The P-I-E-N-O Parkinsn's List Drug Database
cholestyramine / QuestranTM
CHOLESTEROL CONTROL :
Description: Cholestyramine is a polymeric resin, administered orally to bind bile acids. Originally, cholestyramine was used to treat pruritis secondary to cholestasis, but its main use today is to treat hypercholesterolemia with concomitant hypertriglyceridemia. Cholestyramine also has been used to treat Clostridium difficile enterocolitis, although traditional antibiotics are more effective. Since cholestyramine and the related agent colestipol are not absorbed orally, they are the drugs of choice for treating hyperlipidemia in pregnant women. Cholestyramine was approved by the FDA in 1966.
Mechanism of Action: Cholestyramine resin releases chloride and combines with bile acids in the intestine to form insoluble, nonabsorbable complexes that are excreted in the feces along with unchanged resin. Bile acids undergo enterohepatic circulation. Since cholesterol is the precursor of bile acids, interference with reuptake of bile acids actually stimulates cholesterol synthesis via an increase in the activity of HMG-CoA reductase. Plasma cholesterol levels do not rise, however, since the newly formed cholesterol is shunted into the bile acid- synthesis pathway. In addition, the hepatocyte responds to this change in plasma cholesterol by intensifying uptake of low- density lipoprotein (LDL) cholesterol, thereby decreasing plasma cholesterol. Plasma cholesterol and LDL concentrations fall in patients with primary type II hyperlipoproteinemia. Plasma cholesterol concentrations decrease by 20-50% when these patients receive 12-32 g of cholestyramine resin daily.
Pharmacokinetics: Since cholestyramine is not absorbed orally, serum concentrations and half-life parameters do not apply. Reduction of plasma cholesterol usually is seen within the first month of therapy and returns to pretreatment levels within 1 month of discontinuation. Relief of pruritus associated with biliary stasis usually takes 1-3 weeks.
CONTRAINDICATIONS/PRECAUTIONS: Cholestyramine is contraindicated in patients with cholelithiasis or complete biliary obstruction. In these conditions, secretion of bile acids into the GI tract is impaired. Cholestyramine is also contraindicated in patients with primary biliary cirrhosis because it can further raise serum cholesterol.
Cholestyramine is relatively contraindicated in constipated patients because of the danger of fecal impaction. Cholestyramine is relatively contraindicated in patients with coronary artery disease or hemorrhoids because constipation can aggravate these conditions.
Because cholestyramine can bind with vitamin K, cholestyramine is relatively contraindicated in patients with any preexisting bleeding disorder or coagulopathy (see Interactions).
Cholestyramine is absolutely contraindicated in phenylketonuria because the sugar-free preparation is sweetened with aspartame, which contains phenylalanine.
Because cholestyramine can bind with exogenous thyroid hormones if administered simultaneously, cholestyramine is relatively contraindicated in patients with hypothyroidism (see Interactions).
Cholestyramine is relatively contraindicated in patients with renal disease because colestipol releases chloride, which can increase the risk of developing hyperchloremic metabolic acidosis.
Although adequate reproduction studies have not been performed in humans, cholestyramine is not absorbed systemically and is therefore not expected to cause fetal harm during pregnancy. However, cholestyramine is known to interfere with the absorption of fat-soluble vitamins, which may lead to deficiencies even with supplementation.
DRUG INTERACTIONS: Cholestyramine can bind with and possibly decrease the oral absorption of thiazide diuretics, oral furosemide, oral penicillin G, propranolol, oral tetracyclines, orally administered vancomycin, and fat-soluble vitamins such as vitamin A, vitamin D, and vitamin K, including orally- administered phytonadione. Cholestyramine can bind with and delay or prevent absorption of thyroid hormones including dextrothyroxine. Cholestyramine also can bind with chenodiol or ursodiol. Staggering the doses of these agents by several hours should prevent binding with cholestyramine.
Cholestyramine can decrease the serum concentrations of imipramine. While it is logical to conclude that staggering the times of administration may avoid this interaction, doing so did not prevent a similar interaction between cholestyramine and doxepin even when the doses were separated by 6 hours. Until more data are available, clinicians should avoid using cholestyramine in patients stabilized on doxepin or imipramine.
