What are the side effects of Cholestyramine (bile acid sequestrant)?

From the Guidelines

Cholestyramine, a bile acid sequestrant, commonly causes gastrointestinal side effects including constipation, bloating, abdominal pain, nausea, and flatulence, with constipation being the most frequent issue, affecting up to 30% of patients, as reported in the most recent study 1. The medication works by binding to bile acids in the intestine, preventing their reabsorption and altering digestive processes. Some key points to consider when using cholestyramine include:

• Decreased absorption of fat-soluble vitamins (A, D, E, K), which may lead to deficiencies over time, and reduced absorption of certain medications like warfarin, thyroid hormones, and some antibiotics.
• Potential to cause heartburn, vomiting, diarrhea, and steatorrhea (fatty stools).
• May increase triglyceride levels in some patients, so it should be used cautiously in those with hypertriglyceridemia.
• Less common side effects include headache, dizziness, anxiety, fatigue, and skin rashes. To minimize side effects, patients should:
• Start with a low dose and gradually increase it.
• Take the medication with meals.
• Ensure adequate fluid intake.
• Possibly supplement with fiber and fat-soluble vitamins if using the medication long-term, as suggested by 1 and 1. It's also important to note that cholestyramine can be used to control bile acid diarrhea, with a response rate of 73% reported in a study cohort of 39 patients with Crohn's disease who had undergone ileal resection, as mentioned in 1. However, in severe cases of bile acid malabsorption, steatorrhea may worsen as a result of cholestyramine treatment, as noted in 1.

From the FDA Drug Label

ADVERSE REACTIONS The most common adverse reaction is constipation. When used as a cholesterol-lowering agent predisposing factors for most complaints of constipation are high dose and increased age (more than 60 years old). Most instances of constipation are mild, transient and controlled with conventional therapy. Some patients require a temporary decrease in dosage or discontinuation of therapy Less Frequent Adverse Reactions - Abdominal discomfort and/or pain, flatulence, nausea, vomiting, diarrhea, eructation, anorexia, steatorrhea, bleeding tendencies due to hypoprothrombinemia (Vitamin K deficiency) as well as Vitamin A (one case of night blindness reported) and D deficiencies, hyperchloremic acidosis in children, osteoporosis, rash and irritation of the skin, tongue and perianal area. Rare reports of intestinal obstruction, including two deaths, have been reported in pediatric patients. The side effects of Cholestyramine include:

• Constipation (most common)
• Abdominal discomfort and/or pain
• Flatulence
• Nausea
• Vomiting
• Diarrhea
• Eructation
• Anorexia
• Steatorrhea
• Bleeding tendencies due to hypoprothrombinemia (Vitamin K deficiency)
• Vitamin A and D deficiencies
• Hyperchloremic acidosis in children
• Osteoporosis
• Rash and irritation of the skin, tongue and perianal area
• Intestinal obstruction (rare, including two deaths in pediatric patients) 2

From the Research

Cholestyramine Side Effects

• The most common side effects of cholestyramine include constipation, nausea, borborygmi, flatulence, bloating, and abdominal pain 3
• Cholestyramine may also slow gastric emptying of liquids and reduce appetite in healthy subjects 4
• Other potential side effects of cholestyramine include:
  • Reduced bioavailability of co-administered agents 5
  • Poor tolerability 5
  • Increased bloating 4
• It is worth noting that cholestyramine is generally effective in treating gastrointestinal symptoms from bile acid malabsorption, but may be poorly tolerated by some patients 5

Mechanism of Action

• Cholestyramine is a bile acid sequestrant that binds to bile acids in the intestine to form an insoluble complex, which is excreted in the feces 6
• This mechanism of action can help to reduce the symptoms of bile acid malabsorption, but may also lead to side effects such as constipation and bloating 3

Clinical Applications

• Cholestyramine is used to treat primary hypercholesterolemia and hypercholesterolemia associated with mild hypertriglyceridemia, as well as pruritus associated with cholestatic disease 6
• It is also used to treat diarrhea from bile acid malabsorption, and may be effective in managing diabetes mellitus 6, 3