Cholestyramine Treatment for High Cholesterol
For patients with primary hypercholesterolemia, cholestyramine should be dosed at 8-16 g/day divided into two doses, taken with meals, with the evening dose administered 30 minutes before dinner for maximum LDL-C reduction. 1, 2, 3
Recommended Dosing Strategy
Starting dose: Begin with 4 g once or twice daily (one packet or scoop), then gradually titrate upward with lipid assessments every 4 weeks 2
Maintenance dose: 8-16 g/day divided into two doses provides optimal balance between efficacy and tolerability 1, 2
- 8 g/day achieves 17-27% LDL-C reduction 4, 5
- 16 g/day achieves 26-31% LDL-C reduction 4, 5
- The incremental benefit from 8 g to 16 g is modest (only 4-5% additional LDL-C reduction) 6, 5
Maximum dose: 24 g/day (six packets), though rarely necessary given diminishing returns 2
Administration Timing for Maximum Efficacy
The evening dose should be taken 30 minutes before dinner to achieve the greatest LDL-C reduction, as this timing optimally intercepts bile acid secretion during meal digestion 3
The morning dose can be taken with breakfast, but maintaining the pre-dinner timing for the evening dose is critical—this schedule produces significantly greater LDL-C reduction compared to mid-afternoon dosing 3
Preparation and Administration
Never take cholestyramine as dry powder—always mix with at least 2-3 ounces of water or non-carbonated beverage 2
Alternative mixing options include highly fluid soups or pulpy fruits with high moisture content (applesauce, crushed pineapple) 2
Critical Drug Interaction Management
All other medications must be taken at least 1 hour before or 4 hours after cholestyramine to prevent impaired absorption 1, 4
This timing is particularly critical for:
- Thyroid hormone replacement 1, 4
- Warfarin (monitor INR frequently during initiation, then periodically) 1, 4
- Oral contraceptives 1, 4
- Cyclosporine 1
- Phenytoin 1
- Sulfonylureas 1
Practical scheduling approach: Take other medications first thing in the morning (1+ hours before cholestyramine) or at bedtime (4+ hours after the evening dose) 7
Vitamin Supplementation Requirements
Monitor for and supplement fat-soluble vitamins (A, D, E, K) and folate, as cholestyramine can cause deficiencies 1
Oral vitamin supplements should be taken at least 4 hours before cholestyramine 1, 4
Vitamin D and folate supplementation is specifically recommended based on pediatric studies showing reductions during long-term therapy 1
Expected Efficacy and Cardiovascular Outcomes
Cholestyramine monotherapy reduces LDL-C by 10-27% depending on dose 1, 6, 5
Cholestyramine has proven cardiovascular mortality benefit—the LRC-CPPT trial demonstrated a 19% reduction in definite CHD death and/or nonfatal MI over 7.4 years in asymptomatic middle-aged men with primary hypercholesterolemia 1, 4
When combined with statins, cholestyramine provides additive LDL-C lowering effects of 10-16% beyond statin monotherapy 1
Contraindications and Precautions
Absolute contraindications: History of serious hypersensitivity to cholestyramine 1
Monitor triglycerides closely—cholestyramine may increase triglyceride levels and should be avoided or used with extreme caution if baseline triglycerides >500 mg/dL due to pancreatitis risk 1
Avoid in patients with:
- Complete bowel obstruction 1
- Gastroparesis or significant GI motility disorders 1
- History of major GI surgery with bowel obstruction risk 1
Common Adverse Effects and Management
The most common side effects are gastrointestinal: constipation, dyspepsia, and nausea 1, 7
These GI effects contribute to poor long-term compliance, particularly in pediatric populations where compliance rates are notably low 1
Gradual dose titration and adequate fluid intake may help mitigate GI symptoms 2
Special Populations
Children and adolescents (ages 10-17): Cholestyramine is indicated for heterozygous familial hypercholesterolemia when LDL-C ≥190 mg/dL (or ≥160 mg/dL with positive family history or ≥2 additional CV risk factors) after dietary therapy fails 4
However, compliance is particularly challenging in this population, and statins are generally preferred when pharmacotherapy is indicated 1
Pregnancy and lactation: Cholestyramine is considered safe to use during pregnancy and lactation 1
Clinical Pitfalls to Avoid
Do not use cholestyramine as first-line monotherapy in modern practice—statins are more effective, better tolerated, and have superior cardiovascular outcomes data 1
Cholestyramine's primary role is as add-on therapy when statins alone (including higher doses and higher-potency statins) fail to achieve LDL-C goals 1
Do not overlook the triglyceride-raising effect—this can be clinically significant (increases of 64-85% in some studies) and may necessitate discontinuation 6, 8
Do not forget to adjust timing of other medications—this is the most common cause of treatment failure with other drugs the patient is taking 1, 4