How should I prescribe colestipol (Colestid) for an adult with primary hypercholesterolemia or mixed dyslipidemia whose LDL‑C remains elevated despite diet and exercise?

How to Prescribe Colestipol for Primary Hypercholesterolemia

Colestipol is a second-line bile acid sequestrant reserved for patients who cannot tolerate statins or require additional LDL-lowering beyond maximally tolerated statin therapy; it should never be used as first-line monotherapy when statins are appropriate.

When to Consider Colestipol

• Statins remain the first-line pharmacologic treatment for elevated LDL-C in adults with primary hypercholesterolemia, with proven reduction in cardiovascular morbidity and mortality 1, 2.
• Colestipol may be considered when:
  • Statins are contraindicated (e.g., pregnancy, severe statin intolerance with documented myopathy) 3, 4
  • Additional LDL-C lowering is needed after maximally tolerated statin therapy 1, 2
  • The patient has statin intolerance and ezetimibe alone is insufficient 1

Dosing and Administration

Starting Dose and Titration

• Begin with colestipol granules 5 g twice daily (with breakfast and dinner) or colestipol tablets 2 g twice daily to minimize gastrointestinal side effects 5, 4.
• Titrate upward every 4–6 weeks based on LDL-C response and tolerability 5, 4.
• Target maintenance dose: 10–16 g daily in divided doses (granules 5–8 g twice daily or tablets 4–8 g twice daily) 5, 4.
• Maximum dose: 30 g daily, though doses above 16 g daily rarely provide additional LDL-C reduction and increase side effects 3, 5.

Formulation Options

• Colestipol tablets and granules are therapeutically equivalent, producing identical 12% LDL-C reduction at 4 g/day and 24–25% reduction at 16 g/day 4.
• Tablets are preferred by most patients due to improved palatability and convenience (odorless, tasteless) 3, 4.
• Granules must be mixed with water, juice, or other beverages; never take dry 3.

Expected Efficacy

• At 16 g/day, colestipol reduces LDL-C by approximately 24–26% and total cholesterol by 15–16% 5, 4.
• At 4 g/day, expect 12% LDL-C reduction and 7–8% total cholesterol reduction 5, 4.
• HDL-C may increase by 5–23% in a dose-dependent manner 5, 4.
• Triglycerides may increase by 10–20%, particularly at higher doses; colestipol is contraindicated in patients with baseline triglycerides >300 mg/dL 3, 5, 4.

Critical Drug Interactions

• Colestipol binds many orally administered medications, reducing their absorption 3.
• Administer all other medications at least 1 hour before or 4 hours after colestipol to avoid binding 3.
• Particularly affected drugs include:
  • Thyroid hormones (levothyroxine)
  • Warfarin
  • Digoxin
  • Thiazide diuretics
  • Fat-soluble vitamins (A, D, E, K) 3

Monitoring Protocol

• Obtain fasting lipid panel 4–6 weeks after initiation or dose adjustment to assess LDL-C response 5, 4.
• Once LDL-C goal is achieved, perform annual fasting lipid assessments 2, 6.
• Monitor for fat-soluble vitamin deficiency (vitamins A, D, E, K) with prolonged use, especially in patients on restricted diets 3.
• Assess triglyceride levels at each visit; discontinue if triglycerides rise above 400 mg/dL 3, 5.

Common Adverse Effects and Management

• Gastrointestinal symptoms (constipation, bloating, nausea) occur in 20–30% of patients and are the primary reason for discontinuation 3, 4.
• To minimize GI side effects:
  • Start at low dose (5 g granules or 2 g tablets twice daily) and titrate slowly 5, 4
  • Take with meals and adequate fluid 3, 4
  • Increase dietary fiber and fluid intake to prevent constipation 3
  • Consider stool softeners or psyllium if constipation persists 3

Critical Pitfalls to Avoid

• Do not use colestipol as first-line monotherapy when statins are appropriate; statins have superior cardiovascular outcomes data 1, 2.
• Do not prescribe colestipol to patients with triglycerides >300 mg/dL or type III, IV, or V hyperlipoproteinemia, as it will worsen hypertriglyceridemia 3, 5.
• Do not administer other medications within 1 hour before or 4 hours after colestipol due to binding interactions 3.
• Do not start at high doses (>10 g/day); this dramatically increases GI side effects and reduces compliance 5, 4.
• Do not overlook the need for concurrent therapeutic lifestyle changes (saturated fat <7% of calories, dietary cholesterol <200 mg/day, plant stanols/sterols 2 g/day, soluble fiber 10–25 g/day) 1.

Combination Therapy Considerations

• When combining colestipol with a statin, administer the statin at least 1 hour before or 4 hours after colestipol to avoid binding 3.
• Combination therapy (statin + colestipol) can achieve 40–50% LDL-C reduction but significantly increases GI side effects 3, 4.
• Ezetimibe is generally preferred over colestipol as add-on therapy to statins due to superior tolerability and once-daily dosing 1, 2.