Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral:
Prevalite: 4 g (1 ea, 42 ea, 60 ea) [contains aspartame; orange flavor]
Questran: 4 g (1 ea, 60 ea) [contains fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow); orange flavor]
Generic: 4 g (1 ea, 60 ea)
Powder, Oral:
Prevalite: 4 g/dose (231 g) [contains aspartame; orange flavor]
Questran: 4 g/dose (378 g) [contains fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow); orange flavor]
Questran Light: 4 g/dose (210 g) [sugar free; contains aspartame, fd&c red #40, fd&c yellow #10 (quinoline yellow); orange flavor]
Generic: 4 g/dose (210 g, 231 g, 239.4 g, 378 g)
Pharmacology
Mechanism of Action
Forms a nonabsorbable complex with bile acids in the intestine, releasing chloride ions in the process; inhibits enterohepatic reuptake of intestinal bile salts and thereby increases the fecal loss of bile salt-bound low density lipoprotein cholesterol
Pharmacokinetics/Pharmacodynamics
Absorption
None
Excretion
Feces (as insoluble complex with bile acids)
Onset of Action
Peak effect: 21 days
Use: Labeled Indications
Dyslipidemia: Adjunct in the management of primary hypercholesterolemia; regression of arteriolosclerosis
Pruritus associated with cholestasis: Treatment of pruritus associated with partial biliary obstruction
Use: Off Label
Chronic diarrhea due to bile acid malabsorptioncyes
Data from a limited number of patients studied suggests that cholestyramine resin may be effective in the treatment of chronic diarrhea related to bile acid malabsorption Borghede 2011, Wilcox 2014. Additional data may be necessary to further define the role of cholestyramine resin in this condition.
Based on the American Gastroenterological Association guidelines for the evaluation and management of chronic diarrhea, cholestyramine resin may be used to diagnosis bile acid-induced diarrhea AGA 1999.
Hyperthyroidism (Graves’ disease) (adjunctive therapy)c
Data from a limited number of patients studied suggests that low doses of cholestyramine resin may be effective as adjunctive therapy for the treatment of hyperthyroidism (Graves’ Disease) Alswat 2015, Mercado 1996, Tsai 2005.
Contraindications
Hypersensitivity to bile acid sequestering resins or any component of the formulation; complete biliary obstruction
Dosage and Administration
Dosing: Adult
Note: Dosages are expressed in terms of anhydrous resin:
Dyslipidemia: Oral: Initial: 4 g 1 to 2 times/day; increase gradually over ≥1-month intervals; maintenance: 8 to 16 g/day divided in 2 doses; maximum: 24 g/day. Note: May be considered in patients with fasting triglyceride level ≤300 mg/dL who do not meet cholesterol treatment goals with dietary modification and other lipid-lowering therapies (eg, maximally tolerated statin and ezetimibe) (AHA/ACC [Grundy 2018]).
Chronic diarrhea due to bile acid malabsorption (off-label use): Oral: Initial: 4 g once daily; increase by 4 g at weekly intervals in 1 to 4 divided doses; maximum: 36 g/day (Wilcox 2014). Additional data may be needed to further define the role of cholestyramine resin in this condition.
Hyperthyroidism (Graves disease) (adjunctive therapy) (off-label use): Oral: 4 g twice daily (Tsai 2005) or 4 g 3 times daily (Mercado 1996). Note: Use in combination with an antithyroid drug (eg, methimazole, propylthiouracil) and propranolol.
Pruritus associated with cholestasis: Oral: Initial: 4 g once or twice daily; may increase dose gradually up to 16 g/day in 2 divided doses (Lindor 2018; manufacturer labeling).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
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 petrolatum as the base for compounding (Preckshot 2001; White 2003; Williams 2011)
Dyslipidemia: Limited data available: Oral: Note: Dosages are expressed in terms of anhydrous resin:
Age-directed (fixed-dosing): Children ≥6 years and Adolescents: 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 daily dose of 4 g (McCrindle 2007; Sprecher 1996; Tonstad 1996); 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); if patients cannot tolerate once daily dosing, the total daily dose may be divided into 2 doses and administered with the morning and evening meals; may also be administered in 3 divided doses daily (Daniels 2002); doses >8 g/day may not provide additional significant cholesterol-lowering effects, but may increase adverse effects (Sprecher 1996)
Weight-directed dosing: Children and Adolescents: 240 mg/kg/day in 3 divided doses; titrate to effect, maximum daily dose: 8 g/day
Pruritus secondary to cholestasis: Limited data available: Oral: Note: Dosages are expressed in terms of anhydrous resin:
Children ≤10 years: 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: 3-9 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 (Cies 2007; Sprecher 1996)
Children >10 years and Adolescents: 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 (Cies 2007; Imam 2012; Lindor 2009; Sprecher 1996).
