Cholestyramine

Cholestyramine for Oral Suspension, USP powder is contraindicated in patients with complete biliary obstruction where bile is not secreted into the intestine and in those individuals who have shown hypersensitivity to any of its components.

• General Chronic use of cholestyramine resin may be associated with increased bleeding tendency due to hypoprothrombinemia associated with Vitamin K deficiency.
• This will usually respond promptly to parenteral Vitamin K1 and recurrences can be prevented by oral administration of Vitamin K1.
• Reduction of serum or red cell folate has been reported over long term administration of cholestyramine resin.
• Supplementation with folic acid should be considered in these cases.
• There is a possibility that prolonged use of cholestyramine resin, since it is a chloride form of anion exchange resin, may produce hyperchloremic acidosis.
• This would especially be true in younger and smaller patients where the relative dosage may be higher.
• Caution should also be exercised in patients with renal insufficiency or volume depletion and in patients receiving concomitant spironolactone.
• Cholestyramine resin may produce or worsen preexisting constipation.
• The dosage should be increased gradually in patients to minimize the risk of developing fecal impaction.
• In patients with preexisting constipation, the starting dose should be 1 pouch or 1 scoop once daily for 5 to 7 days, increasing to twice daily with monitoring of constipation and of serum lipoproteins, at least twice, 4 to 6 weeks apart.
• Increased fluid intake and fiber intake should be encouraged to alleviate constipation and a stool softener may occasionally be indicated.
• If the initial dose is well tolerated, the dose may be increased as needed by one dose/day (at monthly intervals) with periodic monitoring of serum lipoproteins.
• If constipation worsens or the desired therapeutic response is not achieved at one to six doses/day, combination therapy or alternate therapy should be considered.
• Particular effort should be made to
• avoid constipation in patients with symptomatic coronary artery disease.
• Constipation associated with cholestyramine resin may aggravate hemorrhoids.
• Information for Patients Inform your physician
• Laboratory Tests Serum cholesterol levels should be determined frequently during the first few months of therapy and periodically thereafter.
• Serum triglyceride levels should be measured periodically to detect whether significant changes have occurred.
• The LRC-CPPT showed a dose-related increase in serum triglycerides of 10.7% to 17.1% in the cholestyramine-treated group, compared with an increase of 7.9% to 11.7% in the placebo group.
• Based on the mean values and adjusting for the placebo group, the cholestyramine-treated group showed an increase of 5% over pre-entry levels the first year of the study and an increase of 4.3% the seventh year.
• Drug Interactions Cholestyramine resin may delay or reduce the absorption of concomitant oral medication such as phenylbutazone, warfarin, thiazide diuretics (acidic) or propranolol (basic), as well as tetracycline, penicillin G, phenobarbital, thyroid and thyroxine preparations, estrogens and progestins and digitalis.
• Carcinogenesis, Mutagenesis, Impairment of Fertility In studies conducted in rats in which cholestyramine resin was used as a tool to investigate the role of various intestinal factors, such as fat, bile salts and microbial flora, in the development of intestinal tumors induced by potent carcinogens, the incidence of such tumors was observed to be greater in cholestyramine resin-treated rats than in control rats.
• The relevance of this laboratory observation from studies in rats to the clinical use of cholestyramine resin is not known.
• In the LRCCPPT study referred to above, the total incidence of fatal and nonfatal neoplasms was similar in both treatment groups.
• When the many different categories of tumors are examined, various alimentary system cancers were somewhat more prevalent in the cholestyramine group.
• The small numbers and the multiple categories prevent conclusions from being drawn.
• However, in view of the fact that cholestyramine resin is confined to the GI tract and not absorbed and in light of the animal experiments referred to above, a six-year post-trial follow-up of the LRC-CPPT5 patient population has been completed (a total of 13.4 years of in-trial plus post-trial follow-up) and revealed no significant difference in the incidence of cause-specific mortality or cancer morbidity between cholestyramine and placebo treated patients.
• Pregnancy There are no adequate and well controlled studies in pregnant women.
• Nursing Mothers Caution should be exercised when cholestyramine resin is administered to a nursing mother.
• Pediatric Use Although an optimal dosage schedule has not been established, standard texts( 6,7 ) list a usual pediatric dose of 240 mg/kg/day of anhydrous cholestyramine resin in two to three divided doses, normally not to exceed 8 g/day with dose titration based on response and tolerance.
• General Chronic use of cholestyramine resin may be associated with increased bleeding tendency due to hypoprothrombinemia associated with Vitamin K deficiency.
• This will usually respond promptly to parenteral Vitamin K1 and recurrences can be prevented by oral administration of Vitamin K1.
• Reduction of serum or red cell folate has been reported over long term administration of cholestyramine resin.
• Supplementation with folic acid should be considered in these cases.
• There is a possibility that prolonged use of cholestyramine resin, since it is a chloride form of anion exchange resin, may produce hyperchloremic acidosis.
• This would especially be true in younger and smaller patients where the relative dosage may be higher.
• Caution should also be exercised in patients with renal insufficiency or volume depletion and in patients receiving concomitant spironolactone.
• Cholestyramine resin may produce or worsen preexisting constipation.
• The dosage should be increased gradually in patients to minimize the risk of developing fecal impaction.
• In patients with preexisting constipation, the starting dose should be 1 pouch or 1 scoop once daily for 5 to 7 days, increasing to twice daily with monitoring of constipation and of serum lipoproteins, at least twice, 4 to 6 weeks apart.
• Increased fluid intake and fiber intake should be encouraged to alleviate constipation and a stool softener may occasionally be indicated.
• If the initial dose is well tolerated, the dose may be increased as needed by one dose/day (at monthly intervals) with periodic monitoring of serum lipoproteins.
• If constipation worsens or the desired therapeutic response is not achieved at one to six doses/day, combination therapy or alternate therapy should be considered.
• Particular effort should be made to
• avoid constipation in patients with symptomatic coronary artery disease.
• Constipation associated with cholestyramine resin may aggravate hemorrhoids.

