1. Drug Class

• Bile Acid Sequestrant (BAS)
• Non-systemic, polymeric resin

2. Mechanism of Action

• Binds bile acids in the intestine, forming insoluble complexes excreted in feces
• ↓ enterohepatic bile acid recycling → ↑ hepatic conversion of cholesterol to bile acids
• ↑ LDL receptor expression → ↓ LDL-C

Glycemic effect (Type 2 DM):

• Exact mechanism unclear
• Likely ↓ intestinal glucose absorption and modulation of FXR/TGR5 pathways → modest HbA1c reduction

3. Indications

Approved indications:

• Primary hyperlipidemia (↓ LDL-C)
• Adjunct therapy in Type 2 Diabetes Mellitus to improve glycemic control

Off-label / clinical use:

• Bile acid–induced diarrhea (e.g., post-cholecystectomy)
• Alternative lipid-lowering agent when statins are contraindicated or not tolerated

4. Dosing & Administration

Dosing options

• 6 tablets (625 mg each) once daily
• OR 3 tablets twice daily
• Powder for suspension available

Administration tips

• Take with meals
• Swallow tablets whole (large tablets—adherence issue)
• Powder must be fully mixed with liquid

5. Lipid Effects (Clinical Expectations)

⚠️ Avoid if baseline TG ≥ 500 mg/dL

6. Glycemic Effects (T2DM)

• HbA1c reduction: ~0.3–0.5%
• Best used as adjunct, not monotherapy
• No hypoglycemia risk when used alone

7. Adverse Effects

Common:

• Constipation (most frequent)
• Dyspepsia, bloating, nausea
• Flatulence

Less common but clinically important:

• Hypertriglyceridemia
• Bowel obstruction (rare, ↑ risk in severe constipation or GI disease)

8. Drug–Drug Interactions (Key Pharmacist Focus)

Colesevelam binds other drugs in the gut, reducing absorption.

Drugs of concern:

• Levothyroxine
• Warfarin
• Phenytoin
• Carbamazepine
• Digoxin
• Oral contraceptives (ethinyl estradiol)
• Fat-soluble vitamins (A, D, E, K)

Management strategy:

Administer interacting medications ≥ 4 hours before colesevelam

✅ Colesevelam has fewer interactions than cholestyramine/colestipol but risk still exists.

9. Contraindications & Cautions

Contraindications:

• TG ≥ 500 mg/dL
• History of hypertriglyceridemia-induced pancreatitis
• Bowel obstruction

Use with caution:

• Chronic constipation
• GI motility disorders
• Patients with swallowing difficulties

10. Monitoring Parameters

11. Clinical Pearls for Pharmacists

• Good option when statins are not tolerated, especially if LDL lowering is modestly needed
• Avoid in patients with elevated triglycerides
• Large tablet size → adherence counseling is critical
• Useful dual benefit in T2DM + dyslipidemia
• Does not cause systemic toxicity (non-absorbed)

12. Comparison with Other BAS (Quick Insight)