Questran (Cholestyramine) for Capecitabine-Induced Diarrhea
Questran powder (cholestyramine) may be considered as adjuvant therapy for capecitabine-induced diarrhea specifically when bile salt malabsorption is suspected, but it is not a first-line treatment and should only be used after standard antidiarrheal therapy has been initiated. 1
Primary Treatment Algorithm
The standard approach to capecitabine-induced diarrhea follows a stepwise escalation:
First-Line Management
- Start with loperamide 4 mg initially, followed by 2 mg every 2-4 hours or after every unformed stool (maximum 16 mg/day) 1, 2
- Implement dietary modifications: eliminate lactose-containing products (except yogurt and firm cheeses), avoid coffee, alcohol, and spicy foods 1
- Maintain oral hydration with 8-10 large glasses of clear liquids daily 2
Second-Line Management (if no improvement after 24-48 hours)
- Switch to octreotide 100-150 μg subcutaneously or intravenously three times daily, with dose escalation up to 500 μg three times daily if needed 1, 2
Severe Cases (Grade 3-4)
- Hospitalize patients with neutropenia, fever/sepsis, signs of dehydration, or imaging changes 2
- Provide IV fluid resuscitation and electrolyte replacement 2
- Consider uridine triacetate (10 g orally every 6 hours for 20 doses) if severe toxicity occurs within 96 hours of capecitabine administration 1
Role of Cholestyramine (Questran)
Cholestyramine is specifically indicated only when bile salt malabsorption is the underlying mechanism of diarrhea 1. This is a Level III, Grade B recommendation from ESMO guidelines 1.
When to Consider Bile Acid Sequestrants:
- Diarrhea persists despite standard loperamide therapy
- Clinical suspicion of bile salt malabsorption (watery diarrhea, often worse after meals, particularly fatty meals)
- Used as adjuvant therapy alongside, not instead of, primary antidiarrheal agents 1
Important Caveats:
- Cholestyramine is not mentioned in the specific capecitabine diarrhea management algorithm from recent comprehensive guidelines 2
- The evidence supporting bile acid sequestrants is weaker (Level III) compared to loperamide (Level II) and octreotide (Level IV) 1
- Budesonide (oral corticosteroid) has stronger evidence for refractory capecitabine-induced diarrhea that fails loperamide, with case reports showing resolution when standard therapy failed 3
Alternative for Refractory Cases
If standard therapy fails, oral budesonide may be more appropriate than cholestyramine for treatment-refractory capecitabine-induced diarrhea 1, 3. Budesonide 9 mg once daily can be added for Grade 2 diarrhea without bloody stools 1, and has documented success in capecitabine-specific cases 3.
Clinical Pitfalls
- Do not use cholestyramine as first-line therapy—it bypasses proven effective treatments 1, 2
- Capecitabine can cause terminal ileitis, which presents as severe, treatment-refractory diarrhea and requires drug discontinuation, not just symptomatic management 4, 5
- Hand-foot syndrome occurs in 73% of patients on capecitabine, so diarrhea management must be balanced with other toxicities 6
- Elderly patients (≥70 years) have 30-50% higher risk of requiring dose reduction and are more vulnerable to dehydration and electrolyte imbalances 2