Cholestyramine can either increase or decrease the hypoprothrombinemic actions of warfarin. Cholestyramine can bind with vitamin K in the diet, impairing vitamin K absorption, which, in turn, may increase warfarin's hypoprothrombinemic effect. Conversely, cholestyramine can bind with warfarin directly and impair warfarin bioavailability. Metabolites of the more potent warfarin S-isomer, although inactive, are eliminated via the bile. Cholestyramine has been shown to accelerate the clearance of IV warfarin (no longer marketed). To prevent altering warfarin pharmacokinetics, doses of warfarin and cholestyramine should be staggered by at least 4-6 hours. Cholestyramine should be prescribed cautiously to any patient receiving warfarin since cholestyramine may enhance systemic warfarin clearance.
Cholestyramine can bind with digitoxin and enhance its clearance. Because digitoxin undergoes enterohepatic recirculation, staggering the administration times of each agent may not prevent this drug interaction. Cholestyramine should be used cautiously in patients receiving digitoxin. Patients should be observed for loss of digitalis effect if cholestyramine is added or for digitalis toxicity if cholestyramine is discontinued in a patient stabilized on cardiac glycosides. Digoxin also can be similarly affected, albeit to a lesser degree since it undergoes less enterohepatic recirculation than digitoxin. Parenteral digoxin does not seem to be affected.
Cholestyramine has been shown to reduce the bioavailability of glipizide but appears to have no effect on tolbutamide absorption. The effect of cholestyramine on the bioavailability of other oral sulfonylureas is unknown.
Cholestyramine enhances the clearance of methotrexate from the systemic circulation. This interaction has actually been used therapeutically in patients with methotrexate toxicity, although activated charcoal is more effective.
ADVERSE REACTIONS: The most common side effect of cholestyramine use is constipation. It usually is mild and transient but can produce fecal impaction. Cholestyramine can also worsen preexisting constipation and aggravate hemmorroids. Every effort should be made to avert possible constipation; the patient should be instructed to drink plenty of water. Other GI effects include cholelithiasis, pancreatitis, GI bleeding, peptic ulcer, steatorrhea, anorexia, malabsorption syndrome, distention, bloating, flatulence, nausea/vomiting, and diarrhea.
Chronic use of cholestyramine resin can cause bleeding due to hypoprothrombinemia secondary to vitamin K deficiency.
Because cholestyramine releases chloride ions, hyperchloremic acidosis could occur, particularly in smaller patients or children.
PATIENT INFORMATION:
What do cholestyramine tablets do?
Cholestyramine (QuestranTM Tablets) absorbs and combines with bile acids, which increases removal of cholesterol. It lowers blood fats and cholesterol for patients who are at risk of getting heart disease or a stroke. It is only for patients whose cholesterol level is not controlled by diet. It is not a cure. Cholestyramine also helps to relieve itching in patients with liver disease. Generic cholestyramine tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take cholestyramine?
They need to know if you have any of these conditions:
How should I take this medicine?
Take cholestyramine tablets by mouth. Follow the directions on the prescription label. Swallow the tablets one at a time, taking a mouthful of water with each tablet. Drink at least 4 fluid ounces of water with each dose of cholestyramine. Take your doses at regular intervals. Do not take your medicine more often than directed.
Special precautions for use in children:
This medicine is not for children under 6 years old.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with cholestyramine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking cholestyramine?
Serious side effects with cholestyramine include:
Call y our doctor as soon as you can if you get any of these side effects.
Minor side effects with cholestyramine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take cholestyramine?
Cholestyramine will not cure your condition, but taken regularly it will help keep down your cholesterol level. Visit your doctor for regular checks on your progress. Do not stop taking cholestyramine, except on your doctor's advice.
Cholestyramine is only part of a total cholesterol-lowering program. Your doctor or dietician can suggest a low-cholesterol and low-fat diet that will reduce your risk of getting heart and blood vessel disease. Avoid alcohol and smoking, and keep a proper exercise schedule.
Drink plenty of water while you are taking cholestyramine, to reduce the chance of getting constipated.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Protect from moisture. Keep container tightly closed. Throw away any unused medicine after the expiration date.
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