Cholestyramine

Cholestyramine is an Nonabsorbed bile acid sequestrant belonging to the Hyperlipidemia class.

Cholestyramine is used in the treatment of Dyslipidemia and Pruritus associated with cholestasis. It is also used to treat Chronic diarrhea due to bile acid malabsorption, Enhanced elimination of leflunomide, Hyperthyroidism associated with Graves disease.

Cholestyramine is not absorbed from the gastrointestinal tract following oral administration. Cholestyramine resin adsorbs and combines with the bile acids in the intestine to form an insoluble complex that is excreted in the feces.

Cholestyramine shows common side effects like Headache, dizziness, diarrhea, sore throat, runny nose, sneezing, joint pain, etc.

Cholestyramine is available in the form of an Oral Tablet and Suspension

Colestyramine releases Cl ions and binds w/ bile acids in the intestine to form a nonabsorbable complex excreted in the faeces, resulting in partial removal of bile acids from the enterohepatic circulation, thereby increasing the bile salt-bound LDL cholesterol.

Cholestyramine is available in the form of Oral Powder.

Oral: Administer prepared suspension orally. Not to be taken in dry form. Suspension should not be sipped or held in the mouth for prolonged periods (may cause tooth discoloration or enamel decay). Administration at mealtime is recommended. Twice-daily dosing is recommended but may be administered in 1 to 6 doses daily. In general, administer other oral medications ≥1 hour before or 4 to 6 hours after cholestyramine; Consult drug interactions database for additional information.

Cholestyramine is used in the treatment of Dyslipidemia and Pruritus associated with cholestasis. It is also used to treat Chronic diarrhea due to bile acid malabsorption; Enhanced elimination of leflunomide; Hyperthyroidism associated with Graves disease

Cholestyramine forms a resin that acts as a bile acid sequestrant to limit the reabsorption of bile acids in the gastrointestinal tract. Cholestyramine resin is a strong anion exchange resin, allowing it to exchange its chloride anions with anionic bile acids present in the gastrointestinal tract and form a strong resin matrix. Cholestyramine consists of a functional group, which is a quaternary ammonium group attached to an inert styrene-divinylbenzene copolymer, in the anion exchange resin.

Cholestyramine is approved for use in the following clinical indications

• Dyslipidemia:  Adjunct in the management of primary hypercholesterolemia; regression of arteriolosclerosis
• Pruritus associated with cholestasis: Treatment of pruritus associated with partial biliary obstruction
• Although not approved, there have been certain off label use documented for Cholestyramine which include:-

Chronic diarrhea due to bile acid malabsorption; Enhanced elimination of leflunomide; Hyperthyroidism associated with Graves disease

Cholestyramine is available in various strengths as 4 g/dose (201.6 g, 210 g, 231 g, 239.4 g, 348.6 g, 368.76 g, 378 g).

Cholestyramine is available in the form of Oral powder .

• Dosage Adjustment for Pediatric Patients:

Diaper dermatitis: Limited data available: Topical: Infants and Children: Apply to affected area with each diaper change. Note: Product not commercially available; may be prepared as an extemporaneously compounded ointment or paste in Aquaphor or polyethylene glycol; usual concentration 5% to 10%, although higher concentrations (up to 20%) have been compounded; some centers have also used petroleum jelly as the base for compounding.

• Hyperlipidemia: Limited data available: Note: Begin treatment after an adequate trial (6 to 12 months) of intensive lifestyle modification emphasizing body weight normalization and diet. Should not be used in pediatric patients with hypertriglyceridemia (AACE).

Dosages are expressed in terms of anhydrous resin:

Age-directed (fixed-dosing): Children ≥6 years and Adolescents: Oral: Initial: 2 to 4 g/day for 1 week, then increase as tolerated to 8 g/day; children <10 years of age may only tolerate a daily dose of 4 g ; lipid-lowering effects are better if dose is administered as a single daily dose with the evening meal (single daily morning doses are less effective); however, for patients unable to tolerate doses administered as a single dose, total daily doses may be divided into 2 or 3 divided doses with meals ; doses >8 g/day may not provide additional significant cholesterol-lowering effects, but may increase adverse effects .

Weight-directed dosing: Children and Adolescents: Oral: 240 mg/kg/day in 3 divided doses; titrate to effect, maximum daily dose: 8 g/day.

• Pruritus secondary to cholestasis: Limited data available: Note: Dosages are expressed in terms of anhydrous resin:

Children ≤10 years: Oral: 240 mg/kg/day in 2 or 3 divided doses administered in the morning around breakfast and if necessary, the third dose at lunch ; may titrate dose to effect. Some experts have suggested a maximum daily dose of 4 g/day; however, higher doses have been reported to treat pruritus in pediatric patients <10 years; in a case report (age: 9 years), the reported effective dose range was 3.3 to 6.6 g/day; in another case series (n=3; ages: 3 to 9 years), the reported range was 1.7 to 10 g/day; in some patients, higher doses were associated with increased steatorrhea and required dosage reduction.

Children >10 years and Adolescents: Oral: 240 mg/kg/day administered in the morning before breakfast; may titrate dose to effect. Some experts have suggested a maximum daily dose of 8 g/day; in adult patients, the AASLD guidelines recommend an initial dose of 4 g/day; may titrate up to 16 g/day; in some patients, higher doses have been associated with increased steatorrhea requiring dose reduction.

