What is the recommended rate of dose increase for cholestyramine in treating diarrhea?

Cholestyramine Dose Titration for Diarrhea

Start cholestyramine at 4 grams once daily and increase gradually every few days, with clinical experience suggesting increases of approximately 4 grams every 2-3 days as tolerated, titrating to symptom control up to a maintenance dose of 8-16 grams daily divided into two doses. 1, 2

Initial Dosing Strategy

• Begin with 4 grams (one sachet/scoop) once or twice daily, taken with meals rather than on an empty stomach to improve tolerance 1, 3, 2
• The FDA label specifies starting at 4 grams once or twice daily, with gradual dose increases 2
• Taking the medication with food significantly reduces gastrointestinal side effects like bloating, nausea, and abdominal discomfort 1

Titration Schedule

• Increase the dose gradually over "a few days" according to the British Society of Gastroenterology, with the specific recommendation to slowly titrate to symptoms 1
• The Canadian Association of Gastroenterology designates gradual daily dose titration as a "good practice statement" to minimize side effects 1
• The FDA label recommends gradual increases with periodic assessment, though it specifies 4-week intervals for lipid monitoring in hyperlipidemia (this timeline is less relevant for diarrhea management) 2
• In practical terms, increase by 4 grams every 2-3 days as tolerated until symptoms improve 1, 3

Target Maintenance Dose

• Aim for 8-16 grams daily divided into two doses for most patients 3, 2
• Maximum dose is 24 grams daily (six sachets/scoops) if needed 3, 2
• Once symptoms are controlled, use the lowest dose needed to maintain symptom control 1

Expected Response Timeline

• Initial clinical response typically occurs within days to 1-2 weeks 4
• One pediatric study showed normalization of stools within 2-4 days at doses of 2 grams twice daily 5
• Long-term response improves over time, particularly in patients with confirmed bile acid malabsorption 4

Critical Dosing Considerations

• Space cholestyramine at least 4 hours apart from other medications to prevent binding and loss of efficacy 3, 2
• Approximately 11% of patients cannot tolerate cholestyramine due to unpalatability or side effects, with constipation being the most common issue 3
• Avoid cholestyramine entirely in patients with Crohn's disease and extensive ileal resection (>100 cm), as it paradoxically worsens steatorrhea 1, 3

Alternative Approach for Poor Tolerance

• If side effects are intolerable during titration, consider starting at an even lower dose (¼ sachet = 1 gram) and increasing more slowly 1
• Switch to colesevelam (625 mg tablets, starting at 3 tablets twice daily) if cholestyramine remains poorly tolerated, as it has fewer side effects 1, 3

Maintenance Strategy

• Once symptoms are controlled, attempt intermittent on-demand dosing rather than continuous daily therapy to minimize side effects and improve compliance 1, 3
• If symptoms recur or worsen despite stable dosing, conduct diagnostic re-evaluation rather than simply increasing the dose 1