Colestipol

Identification

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Name
Colestipol
Accession Number
DB00375  (APRD00884)
Type
Small Molecule
Groups
Approved
Description

Bile acid sequestrants like colestipol have been in use since the 1970s.Label,4,6,3 And even though such an agent may very well be useful in reducing elevated cholesterol levels and decreasing the risk for atherosclerotic vascular disease due to hypercholesterolemia, colestipol is still generally only employed as an adjunct therapy and the relatively physical nature of its pharmacological activity sometimes limits its usefulness.Label,4,6,3

In particular, as colestipol's general mechanism of action ultimately results in the decreased absorption and enhanced secretion of bile acids and lipids in the feces, patients who take complicated medication regimens, experience constipation or biliary obstruction, etc. may not be good candidates for using the agent owing to its physical effects on the gut.Label,4,6,3

Alternatively, colestipol predominantly elicits its activities within the gut environment because it undergoes little absorption and metabolism.Label,4,6,3 The resultant lack of systemic exposure consequently means the medication generally demonstrates very few adverse effects inside the body.Label,4,6,3

Synonyms
  • Colestipol
  • Colestipolum
  • Copolymer of bis(2-aminoethyl)amine and 2-(chloromethyl)oxirane
  • Epichlorohydrin-tetraethylenepentamine polymer
External IDs
U 26597 A
Product Ingredients
IngredientUNIICASInChI Key
Colestipol hydrochlorideX7D10K905G37296-80-3Not applicable
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ColestidGranule, for suspension5 g/5gOralPhysicians Total Care, Inc.1977-04-042010-06-30Us
ColestidTablet1 g/1OralPharmacia and Upjohn Company LLC1994-07-19Not applicableUs
ColestidGranule, for suspension5 g/5gOralPharmacia and Upjohn Company LLC1977-04-04Not applicableUs
Colestid GranulesGranule5 gOralPfizer1985-12-31Not applicableCanada
Colestid Orange GranulesGranule5 gOralPfizer1995-12-31Not applicableCanada
Colestid Tablets 1 GTablet1 gOralPfizer1995-12-31Not applicableCanada
Flavored ColestidGranule, for suspension5 g/7.5gOralPhysicians Total Care, Inc.1977-04-042011-06-30Us
Flavored ColestidGranule, for suspension5 g/7.5gOralPharmacia and Upjohn Company LLC1977-04-04Not applicableUs
Additional Data Available
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  • Product Code
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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Colestipol HydrochlorideTablet1 g/1OralPhysicians Total Care, Inc.2007-02-28Not applicableUs54868 061020180906 25352 dqp43k
Colestipol HydrochlorideSuspension5 g/1OralAmneal Pharmaceuticals of New York Llc2006-05-02Not applicableUs
Colestipol HydrochlorideTablet, film coated1 g/1OralAmneal Pharmaceuticals of New York Llc2006-10-24Not applicableUs
Colestipol HydrochlorideGranule, for suspension5 g/5gOralGreenstone LLC1977-04-04Not applicableUs
Colestipol HydrochlorideTablet1 g/1OralAvera McKennan Hospital2015-03-202018-06-27Us
Colestipol HydrochlorideTablet1 g/1OralGreenstone LLC1994-07-19Not applicableUs59762 0450 01 nlmimage10 863a4302
Colestipol HydrochlorideTablet1 g/1OralCarilion Materials Management1994-07-19Not applicableUs68151 436120180907 15195 a7sxr3
Colestipol HydrochlorideSuspension5 g/1OralAmneal Pharmaceuticals of New York Llc2006-05-02Not applicableUs
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  • Product Code
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International/Other Brands
Cholestabyl / Lestid (Pfizer)
Categories
UNII
K50N755924
CAS number
26658-42-4

Pharmacology

Indication

Colestipol is indicated as adjunctive therapy to diet for the reduction of elevated serum total and low-density lipoprotein cholesterol (LDL-C) in patients with primary hypercholesterolemia (a condition that features elevated LDL-C) who do not respond adequately to diet Label,1,4.

Therapy with lipid-altering agents like colestipol should be a component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia Label,1,4. Treatment should begin and continue with dietary therapy Label,1,4. In general, a minimum of six months of intensive dietary therapy and counseling should be carried out prior to initiation of drug therapy such as that with colestipol Label,4. Shorter periods may be considered in patients with severe elevations of LDL-C or with definite coronary heart disease Label,4.

