What is the recommended dosing for Colesevelam (bile acid sequestrant)?

Colesevelam Dosing

For adults with primary hyperlipidemia, the recommended dose of colesevelam is 3.75 grams daily, administered either as 6 tablets (625 mg each) once daily or 3 tablets twice daily with meals, or as one 3.75-gram oral suspension packet once daily mixed with 4-8 ounces of liquid and taken with a meal. 1, 2

Standard Adult Dosing Regimens

Tablet Formulation

• 6 tablets (625 mg each) once daily with a meal and liquid 1, 3, 2
• Alternative: 3 tablets twice daily with meals and liquid 1, 3, 2

Oral Suspension Formulation

• One 3.75-gram packet once daily mixed with 4-8 ounces of water, fruit juice, or diet soft drink, taken with a meal 1, 3, 2
• Alternative: One 1.875-gram packet twice daily (equivalent to 3 tablets per dose) 1, 3

Pediatric Dosing (Ages 10-17 Years)

For boys and postmenarchal girls aged 10-17 years with heterozygous familial hypercholesterolemia, the recommended dose is 3.75 grams daily, administered as monotherapy or in combination with a statin. 1, 2, 4

• The same dosing regimens apply as for adults (6 tablets once daily or 3 tablets twice daily with meals) 2, 4
• This dosing has been studied for up to 26 weeks in pediatric patients and demonstrated sustained efficacy and tolerability 4

Expected LDL-C Reduction

Monotherapy

• Colesevelam 3.75 grams daily as monotherapy reduces LDL-C by approximately 15% 1

Combination Therapy with Statins

• When added to low- to moderate-intensity statins, colesevelam provides an additional 10-16% reduction in LDL-C 1
• Combination therapy appears more effective than monotherapy for achieving LDL-C goals 5

Critical Administration Requirements

Timing with Meals

Colesevelam must be taken with meals to ensure optimal interaction with bile acids released during digestion. 3

• The drug binds bile acids in the intestine, which are released during meal digestion 3
• Taking with food maximizes bile acid sequestration and lipid-lowering efficacy 3
• Practical scheduling: Take with breakfast and/or dinner 3

Drug Interaction Management

All other medications must be taken at least 1 hour before or 4 hours after colesevelam to avoid impaired absorption. 1, 3, 2

High-Risk Medications Requiring Strict Separation

The following drugs have narrow therapeutic windows and require careful timing 1, 3, 2:

• Thyroid hormone replacement therapy
• Warfarin
• Phenytoin
• Oral contraceptives (ethinyl estradiol/norethindrone)
• Cyclosporine
• Olmesartan medoxomil
• Sulfonylureas (glimepiride, glipizide, glyburide)

Practical implementation: Take other medications either first thing in the morning (1+ hours before colesevelam) or at bedtime (4+ hours after colesevelam). 3

Special Populations and Considerations

Type 2 Diabetes

• Colesevelam 3.75 grams daily is FDA-approved as adjunct therapy to improve glycemic control in adults with type 2 diabetes 1, 2
• The drug lowers HbA1c by approximately 0.5% when used in diabetic patients 1
• Long-term use (52 weeks) demonstrated safety without weight gain (mean 0.2 kg reduction) 6

Bile Acid Diarrhea (Off-Label)

• For bile acid diarrhea, colesevelam is typically dosed as 2 tablets (625 mg) three times daily with meals 1
• Colesevelam is generally reserved as second-line therapy after cholestyramine failure or intolerance 1
• Success rate as second-line therapy ranges from 42-100% in observational studies 1

Contraindications

Do not use colesevelam in patients with: 2

• Serum triglyceride levels >500 mg/dL
• History of hypertriglyceridemia-induced pancreatitis
• History of bowel obstruction
• Complete biliary obstruction

Safety and Tolerability Profile

Common Adverse Effects

The most common adverse effects are gastrointestinal: constipation, dyspepsia, and nausea, occurring at rates similar to placebo (approximately 40%). 1

• In long-term studies (52 weeks), 70.9% of patients experienced adverse events, with 88.1% being mild or moderate 6
• Only 6.9% discontinued due to adverse events 6
• Colesevelam has significantly better tolerability than traditional bile acid sequestrants like cholestyramine 1, 7

Compliance Advantages

• Compliance rates with colesevelam reach 93%, substantially higher than traditional bile acid sequestrants 7
• The tablet formulation eliminates the palatability issues associated with cholestyramine powder 1
• Colesevelam is 4-6 times more potent than traditional bile acid sequestrants, allowing for lower pill burden 7

Clinical Pearls and Pitfalls

Vitamin Supplementation

Patients requiring oral vitamin supplementation (especially fat-soluble vitamins A, D, E, K) should take vitamins at least 4 hours before colesevelam. 1, 2

• Patients on warfarin are at particular risk for vitamin K deficiency 2
• Patients with malabsorption syndromes require monitoring for fat-soluble vitamin deficiencies 2

Triglyceride Monitoring

Monitor triglyceride levels before starting and periodically during therapy, as colesevelam may increase triglycerides. 2

• Instruct patients to discontinue colesevelam and seek immediate medical attention if symptoms of acute pancreatitis develop 2

Phenylketonuria Warning

Colesevelam oral suspension contains 33.6 mg phenylalanine per 3.75-gram packet and should be avoided in patients with PKU. 2

Gastrointestinal Motility Disorders

Colesevelam is not recommended in patients with gastroparesis, other GI motility disorders, or those who have had major GI surgery due to risk of bowel obstruction. 2