What is Cholestipol (bile acid sequestrant) used for?

What is Cholestipol Used For?

Cholestipol is a bile acid sequestrant primarily used to lower LDL cholesterol in patients with primary hypercholesterolemia (Type IIa hyperlipoproteinemia), reducing LDL by approximately 10-20% and total cholesterol by 7-17%. 1

Primary Mechanism and Cardiovascular Benefit

Cholestipol binds bile acids in the intestinal lumen, preventing their enterohepatic reuptake and depleting the hepatic cholesterol pool. 1 This triggers upregulation of LDL surface receptors on hepatocytes, increasing clearance of LDL from circulation. 1

• Cardiovascular outcomes data: The Lipid Research Clinics Coronary Primary Prevention Trial demonstrated that bile acid sequestrants reduce coronary heart disease events, with benefit proportional to the degree of LDL lowering. 1
• The evidence supports that "lower is better" for LDL cholesterol reduction, whether achieved with statins or bile acid sequestrants. 1

Dosing and Administration

Start at 2-5 g daily and titrate gradually to minimize gastrointestinal side effects, with maximum doses up to 20 g daily. 1, 2

• At daily doses of 20 g colestipol, LDL cholesterol is reduced 18-25%. 1
• In pediatric patients with familial hypercholesterolemia, doses of 10 g/day achieved 10% LDL reduction. 1
• Critical timing: All other medications must be taken at least 1 hour before or 4 hours after colestipol to avoid impaired absorption. 2, 3

Specific Patient Populations

Pediatric Use

• The 1992 NCEP guidelines advocated bile acid-binding resins as initial drug therapy in children with familial hypercholesterolemia. 1
• However, compliance is poor due to palatability issues and gastrointestinal complaints. 1
• Folate and vitamin D supplementation is recommended during long-term use in children. 1

Combination Therapy

• Colestipol augments LDL-lowering effects when combined with statins, providing additive benefit in severe hypercholesterolemia. 1, 4
• In pediatric studies, pravastatin 10 mg with colestipol 5 g achieved 17% LDL reduction. 1

Important Contraindications and Precautions

Avoid in These Situations:

• Patients with hypertriglyceridemia: Colestipol may increase triglyceride levels and is not indicated when LDL is low or normal despite elevated total cholesterol. 1, 2
• Liver transplant recipients taking mycophenolate: Bile acid sequestrants decrease plasma mycophenolate levels by 35% and should be avoided. 1, 2, 3
• Patients with pre-existing severe constipation: Start at 2 g once or twice daily with increased fluid and fiber intake. 2

Drug Interactions Requiring Dose Separation:

Colestipol significantly reduces absorption of: 2, 3

• Tetracycline, furosemide, penicillin G, hydrochlorothiazide, gemfibrozil (when given simultaneously)
• Chlorothiazide (even when given 1 hour before colestipol)
• Warfarin, digoxin, digitoxin (conflicting data—use particular caution)
• Propranolol (delays time to maximum concentration by 30 minutes)

Vitamin Deficiency Risk:

• Long-term use interferes with absorption of fat-soluble vitamins (A, D, E, K) and folic acid. 1, 2
• Chronic use may cause hypoprothrombinemia from vitamin K deficiency, increasing bleeding tendency. 2
• Supplementation with water-miscible or parenteral forms of fat-soluble vitamins is recommended. 4

Common Pitfalls

The major limitation is poor tolerability: 1

• Gastrointestinal upset (bloating, constipation, abdominal pain) is the most common adverse effect
• Poor palatability leads to low compliance rates
• Many patients withdraw from therapy due to these issues

Given these limitations, statins have largely replaced bile acid sequestrants as first-line monotherapy for hypercholesterolemia in adults, though colestipol remains useful as adjunctive therapy or in patients who cannot tolerate statins. 1