Cholestyramine Dosing Frequency
Cholestyramine should be taken twice daily (divided into two doses) as the standard maintenance regimen, though it can be administered anywhere from once daily up to six times daily depending on tolerability and total dose. 1
Standard Dosing Schedule
The American College of Cardiology recommends starting at 4 grams once or twice daily, then titrating to a maintenance dose of 8-16 grams daily divided into two doses, with a maximum of 24 grams daily if needed. 2 The FDA label confirms this twice-daily approach as the recommended schedule, though explicitly states the medication may be administered in 1 to 6 doses per day. 1
Practical Dosing Options by Total Daily Dose:
- 8-16 grams daily: Divide into 2 doses (most common maintenance regimen) 2, 1
- 24 grams daily: Divide into 2 doses (due to bulk volume considerations) 3
- Lower doses: Can be given once daily if preferred 1, 3
- Higher frequency: Up to 6 times daily is permissible for tolerability 1
Evidence Supporting Flexible Dosing Frequency
Research demonstrates that twice-daily dosing is equally effective as four-times-daily dosing for the same total dose. 4 Additionally, a 1975 study showed that single daily dosing of 12-16 grams produces cholesterol lowering equal to or greater than traditional three-times-daily administration, with 21.58% average reduction in serum cholesterol. 3
Critical Timing Considerations
All other medications must be taken at least 1 hour before or 4 hours after cholestyramine to avoid impaired absorption. 2 This is particularly critical for:
- Thyroid hormones
- Warfarin
- Oral contraceptives
- Cyclosporine
- Phenytoin
- Sulfonylureas 2
The suggested time of administration is at mealtime, though this may be modified to avoid interference with other medications. 1
Titration Strategy
Increases in dose should be gradual with periodic assessment of lipid levels at intervals of not less than 4 weeks. 1 This gradual titration minimizes gastrointestinal side effects, particularly constipation, dyspepsia, and nausea. 2
Dose-Response Relationship
The benefit of increasing frequency or total dose has diminishing returns:
- 8 grams daily: 16-22% LDL-C reduction 2
- 16 grams daily: 23-27% LDL-C reduction 2
- 24 grams daily: 27-28% LDL-C reduction 2
Doses above 16 grams provide only modest additional benefit, and escalating beyond 16 grams yields diminishing returns. 2
Common Pitfalls
- Vitamin K deficiency can occur with long-term use; oral vitamins should be administered at least 4 hours before cholestyramine. 2
- Never take cholestyramine in dry powder form; always mix with water or other fluids before ingesting. 1
- Monitor TSH in patients on thyroid replacement, as cholestyramine may increase TSH levels. 2
- Post-marketing reports include bowel obstruction, esophageal obstruction, and fecal impaction, emphasizing the importance of adequate fluid intake. 2