Medications> Dyslipidemia>

INDICATIONS

• Hypercholesterolemia: To prevent cardiovascular disease or its complications
• Poorly controlled type 2 diabetes: To lower HbA1c (colesevelam)
• Relief of pruritus associated with partial biliary obstruction (cholestyramine)

MECHANISM

• Binds bile acids in the intestine and removes them in the stools. In compensation, the liver converts more cholesterol to bile acids.
• The fall in liver free cholesterol leads to synthesis of the hepatic LDL receptor, increases the removal of LDL from the blood, and lowers serum levels of total and LDL cholesterol.

USUAL ADULT DOSING

• Cholestyramine powder: administer  1 or 2 packets or 1 or 2 level scoopful once or twice a day. Maintenance dose: 2 to 4 packets or scoopfuls daily (8-16 grams anhydrous cholestyramine resin), divided into two doses; take with meals.  
• Colestid tablets: 2 to 16 g (2 to 16 tabs)  daily given once or in divided doses. Starting dose: 2 grams once or twice daily. Titrate by 2 grams over a 1- or 2-month intervals to maintenance dose, OR Colestid granmules: 5 to 30 g (one to six packets or level scoopfuls given once or in divided doses). Treatment should be started with one dose once or twice daily.
• Colesevelam hydochloride 6 tablets (3.75 g) once daily or 3 tablets (1.875 g) twice daily with a meal or liquid
• Thoroughly stir or use Waring blender to mix powder before ingestion.

FORMS

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

DOSING IN SPECIAL POPULATIONS

• No data. Usual dose likely.

• No data. Usual dose likely.

• Category B

• Not found in breast milk; however, bile acid sequestrants interferes with absorption of fat-soluble vitamins and should be used with caution in nursing women.

ADVERSE DRUG REACTIONS

• Except for causing constipation, bile acid sequestrants are well tolerated.

• Constipation

• Belching, bloating

• Stomach pain
• Nausea and vomiting

DRUG INTERACTIONS

• Can interfere with the absorption of many orally administered medications. To minimize drug interactions, administer all drugs at least 1 hour before or at least 4-6 hours after the administration of cholestyramine. Medications should be taken 4 hours before a dose of colesevelam.
• Drug-drug interactions with the following medications, causing potential lost of therapeutic efficacy: thiazide diuretic, furosemide, glipizide, propranolol, oral penicillin, oral vancomycin, tetracyclines, fat-soluble vitamins (e.g., ADEK), iron supplement, levothyroxine, raloxifene, digoxin, methotrexate, ursodiol, imipramine, valproic acid, certain NSAID, gemfibrozil, and fenofibrate.
• Warfarin: may increase or decrease INR with co-administration.
• Ezetimibe: efficacy may be decreased. Ezetimibe should be administered at least 2 hours before or 4 hours after administration of a bile acid sequestrant.

PHARMACOKINETIC

COMMENTS

• Bile acid sequestrants can lower LDL cholesterol by 15 to 25% depending on the amount taken, and may raise HDL cholesterol by about 2%. 
• Can raise triglyceride levels (Crouse), and should not be taken by people with hypertriglyceridemia.
• The powders and granules are inconvenient because they must be thoroughly mixed with a liquid., Colestid pills are large and may be difficult to swallow.
• Colesevelam is form most commonly used, is more convenient to take and is associated with fewer side effects (Davidson).
• To avoid interference with absorption of medications by cholestyramine or colested, take them one hour before or 4 to 6 hours after taking the sequestrant. Or take medications 4 hours before colesevelam.  
• Sequestrants may interfere with the absorption of fat soluble vitamins.
• Colesevelam can lower HbA1c slightly in patients with type 2 diabetes (Fonseca;Bays)
• Do not use bile acid sequestrants with biliary or intestinal obstruction, gastroparesis or other problems with gastrointestinal motility.
• Colesevelam and colestid tablets should be used with caution in people with dysphagia or swallowing disorders.

REFERENCES