What should be done for a patient who developed severe gastrointestinal side effects, including urgent diarrhea and increased acid reflux, after starting cholestyramine (a bile acid sequestrant) 2 days ago?

Discontinue Cholestyramine Immediately

This patient is experiencing paradoxical worsening of diarrhea from cholestyramine, which occurs in a subset of patients and indicates the medication should be stopped immediately. 1

Why This Patient Cannot Tolerate Cholestyramine

The clinical presentation strongly suggests cholestyramine intolerance rather than bile acid diarrhea:

• Urgent diarrhea occurring during fasting periods (after 8-9 hours without food) is inconsistent with bile acid diarrhea, which typically worsens with meals when bile acids are released 2
• Worsening acid reflux is a recognized adverse effect of cholestyramine, though one older study found it ineffective for reflux gastritis 3
• Paradoxical diarrhea worsening is a documented side effect occurring in 11-45% of patients who discontinue due to intolerance 1, 4
• The timing (immediate onset within 2 days) suggests direct drug intolerance rather than therapeutic failure

Immediate Management Steps

Stop Cholestyramine Now

• Approximately 11% of patients find cholestyramine intolerable due to side effects, with 45% of treatment failures related to medication intolerance 1, 4
• Common adverse effects include abdominal bloating, pain, dyspepsia, nausea, flatulence, and paradoxically worsening diarrhea 1

Address Acute Symptoms

• Continue Imodium (loperamide) as needed for symptomatic diarrhea control 1
• Consider short-term acid suppression (PPI or H2-blocker) for the reflux symptoms that developed during cholestyramine use

Alternative Treatment Options

If Bile Acid Diarrhea Diagnosis is Confirmed

Switch to colesevelam as second-line bile acid sequestrant:

• Colesevelam (625 mg tablets, 3 tablets twice daily or 6 tablets once daily) has a 47-57% response rate in cholestyramine failures 2
• Colesevelam has fewer gastrointestinal side effects and better tolerability than cholestyramine 2, 4
• Greater specificity for bile acids reduces drug interactions and constipation tendency 5

If Bile Acid Sequestrants Remain Intolerable

• The Canadian Association of Gastroenterology recommends using alternative anti-diarrheal agents (such as loperamide) for long-term symptomatic therapy in patients unable to tolerate bile acid sequestrants 1

Critical Pitfall to Avoid

Do not increase the cholestyramine dose or continue "pushing through" side effects. The guideline recommendation to start at 4 grams once daily and titrate gradually over 2-3 days exists specifically to identify intolerant patients early 2, 4. This patient has already demonstrated clear intolerance at the starting dose.

Diagnostic Reconsideration

Given the atypical presentation (fasting diarrhea, immediate intolerance, reflux worsening), reconsider whether bile acid diarrhea is the correct diagnosis:

• True bile acid diarrhea typically improves with fasting and worsens postprandially 2
• Consider alternative diagnoses such as microscopic colitis, IBS-D without bile acid malabsorption, or other causes of chronic diarrhea
• If bile acid diarrhea testing (SeHCAT or serum 7α-hydroxy-4-cholesten-3-one) was not performed, consider testing before attempting another bile acid sequestrant 1