inc.2018-06-18Not applicableUs
Colesevelam HydrochlorideTablet625 mg/1OralDr.Reddys Laboratories Inc2018-10-05Not applicableUs
Colesevelam HydrochloridePowder, for suspension1.875 g/1OralGlenmark Pharmaceuticals Inc.,Usa2018-07-17Not applicableUs
Colesevelam HydrochlorideTablet, film coated625 mg/1OralGlenmark Pharmaceuticals Inc.,Usa2018-05-18Not applicableUs
International/Other Brands
CholestaGel (Genzyme)
Categories
UNII
1XU104G55N
CAS number
182815-43-6
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

For use, alone or in combination with an HMG-CoA reductase inhibitor, as adjunctive therapy to diet and exercise for the reduction of elevated LDL cholesterol in patients with primary hypercholesterolemia (Fredrickson Type IIa).

Associated Conditions
Pharmacodynamics

Colesevelam is a high capacity bile-acid binding molecule. Colesevelam binds to bile acids in the intestine which reduces the amount of bile acids that are returned to the liver via enterohepatic circulation. Clinical studies have demonstrated that elevated levels of total cholesterol (total-C), LDL-C, and apolipoprotein B (Apo B, a protein associated with LDL-C) are associated with an increased risk of atherosclerosis in humans. Similarly, decreased levels of high-density lipoprotein cholesterol (HDL-C) are associated with the development of atherosclerosis. Epidemiological investigations have established that cardiovascular morbidity and mortality vary directly with the levels of total-C and LDL-C, and inversely with the level of HDL-C. The combination of colesevelam and an HMG-CoA reductase inhibitor is effective in further lowering serum total-C and LDL-C levels beyond that achieved by either agent alone.

Mechanism of action

Colesevelam 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-(alpha)-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, hydroxymethyl-glutaryl-coenzyme A (HMG-CoA) reductase, and increasing the number of hepatic low-density lipoprotein (LDL) receptors. These compensatory effects result in increased clearance of LDL cholesterol (LDL-C) from the blood, resulting in decreased serum LDL-C levels. Serum triglyceride levels may increase or remain unchanged. The end result is increased clearance of LDL-cholesterol from the blood with decreased serum LDL-cholesterol.

TargetActionsOrganism
ABile acids
binder
Human
Absorption

Not hydrolyzed by digestive enzymes and is not absorbed.

Volume of distribution
Not Available
Protein binding

Not applicable (not hydrolyzed by digestive enzymes and not absorbed).

Metabolism

Not applicable (not hydrolyzed by digestive enzymes and not absorbed).

Route of elimination

Excretion: In 16 healthy volunteers, an average of 0.05% of administered radioactivity from a single 14C-labeled colesevelam hydrochloride dose was excreted in the urine.

Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms of overdose may include eye irritation, constipation, abdominal cramps, nausea, vomiting, diarrhea, and hypersensitivity. However, as colesevelam is not absorbed, the risk of systemic toxicity is low. Doses in excess of 4.5 g per day have not been tested.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinColesevelam can cause a decrease in the absorption of (R)-warfarin resulting in a reduced serum concentration and potentially a decrease in efficacy.
(S)-WarfarinColesevelam can cause a decrease in the absorption of (S)-Warfarin resulting in a reduced serum concentration and potentially a decrease in efficacy.
1alpha-Hydroxyvitamin D5The serum concentration of 1alpha-Hydroxyvitamin D5 can be decreased when it is combined with Colesevelam.
3,5-diiodothyropropionic acidColesevelam can cause a decrease in the absorption of 3,5-diiodothyropropionic acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
4-hydroxycoumarinColesevelam can cause a decrease in the absorption of 4-hydroxycoumarin resulting in a reduced serum concentration and potentially a decrease in efficacy.
AbaloparatideColesevelam can cause a decrease in the absorption of Abaloparatide resulting in a reduced serum concentration and potentially a decrease in efficacy.
AceclofenacColesevelam can cause a decrease in the absorption of Aceclofenac resulting in a reduced serum concentration and potentially a decrease in efficacy.
AcemetacinColesevelam can cause a decrease in the absorption of Acemetacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
AcenocoumarolColesevelam can cause a decrease in the absorption of Acenocoumarol resulting in a reduced serum concentration and potentially a decrease in efficacy.
AcetyldigitoxinColesevelam can cause a decrease in the absorption of Acetyldigitoxin resulting in a reduced serum concentration and potentially a decrease in efficacy.
Food Interactions
  • Drink liberally.
  • Take with a meal.

