indication

Indicated as adjunctive therapy to diet for the reduction of elevated serum cholesterol in patients with primary hypercholesterolemia (elevated low density lipoprotein [LDL] cholesterol) who do not respond adequately to diet. Also for the relief of pruritus associated with partial biliary obstruction.

pharmacology

Cholesterol is probably the sole precursor of bile acids. During normal digestion, bile acids are secreted into the intestines. A major portion of the bile acids is absorbed from the intestinal tract and returned to the liver via the enterohepatic circulation. Only very small amounts of bile acids are found in normal serum. Cholestyramine resin adsorbs and combines with the bile acids in the intestine to form an insoluble complex which is excreted in the feces. This results in a partial removal of bile acids from the enterohepatic circulation by preventing their absorption.

mechanism of action

Cholestyramine binds bile in the gastrointestinal tract to prevent its reabsorption. The resin is a strong anion exchange resin, which means that it can exchange its chloride anions with anionic bile acids in the gastrointestinal tract and bind them strongly in the resin matrix. The functional group of the anion exchange resin is a quaternary ammonium group attached to an inert styrene-divinylbenzene copolymer.

toxicity

Overdose may result in blockage of intestine or stomach.

biotransformation

Bile acids

absorption

Not absorbed from the gastrointestinal tract following oral administration.

half life

6 minutes

route of elimination

Cholestyramine resin adsorbs and combines with the bile acids in the intestine to form an insoluble complex which is excreted in the feces.

drug interactions

Acenocoumarol: The bile acid sequestrant, cholestyramine, may decrease the anticoagulant effect of acenocoumarol by decreasing its absorption.

Anisindione: The bile acid sequestrant, cholestyramine, may decrease the anticoagulant effect of anisindione by decreasing its absorption.

Bezafibrate: Bile acid sequestrants like cholestyramine may decrease the absorption of fibric acid derivatives like bezafibrate. Therapy modification should be considered. If concomitant therapy is used, separate doses by at least 2 hours to minimize this interaction. Fenofibric acid labeling recommends administration one hour prior to or 4-6 hours after a bile acid sequestrant.

Chlorothiazide: Bile acid sequestrants may decrease the absorption of thiazide diuretics such as chlorothiazide. The diuretic response is likewise decreased. Monitor for decreased therapeutic effects of thiazide diuretics if coadministered with a bile acid sequestrant. If these agents are used concomitantly, separate doses 2 or more hours to minimize the interaction.

Cholecalciferol: Bile acid sequestrants such as cholestyramine may decrease the serum concentration of Vitamin D analogs such as cholecalciferol. More specifically, bile acid sequestrants may impair absorption of Vitamin D analogs. Avoid concomitant administration of vitamin D analogs and bile acid sequestrants. Monitor plasma calcium concentrations in patients receiving combined therapy with these agents. This is particularly important in patients receiving higher doses of a bile acid sequestant (i.e., 30 g/day or more of cholestyramine or equivalent) or in patients experiencing bile acid sequestrant-induced steatorrhea. Specific recommendations regarding the separation of administration of these agents are not defined; however, it would seem prudent to separate the administration of these agents by several hours to minimize the potential risk of interaction. Similar precautions do not apply to parenterally administered vitamin D analogs.

Dicumarol: The bile acid sequestrant, cholestyramine, may decrease the anticoagulant effect of dicumarol by decreasing its absorption.

Digoxin: The resin decreases the effect of digoxin

Ezetimibe: Cholestyramine may decrease the levels of ezetimibe.

Fluvastatin: Increased/decreased effect according to spacing

Hydrocortisone: Cholestyramine may decrease the effect of hydrocortisone.

Levothyroxine: The resin, cholestyramine, decreases the absorption of the thyroid hormone, levothyroxine.

Liothyronine: The resin, cholestyramine, decreases the absorption of the thyroid hormones, liothyronine.

Liotrix: The resin, cholestyramine, decreases the absorption of the thyroid hormone, liotrix.

Methotrexate: Decreased levels of methotrexate

Raloxifene: The resin decreases the effect of raloxifene

Spironolactone: Increased risk of acidosis and hyperkalemia

Sulindac: The bile acid sequestrant, cholestyramine, may decrease the absorption of the NSAID, sulindac. Monitor for changes in the therapeutic and adverse effects of sulindac if cholestyramine is initiated, discontinued or dose changed. Administering the two agents 2 or more hours apart may reduce, but not eliminate, the risk of this interactions.

Tenoxicam: Cholestyramine may decrease the serum concentration of Tenoxicam by increasing clearance. Monitor for changes in Tenoxicam therapeutic and adverse effects if Cholestyramine is initiated, discontinued or dose changed.

Thyroglobulin: The resin, cholestyramine, decreases the absorption of the thyroid hormone, thyroglobulin.

Tiaprofenic acid: The bile acid sequestrant, Cholestyramine resin, may reduce Tiaprofenic acid absorption and therapeutic effect.

Tolmetin: Cholestyramine may decrease the absorption of Tolmetin. Monitor for changes in the therapeutic and adverse effects of Tolmetin if Cholestyramine is initiated, discontinued or dose changed. Spacing administration by at least 2 hours may reduce the risk of interaction.

Torasemide: Cholestyramine may decrease the bioavailability of Torasemide by inhibiting Torasemide absorption. Monitor for changes in the therapeutic and adverse effects of Torasemide if Cholestyramine is initiated, discontinued or dose changed. Spacing administration by at least 2 hours may reduce the risk of interaction.

Trichlormethiazide: The bile acid sequestrant, Cholestyramine resin, may inhibit the absorption of Trichlormethiazide.

Troglitazone: Decreases the effect of troglitazone

Ursodeoxycholic acid: The resin decreases the effect of ursodiol

Warfarin: The bile acid sequestrant, cholestyramine, may decrease the anticoagulant effect of warfarin by decreasing its absorption.