Diarrhea secondary to intestinal failure, short-bowel syndrome: Limited data available: Children and Adolescents: Oral: 240 mg/kg/day in 3 divided doses; maximum daily dose: 8 g/day has been suggested (Ching 2009); however, trials have not been completed in pediatric patients and others have recommended avoiding use at this time (ASPEN Core Curriculum 2010).
Reconstitution
Powder for suspension: Prior to administration, add powder to 60-180 mL water or other noncarbonated liquid and mix well. May also be mixed with highly fluid soups, applesauce or crushed pineapple.
Administration
Oral: Administer prepared suspension orally. Not to be taken in dry form. Suspension should not be sipped or held in 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.
Dietary Considerations
Supplementation of vitamins A, D, E, and K, folic acid, and iron may be required with high-dose, long-term therapy. Some products may contain phenylalanine.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Drug Interactions
Amiodarone: Bile Acid Sequestrants may decrease the bioavailability of Amiodarone. Consider therapy modification
Cardiac Glycosides: Bile Acid Sequestrants may decrease the absorption of Cardiac Glycosides. Monitor therapy
Chenodiol: Bile Acid Sequestrants may decrease the serum concentration of Chenodiol. Management: Administration of chenodiol 5 hours or more after bile acid sequestrants may reduce chenodiol adsorption in the gastrointestinal tract. Monitor for decreased therapeutic effects of chenodiol in patients receiving bile acid sequestrants. Consider therapy modification
Cholic Acid: Bile Acid Sequestrants may decrease the absorption of Cholic Acid. Management: Administer cholic acid at least 1 to 4 hours before or 4 to 6 hours after administration of any bile acid-binding products to minimize the potential for a significant interaction. Consider therapy modification
Corticosteroids (Oral): Bile Acid Sequestrants may decrease the absorption of Corticosteroids (Oral). Monitor therapy
Deferasirox: Bile Acid Sequestrants may decrease the serum concentration of Deferasirox. Management: Avoid combination when possible; if the combination must be used, consider a 50% increase in initial deferasirox dose, with monitoring of serum ferritin concentrations and clinical responses to guide further dosing. Consider therapy modification
Estrogen Derivatives (Contraceptive): Bile Acid Sequestrants may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Administer estrogen-based oral contraceptives at least 1 to 4 hours prior to or 4 to 6 hours after administration of a bile acid sequestrant. Consider therapy modification
Ezetimibe: Bile Acid Sequestrants may decrease the absorption of Ezetimibe. Management: Administer ezetimibe at least 2 hours before or 4 hours after any bile acid sequestrant. Consider therapy modification
Fibric Acid Derivatives: Bile Acid Sequestrants may decrease the absorption of Fibric Acid Derivatives. Management: Separate doses by at least 2 hours to minimize this interaction; fenofibric acid labeling recommends administration one hour prior to or 4-6 hours after a bile acid sequestrant. Consider therapy modification
Fluvastatin: Cholestyramine Resin may decrease the serum concentration of Fluvastatin. Management: Administer fluvastatin at least 1 hour or greater (particularly with extended-release form) before, or at least 4 hours after cholestyramine to minimize the risk for any significant interaction. Consider therapy modification
Leflunomide: Bile Acid Sequestrants may decrease serum concentrations of the active metabolite(s) of Leflunomide. Management: Unless using this combination to intentionally enhance leflunomide elimination, consider an alternative to the bile acid sequestrants when possible. Separating drug administration is not likely to be effective at avoiding this interaction. Consider therapy modification
Lomitapide: Bile Acid Sequestrants may decrease the absorption of Lomitapide. Management: Administer lomitapide at least 4 hours before or after administration of a bile acid sequestrant. Consider therapy modification
Loop Diuretics: Bile Acid Sequestrants may decrease the absorption of Loop Diuretics. Consider therapy modification
Methotrexate: Bile Acid Sequestrants may decrease the absorption of Methotrexate. Monitor therapy
Methylfolate: Cholestyramine Resin may decrease the serum concentration of Methylfolate. Monitor therapy
