Colestyramine: Difference between revisions

{{Short description|Pharmaceutical drug}}

{{Drugbox

| Verifiedfields = changed

| verifiedrevid = 412216968

| IUPAC_name =

<!--Clinical data -->

| pronounce = {{IPAc-en|k|oʊ-|ˈ|l|ɛ|s|t|ə|r|ə|m|iː|n}}, {{IPAc-en|k|oʊ-|l|ᵻ|ˈ|s|t|aɪ|r|ə|m|iː|n}}

| tradename = Questran, Cholybar, Olestyr, others

| Drugs.com = {{drugs.com|monograph|cholestyramine-resin}}

| MedlinePlus = a682672

| pregnancy_AU = B2

| pregnancy_AU_comment =

| pregnancy_category=

| routes_of_administration = [[Oral administration|By mouth]]

| ATC_suffix = AC01

| ATC_supplemental =

| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->

| legal_UK = <!-- GSL / P / POM / CD -->

| legal_US = Rx-only

| legal_status = Rx-only

<!--Pharmacokinetic data -->

| bioavailability = low

| protein_bound = unknown

| metabolism = bile acids

| elimination_half-life = 1 hour

| excretion = Faecal

<!--Identifiers -->

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 11041-12-6

| PubChem =

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = 4B33BGI082

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1201625

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = none

<!--Chemical data -->

| molecular_weight = In average, exceeds 1×10⁶ g/mol

'''Colestyramine''' ([[International nonproprietary name|INN]]) or '''cholestyramine''' ([[United States Adopted Name|USAN]]) (trade names '''Questran''', '''Questran Light''', '''Cholybar''', '''Olestyr''') is a [[bile acid sequestrant]], which binds [[bile]] in the [[gastrointestinal tract]] to prevent its reabsorption. It is a strong [[ion exchange resin]], which means it can exchange its [[chloride]] [[anion]]s with anionic [[bile acid]]s in the gastrointestinal tract and bind them strongly in the resin matrix. The functional group of the anion exchange resin is a [[quaternary ammonium|quaternary]] [[ammonium group]] attached to an inert [[styrene]]-[[divinylbenzene]] [[copolymer]].

Colestyramine removes bile acids from the body by forming [[insoluble]] complexes with bile acids in the [[intestine]], which are then excreted in the [[feces]].<ref name=livertox/> As a result of this loss of bile acids, more [[blood plasma|plasma]] [[cholesterol]] is converted to bile acids in the liver to normalise levels.<ref name=livertox>{{cite book | title = LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. | location = Bethesda (MD) | publisher = National Institute of Diabetes and Digestive and Kidney Diseases | chapter = Cholestyramine | date = September 2017 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK548431/ | pmid = 31643750 | id = NBK548431 | access-date = 22 June 2016 }}</ref> This conversion of cholesterol into bile acids lowers [[plasma cholesterol level]]s.<ref name=livertox/>

==Medical uses==

Bile acid sequestrants such as colestyramine were first used to treat [[hypercholesterolemia]], but since the introduction of [[statin]]s, now have only a minor role for this indication. They can also be used to treat the [[pruritus]], or itching, that often occurs during [[liver failure]] and other types of [[cholestasis]] where the ability to eliminate bile acids is reduced.{{citation needed|date=March 2022}}

Colestyramine is commonly used to treat [[diarrhea]] resulting from [[bile acid malabsorption]].<ref name="pmid24602022">{{cite journal | vauthors = Wilcox C, Turner J, Green J | title = Systematic review: the management of chronic diarrhoea due to bile acid malabsorption | journal = Alimentary Pharmacology & Therapeutics | volume = 39 | issue = 9 | pages = 923–939 | date = May 2014 | pmid = 24602022 | doi = 10.1111/apt.12684 | s2cid = 12016216 | doi-access = free }}</ref> It was first used for this in [[Crohn's disease]] patients who had undergone ileal resection.<ref name="pmid4894463">{{cite journal | vauthors = Hofmann AF, Poley JR | title = Cholestyramine treatment of diarrhea associated with ileal resection | journal = The New England Journal of Medicine | volume = 281 | issue = 8 | pages = 397–402 | date = August 1969 | pmid = 4894463 | doi = 10.1056/NEJM196908212810801 }}</ref> The terminal portion of the [[small bowel]] (ileum) is where bile acids are reabsorbed. When this section is removed, the bile acids pass into the large bowel and cause diarrhea due to stimulation of chloride/fluid secretion by the colonocytes resulting in a secretory diarrhea. Colestyramine prevents this increase in water by making the bile acids insoluble and osmotically inactive.

