Examples of Bile Acid Sequestrants
The three main bile acid sequestrants available are cholestyramine, colestipol, and colesevelam, which bind bile acids in the intestinal lumen to lower LDL cholesterol by 18-25% at standard doses. 1
First-Generation Agents
- Cholestyramine is dosed at up to 24 g daily and has been used since the 1980s as a proven lipid-lowering agent 1
- Colestipol requires doses up to 20 g daily to achieve comparable LDL cholesterol reduction 1
- Both first-generation agents have significant gastrointestinal side effects including bloating, constipation, and palatability issues that limit patient compliance 1, 2
Second-Generation Agents
- Colesevelam (also called colesevelam hydrochloride) is dosed at 4.5 g daily and represents a major advancement with improved tolerability 1
- Colesevelam has a different chemical structure that maximizes bile salt binding while reducing drug-drug interactions compared to older agents 1
- This second-generation agent causes fewer gastrointestinal adverse effects, making it the preferred bile acid sequestrant 3
Additional Second-Generation Options
- Colestilan and colextran are other second-generation bile acid sequestrants mentioned in the literature, though less commonly used in clinical practice 4, 5
Critical Drug Interaction Considerations
- All other medications must be taken at least 1 hour before or 4-6 hours after bile acid sequestrants to avoid impaired absorption 1, 6
- Cholestyramine and colestipol can significantly reduce absorption of warfarin, thyroid preparations, digoxin, mycophenolate (by 35%), and fat-soluble vitamins 1, 6
- Colesevelam has fewer drug interactions but still reduces absorption of glyburide, levothyroxine, and oral contraceptives 1
- In liver transplant patients, bile acid sequestrants should generally be avoided due to the 35% reduction in mycophenolate levels 1
Important Safety Monitoring
- Fat-soluble vitamins (A, D, E, K) may require supplementation during long-term use, particularly vitamin K monitoring via INR/prothrombin time 1, 6, 7
- Colesevelam is contraindicated when triglycerides exceed 500 mg/dL due to risk of hypertriglyceridemia-induced pancreatitis 7
- Bowel obstruction risk requires caution in patients with gastroparesis or history of major gastrointestinal surgery 7