Welchol (Colesevelam) Dosing for Bile Acid Diarrhea
For bile acid diarrhea, start colesevelam at 1,875 mg (three 625-mg tablets) twice daily for a total of 3.75 g/day, which can be taken as 6 tablets once daily or divided into two doses. 1, 2
Standard Dosing Regimen
- Initial dose: 1,875 mg (3 tablets of 625 mg) twice daily, or 3.75 g/day as 6 tablets once daily 1
- No gradual titration is required for colesevelam, unlike cholestyramine or colestipol 1
- The full therapeutic dose can be started immediately without the need for slow uptitration 1
Alternative Lower Starting Dose
- Some studies have used a lower starting dose of 1,250 mg (2 tablets) daily, particularly in specific populations like patients with lenalidomide-associated diarrhea 3
- This lower dose may be considered if concerns about tolerability exist, though standard dosing is 3.75 g/day 3
Expected Response and Efficacy
- Response occurs rapidly, typically within the first 2 weeks of treatment 3
- In the highest-quality randomized controlled trial (2023), 64% of patients with bile acid diarrhea achieved remission on colesevelam versus 16% on placebo 2
- For patients who failed cholestyramine, colesevelam has a 47-57% response rate as second-line therapy 1
- Overall improvement rates range from 62-88% across various symptoms including diarrhea, urgency, frequency, and steatorrhea 4
Clinical Context and Positioning
- Colesevelam is recommended as second-line therapy after cholestyramine failure or intolerance, not as first-line treatment 1
- The Canadian Association of Gastroenterology suggests reserving colesevelam for second-line use due to limited clinical experience and higher cost, despite its favorable benefit-to-risk profile and easier administration (tablets vs powder) 1
- Colesevelam is better tolerated than cholestyramine, with side effect rates similar to placebo in most studies 1, 2
Tolerability and Side Effects
- Common mild side effects include constipation, bloating, nausea, and abdominal pain, occurring in approximately 40% of patients (similar to placebo rates) 1, 2
- Only 9% of patients are unable to tolerate colesevelam due to unpalatability or side effects, compared to higher intolerance rates with cholestyramine 1
- In the 2023 RCT, there were no serious adverse events, and no participants withdrew due to adverse events 2
- Adverse events are typically transient and resolve within 10-21 days 2
Duration and Maintenance
- Colesevelam has been used successfully for up to 44 months in clinical studies 1
- Once symptoms are controlled, use the lowest effective dose to maintain symptom control 1
- Consider intermittent or on-demand dosing rather than continuous daily therapy to minimize side effects, improve compliance, and reduce costs 1
Important Contraindications
- Avoid colesevelam in patients with Crohn's disease and extensive ileal resection (>100 cm), as bile acid sequestrants can paradoxically worsen steatorrhea and increase caloric loss 5
When to Reassess
- If symptoms recur or worsen despite stable dosing, conduct diagnostic re-evaluation rather than simply increasing the dose 1
- Consider alternative diagnoses such as microscopic colitis, celiac disease, SIBO, or functional bowel disease 1
Special Populations
- In cancer patients with radiation-induced diarrhea or bile salt malabsorption, colesevelam is effective with 67% of patients showing improvement even after failing cholestyramine 1, 4
- For lenalidomide-associated diarrhea in multiple myeloma, colesevelam at 1,250 mg daily achieved 88% response rate with 68% complete resolution, without affecting lenalidomide pharmacokinetics 3