Colestyramine is also used in the control of other types of [[bile acid diarrhea]]. The primary, idiopathic form of bile acid diarrhea is a common cause of chronic functional diarrhea, often misdiagnosed as diarrhea-predominant irritable bowel syndrome (IBS-D), and most of these patients respond to colestyramine.<ref name="pmid19570102">{{cite journal | vauthors = Wedlake L, A'Hern R, Russell D, Thomas K, Walters JR, Andreyev HJ | title = Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome | journal = Alimentary Pharmacology & Therapeutics | volume = 30 | issue = 7 | pages = 707–717 | date = October 2009 | pmid = 19570102 | doi = 10.1111/j.1365-2036.2009.04081.x | s2cid = 11327665 | doi-access = free }}</ref> It is beneficial in the treatment of [[postcholecystectomy syndrome]] chronic diarrhea.<ref name="pmid1449156">{{cite journal | vauthors = Sciarretta G, Furno A, Mazzoni M, Malaguti P | title = Post-cholecystectomy diarrhea: evidence of bile acid malabsorption assessed by SeHCAT test | journal = The American Journal of Gastroenterology | volume = 87 | issue = 12 | pages = 1852–1854 | date = December 1992 | pmid = 1449156 }}</ref><ref name="pmid21977493">{{cite journal | vauthors = Danley T, St Anna L | title = Clinical inquiry. Postcholecystectomy diarrhea: what relieves it? | journal = The Journal of Family Practice | volume = 60 | issue = 10 | pages = 632c–632d | date = October 2011 | pmid = 21977493 }}</ref> Colestyramine is also useful in treating [[post-vagotomy diarrhea]].<ref>{{cite journal | vauthors = George JD, Magowan J | title = Diarrhea after total and selective vagotomy | journal = The American Journal of Digestive Diseases | volume = 16 | issue = 7 | pages = 635–640 | date = July 1971 | pmid = 5563217 | doi = 10.1007/BF02239223 | s2cid = 45276562 }}</ref><ref>{{cite journal | vauthors = Gorbashko AI | title = [The pathogenesis, diagnosis and treatment of postvagotomy diarrhea] | journal = Vestnik Khirurgii Imeni I. I. Grekova | volume = 148 | issue = 3 | pages = 254–262 | date = March 1992 | pmid = 8594740 }}</ref>

Colestyramine can be helpful in the treatment of ''[[Clostridium difficile colitis|Clostridium difficile]]'' infections, to absorb toxins A and B, and reduce the diarrhea and the other symptoms these toxins cause. However, because it is not an anti-infective, it is used in concert with [[vancomycin]].<ref name="pmid15149585">{{cite journal | vauthors = Stroehlein JR | title = Treatment of Clostridium difficile Infection | journal = Current Treatment Options in Gastroenterology | volume = 7 | issue = 3 | pages = 235–239 | date = June 2004 | pmid = 15149585 | doi = 10.1007/s11938-004-0044-y | s2cid = 25356792 }}</ref>

It is also used in the "wash out" procedure in patients taking [[leflunomide]] or teriflunomide to aid drug elimination in the case of drug discontinuation due to severe side effects caused by leflunomide or teriflunomide.<ref name="pmid19955995">{{cite journal | vauthors = Wong SP, Chu CM, Kan CH, Tsui HS, Ng WL | title = Successful treatment of leflunomide-induced acute pneumonitis with cholestyramine wash-out therapy | journal = Journal of Clinical Rheumatology | volume = 15 | issue = 8 | pages = 389–392 | date = December 2009 | pmid = 19955995 | doi = 10.1097/RHU.0b013e3181c3f87e }}</ref>

A case report suggests that colestyramine may be useful for [[cyanobacteria]]l ([[microcystin]]) poisoning in dogs.<ref name="pmid23888515">{{cite journal | vauthors = Rankin KA, Alroy KA, Kudela RM, Oates SC, Murray MJ, Miller MA | title = Treatment of cyanobacterial (microcystin) toxicosis using oral cholestyramine: case report of a dog from Montana | journal = Toxins | volume = 5 | issue = 6 | pages = 1051–1063 | date = June 2013 | pmid = 23888515 | pmc = 3717769 | doi = 10.3390/toxins5061051 | doi-access = free }}</ref>