• There are no adequate and well controlled studies in pregnant women.
• The use of cholestyramine in pregnancy or lactation or by women of childbearing age requires that the potential benefits of drug therapy be weighted against the possible hazards to the mother and child.
• Cholestyramine is not absorbed systemically, however, it is known to interfere with absorption of fat-soluble vitamins; accordingly, regular prenatal supplementation may not be adequate (see PRECAUTIONS, Drug Interactions ).
• Caution should be exercised when cholestyramine resin is administered to a nursing mother. The possible lack of proper vitamin absorption described in the “Pregnancy” section may have an effect on nursing infants.

• Cholestyramine resin may delay or reduce the absorption of concomitant oral medication such as phenylbutazone, warfarin, thiazide diuretics (acidic) or propranolol (basic), as well as tetracycline, penicillin G, phenobarbital, thyroid and thyroxine preparations, estrogens and progestins and digitalis.
• Interference with the absorption of oral phosphate supplements has been observed with another positivelycharged bile acid sequestrant.
• Cholestyramine resin may interfere with the pharmacokinetics of drugs that undergo enterohepatic circulation.
• The discontinuance of cholestyramine resin could pose a hazard to health if a potentially toxic drug such as digitalis has been titrated to a maintenance level while the patient was taking cholestyramine resin.
• Because cholestyramine binds bile acids, cholestyramine resin may interfere with normal fat digestion and absorption and thus may prevent absorption of fat soluble vitamins such as A, D, E and K.
• When cholestyramine resin is given for long periods of time, concomitant supplementation with water-miscible (or parenteral) forms of fat soluble vitamins should be considered.
• SINCE CHOLESTYRAMINE RESIN MAY BIND OTHER DRUGS GIVEN CONCURRENTLY, IT IS RECOMMENDED THAT PATIENTS TAKE OTHER DRUGS AT LEAST 1 HOUR BEFORE OR 4 TO 6 HOURS AFTER CHOLESTYRAMINE RESIN (OR AT AS GREAT AN INTERVAL AS POSSIBLE) TO
• AVOID IMPEDING THEIR ABSORPTION.

• Overdosage of cholestyramine resin has been reported in a patient taking 150% of the maximum recommended daily dosage for a period of several weeks.
• No ill effects were reported.
• Should an overdosage occur, the chief potential harm would be obstruction of the gastrointestinal tract.
• The location of such potential obstruction, the degree of obstruction and the presence or absence of normal gut motility would determine treatment.