Multivitamins/Fluoride (with ADE): Bile Acid Sequestrants may decrease the serum concentration of Multivitamins/Fluoride (with ADE). Management: Avoid concomitant administration of multivitamins and bile acid sequestrants (eg, cholestyramine). Separate administration of these agents by several hours to minimize the risk of an interaction. Consider therapy modification
Multivitamins/Minerals (with ADEK, Folate, Iron): Bile Acid Sequestrants may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, bile acid sequestrants may impair the absorption of fat-soluble vitamins. Management: Avoid concomitant administration of multivitamins and bile acid sequestrants (eg, cholestyramine). Separate administration of these agents by several hours to minimize the risk of an interaction. Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): Bile Acid Sequestrants may decrease the serum concentration of Multivitamins/Minerals (with AE, No Iron). Management: Avoid concomitant administration of multivitamins and bile acid sequestrants (e.g., cholestyramine). Separate administration of these agents by several hours to minimize the risk of an interaction. Consider therapy modification
Mycophenolate: Cholestyramine Resin may decrease the serum concentration of Mycophenolate. Avoid combination
Niacin: Bile Acid Sequestrants may decrease the absorption of Niacin. Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: Bile Acid Sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Consider therapy modification
Obeticholic Acid: Bile Acid Sequestrants may decrease the serum concentration of Obeticholic Acid. Management: Administer obeticholic acid at least 4 hours before or at least 4 hours after the administration of bile acid sequestrants. Consider therapy modification
PHENobarbital: Cholestyramine Resin may decrease the serum concentration of PHENobarbital. Management: Administer phenobarbital at least 1 hour before or 4-6 hours after administration of cholestyramine in order to minimize the risk for any significant interaction. Consider therapy modification
Pravastatin: Bile Acid Sequestrants may decrease the serum concentration of Pravastatin. Management: Administer pravastatin at least 1 hour before or 4 hours after administration of bile-acid resins (eg, cholestyramine, colestipol, colesevelam) to minimize the risk for any significant interaction. Consider therapy modification
Progestins (Contraceptive): Bile Acid Sequestrants may decrease the serum concentration of Progestins (Contraceptive). Management: Administer oral progestin-containing contraceptives at least 1 to 4 hours prior to or 4 to 6 hours after administration of a bile acid sequestrant. Consider therapy modification
Propranolol: Bile Acid Sequestrants may decrease the serum concentration of Propranolol. Monitor therapy
Raloxifene: Bile Acid Sequestrants may decrease the absorption of Raloxifene. Consider therapy modification
Rosiglitazone: Cholestyramine Resin may decrease the serum concentration of Rosiglitazone. Management: Administer rosiglitazone at least 2 hours prior to cholestyramine in order to minimize the likelihood of an interaction, and monitor patients closely for evidence of reduced rosiglitazone effectiveness. Consider therapy modification
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Consider therapy modification
Spironolactone: Cholestyramine Resin may enhance the adverse/toxic effect of Spironolactone. Specifically, the risks of developing metabolic acidosis and hyperkalemia may be elevated with this combination. Monitor therapy
Teriflunomide: Bile Acid Sequestrants may decrease the serum concentration of Teriflunomide. Management: Unless using this combination to intentionally enhance teriflunomide elimination, consider an alternative to the bile acid sequestrants when possible. Separating drug administration is unlikely to be effective at avoiding the interaction. Consider therapy modification
Tetracyclines: Bile Acid Sequestrants may decrease the absorption of Tetracyclines. Exceptions: Eravacycline. Consider therapy modification
Thiazide and Thiazide-Like Diuretics: Bile Acid Sequestrants may decrease the absorption of Thiazide and Thiazide-Like Diuretics. The diuretic response is likewise decreased. Consider therapy modification
Thyroid Products: Bile Acid Sequestrants may decrease the serum concentration of Thyroid Products. Management: Administer oral thyroid products at least 4 h prior to colesevelam, and at least 1 h before or 4-6 h after cholestyramine. Specific recommendations for colestipol are not available. Monitor for decreased concentrations/effects of the thyroid product. Consider therapy modification