Although colestipol is effective in all types of hypercholesterolemia, some regional prescribing information note in particular that it is medically most appropriate in patients with Fredrickson's type II hyperlipoproteinemia 1. Nevertheless, in patients with combined hypercholesterolemia and hypertriglyceridemia, although colestipol may be helpful in reducing elevated cholesterol, it is not formally indicated where hypertriglyceridemia is the abnormality of greatest concern 6.

Associated Conditions
Pharmacodynamics

Cholesterol is the major, and probably the sole precursor of bile acids Label,4. During normal digestion, bile acids are secreted via the bile from the liver and gall bladder into the intestines Label,4. Bile acids emulsify the fat and lipid materials present in food, thus facilitating absorption Label,4. A major portion of the bile acids secreted is reabsorbed from the intestines and returned via the portal circulation to the liver, thus completing the enterohepatic cycle Label,4. Only very small amounts of bile acids are found in normal serum Label,4.

Colestipol hydrochloride binds bile acids in the intestine forming a complex that is excreted in the feces Label,4. This nonsystemic action results in a partial removal of the bile acids from the enterohepatic circulation, preventing their reabsorption Label,4. Since colestipol hydrochloride is an anion exchange resin, the chloride anions of the resin can be replaced by other anions, usually those with a greater affinity for the resin than the chloride ion Label,4.

Mechanism of action

Colestipol is a lipid-lowering polymer that binds with bile acids in the intestine forming a complex that is excreted in the feces Label,4,6. This non-systemic action results in a continuous, partial removal of bile acids from the enterohepatic circulation preventing their reabsorption Label,4,6. This increased fecal loss of bile acids due to colestipol hydrochloride administration leads to increased oxidation of cholesterol to bile acids Label,4,6. This results in an increase in the number of hepatic low-density lipoprotein (LDL) receptors, and consequently an increased uptake of LDL and a decrease in serum/plasma beta lipoprotein or total and LDL cholesterol levels Label,4,6. Although hydrochloride produces an increase in the hepatic synthesis of cholesterol in man, serum cholesterol levels fall Label,4,6.

TargetActionsOrganism
ABile acids
binder
Humans
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Absorption

Colestipol is hydrophilic, but it is virtually water-insoluble (99.75%) Label,1,4,6. This water insolubility, combined with the high molecular weight polymer in colestipol basically means the agent and the complexes it forms when it binds with bile acids are not absorbed Label,1,4,6. The action of colestipol is ultimately limited to the lumen of the gastrointestinal tract Label,1,4,6. It binds bile acids in the intestinal lumen and causes them to be excreted in the feces together with the polymer Label,1,4,6. When the enterohepatic circulation of bile acids is interrupted, cholesterol conversion to bile acids is enhanced and plasma cholesterol levels are thereby lowered Label,1,4,6.

Volume of distribution

Colestipol is not absorbed into the systemic circulation Label,1,4,6.

Protein binding

Colestipol is not absorbed into the systemic circulation Label,1,4,6.

Metabolism

Colestipol is not absorbed into the systemic circulation nor is it hydrolyzed by any digestive enzymes Label,1,4,6.

Route of elimination

Colestipol hydrochloride binds bile acids in the intestine forming a complex that is then ultimately excreted in the feces Label,1,4,6. In humans, less than 0.17% of a single 14C-labeled colestipol hydrochloride dose is excreted in the urine when given following 60 days of chronic dosing of 20 grams of colestipol hydrochloride per day Label,4. The increased fecal loss of bile acids due to colestipol hydrochloride administration leads to increased oxidation of cholesterol to bile acids Label,4.

Half life

Colestipol is not absorbed into the systemic circulation nor is it hydrolyzed by any digestive enzymes Label,1,4,6. Its action is ultimately limited to the lumen of the gastrointestinal tract, where it is eventually passed into the feces Label,1,4,6.

Clearance

Colestipol is not absorbed into the systemic circulation Label,1,4,6.

Toxicity

Overdosage with colestipol has not been reported Label,1,4,6. Regardless, in the case of overdosage, the chief potential harm would be obstruction of the gastrointestinal tract Label,1,4,6. The location of such potential obstruction, the degree of obstruction and the presence or absence of normal gut motility would determine treatment Label,1,4,6.

