Major Side Effect of Cholestyramine
The major side effect of cholestyramine is gastrointestinal disturbance, including constipation, bloating, gas, abdominal cramps, dyspepsia, and nausea, which limits its use in a substantial proportion of patients. 1
Gastrointestinal Side Effects
Gastrointestinal adverse effects are the predominant limitation of bile acid sequestrants like cholestyramine, with these effects being significant enough to cause treatment discontinuation in many patients. 1
Specific GI symptoms include gas, bloating, constipation, abdominal cramps, dyspepsia, nausea, flatulence, and abdominal pain. 1, 2
Approximately 11% of patients find cholestyramine intolerable due to unpalatability or side effects, with 45% of treatment failures in some cohorts being related to medication intolerance rather than lack of efficacy. 2
Paradoxically, cholestyramine can worsen diarrhea in some patients, which should prompt immediate discontinuation. 2
Drug Interactions and Malabsorption
All other medications must be taken at least 1 hour before or 4-6 hours after cholestyramine to avoid impaired absorption, as it binds medications in the intestinal lumen. 1, 3, 2
Cholestyramine significantly reduces absorption of warfarin (requiring frequent INR monitoring), thyroid preparations, digoxin, oral contraceptives, mycophenolate (by 35%), and fat-soluble vitamins (A, D, E, K). 1, 3
Fat-soluble vitamin deficiencies may develop with long-term use, particularly vitamin K (monitor via INR/prothrombin time) and vitamin D (occurring in 20% of patients), requiring supplementation. 3, 2
Metabolic Complications
Cholestyramine may increase triglyceride levels, which can lead to acute pancreatitis in susceptible patients; triglycerides should be monitored and the drug discontinued if signs of pancreatitis occur. 1
Hyperchloremic metabolic acidosis can occur, particularly in patients with renal impairment or volume depletion. 2
Clinical Pitfalls to Avoid
The high rate of GI side effects means extensive patient counseling about expected tolerability issues is essential before initiating therapy to improve adherence and set realistic expectations. 2
Start with the lowest effective dose (4 grams once or twice daily) and titrate gradually to minimize GI side effects and improve long-term compliance. 2
If cholestyramine fails due to intolerance rather than lack of efficacy, switching to alternative bile acid sequestrants like colesevelam or colestipol is reasonable, as these newer agents may have better tolerability profiles. 2, 4
Contraindications include triglycerides >500 mg/dL, history of hypertriglyceridemia-induced pancreatitis, and bowel obstruction; avoid in patients with gastroparesis or other GI motility disorders. 1