What is the recommended dosage and treatment approach for Cholestyramine (bile acid sequestrant) in patients with hypercholesterolemia?

Cholestyramine Dosing and Treatment Approach for Hypercholesterolemia

For adults with primary hypercholesterolemia, start cholestyramine at 8-16 g/day divided into two doses, taken with meals and liquid, as adjunctive therapy to diet. 1, 2

Standard Dosing Regimen

Adults:

• Initial dose: 8 g/day orally divided into 2 doses (4 g twice daily) 1, 2
• Maintenance dose: 8-16 g/day divided into 2 doses 1, 2
• Maximum dose: Up to 24 g/day, though additional benefit beyond 16 g/day is modest 1, 3
• Take with meals and mix powder with 4-8 ounces of water, fruit juice, or soft drink 1

Pediatric patients (10-17 years with familial hypercholesterolemia):

• Dosing starts at 4-5 g/day and can be titrated up to 20 g/day as tolerated 1
• The minimum effective dose can be predicted from pretreatment LDL cholesterol levels 4
• In children, doses averaging 7 g/day brought LDL cholesterol within normal range in most patients 4

Expected LDL-C Reduction

Monotherapy efficacy:

• 8 g/day: 17-27% reduction in LDL cholesterol 5, 3
• 16 g/day: 26-31% reduction in LDL cholesterol 5, 3
• The dose-response curve plateaus around 11-16 g/day, with diminishing returns at higher doses 4, 3

Combination therapy with statins:

• Adds an additional 10-16% LDL-C reduction when combined with low- to moderate-intensity statins 1

Critical Administration Timing

Drug interaction management is essential:

• All other medications must be taken at least 1 hour before or 4 hours after cholestyramine 1
• This is particularly critical for medications with narrow therapeutic windows: warfarin (monitor INR frequently during initiation), thyroid hormone replacement (can increase TSH), phenytoin, oral contraceptives, cyclosporine, and olmesartan 1
• Fat-soluble vitamins (A, D, E, K) should be given at least 4 hours before cholestyramine to prevent deficiency 1

Contraindications and Precautions

Absolute contraindications:

• Complete biliary obstruction 1, 2
• History of serious hypersensitivity to cholestyramine 1, 2

Relative contraindications and warnings:

• Triglycerides >400-500 mg/dL (may worsen hypertriglyceridemia and cause pancreatitis) 1, 2
• Gastroparesis or other GI motility disorders (risk of bowel obstruction) 1
• History of major GI tract surgery with risk for bowel obstruction 1
• Monitor triglycerides during therapy and discontinue if signs of acute pancreatitis occur 1

Common Adverse Effects

Gastrointestinal side effects are the primary limitation:

• Constipation, dyspepsia, and nausea are most common 1
• Poor palatability leads to poor compliance, particularly in pediatric patients 1
• Post-marketing reports include bowel obstruction, dysphagia, esophageal obstruction, and fecal impaction 1

Monitoring Strategy

Initial assessment:

• Exclude secondary causes of hypercholesterolemia (poorly controlled diabetes, hypothyroidism, nephrotic syndrome, obstructive liver disease) before initiating therapy 2
• Obtain baseline lipid panel (total cholesterol, LDL-C, HDL-C, triglycerides) 2

Ongoing monitoring:

• Check lipid panel monthly during the first few months to confirm response 2
• Monitor triglycerides regularly, as cholestyramine may increase TG levels by 13-26% 1, 6
• Monitor for vitamin K and fat-soluble vitamin deficiencies, particularly vitamin D and folate 1, 4
• For patients on warfarin, monitor INR frequently during initiation and periodically thereafter 1
• Annual lipoprotein analysis including LDL-C determination 2

Cardiovascular Outcomes Evidence

The LRC-CPPT trial provides the only cardiovascular outcomes data for bile acid sequestrants:

• In 3,806 asymptomatic middle-aged men with primary hypercholesterolemia, cholestyramine reduced the risk of definite CHD death and/or definite nonfatal MI by 19% over 7.4 years (p<0.05) 1
• This benefit was proportional to the degree of LDL cholesterol lowering achieved 1
• No cardiovascular outcomes data exist for colesevelam or colestipol 1

Special Populations

Diabetes mellitus:

• In patients with well-controlled NIDDM and LDL-C >130 mg/dL with triglycerides <300 mg/dL, cholestyramine (8 g twice daily) reduced LDL-C by 28% and may improve glycemic control 6
• Mean plasma glucose decreased by 13% and urinary glucose excretion decreased in diabetic patients 6

Pregnancy and lactation:

• Considered safe to use during pregnancy and lactation 1

Practical Implementation Algorithm

1. Confirm indication: Primary hypercholesterolemia with LDL-C above target despite dietary therapy 2
2. Screen for contraindications: Check triglycerides (<400-500 mg/dL), assess for biliary obstruction, GI motility disorders 1, 2
3. Start at 8 g/day divided into 2 doses (4 g with breakfast and dinner) 1, 2
4. Separate other medications: Schedule critical medications 1 hour before or 4 hours after cholestyramine 1
5. Titrate based on response: If LDL-C target not achieved after 1 month, increase to 16 g/day 2, 3
6. Consider combination therapy: If monotherapy insufficient, add statin rather than exceeding 16 g/day of cholestyramine 1, 3

Common Pitfalls to Avoid

• Do not use cholestyramine as monotherapy when triglycerides are elevated (>400 mg/dL), as it may worsen hypertriglyceridemia and precipitate pancreatitis 1, 2
• Do not exceed 16 g/day without clear benefit, as the dose-response curve plateaus and side effects increase 4, 3
• Do not forget to supplement fat-soluble vitamins and folate, particularly in long-term therapy and in children 1, 4
• Do not co-administer with other medications without proper timing separation (1 hour before or 4 hours after) 1