Ursodiol: Bile Acid Sequestrants may decrease the serum concentration of Ursodiol. Management: Administer ursodiol 2 to 4 hours before or at least 2 to 5 hours after bile acid sequestrants to minimize the potential for any significant interaction. Monitor for decreased therapeutic effects of ursodiol in patients receiving bile acid sequestrants. Consider therapy modification
Valproic Acid and Derivatives: Cholestyramine Resin may decrease the serum concentration of Valproic Acid and Derivatives. Management: Separate administration of valproic acid and cholestyramine by at least 3 hours whenever possible in order to minimize the potential for a significant interaction. Consider therapy modification
Vancomycin: Bile Acid Sequestrants may diminish the therapeutic effect of Vancomycin. Management: Avoid concurrent administration of oral vancomycin and bile acid sequestrants when possible. If use of both agents is necessary, consider separating doses by at least 2 hours to minimize the significance of the interaction. Consider therapy modification
Vitamin D Analogs: Bile Acid Sequestrants may decrease the serum concentration of Vitamin D Analogs. More specifically, bile acid sequestrants may impair absorption of Vitamin D Analogs. Management: Avoid concomitant administration of vitamin D analogs and bile acid sequestrants (eg, cholestyramine). Separate administration of these agents by several hours to minimize the potential risk of interaction. Monitor plasma calcium concentrations. Exceptions: Calcipotriene; Calcitriol (Topical); Tacalcitol. Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Bile Acid Sequestrants may decrease the absorption of Vitamin K Antagonists. Monitor therapy
Test Interactions
Increased prothrombin time
Adverse Reactions
Frequency not defined.
Cardiovascular: Edema, syncope
Central nervous system: Anxiety, dizziness, drowsiness, fatigue, headache, neuralgia, paresthesia, vertigo
Dermatologic: Perianal skin irritation, skin irritation, skin rash, urticaria
Endocrine & metabolic: Hyperchloremic metabolic acidosis (children), increased libido, weight gain, weight loss
Gastrointestinal: Abdominal pain, anorexia, biliary colic, constipation, dental bleeding, dental caries, dental discoloration, diarrhea, diverticulitis, duodenal ulcer with hemorrhage, dysgeusia, dysphagia, eructation, flatulence, gallbladder calcification, gastric ulcer, gastrointestinal hemorrhage, hemorrhoidal bleeding, hiccups, intestinal obstruction (rare), melena, nausea, pancreatitis, rectal pain, steatorrhea, tongue irritation, tooth enamel damage (dental erosion), vomiting
Genitourinary: Diuresis, dysuria, hematuria
Hematologic & oncologic: Adenopathy, anemia, bruise, hemorrhage, hypoprothrombinemia, prolonged prothrombin time, rectal hemorrhage
Hepatic: Abnormal hepatic function tests
Neuromuscular & skeletal: Arthralgia, arthritis, back pain, myalgia, osteoporosis
Ophthalmic: Nocturnal amblyopia (rare), uveitis
Otic: Tinnitus
Respiratory: Asthma, dyspnea, wheezing
Warnings/Precautions
Concerns related to adverse effects:
- Bleeding: Chronic use may be associated with bleeding problems (especially in high doses); may be prevented with 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).
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
- 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.
Dosage form specific issues:
- Phenylalanine: Some products may contain phenylalanine.
Other warnings/precautions:
- Hyperlipidemia: Secondary causes of hyperlipidemia should be ruled out prior to therapy.
Monitoring Parameters
ACC/AHA Blood Cholesterol Guideline recommendations (ACC/AHA [Grundy 2018]; ACC/AHA [Stone 2013]): Lipid profile (fasting or nonfasting) before initiating treatment. Fasting lipid profile should be rechecked 4 to 12 weeks after starting therapy and every 3 to 12 months thereafter.
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Lipid concentrations increase during pregnancy as required for normal fetal development. When increases are greater than expected, supervised dietary intervention should be initiated. Bile acid sequestrants are recommended when treatment is needed (Avis 2009; Jacobson 2015).
Cholestyramine is not absorbed systemically, but may interfere with maternal vitamin absorption; therefore, regular prenatal supplementation may not be adequate.
Patient Education
What is this drug used for?
- It is used to lower cholesterol, to treat itching caused by bile duct blockage, or it may be given to you for other reasons. Talk with the doctor.
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Severe abdominal pain
- Severe constipation
- Bruising
- Bleeding
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
