Role of Questran (Cholestyramine) in Non-Infectious Diarrhea
Cholestyramine (Questran) is recommended for the treatment of bile acid diarrhea but is not a first-line agent for general non-infectious diarrhea management. 1
Mechanism of Action and Primary Indication
Cholestyramine is a bile acid sequestrant that works by binding bile acids in the intestine, preventing their reabsorption and reducing their secretory effects on the colon. This mechanism makes it particularly effective for:
- Bile acid diarrhea (BAD)
- Diarrhea resulting from bile acid malabsorption
- Post-cholecystectomy diarrhea
- Some cases of functional diarrhea with underlying bile acid issues
Treatment Algorithm for Non-Infectious Diarrhea
First-Line Treatments
- Oral rehydration solution (ORS) and fluid replacement 2
- Loperamide for non-inflammatory diarrhea: 4 mg initially, then 2 mg after each loose stool (max 16 mg/day) 2
- Racecadotril (antisecretory agent): 100 mg three times daily for adults 2
Second-Line Treatments
- Cholestyramine (Questran) - specifically for suspected bile acid diarrhea 1
- Octreotide (100-150 μg SC TID) for severe diarrhea 1
- Psyllium seeds for therapy-associated diarrhea 1
When to Consider Cholestyramine
Cholestyramine should be considered in the following scenarios:
Confirmed Bile Acid Diarrhea: When SeHCAT testing or C4 assay confirms BAD 1
Clinical Suspicion of BAD: Patients with risk factors such as:
- History of ileal resection
- Cholecystectomy
- Radiation enteritis
- Chronic pancreatitis
- Celiac disease
- Microscopic colitis
Failure of First-Line Agents: When loperamide and other conventional antidiarrheals fail
Dosing and Administration
- Initial dosing: Start with low doses (e.g., 2-4g once or twice daily) and gradually titrate up 1
- Maintenance: Use the lowest effective dose to minimize side effects 1
- Administration: Take before meals and at bedtime; mix with water or other non-carbonated beverages
- Timing: Separate from other medications by at least 2 hours (before or 4-6 hours after) to prevent interference with absorption
Efficacy Evidence
The Canadian Association of Gastroenterology clinical practice guideline suggests using cholestyramine over no treatment for induction of clinical response in patients with BAD (conditional recommendation, very-low-certainty evidence) 1. They also suggest using cholestyramine over other bile acid sequestrants as initial therapy for BAD 1.
Limited evidence from older studies shows that cholestyramine may shorten the duration of watery diarrhea in acute cases (0.8 ± 0.6 vs. 2.3 ± 1.6 days, p < 0.005) 3, but this is not its primary indication.
Limitations and Side Effects
- Common side effects: Constipation, bloating, flatulence, abdominal discomfort
- Drug interactions: Can bind to and reduce absorption of many medications
- Palatability issues: Poor taste and grittiness can reduce adherence
- Contraindications: Complete biliary obstruction, bowel obstruction
Important Considerations
- Review concurrent medications before initiating cholestyramine to minimize drug interactions 1
- Gradual dose titration is recommended to minimize side effects 1
- Intermittent, on-demand dosing can be tried in patients who respond to treatment 1
- Alternative antidiarrheal agents should be considered if cholestyramine is not tolerated 1
Practical Recommendations
- For suspected bile acid diarrhea: Consider cholestyramine as a therapeutic trial
- For general non-infectious diarrhea: Start with loperamide before considering cholestyramine
- For therapy-associated diarrhea (e.g., chemotherapy-induced): Loperamide is first-line, with octreotide or psyllium seeds as alternatives 1
- For chronic diarrhea: Consider diagnostic evaluation for BAD before empiric cholestyramine therapy 1
Cholestyramine is a valuable but specialized treatment option that should be reserved for specific causes of non-infectious diarrhea, particularly those related to bile acid malabsorption, rather than used as a general antidiarrheal agent.