No clinical data are available on the use of colestipol in pregnant women and during lactation Label,1,4,6. Colestipol does not appear to be absorbed systematically Label,1,4,6. Due to its known interference with absorption of fat-soluble vitamins, the use of colestipol in pregnancy or lactation or by women of childbearing potential requires that the benefits of drug therapy be weighed against the possible hazards to the mother and the child Label,1,4,6.

There are no data on the effect of colestipol on fertility in humans Label,1,4,6.

The use of colestipol in children is limited Label,1,4,6. Clinical trials conducted in children with colestipol ranules have usually employed doses of 5 to 20 g/day Label,1,4,6. The National Cholesterol Education Program (NCEP) Expert Panel recommends drug therapy be considered in children 10 years or older, who have previously undergone an adequate trial of diet therapy but still have unacceptably high serum cholesterol levels Label,1,4,6. In certain situations where a young child has extremely high serum cholesterol levels, drug treatment may even be initiated before 10 years of age Label,1,4,6. If the child is started on drug therapy, a carefully assessed diet therapy should also be continued in order to obtain optimal results Label,1,4,6. However, the safety of using colestipol tablets in patients under the age of 18 years has not been established Label,1,4,6. Furthermore, because bile acid sequestrants like colestipol may interfere with the absorption of fat-soluble vitamins, appropriate monitoring of growth and development is essential if colestipol is used in children Label,1,4,6.

Appropriate studies on the relationship of age to the effects of colestipol have not been performed in the geriatric population Label,1,4,6. However, patients over 60 years of age may be more likely to experience gastrointestinal side effects, as well as adverse nutritional effects Label,1,4,6.

Additionally, it has been determined that the oral LD50 in rats is > 1000 mg/kg MSDS.

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

Interactions

Drug Interactions
DrugInteraction
(6R)-Folinic acidThe serum concentration of (6R)-Folinic acid can be decreased when it is combined with Colestipol.
(6S)-5,6,7,8-tetrahydrofolateThe serum concentration of (6S)-5,6,7,8-tetrahydrofolate can be decreased when it is combined with Colestipol.
(R)-warfarinColestipol can cause a decrease in the absorption of (R)-warfarin resulting in a reduced serum concentration and potentially a decrease in efficacy.
(S)-WarfarinColestipol 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 Colestipol.
1alpha,24S-Dihydroxyvitamin D2The serum concentration of 1alpha,24S-Dihydroxyvitamin D2 can be decreased when it is combined with Colestipol.
3,5-diiodothyropropionic acidThe serum concentration of 3,5-diiodothyropropionic acid can be decreased when it is combined with Colestipol.
3,5-DiiodotyrosineThe serum concentration of 3,5-Diiodotyrosine can be decreased when it is combined with Colestipol.
4-hydroxycoumarinColestipol can cause a decrease in the absorption of 4-hydroxycoumarin resulting in a reduced serum concentration and potentially a decrease in efficacy.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineColestipol can cause a decrease in the absorption of 5-(2-methylpiperazine-1-sulfonyl)isoquinoline resulting in a reduced serum concentration and potentially a decrease in efficacy.
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Food Interactions
  • Take with food.

References

Synthesis Reference

Lednicer, D. and Peery,C.Y.; US. Patent 3,803,237; April 9, 1974; assigned to The Upjohn Co.

General References
  1. Electronic Medicines Compendium: Colestid (colestipol hydrochloride) Orange 5g Monograph [Link]
  2. NCBI LactMed@NIH Drugs and Lactation Database (LactMed) [Internet]: Colestipol Profile [Link]
  3. Colestipol ScienceDirect Profile [Link]
  4. Colestid/Flavored Colestid (colestipol hydrochloride for oral suspension) [File]
  5. Pfizer MSDS for Colestipol Hydrochloride for Oral Suspension [File]
  6. Colestipol hydrochloride Canadian Product Monograph [File]
External Links
Human Metabolome Database
HMDB0014519
KEGG Compound
C06925
PubChem Compound
62816
PubChem Substance
46505777
ChemSpider
56550
ChEMBL
CHEMBL1909303
PharmGKB
PA449096
Wikipedia
Colestipol
ATC Codes
C10AC02 — Colestipol
AHFS Codes
  • 24:06.04 — Bile Acid Sequestrants
FDA label
Download (135 KB)
MSDS
Download (53.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1TerminatedOtherHealthy Volunteers / Teriflunomide Elimination1
2RecruitingTreatmentEarly Stage HER2+ Breast Cancer1
2, 3CompletedTreatmentProtoporphyria, Erythropoietic1
3CompletedTreatmentArterial Occlusive Diseases / Atherosclerosis / Cardiovascular Disease (CVD) / Carotid Artery Diseases / Cerebral Arteriosclerosis / Cerebrovascular Diseases / Coronary Arteriosclerosis / Coronary Heart Disease (CHD) / Heart Diseases / Myocardial Ischemia1
3CompletedTreatmentCardiovascular Disease (CVD) / Coronary Arteriosclerosis / Coronary Heart Disease (CHD) / Heart Diseases / Myocardial Ischemia1
4CompletedTreatmentHigh Cholesterol / Hyperlipidemias1

