Cholestyramine for High Cholesterol: Use and Dosage
Cholestyramine is dosed at 8-16 g/day orally divided into 2 doses as adjunctive therapy to diet for reducing elevated LDL cholesterol in primary hypercholesterolemia, achieving approximately 10-27% LDL reduction depending on dose. 1
FDA-Approved Indication
Cholestyramine is indicated as adjunctive therapy to diet for reduction of elevated serum cholesterol in patients with primary hypercholesterolemia (elevated LDL cholesterol) who do not respond adequately to diet alone. 2 It may be useful in patients who also have hypertriglyceridemia, but is not indicated where hypertriglyceridemia is the primary abnormality of concern. 2
Dosing Regimen
Standard Dosing
- Starting and maintenance dose: 8-16 g/day orally divided into 2 doses 1
- The dose can be given as a single daily dose or divided (typically twice daily) 3
- Maximum dose: Up to 24 g/day may be used in severe cases, typically divided into twice-daily administration due to bulk 3
Dose-Response Relationship
The LDL-lowering effect is dose-dependent:
- 12 g/day achieves approximately 10.4% LDL reduction vs placebo 1
- Higher doses up to 16 g/day can achieve greater reductions 1
- Studies show single daily dosing achieves 21.6% cholesterol reduction, while twice-daily dosing achieves 27.6% reduction 3
Administration Guidelines
Preparation and Timing
- Mix powder with 4-8 ounces of water, fruit juice, or other non-carbonated beverages 1
- Can be taken without reference to meals, though traditionally given with meals 3
- Single daily dosing is as effective as divided dosing and may improve adherence 3
Critical Drug Interaction Management
All other medications must be taken at least 1 hour before or 4 hours after cholestyramine to avoid impaired absorption. 1, 4 This is particularly critical for:
- Warfarin (risk of decreased INR) 1
- Thyroid hormone replacement (risk of increased TSH) 1
- Phenytoin (risk of decreased levels/increased seizures) 1
- Oral contraceptives 4
- Fat-soluble vitamins 4
Expected Efficacy
Lipid Effects
- Total cholesterol reduction: 12-28% 5, 6
- LDL cholesterol reduction: 10-33% 1, 5
- Apolipoprotein B reduction: 18% 5
- HDL cholesterol may increase modestly (mechanism: reduced CETP activity) 7
- Triglycerides may increase or remain unchanged 1—this is a critical caveat
Cardiovascular Outcomes
The landmark LRC-CPPT trial demonstrated that cholestyramine achieved a 19% reduction in risk (p<0.05) of definite CHD death and/or definite nonfatal MI over 7.4 years in asymptomatic middle-aged men with primary hypercholesterolemia. 1 This is the only bile acid sequestrant with proven cardiovascular mortality benefit.
Adverse Effects and Contraindications
Common Side Effects
- Constipation, dyspepsia, and nausea are the most common gastrointestinal effects 1
- Gradual dose titration minimizes GI symptoms 4
- May cause vitamin K or fat-soluble vitamin deficiencies 4
Contraindications
- Complete biliary obstruction 4
- History of serious hypersensitivity to cholestyramine 4
- Hypertriglyceridemia as primary abnormality (cholestyramine may worsen triglycerides) 2, 8
Clinical Pearls
Before initiating therapy, exclude secondary causes of hypercholesterolemia (poorly controlled diabetes, hypothyroidism, nephrotic syndrome, obstructive liver disease, alcoholism) and ensure adequate dietary trial. 2
Monitor response within the first month—a favorable trend in cholesterol reduction should occur during this period. 2 If adequate LDL-C reduction is not achieved, consider increasing the dose or adding combination therapy with a statin (which provides an additional 10-16% LDL reduction). 1, 8
Cholestyramine is safe during pregnancy and lactation as it is not systemically absorbed. 4
The major limitation is pill burden, inconvenience of preparation, GI side effects, and potential exacerbation of hypertriglyceridemia. 1 These factors often limit long-term adherence compared to statins, which are now first-line therapy for most patients with hypercholesterolemia.