Cholestyramine Uses
Cholestyramine is primarily indicated for lowering LDL cholesterol in hypercholesterolemia and for managing cholestatic pruritus in patients with partial biliary obstruction, with emerging evidence supporting its use in bile acid diarrhea. 1
Primary FDA-Approved Indications
Hypercholesterolemia and Cardiovascular Risk Reduction
- Cholestyramine reduces LDL cholesterol by 18-25% at standard doses (24 g daily), working by binding bile acids in the intestinal lumen and interrupting enterohepatic circulation. 2
- The Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT) demonstrated a 19% reduction in combined coronary heart disease death plus non-fatal myocardial infarction over seven years in hypercholesterolemic men treated with cholestyramine. 1
- Cholestyramine monotherapy has been shown to slow progression and promote regression of atherosclerotic lesions in coronary arteries of patients with documented coronary artery disease. 1
- The mechanism involves depleting hepatic bile acids, which upregulates 7-alpha-hydroxylase activity and increases LDL receptor expression, thereby reducing circulating LDL cholesterol levels. 2
Cholestatic Pruritus
- Cholestyramine is indicated for relief of pruritus associated with partial biliary obstruction. 1
- In genetic cholestatic liver diseases (Alagille syndrome, PFIC subtypes), cholestyramine shows marginal efficacy for decreasing cholestatic pruritus but is used off-label due to its safety profile. 2
- The mechanism involves forming insoluble complexes with bile acids in the intestine, reducing their reabsorption and potentially decreasing pruritogenic substances. 2
Off-Label and Emerging Uses
Bile Acid Diarrhea (BAD)
- Cholestyramine is recommended as first-line therapy for bile acid diarrhea, with a success rate of approximately 70% in patients with documented BAD. 2
- The Canadian Association of Gastroenterology (2020) suggests using cholestyramine over other bile acid sequestrants as initial therapy, despite only marginal quality evidence. 2
- Starting dose should be 2-4 g daily with gradual titration to minimize gastrointestinal side effects, with maximum doses up to 24 g daily. 2
- Approximately 11% of patients find cholestyramine intolerable due to unpalatability or side effects including bloating, constipation, and abdominal pain. 2
Combination Therapy for Lipid Management
- Cholestyramine augments LDL-lowering effects when combined with statins, providing additive benefit in severe hypercholesterolemia. 2
- In pediatric type 1 diabetes with hypercholesterolemia, cholestyramine has been used when LDL remains elevated despite dietary management, though bile acid sequestrants have modest effects (10-25% LDL reduction) and poor compliance. 2
Important Clinical Considerations
Dosing and Administration
- Standard dosing for hypercholesterolemia: Start with one 4-g dose daily, titrate gradually to effect, maximum 24 g/day. 1
- For bile acid diarrhea: Start at 2-4 g daily, increase gradually based on response and tolerability. 2
- Each dose should be mixed in at least 2-6 ounces of fluid before taking; never take the powder dry. 1
- Pediatric dosing: 240 mg/kg/day of anhydrous cholestyramine in 2-3 divided doses, not to exceed 8 g/day. 1
Critical Drug Interactions
- All other medications must be taken at least 1 hour before or 4-6 hours after cholestyramine to avoid impaired absorption. 1
- Cholestyramine can significantly reduce absorption of warfarin, thyroid preparations, thiazide diuretics, digoxin, tetracycline, fat-soluble vitamins (A, D, E, K), and mycophenolic acid. 2, 1
- In liver transplant patients, bile acid sequestrants can decrease plasma mycophenolate levels by 35% and should generally be avoided in this population. 2
Contraindications and Cautions
- Avoid cholestyramine in Crohn's disease patients with extensive ileal resection (>100 cm) as it may worsen steatorrhea and increase caloric loss. 2
- Constipation is a major limiting factor; increased fluid and fiber intake should be encouraged, and stool softeners may be needed. 1
- Particular caution is needed in patients with symptomatic coronary artery disease, as constipation may aggravate their condition. 1
- Prolonged contact with teeth can cause discoloration, enamel erosion, or decay; good oral hygiene is essential. 1
Long-Term Monitoring
- Serum cholesterol and triglyceride levels should be monitored frequently during the first few months, then periodically. 1
- Cholestyramine raises triglycerides by 10-17% due to increased 7-alpha-hydroxylase activity. 2, 1
- Long-term use requires supplementation with water-miscible or parenteral forms of fat-soluble vitamins (A, D, E, K) to prevent deficiency. 1
- While routine annual vitamin monitoring lacks strong evidence, periodic assessment of vitamin K status (via INR/prothrombin time) may be prudent during long-term treatment. 2