Cholestyramine Information
Cholestyramine ()
Cholestyramine () Description
Cholestyramine () for Oral Suspension, USP powder, the chloride salt of a basic anion exchange resin, a cholesterol lowering agent, is intended for oral administration. Cholestyramine () resin is quite hydrophilic, but insoluble in water. Cholestyramine () resin is not absorbed from the digestive tract. Nine grams of Cholestyramine () for Oral Suspension, USP powder contain 4 grams of Cholestyramine () resin. It is represented by the following structural formula:
Cholestyramine () Clinical 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.
The increased fecal loss of bile acids due to Cholestyramine () resin administration leads to an increased oxidation of cholesterol to bile acids, a decrease in beta lipoprotein or low density lipoprotein plasma levels and a decrease in serum cholesterol levels. Although in man, Cholestyramine () resin produces an increase in hepatic synthesis of cholesterol, plasma cholesterol levels fall.
In patients with partial biliary obstruction, the reduction of serum bile acid levels by Cholestyramine () resin reduces excess bile acids deposited in the dermal tissue with resultant decrease in pruritus.
Cholestyramine () Indications And Usage
1) Cholestyramine () for Oral Suspension, USP powder is 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. Cholestyramine () for Oral Suspension, USP powder may be useful to lower LDL cholesterol in patients who also have hypertriglyceridemia, but it is not indicated where hypertriglyceridemia is the abnormality of most concern.
Therapy with lipid-altering agents should be a component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Treatment should begin and continue with dietary therapy specific for the type of hyperlipoproteinemia determined prior to initiation of drug therapy. Excess body weight may be an important factor and caloric restriction for weight normalization should be addressed prior to drug therapy in the overweight.
Prior to initiating therapy with Cholestyramine () resin, secondary causes of hypercholesterolemia (e.g., poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism), should be excluded and a lipid profile performed to assess Total cholesterol, HDL-C and triglycerides (TG). For individuals with TG less than 400 mg/dL (
LDL-C = Total cholesterol - [(TG/5) + HDL-C]
For TG levels > 400 mg/dL, this equation is less accurate and LDL-C concentrations should be determined by ultracentrifugation. In hypertriglyceridemic patients, LDL-C may be low or normal despite elevated Total-C. In such cases Cholestyramine () resin may not be indicated.
Serum cholesterol and triglyceride levels should be determined periodically based on NCEP guidelines to confirm initial and adequate long-term response. A favorable trend in cholesterol reduction should occur during the first month of Cholestyramine () resin therapy. The therapy should be continued to sustain cholesterol reduction. If adequate cholesterol reduction is not attained, increasing the dosage of Cholestyramine () resin or adding other lipid-lowering agents in combination with Cholestyramine () resin should be considered.
Since the goal of treatment is to lower LDL-C, the NCEP recommends that LDL-C levels be used to initiate and assess treatment response. If LDL-C levels are not available then Total-C alone may be used to monitor long-term therapy. A lipoprotein analysis (including LDL-C determination) should be carried out once a year. The NCEP treatment guidelines are summarized below.
Cholestyramine () resin monotherapy has been demonstrated to retard the rate of progression and increase the rate of regression of coronary atherosclerosis.
2) Cholestyramine () for Oral Suspension, USP powder is indicated for the relief of pruritus associated with partial biliary obstruction. Cholestyramine () resin has been shown to have a variable effect on serum cholesterol in these patients. Patients with primary biliary cirrhosis may exhibit an elevated cholesterol as part of their disease.
Cholestyramine () Contraindications
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.
Cholestyramine () Precautions
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 K and recurrences can be prevented by oral administration of Vitamin K. 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.
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.
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 positively-charged 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 OR 4 TO 6 HOURS Cholestyramine () RESIN (OR AT AS GREAT AN INTERVAL AS POSSIBLE) TO AVOID IMPEDING THEIR ABSORPTION.
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 LRC-CPPT 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-CPPT 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.
Although an optimal dosage schedule has not been established, standard texts 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.
In calculating pediatric dosages, 44.4 mg of anhydrous Cholestyramine () resin are contained in 100 mg of Cholestyramine () for Oral Suspension, USP.
The effects of long-term drug administration, as well as its effect in maintaining lowered cholesterol levels in pediatric patients, are unknown. Also see .