Ointments containing colestyramine compounded with [[Aquaphor]] have been used in topical treatment of diaper rash in infants and toddlers.<ref>{{cite journal | vauthors = White CM, Gailey RA, Lippe S | title = Cholestyramine ointment to treat buttocks rash and anal excoriation in an infant | journal = The Annals of Pharmacotherapy | volume = 30 | issue = 9 | pages = 954–956 | date = September 1996 | pmid = 8876854 | doi = 10.1177/106002809603000907 | s2cid = 19929362 }}</ref>

Cholestyramine also binds with oxalate in the GI tract, ultimately reducing urine oxalate and calcium oxalate stone formation.<ref>{{cite news|url=https://www.nytimes.com/health/guides/disease/kidney-stones/medications.html |archive-url=https://web.archive.org/web/20131121234357/https://www.nytimes.com/health/guides/disease/kidney-stones/medications.html |archive-date=2013-11-21 |title=Kidney Stones – Medications |work=The New York Times}}</ref>

==Available forms==

Colestyramine is available as powder form, in 4-g packets, or in larger canisters. In the [[United States]], it can be purchased either as a generic medicine, or as Questran or Questran Light ([[Bristol-Myers Squibb]]).

==Dosage==

A typical dose is 4 to 8 g once or twice daily, with a maximum dose of 24 g/d.

== Side effects ==

These side effects have been noted:<ref name="Questran"/>

* Most frequent: [[constipation]]

* Increased plasma triglycerides<ref>{{MedlinePlusEncyclopedia|003493|Triglyceride level}}</ref>

[[Intestinal obstruction]] has been reported in patients with previous bowel surgery who should use colestyramine cautiously.<ref>{{cite journal | vauthors = Merten DF, Grossman H | title = Intestinal obstruction associated with cholestyramine therapy | journal = AJR. American Journal of Roentgenology | volume = 134 | issue = 4 | pages = 827–828 | date = April 1980 | pmid = 6767374 | doi = 10.2214/ajr.134.4.827 | doi-access = free }}</ref><ref name="pmid17368279">{{cite journal | vauthors = Jacobson TA, Armani A, McKenney JM, Guyton JR | title = Safety considerations with gastrointestinally active lipid-lowering drugs | journal = The American Journal of Cardiology | volume = 99 | issue = 6A | pages = 47C–55C | date = March 2007 | pmid = 17368279 | doi = 10.1016/j.amjcard.2006.11.022 }}</ref> Cholestyramine-induced hyperchloremic [[metabolic acidosis]] has also been reported rarely.<ref>{{cite journal | vauthors = Kamar FB, McQuillan RF | title = Hyperchloremic Metabolic Acidosis due to Cholestyramine: A Case Report and Literature Review | journal = Case Reports in Nephrology | volume = 2015 | pages = 309791 | date = 2015 | pmid = 26425378 | pmc = 4573617 | doi = 10.1155/2015/309791 | doi-access = free }}</ref>

Patients with [[hypothyroidism]], [[diabetes]], [[nephrotic syndrome]], dysproteinemia, obstructive liver disease, [[kidney disease]], or [[alcoholism]] should consult their doctor before taking this medication.<ref name="Questran"/> Other drugs should be taken at least one hour before or four to six hours after colestyramine to reduce possible interference with absorption. Patients with [[phenylketonuria]] should consult with a physician before taking Questran Light because that product contains [[phenylalanine]].

== Drug interactions ==

Interactions with these drugs have been noted:<ref name="Questran"/>

* [[Digoxin|Digitalis]]

* [[Estrogens]] and [[progestins]]

* Oral [[diabetes]] drugs

* [[Penicillin#Benzylpenicillin (penicillin G)|Penicillin G]]

* [[Phenobarbital]]

* [[Spironolactone]]

* [[Tetracycline]]

* [[Thiazide]]-type diuretic pills

* [[Thyroid]] medication

* [[Warfarin]]

* [[Leflunomide]]

Most interactions are due to the risk of decreased absorption of these drugs.<ref name="pmid17368279"/> The duration of treatment is not limited, but the prescribing physician should reassess at regular intervals if continued treatment is still necessary. The principal overdose risk is blockage of intestine or stomach.

Colestyramine may interfere in the absorption of fat-soluble vitamins such as vitamins [[Vitamin A|A]], [[Vitamin D|D]], [[Vitamin E|E]], and [[Vitamin K|K]]. No special considerations regarding alcohol consumption are made.<ref name="Questran">{{cite web |url=http://www.pdrhealth.com/drugs/questran |title=Questran |work=PDRHealth |access-date=July 7, 2012}}</ref>

== Notes and references ==

* {{Cite book|title=The Merck Index|edition=12|page=2257}}

{{Lipid modifying agents}}