Cholestyramine - Drug Monograph

Introduction

Cholestyramine is a bile acid sequestrant medication primarily used to manage hyperlipidemia and treat pruritus associated with partial biliary obstruction. As a non-absorbed polymeric resin, it represents one of the oldest classes of lipid-lowering agents still in clinical use today. This anion-exchange resin works within the gastrointestinal tract to bind bile acids, leading to increased cholesterol conversion to bile acids and subsequent reduction in serum cholesterol levels.

Mechanism of Action

Cholestyramine acts as a bile acid sequestrant in the gastrointestinal tract. It binds bile acids in the intestine, forming an insoluble complex that is excreted in feces. This interruption of the enterohepatic circulation of bile acids leads to increased conversion of hepatic cholesterol to bile acids via upregulation of cholesterol 7-alpha-hydroxylase, the rate-limiting enzyme in bile acid synthesis. The resulting depletion of hepatic cholesterol stores increases hepatic LDL receptor activity and clearance of LDL cholesterol from plasma, ultimately reducing serum LDL cholesterol levels by 15-30%.

Indications

• Primary hyperlipidemia: Adjunct to diet and lifestyle modification for reduction of elevated LDL cholesterol in patients with primary hypercholesterolemia
• Pruritus associated with partial biliary obstruction: Relief of itching in patients with biliary cirrhosis and other forms of cholestasis
• Diarrhea: Management of bile acid-induced diarrhea following cholecystectomy or due to other gastrointestinal disorders
• Digitalis toxicity: Adjunct treatment for digitoxin overdose (though less commonly used with modern management approaches)

Dosage and Administration

• Always mix powder with water or other fluids (3-6 ounces) before administration
• Administer with meals to enhance bile acid binding efficacy
• Gradually titrate dose over weeks to minimize gastrointestinal effects
• Other medications should be taken at least 1 hour before or 4-6 hours after cholestyramine to avoid binding interactions

• Pediatric patients: Safety and effectiveness not established for children
• Geriatric patients: Use with caution due to potential for constipation and drug interactions
• Renal/hepatic impairment: No specific dosage adjustments required

Pharmacokinetics

Contraindications

• Complete biliary obstruction (lack of bile acids makes therapy ineffective)
• Hypersensitivity to cholestyramine or any component of the formulation
• Phenylketonuria (for certain flavored formulations containing phenylalanine)

Warnings and Precautions

• Gastrointestinal effects: May cause constipation, which can be severe; adequate fluid intake and fiber consumption recommended
• Hypertriglyceridemia: May increase serum triglycerides; monitor triglyceride levels periodically
• Fat-soluble vitamin deficiency: Long-term use may impair absorption of vitamins A, D, E, and K; consider supplementation
• Bleeding tendency: May potentiate hypoprothrombinemia effects from vitamin K deficiency
• Pregnancy: Category C; use only if clearly needed and potential benefit justifies potential risk
• Pediatric use: Not recommended due to risk of hyperchloremic acidosis and other potential adverse effects

Drug Interactions

Cholestyramine binds numerous medications in the GI tract, significantly reducing their absorption:

• Warfarin: Reduced anticoagulant effect; monitor INR closely
• Thyroid hormones: Reduced absorption; administer levothyroxine至少 4 hours before cholestyramine
• Digoxin: Reduced serum levels; separate administration by至少 4 hours
• Thiazide diuretics, Propranolol: Reduced absorption and efficacy
• Fat-soluble vitamins: Reduced absorption (A, D, E, K)
• Statins, Fibrates: May reduce absorption; administer至少 2 hours apart
• Oral contraceptives: Potential reduced efficacy; recommend alternative contraception methods

Adverse Effects

• Constipation (most frequent, may be severe)
• Abdominal discomfort, bloating, flatulence
• Nausea, vomiting
• Heartburn, indigestion

• Diarrhea
• Steatorrhea
• Anorexia, weight loss
• Hyperchloremic acidosis (especially in children)

• Gallstone formation
• Intestinal obstruction
• Bleeding tendencies (vitamin K deficiency)
• Osteomalacia (vitamin D deficiency)
• Rash, urticaria

Monitoring Parameters

• Lipid profile: Baseline, 4-6 weeks after initiation, and every 3-6 months thereafter
• Liver function tests: Baseline and periodically
• Triglyceride levels: Monitor for paradoxical increases
• Complete blood count: Baseline and as clinically indicated
• Prothrombin time/INR: Especially in patients on warfarin therapy
• Electrolytes: Particularly in pediatric patients or those with renal impairment
• Clinical symptoms: Bowel function, signs of bleeding, nutritional status
• Fat-soluble vitamin levels: Consider monitoring with long-term therapy

Patient Education

• Mix powder thoroughly with 3-6 ounces of water or other fluid before drinking
• Never take the dry powder alone
• Take with meals for maximum effectiveness
• Other medications should be taken at least 1 hour before or 4-6 hours after cholestyramine
• Maintain adequate fluid intake and high-fiber diet to prevent constipation
• Report severe constipation, abdominal pain, or rectal bleeding immediately
• Notify all healthcare providers about cholestyramine use, especially before new prescriptions
• Long-term use may require vitamin supplementation; discuss with healthcare provider
• Continue dietary and lifestyle modifications alongside medication therapy

References

1. INSERM. Cholestyramine. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. 2. American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults. Circulation. 2014;129(25 Suppl 2):S1-S45. 3. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th ed. New York, NY: McGraw-Hill Education; 2017. 4. Lexicomp Online. Cholestyramine: Drug Information. Wolters Kluwer Clinical Drug Information, Inc.; 2023. 5. National Lipid Association. Recommendations for patient-centered management of dyslipidemia. J Clin Lipidol. 2015;9(2):129-169. 6. UpToDate. Cholestyramine: Drug information. Wolters Kluwer Health; 2023. 7. FDA prescribing information for cholestyramine powder. Revised 2019.