Colesevelam is a bile acid sequestrant. Colesevelam is used with exercise and diet changes (restriction of cholesterol and fat intake) to reduce the amount of cholesterol and certain fatty substances in the blood. It works by binding bile acids in the intestine. Bile acids are made when cholesterol is broken down in the body. Removing these bile acids helps to lower blood cholesterol.
Indication
For use, alone or in combination with an HMG-CoA reductase inhibitor, as adjunctive therapy to diet and exercise for the reduction of elevated LDL cholesterol in patients with primary hypercholesterolemia (Fredrickson Type IIa).
Pharmacology
Colesevelam is a high capacity bile-acid binding molecule. Colesevelam binds to bile acids in the intestine which reduces the amount of bile acids that are returned to the liver via enterohepatic circulation. Clinical studies have demonstrated that elevated levels of total cholesterol (total-C), LDL-C, and apolipoprotein B (Apo B, a protein associated with LDL-C) are associated with an increased risk of atherosclerosis in humans. Similarly, decreased levels of high-density lipoprotein cholesterol (HDL-C) are associated with the development of atherosclerosis. Epidemiological investigations have established that cardiovascular morbidity and mortality vary directly with the levels of total-C and LDL-C, and inversely with the level of HDL-C. The combination of colesevelam and an HMG-CoA reductase inhibitor is effective in further lowering serum total-C and LDL-C levels beyond that achieved by either agent alone.
Toxicity
Symptoms of overdose may include eye irritation, constipation, abdominal cramps, nausea, vomiting, diarrhea, and hypersensitivity. However, as colesevelam is not absorbed, the risk of systemic toxicity is low. Doses in excess of 4.5 g per day have not been tested.
Affected Organisms
Humans and other mammals
Biotransformation
Not applicable (not hydrolyzed by digestive enzymes and not absorbed).
Absorption
Not hydrolyzed by digestive enzymes and is not absorbed.
Protein Binding
Not applicable (not hydrolyzed by digestive enzymes and not absorbed).
Elimination
Excretion: In 16 healthy volunteers, an average of 0.05% of administered radioactivity from a single 14C-labeled colesevelam hydrochloride dose was excreted in the urine.
