When is cholestyramine (bile acid sequestrant) indicated for patients with hyperlipidemia (high cholesterol)?

When to Give Cholestyramine

Cholestyramine is indicated as adjunctive therapy to diet for reducing elevated LDL cholesterol in patients with primary hypercholesterolemia who do not respond adequately to dietary modification alone. 1

Primary Indications for Adults

Use cholestyramine when LDL cholesterol remains elevated despite dietary intervention, specifically:

• LDL-C ≥190 mg/dL without other risk factors 1
• LDL-C ≥160 mg/dL with presence of two or more cardiovascular risk factors 1
• LDL-C ≥130 mg/dL in patients with established atherosclerotic disease 1

The goal is to reduce LDL-C to <160 mg/dL, <130 mg/dL, or ≤100 mg/dL respectively, depending on risk stratification. 1

Pediatric Indications

In children and adolescents (ages 10-17 years), cholestyramine is indicated for heterozygous familial hypercholesterolemia after dietary therapy has failed, defined as:

• LDL-C ≥190 mg/dL regardless of family history, OR 2
• LDL-C ≥160 mg/dL with positive family history of premature CVD or ≥2 additional cardiovascular risk factors 2

Note that colesevelam has FDA approval for this pediatric indication, while cholestyramine and colestipol do not have specific pediatric labeling, though they are used clinically. 2

Use as Monotherapy vs. Combination Therapy

Cholestyramine can be used either as monotherapy or in combination with statins:

• Monotherapy: Reduces LDL-C by approximately 10-28%, depending on dose (8-16 g/day produces 17-27% reduction) 2, 3
• Combination with statins: Provides an additional 10-16% LDL-C reduction when added to low- or moderate-intensity statin therapy 2

The American College of Cardiology guidelines support using bile acid sequestrants when statin therapy alone is insufficient to achieve LDL-C goals. 2

Important Contraindications and Precautions

Do NOT use cholestyramine in the following situations:

• Triglycerides >500 mg/dL or history of hypertriglyceridemia-induced pancreatitis 2
• Triglycerides 200-499 mg/dL: Use with caution, as bile acid sequestrants are relatively contraindicated 2
• Complete biliary obstruction 2
• Bowel obstruction or history of major GI surgery with risk for obstruction 2

Critical caveat: While cholestyramine effectively lowers LDL-C, it can increase triglyceride levels by 13-29%. 4, 5 Therefore, assess baseline triglycerides before initiating therapy and monitor during treatment. 2

Dosing Strategy

Standard dosing is 8-16 g/day divided into two doses, though lower doses may be effective:

• Start with 8 g/day (4 g twice daily), which produces 17-27% LDL-C reduction 2, 3
• Can increase to 16 g/day for additional effect (26-31% LDL-C reduction) 2, 3
• The majority of lipid-lowering effect occurs within 14 days of therapy 4

Drug Interaction Management

All other medications must be taken at least 1 hour before or 4 hours after cholestyramine to avoid impaired absorption. 2 This is particularly critical for:

• Thyroid hormone replacement (cholestyramine can increase TSH) 2
• Warfarin (monitor INR frequently during initiation) 2
• Oral contraceptives, cyclosporine, phenytoin, sulfonylureas 2

Cardiovascular Outcomes Evidence

Cholestyramine has proven cardiovascular benefit: The LRC-CPPT trial demonstrated a 19% reduction in definite CHD death and/or nonfatal MI in asymptomatic middle-aged men with primary hypercholesterolemia over 7.4 years. 2 This makes cholestyramine one of the few bile acid sequestrants with cardiovascular outcomes data, unlike colesevelam or colestipol. 2

Special Consideration: Type 2 Diabetes

Cholestyramine may improve glycemic control in patients with non-insulin-dependent diabetes mellitus, reducing mean plasma glucose by 13% and decreasing urinary glucose excretion. 5 However, colesevelam is the only bile acid sequestrant with an FDA-approved indication for improving glycemic control in type 2 diabetes. 2

Common Pitfalls to Avoid

• Do not use when hypertriglyceridemia is the primary abnormality rather than elevated LDL-C 1
• Exclude secondary causes of hypercholesterolemia (poorly controlled diabetes, hypothyroidism, nephrotic syndrome, obstructive liver disease) before initiating therapy 1
• Monitor for vitamin K and fat-soluble vitamin deficiencies; supplement at least 4 hours before cholestyramine 2
• Anticipate gastrointestinal side effects (constipation, bloating, dyspepsia) which are the most common adverse effects 2