What is Colesevelam (bile acid sequestrant) used for and what are its typical dosing recommendations?

Colesevelam: Uses and Dosing Recommendations

Colesevelam is a bile acid sequestrant primarily used to lower LDL cholesterol and improve glycemic control in type 2 diabetes, with standard dosing of 3.75 g daily as tablets (6 tablets once daily or 3 tablets twice daily) or as oral suspension (one 3.75 g packet daily or one 1.875 g packet twice daily). 1, 2

Primary Indications

Hyperlipidemia Management

• FDA-approved as an adjunct to diet and exercise to reduce elevated LDL cholesterol in:
  • Adults with primary hyperlipidemia 2
  • Boys and postmenarchal girls (10-17 years) with heterozygous familial hypercholesterolemia (HeFH) who cannot reach LDL-C targets despite adequate diet therapy 2

Glycemic Control

• Improves glycemic control in adults with type 2 diabetes 1
• Can reduce HbA1c by approximately 0.5% in patients with type 2 diabetes 3, 4

Mechanism of Action

Colesevelam works through a non-systemic mechanism as a non-absorbed, polymeric bile acid sequestrant that:

• Binds bile acids in the intestine, preventing their reabsorption 1
• Depletes the bile acid pool, upregulating hepatic enzyme cholesterol 7-α-hydroxylase 1
• Increases conversion of cholesterol to bile acids 1
• Increases hepatic LDL receptor activity, enhancing clearance of LDL particles from blood 1
• Results in decreased serum LDL-C levels 1

Dosing Recommendations

For Hyperlipidemia

• Tablets: 6 tablets (3.75 g) once daily or 3 tablets (1.875 g) twice daily; take with meals and liquid 1
• Suspension: One 3.75 g packet daily or one 1.875 g packet twice daily; mix with 8 ounces of water, fruit juice, or soft drink; take with meals 1

For Type 2 Diabetes

• Same dosing as for hyperlipidemia 1

Efficacy

• Monotherapy: Reduces LDL-C by approximately 15-20% 1, 5
• Combination therapy: Provides additional 10-16% reduction in LDL-C when added to statin therapy 1, 6
• Glycemic effects: Reduces HbA1c by approximately 0.5% in type 2 diabetes 3, 4

Contraindications

• Triglyceride levels >500 mg/dL 2
• History of hypertriglyceridemia-induced pancreatitis 2
• Bowel obstruction 2

Warnings and Precautions

• Hypertriglyceridemia: May increase triglyceride levels; monitor levels periodically 2
• Gastrointestinal effects: May cause constipation, dyspepsia, and nausea 1
• Drug interactions: May decrease absorption of other medications; other medications should be taken at least 4 hours before colesevelam 1
• Vitamin absorption: May decrease absorption of fat-soluble vitamins; oral vitamins should be taken at least 4 hours before colesevelam 1

Special Considerations

Pediatric Use

• Approved for boys and postmenarchal girls aged 10-17 years with HeFH 2, 7
• Powder formulation may be preferred for pediatric patients due to tablet size 2

Pregnancy

• Considered safe to use during pregnancy 1

Drug Interactions

• Decreased absorption of: cyclosporine, oral contraceptives, olmesartan, phenytoin, sulfonylureas, thyroid replacement therapy, warfarin 1
• For patients on warfarin: monitor INR frequently 1
• All interacting medications should be given 4 hours before colesevelam 1

Clinical Pearls

• Colesevelam has fewer gastrointestinal side effects compared to older bile acid sequestrants like cholestyramine 5
• Can be used as second-line therapy after failure of cholestyramine 1
• Gradual dose titration may help minimize side effects 1
• Unlike other bile acid sequestrants, colesevelam is available in tablet form, which may improve adherence 5
• Consider colesevelam particularly for patients who need both LDL-C reduction and glycemic control 8

Monitoring

• Obtain baseline lipid parameters, including triglyceride levels, before starting treatment 2
• Monitor lipid levels 4-6 weeks after initiation 2
• For patients on warfarin, monitor INR more frequently when starting or adjusting colesevelam 1

By understanding these key aspects of colesevelam therapy, clinicians can appropriately select patients who would benefit from this medication and optimize its use for reducing cardiovascular risk and improving glycemic control.