• Diarrhea secondary to intestinal failure, short-bowel syndrome:

Children and Adolescents: Oral: 240 mg/kg/day in 2 to 3 divided doses; maximum daily dose: 8 g/day has been suggested. However, robust clinical trials have not been completed in pediatric patients. Note: Therapeutic effect may differ among products due to excipients (eg, sorbitol, sucrose) which could potentially worsen diarrhea.

Hypercholesterolemia:

• Before initiation of therapy, patients should be placed on a standard cholesterol-lowering diet for 3 to 6 months and the diet should be continued during drug therapy. Atorvastatin serum concentration may be increased when taken with grapefruit juice; avoid concurrent intake of large quantities (>1.2 liters/day).

• Red yeast rice contains variable amounts of several compounds that are structurally similar to HMG-CoA reductase inhibitors, primarily monacolin K (or mevinolin) which is structurally identical to lovastatin; concurrent use of red yeast rice with HMG-CoA reductase inhibitors may increase the incidence of adverse and toxic effects

Cholestyramine is contraindicated in patients with

• Hypersensitivity to bile acid sequestering resins or any component of the formulation; complete biliary obstruction

Concerns related to adverse effects:

● Bleeding: Chronic use may be associated with bleeding problems (especially in high doses); may be prevented with the use of oral vitamin K therapy.

● Constipation: May produce or exacerbate constipation problems; initiate therapy at a reduced dose in patients with a history of constipation. Hemorrhoids may be worsened.

Disease-related concerns:

● Hypertriglyceridemia: Bile acid sequestrants should not be used in patients with baseline fasting triglyceride levels ≥300 mg/dL or type III hyperlipoproteinemia since severe triglyceride elevations may occur. Use bile acid sequestrants with caution in patients with triglyceride levels 250 to 299 mg/dL and evaluate a fasting lipid panel in 4 to 6 weeks after initiation; discontinue use if triglycerides are >400 mg/dL (Stone 2013).

● Renal impairment: Use caution in patients with renal impairment.

Concurrent drug therapy issues:

● Decreased absorption (orally administered drugs): Not to be taken simultaneously with many other medicines (decreased absorption).

● Patients susceptible to fat-soluble vitamin deficiencies: Use with caution in patients susceptible to fat-soluble vitamin deficiencies. Absorption of fat-soluble vitamins A, D, E, and K and folic acid may be decreased; patients should take vitamins 1 hour before or ≥4 hours after cholestyramine.

Cholestyramine may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Caution should be exercised when Cholestyramine is administered to a nursing mother.

Teratogenic Effects

Pregnancy Category C

There are no adequate and well controlled studies in pregnant women. The use of Cholestyramine in pregnancy or lactation or by women of childbearing age requires that the potential benefits of drug therapy be weighed against the possible hazards to the mother and child. Cholestyramine is not absorbed systemically, however, it is known to interfere with absorption of fat-soluble vitamins; accordingly, regular prenatal supplementation may not be adequate.

Cholestyramine (especially high doses or long-term therapy) may decrease the absorption of folic acid, calcium, fat-soluble vitamins (vitamins A, D, E, and K), and iron. Management: Supplementation of folic acid, calcium, fat-soluble vitamins (vitamins A, D, E, and K), and iron may be necessary.

• Common Adverse effects

Constipation, faecal impaction, aggravation of haemorrhoids, abdominal discomfort or pain, heartburn, flatulence, nausea, vomiting, diarrhoea

• Less Common Adverse effects:

Increased bleeding tendency (chronic use), steatorrhoea (high doses), skin rashes, pruritus of the tongue, skin and perianal region; hyperchloraemic acidosis

• Rare Adverse effects

Night blindness secondary vit A deficiency, Vit D deficiency.

• Delayed or reduced absorption of folic acid, thiazide diuretics, propranolol, digoxin and related glycosides, loperamide, phenylbutazone, barbiturates, oestrogens, progestogens, thyroid hormones, warfarin and other coumarin-derivative anticoagulants, iron salts, deferasirox and some antibacterials (e.g. tetracycline, penicillin G).
• May prevent absorption of fat-soluble vit. Slightly decreased rate of absorption of clofibrate. May interfere w/ absorption of oral phosphate supplements.

The common side effects of Cholestyramine include the following

Common

• Constipation, diarrhea, Heartburn, pain in the back, arm, or legs, Headache, joint pain.

Symptoms: GI obstruction.

Management: Dependent on the degree and location of obstruction and GI motility. Consult experts for specific recommendations.

Pharmacodynamic

Cholestyramine , as well as some of its metabolites, are pharmacologically active in humans. The liver is the primary site of action and the Principal site of cholesterol synthesis and LDL clearance. Drug dosage, rather than systemic drug concentration, correlates better with LDL-C reduction. Individualization of drug dosage should be based on therapeutic response

Pharmacokinetics

• Absorption

Not absorbed from the gastrointestinal tract following oral administration.

• Distribution

N.A.

• Metabolism

N.A.

• Excretion

Cholestyramine resin adsorbs and combines with the bile acids in the intestine to form an insoluble complex which is excreted in the feces.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021656s029lbl.pdf
• https://www.rxlist.com/Cholestyramine -drug.htm#indications
• https://reference.medscape.com/drug/tricor-lofibra-tablets-Cholestyramine -342451
• https://medlineplus.gov/druginfo/meds/a601052.html#side-effects
• https://www.mims.com/india/drug/info/Cholestyramine ?type=full&mtype=generic
• https://go.drugbank.com/drugs/DB01039
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