Cholestyramine Dosing for Hypercholesterolemia
For adult patients with hypercholesterolemia, start cholestyramine at 4 grams (one packet or scoop) once or twice daily, then titrate to a maintenance dose of 8-16 grams daily divided into two doses, with a maximum of 24 grams daily if needed. 1
Standard Dosing Regimen
Starting dose:
- Begin with 4 grams (one packet/scoop) once or twice daily 1
- This gradual initiation minimizes gastrointestinal side effects, particularly constipation, dyspepsia, and nausea 2, 3
Maintenance dose:
- Target 8-16 grams daily divided into two doses 2, 1
- This range provides optimal balance between efficacy and tolerability 4
Maximum dose:
- Up to 24 grams daily if additional LDL-C reduction is needed 1
- Doses above 16 grams provide only modest additional benefit 5
Expected LDL-C Reduction by Dose
The dose-response relationship is well-established:
- 8 grams daily: approximately 16-22% LDL-C reduction 6
- 12 grams daily: approximately 21-28% LDL-C reduction 7, 4
- 16 grams daily: approximately 23-27% LDL-C reduction 6, 5
- 24 grams daily: approximately 27-28% LDL-C reduction 6
Note that increasing from 8 to 16 grams provides meaningful additional benefit, but escalating beyond 16 grams yields diminishing returns 5.
Administration Instructions
Preparation:
- Never take cholestyramine in dry powder form 1
- Mix each packet/scoop with at least 2-3 ounces of water, non-carbonated beverage, highly fluid soups, or pulpy fruits like applesauce 1
- Stir to uniform consistency before ingesting 1
Timing:
- Preferably administer at mealtime, though this can be modified 1
- May be given once daily, twice daily, or divided into up to 6 doses per day 1
- Single daily dosing is as effective as divided dosing for the same total daily dose 8
Critical Drug Interaction Management
Timing separation is mandatory:
- Administer all other medications at least 1 hour before or 4 hours after cholestyramine 2, 3, 6
- This is particularly critical for medications with narrow therapeutic windows including thyroid hormones, warfarin, phenytoin, oral contraceptives, cyclosporine, and sulfonylureas 6
High-risk interactions:
- Cholestyramine can increase TSH in patients on thyroid hormone replacement 2, 3, 6
- May decrease INR in patients taking warfarin 2
- Can decrease phenytoin levels and increase seizure activity 2
Dose Titration Strategy
Gradual escalation:
- Increase dose gradually with lipid panel assessment at intervals of at least 4 weeks 1
- This approach improves tolerability while monitoring therapeutic response 1
Practical dosing schedule:
- For 8 grams daily: 4 grams twice daily (morning and evening with meals) 2, 1
- For 12 grams daily: 4 grams three times daily or 6 grams twice daily 7, 4
- For 16 grams daily: 8 grams twice daily 2, 1
Common Pitfalls and Management
Gastrointestinal side effects:
- Constipation, dyspepsia, and nausea are most common 2, 3
- Starting at lower doses and gradual titration minimizes these effects 1
- Adequate fluid intake with each dose may help mitigate symptoms 1
Serious adverse events (rare):
- Post-marketing reports include bowel obstruction, esophageal obstruction, fecal impaction, and dysphagia 2, 6
- Hypertriglyceridemia may worsen; monitor triglycerides periodically 2
Vitamin deficiency:
- Long-term use can cause vitamin K deficiency 6
- Administer oral vitamins at least 4 hours before cholestyramine 6
Combination Therapy Considerations
Enhanced efficacy with statins:
- When combined with low- to moderate-intensity statins, cholestyramine provides an additional 10-16% LDL-C reduction beyond statin monotherapy 2
- Additive effects also occur with nicotinic acid 1
- The landmark LRC-CPPT trial demonstrated 19% reduction in cardiovascular events with cholestyramine monotherapy 2
Special Population Notes
Renal impairment:
- No dosage adjustment needed in chronic kidney disease 6
Pediatric patients with familial hypercholesterolemia: