What is the recommended dosage and administration of cholestyramine for treating diarrhea?

Cholestyramine for Diarrhea: Dosing and Administration

Start cholestyramine at 4 grams once daily and gradually titrate upward every 2-3 days to a maintenance dose of 8-16 grams daily divided into two doses, with a maximum of 24 grams daily if needed, taking the medication with meals to minimize gastrointestinal side effects. 1, 2

Initial Dosing Strategy

• Begin with 4 grams (one packet or scoop) once daily, preferably taken with meals to reduce side effects like bloating, nausea, and abdominal discomfort 1, 2
• The FDA-approved starting dose is 1-2 packets daily (4-8 grams), but clinical guidelines favor the lower 4-gram starting point for better tolerability 2, 1
• Always mix the powder with at least 2-3 ounces of water or non-carbonated beverages—never take it in dry form 2

Titration Schedule

• Increase the dose gradually by approximately 4 grams every 2-3 days as tolerated, monitoring for symptom improvement 1
• This gradual titration is designated as a "good practice statement" by the Canadian Association of Gastroenterology to minimize side effects and improve compliance 3, 1
• If side effects are intolerable, consider starting at an even lower dose of 1 gram and increasing more slowly 1

Target Maintenance Dose

• The typical maintenance dose is 8-16 grams daily, divided into two doses (e.g., 4-8 grams twice daily) 1, 2
• The maximum dose is 24 grams daily (6 packets), though most patients respond to lower doses 2, 1
• Once symptoms are controlled, use the lowest effective dose and consider intermittent on-demand dosing rather than continuous daily therapy to minimize side effects and costs 1

Expected Efficacy

• Cholestyramine achieves clinical response in approximately 70% of patients with bile acid malabsorption-related diarrhea 1
• Response rates vary by severity: 67% in patients with severe malabsorption (SeHCAT retention <5%), 73% with moderate malabsorption, and 59% with mild malabsorption 1
• For acute diarrhea in children, cholestyramine 2 grams twice daily significantly shortened the duration of watery diarrhea from 2.3 days to 0.8 days compared to placebo 4, 5

Critical Contraindications and Caveats

• Avoid cholestyramine entirely in patients with Crohn's disease and extensive ileal resection (>100 cm), as it paradoxically worsens steatorrhea and increases caloric loss 3, 1
• Approximately 11% of patients find cholestyramine intolerable due to unpalatability or gastrointestinal side effects (constipation, bloating, abdominal pain, flatulence) 1
• Cholestyramine can interfere with absorption of other medications—administer other drugs at least 1 hour before or 4-6 hours after cholestyramine 2

Second-Line Options for Treatment Failures

• If cholestyramine fails or is not tolerated, switch to colesevelam (625 mg tablets, 3 tablets twice daily or 6 tablets once daily) 3, 1
• Colesevelam has a 47-57% response rate in cholestyramine failures and a more favorable side effect profile with better palatability 3, 1
• Colestipol may be used as an alternative second-line agent, starting at 1 gram twice daily and titrating by 1 gram every other day 6

Special Clinical Scenarios

• Postcholecystectomy diarrhea: Cholestyramine is highly effective, with 88% response rate (23 of 26 patients) 1
• Microscopic colitis with bile acid malabsorption: Cholestyramine may improve diarrhea symptoms but does not affect underlying histopathology 1
• Acute infectious diarrhea in children: Use 2 grams twice daily for 3 days as adjunct therapy after adequate rehydration 4, 7, 5

Monitoring and Adjustment

• Assess clinical response at intervals of 2-4 weeks during titration 2
• If symptoms recur or worsen despite stable dosing, conduct diagnostic re-evaluation rather than simply increasing the dose 1
• Monitor for steatorrhea if using higher doses (>16 grams daily), as excessive bile acid sequestration can paradoxically worsen fat malabsorption 8