Pharmacoeconomics

Manufacturers
  • Pharmacia and upjohn co
  • Impax laboratories inc
Packagers
  • Catalent Pharma Solutions
  • Global Pharmaceuticals
  • Greenstone LLC
  • Impax Laboratories Inc.
  • Kaiser Foundation Hospital
  • Murfreesboro Pharmaceutical Nursing Supply
  • Patheon Inc.
  • Pharmacia Inc.
  • Physicians Total Care Inc.
  • Southwood Pharmaceuticals
Dosage forms
FormRouteStrength
Granule, for suspensionOral5 g/5g
GranuleOral5 g
TabletOral1 g
SuspensionOral5 g/1
TabletOral1 g/1
Tablet, film coatedOral1 g/1
Granule, for suspensionOral5 g/7.5g
Prices
Unit descriptionCostUnit
Colestid 90 5 gm Packets Box252.5USD box
Colestid 30 5 gm Packets Box81.11USD box
Colestid Flavored 5 gm/7.5 gm Packets3.29USD packet
Colestid 5 g Powder Packet1.04USD packet
Colestid Orange 5 g Powder Packet1.04USD packet
Colestid 1 gm tablet0.86USD tablet
Colestipol hcl 1 gm tablet0.66USD tablet
Colestid 5 gm Granules0.33USD gm
Colestid Flavored 5 gm Granules0.31USD gm
Colestid flavored granules0.3USD g
Colestid 1 g Tablet0.29USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5490987No1996-02-132013-02-13Us
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Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsolubleNot Available
logP-2.206Not Available
Predicted Properties
Not Available
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9221
Blood Brain Barrier+0.8825
Caco-2 permeable-0.5102
P-glycoprotein substrateSubstrate0.6506
P-glycoprotein inhibitor INon-inhibitor0.9435
P-glycoprotein inhibitor IINon-inhibitor0.956
Renal organic cation transporterNon-inhibitor0.6803
CYP450 2C9 substrateNon-substrate0.8931
CYP450 2D6 substrateNon-substrate0.7534
CYP450 3A4 substrateNon-substrate0.7558
CYP450 1A2 substrateNon-inhibitor0.7178
CYP450 2C9 inhibitorNon-inhibitor0.8515
CYP450 2D6 inhibitorNon-inhibitor0.8411
CYP450 2C19 inhibitorNon-inhibitor0.7634
CYP450 3A4 inhibitorNon-inhibitor0.8919
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9404
Ames testAMES toxic0.9093
CarcinogenicityNon-carcinogens0.6451
BiodegradationNot ready biodegradable0.9346
Rat acute toxicity2.5333 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.508
hERG inhibition (predictor II)Non-inhibitor0.7601
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

1. Bile acids
Kind
Group
Organism
Humans
Pharmacological action
Yes
Actions
Binder
References
  1. LaRosa JC: The mechanism of action of lipid-lowering drugs. Angiology. 1982 Sep;33(9):562-76. [PubMed:7125296]
  2. Farmer JA, Gotto AM Jr: Currently available hypolipidaemic drugs and future therapeutic developments. Baillieres Clin Endocrinol Metab. 1995 Oct;9(4):825-47. [PubMed:8593127]
  3. Reiner Z: Combined therapy in the treatment of dyslipidemia. Fundam Clin Pharmacol. 2010 Feb;24(1):19-28. doi: 10.1111/j.1472-8206.2009.00764.x. Epub 2009 Aug 14. [PubMed:19682080]

Drug created on June 13, 2005 07:24 / Updated on July 18, 2019 18:48