Cholestyramine () Adverse Reactions
The most common adverse reaction is constipation. When used as a cholesterol-lowering agent predisposing factors for most complaints of constipation are high dose and increased age (more than 60 years old). Most instances of constipation are mild, transient and controlled with conventional therapy. Some patients require a temporary decrease in dosage or discontinuation of therapy.
Less Frequent Adverse Reactions- Abdominal discomfort and/or pain, flatulence, nausea, vomiting, diarrhea, eructation, anorexia, steatorrhea, bleeding tendencies due to hypoprothrombinemia (Vitamin K deficiency) as well as Vitamin A (one case of night blindness reported) and D deficiencies, hyperchloremic acidosis in children, osteoporosis, rash and irritation of the skin, tongue and perianal area. Rare reports of intestinal obstruction, including two deaths, have been reported in pediatric patients.
Occasional calcified material has been observed in the biliary tree, including calcification of the gallbladder, in patients to whom Cholestyramine () resin has been given. However, this may be a manifestation of the liver disease and not drug related.
One patient experienced biliary colic on each of three occasions on which he took a Cholestyramine () for oral suspension product. One patient diagnosed as acute abdominal symptom complex was found to have a “pasty mass” in the transverse colon on x-ray.
Other events (not necessarily drug related) reported in patients taking Cholestyramine () resin include:
Cholestyramine () Overdosage
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.
Cholestyramine () Dosage And Administration
The recommended starting adult dose for Cholestyramine () for Oral Suspension, USP powder is 1 pouch or 1 level scoopful (9 grams of Cholestyramine () for Oral Suspension, USP powder contains 4 grams of anhydrous Cholestyramine () resin) once or twice a day. The recommended maintenance dose for Cholestyramine () for Oral Suspension, USP powder is 2 to 4 pouches or scoopfuls daily (8 to 16 grams anhydrous Cholestyramine () resin) divided into two doses. It is recommended that increases in dose be gradual with periodic assessment of lipid/lipoprotein levels at intervals of not less than 4 weeks. The maximum recommended daily dose is 6 pouches or scoopfuls of Cholestyramine () for Oral Suspension, USP powder (24 grams of anhydrous Cholestyramine () resin). The suggested time of administration is at mealtime but may be modified to avoid interference with absorption of other medications. Although the recommended dosing schedule is twice daily, Cholestyramine () for Oral Suspension, USP powder may be administered in 1 to 6 doses per day.
Cholestyramine () How Supplied
Cholestyramine () for Oral Suspension, USP powder orange flavor is available in cartons of sixty 9 gram pouches and in cans containing 378 grams. Nine grams of Cholestyramine () for Oral Suspension, USP powder contain 4 grams of anhydrous Cholestyramine () resin.
Carton of 60 pouches
Can, 378 g (containing a scoop that is not interchangeable with scoops from other products)
Cholestyramine () References
1. The Lipid Research Clinics Coronary Primary Prevention Trial Results: (I) Reduction in Incidence of Coronary Heart Disease; (II) The Relationship of Reduction in Incidence of Coronary Heart Disease to Cholesterol Lowering. . 1984; 251:351-374
2. Brensike JF, Levy RI, Kelsey SF, et al. Effects of therapy with Cholestyramine () on progression of coronary arteriosclerosis: results of the NHLBI type II coronary intervention study. 1984; 69:313-24.
3. Watts GF, Lewis B, Brunt JNH, Lewis ES, et al. Effects on coronary artery disease of lipid-lowering diet or diet plus Cholestyramine () , in the St. Thomas Atherosclerosis Regression Study (STARS). 1992; 339:563-69.
4. National Cholesterol Education Program. Second Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). 1994 Mar;89 (3): 1333-445.
5. The Lipid Research Clinics Investigators. The Lipid Research Clinics Coronary Primary Prevention Trial Results of 6 Years of Post-Trial Follow-up. 1992; 152:1399-1410.
6. Behrman RE et al (eds): Nelson, , ed 15. Philadelphia, PA, WB Saunders Company, 1996.
7. Takemoto CK et al (eds): , ed 3. Cleveland/Akron, OH, Lexi-Comp, Inc., 1996/1997.
Manufactured for
UPSHER-SMITH LABORATORIES, INC.
Minneapolis, MN 55447
OE1308
Rev. 09-2011
Cholestyramine () Principal Display Panel
Cholestyramine () for Oral Suspension, USP
POWDER
Orange Flavor
4 grams Cholestyramine () resin USP, per scoopful*
Contents: 378 g (168 g Cholestyramine () RESIN USP)
42 MEASURED DOSES