References

General References
Not Available
External Links
PubChem Substance
46505437
PharmGKB
PA449095
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Colesevelam
ATC Codes
C10AC04 — Colesevelam
AHFS Codes
  • 24:06.04 — Bile Acid Sequestrants
FDA label
Download (130 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
2CompletedTreatmentIrritable Bowel Syndrome (IBS) / Severe or persistent diarrhea1
2CompletedTreatmentType 2 Diabetes Mellitus2
2RecruitingOtherBile Acid Malabsorption / Chronic Functional Diarrhea / Diarrhoea Predominant Irritable Bowel Syndrome1
2RecruitingSupportive CareMultiple Myeloma (MM)1
2Unknown StatusTreatmentNonalcoholic Steatohepatitis1
2, 3CompletedTreatmentChronic Liver Diseases (CLD)1
2, 3CompletedTreatmentType 2 Diabetes Mellitus1
3CompletedTreatmentHigh Cholesterol / Pre-Diabetic / Type 2 Diabetes Mellitus1
3CompletedTreatmentHyperlipidemias / Type 2 Diabetes Mellitus1
3CompletedTreatmentImpaired Fasting Glucose (IFG) / Pre-Diabetic1
3CompletedTreatmentType 2 Diabetes Mellitus6
3RecruitingTreatmentBile Acid Malabsorption / Incontinence, Fecal1
4Active Not RecruitingOtherAtherosclerosis / Carotid Artery Diseases / Coronary Artery Disease1
4CompletedBasic ScienceType 2 Diabetes Mellitus2
4CompletedPreventionDyslipidemias / Hyperglycemias / Hyperlipidemias1
4CompletedTreatmentDiarrhoea Predominant Irritable Bowel Syndrome1
4CompletedTreatmentDyslipidemia (Fredrickson Type Ⅱa)1
4CompletedTreatmentDyslipidemias / Hyperlipidemias1
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentHigh Cholesterol3
4CompletedTreatmentHigh Cholesterol / Hyperlipidemia, Familial Combined1
4RecruitingBasic ScienceBileacid Malabsorption1
4RecruitingTreatmentObesity, Severe2
4RecruitingTreatmentType 2 Diabetes Mellitus2
4TerminatedTreatmentBile Acid Malabsorption / Crohns Disease1
Not AvailableCompletedNot AvailableImpaired Glucose Tolerance (IGT) / Type 2 Diabetes Mellitus1
Not AvailableCompletedBasic ScienceBMI >30 kg/m2 / Type 2 Diabetes Mellitus1
Not AvailableCompletedBasic ScienceDiabetes Mellitus (DM)1
Not AvailableCompletedBasic ScienceTo Assess the Impact of Bile Acids on Human Glukagon-like-peptide-1 Secretion1
Not AvailableCompletedTreatmentDiabetes, Diabetes Mellitus Type 1 / Hyperlipidemias1
Not AvailableCompletedTreatmentType 2 Diabetes Mellitus1
Not AvailableNot Yet RecruitingBasic ScienceHomozygous Sitosterolemia1

Pharmacoeconomics

Manufacturers
  • Daiichi sankyo inc
Packagers
  • Daiichi Sankyo
  • Patheon Inc.
  • Physicians Total Care Inc.
  • Quality Care
  • Resource Optimization and Innovation LLC
  • Southwood Pharmaceuticals
Dosage forms
FormRouteStrength
Tablet, film coatedOral625 mg
Powder, for suspensionOral1.875 g/1
Powder, for suspensionOral3.75 g/1
TabletOral625 mg/1
Tablet, coatedOral625 mg/1
Powder, for suspensionOral3.75 g
TabletOral625 mg
For suspensionOral1.875 g/1
For suspensionOral3.75 g/1
Tablet, film coatedOral625 mg/1
Prices
Unit descriptionCostUnit
Welchol 625 mg tablet1.96USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5679717No1994-04-292014-04-29Us
US7229613Yes2002-10-172022-10-17Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsolubleNot Available
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

1. Bile acids
Kind
Group
Organism
Human
Pharmacological action
Yes
Actions
Binder
References
  1. Levy P, Jellinger PS: The potential role of colesevelam in the management of prediabetes and type 2 diabetes mellitus. Postgrad Med. 2010 May;122(3Suppl):1-8. doi: 10.3810/pgm.2010.05.2168. [PubMed:20581432]
  2. Staels B: A review of bile acid sequestrants: potential mechanism(s) for glucose-lowering effects in type 2 diabetes mellitus. Postgrad Med. 2009 May;121(3 Suppl 1):25-30. doi: 10.3810/pgm.2009.05.suppl53.290. [PubMed:19494475]
  3. Corsini A, Windler E, Farnier M: Colesevelam hydrochloride: usefulness of a specifically engineered bile acid sequestrant for lowering LDL-cholesterol. Eur J Cardiovasc Prev Rehabil. 2009 Feb;16(1):1-9. doi: 10.1097/HJR.0b013e32831215db. [PubMed:19237992]
  4. Steinmetz KL, Schonder KS: Colesevelam: potential uses for the newest bile resin. Cardiovasc Drug Rev. 2005 Spring;23(1):15-30. [PubMed:15867945]
  5. Melian EB, Plosker GL: Colesevelam. Am J Cardiovasc Drugs. 2001;1(2):141-6; discussion 147-8. [PubMed:14728043]

Drug created on June 13, 2005 07:24 / Updated on November 12, 2018 07:24