Colesevelam

• High Cholesterol
• Type 2 Diabetes
• Familial Hypercholesterolemia
• LDL Cholesterol Reduction

Colesevelam is a bile acid sequestrant used for the management of hyperlipidemia and type 2 diabetes mellitus. This medication works by binding bile acids in the intestine, reducing cholesterol absorption and providing glycemic benefits through mechanisms that are not fully understood.

Mechanism of Action

Colesevelam is a non-absorbed, lipid-lowering polymer that binds bile acids in the intestine, preventing their reabsorption through enterohepatic circulation. Bile acids are synthesized in the liver from cholesterol; when they are bound by colesevelam and excreted in feces, the liver must synthesize more bile acids from cholesterol, thereby reducing hepatic cholesterol stores. This triggers upregulation of LDL receptors on hepatocytes, increasing clearance of LDL cholesterol from the blood. The mechanism for glucose lowering is less clear but may involve effects on glucose absorption, incretin secretion, or farnesoid X receptor signaling in the intestine.

Available Formulations

Colesevelam is available as tablets (625 mg) and as granules for oral suspension (1.875 g and 3.75 g packets). The tablets should be swallowed whole with liquid and food. The oral suspension should be mixed with 4-8 ounces of water, fruit juice, or diet soft drinks; it should not be taken in dry form. The suspension forms a gel that should be consumed promptly after mixing.

Medical Uses

Colesevelam is FDA-approved as adjunctive therapy to diet and exercise to reduce elevated LDL cholesterol in adults with primary hyperlipidemia (as monotherapy or in combination with statins) and to improve glycemic control in adults with type 2 diabetes mellitus (in combination with other antidiabetic medications, not as monotherapy). It can be used in pediatric patients (10-17 years) with heterozygous familial hypercholesterolemia. It is often used when statins alone are insufficient or in patients who cannot tolerate statins.

Dosing Guidelines

For hyperlipidemia, the recommended dose is 3.75 g once daily or 1.875 g twice daily with meals. This can be given as six 625 mg tablets daily or one 3.75 g packet daily. For type 2 diabetes, the same dosing applies. The tablets should be taken with a meal and liquid. The oral suspension should be taken with meals. Maximum dose is 3.75 g daily for adults and 3.75 g daily for pediatric patients. Combining with a statin provides additive LDL reduction.

Important Safety Information

Colesevelam is contraindicated in patients with bowel obstruction, those with triglyceride levels greater than 500 mg/dL, and in patients with a history of hypertriglyceridemia-induced pancreatitis. Colesevelam can raise triglyceride levels; baseline and periodic monitoring is recommended. It may cause or worsen constipation, potentially leading to bowel obstruction, especially in patients with GI motility disorders or previous GI surgery. The medication can reduce absorption of fat-soluble vitamins (A, D, E, K); supplementation may be needed with long-term use.

Drug Interactions

Colesevelam can reduce the absorption of many medications. Drugs with known interactions include glyburide, levothyroxine, oral contraceptives containing ethinyl estradiol and norethindrone, phenytoin, and warfarin. These medications should be taken at least 4 hours before colesevelam. Other medications with potential for interaction should also be administered separately. Cyclosporine and some statins may have reduced absorption; monitoring is recommended.

Special Populations

Colesevelam is pregnancy category B; it is not absorbed systemically, reducing fetal exposure concerns, but it may interfere with fat-soluble vitamin absorption. Supplementation should be considered during pregnancy. The medication is not expected to be present in breast milk since it is not absorbed. Safety and efficacy have been established in pediatric patients 10-17 years old for familial hypercholesterolemia. Elderly patients may be more susceptible to GI side effects. No dose adjustment is needed for renal or hepatic impairment as the medication is not absorbed.