Questran (Cholestyramine Resin)



Cholestyramine Resin

Antidiarrheal – Antihypercholesterolemic

Action And Clinical Pharmacology: Cholestyramine is a quarternary ammonium anion exchange resin with a polystyrene polymer skeleton. As the chloride salt, it binds bile acids both in vitro and in vivo, exchanging chloride for bile acid.

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 absorbs 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.

Indications And Clinical Uses: As adjunctive therapy to diet and exercise for the reduction of elevated serum cholesterol in patients with primary hypercholesterolemia (elevated low density lipoproteins); such reduction of serum cholesterol may reduce the risks of atherosclerotic coronary artery disease and myocardial infarction. Cholestyramine resin may be useful to lower elevated cholesterol in patients with combined hypercholesterolemia and hypertriglyceridemia but it is not indicated where hypertriglyceridemia is the abnormality of most concern.

Cholestyramine resin is indicated as a symptomatic control of bile acid induced diarrhea due to short bowel syndrome.

Cholestyramine resin is indicated for the relief of pruritus associated with partial biliary obstruction.

Contra-Indications: In patients with complete biliary obstruction where bile is not excreted into the intestine and in those individuals who have shown hypersensitivity to any of its components.

Manufacturers’ Warnings In Clinical States: Cholestyramine resin should not be taken in its dry form. Always admix the drug with water or other fluids before ingesting.

Since cholestyramine resin may bind other drugs given concurrently, patients should 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.

Pregnancy: Since cholestyramine resin is not absorbed systemically, it is not expected to cause fetal harm when administered during pregnancy in recommended dosages. There are, however, no adequate and well-controlled studies in pregnant women and, the known interference with absorption of fat soluble vitamins may be detrimental even in the presence of supplementation.

Lactation: 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.

Use in pregnancy or lactation requires that the potential benefits of drug therapy be weighed against the possible hazards to the mother and the child.

Children: The effects of long-term drug administration, as well as its effect in maintaining lowered cholesterol levels in pediatric patients, are unknown. A pediatric dosage schedule has not been established.

The National Cholesterol Education Program (NCEP) Expert Panel recommends, however, that drug therapy be considered in children 10 years or older, who have previously undergone an adequate trial of diet therapy but still have unacceptable high serum cholesterol levels. In certain situations where a young child has extremely high serum cholesterol levels, drug treatment may even be initiated before 10 years of age. If the child is started on drug therapy, a carefully assessed diet therapy should also be continued in order to obtain optimal results.

Because bile acid sequestrants may interfere with absorption of fat-soluble vitamins, appropriate monitoring of growth and development is essential if cholestyramine is used in children.

Geriatrics: Appropriate studies on the relationship of age to the effects of cholestyramine have not been performed in the geriatric population. However, patients over 60 years of age may be more likely to experience gastrointestinal side effects.

Carcinogenesis and Mutagenesis: Studies were conducted in rats in which cholestyramine resin was used as a tool to investigate the role of various intestinal factors (e.g., fat, bile salts and microbial flora). The incidence of intestinal tumors, induced by potent carcinogens, was observed to be greater in cholestyramine resin treated rats, than in control rats. This observation was not evident in all studies conducted in rats, as results from one study indicated a statistically insignificant increase in tumor incidence whereas a more recent study did not demonstrate any presence of tumors following ingestion of cholestyramine. The relevance of this laboratory observation from studies in rats to the clinical use of cholestyramine resin is not known.

Precautions: Before instituting therapy with cholestyramine resin an attempt should be made to control serum cholesterol by appropriate dietary regimen, weight reduction, and the treatment of any underlying disorder such as hypothyroidism, diabetes mellitus, nephrotic syndrome, dysproteinemias and obstructive liver disease which might be the cause of hypercholesterolemia. In addition, the current medications of the patient should be reviewed for their potential to increase serum LDL-C or total cholesterol. 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.

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.

Cholestyramine resin may produce or worsen pre-existing constipation. Dosage should be reduced or discontinued in such cases. Fecal impaction and aggravation of hemorrhoids may occur. Every effort should be made to avert severe constipation and its inherent problems in those patients with clinically symptomatic coronary artery disease.

Cholestyramine potentially may cause steatorrhea or accentuate pre-existing steatorrhea and this may require reduction and adjustment of dosage.

Effect on Vitamin Absorption: Because cholestyramine binds bile acids, it may interfere with normal fat digestion and absorption and thus may prevent absorption of fat soluble vitamins such as A, D and K. When cholestyramine resin is given for long periods of time, concomitant supplementation of water-miscible parenteral forms of vitamins A and D should be considered.

Chronic use of cholestyramine 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.

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.

Drug Interactions: Since cholestyramine is an anion-exchange resin, it may have strong affinity for anions other than the bile acids. Drugs that are affected by coadministration of bile acid sequestrants vary widely in pharmacologic effect and mechanisms, magnitude of doses, and chemical characteristics. Therefore, it is not possible to predict a priori whether or not co-administration with cholestyramine will interfere with absorption. It should be assumed that concomitantly administered drugs have the potential for interacting with cholestyramine unless clinical studies have shown otherwise.

Cholestyramine resin may delay or reduce the absorption of concomitant oral medication such as phenylbutazone, warfarin, chlorothiazide (acidic), as well as tetracycline, penicillin G, phenobarbital, thyroid and thyroxine preparations, and digitalis. 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. The concomitant drug should be re-titrated to avoid overdosage when cholestyramine is discontinued. Also, cholestyramine resin may interfere with the pharmacokinetics of drugs (e.g., estrogens) that undergo enterohepatic recirculation.

Drug interaction studies have been conducted with cholestyramine and various HMG-CoA reductase inhibitors. Although cholestyramine has been shown to reduce the bioavailability of HMG-CoA reductase inhibitors, the clinical cholesterol-lowering effects of an HMG-CoA reductase inhibitor and cholestyramine have been shown to be additive.

Since cholestyramine resin may bind other drugs given concurrently, patients should 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.

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, flatulence, nausea, vomiting, diarrhea, heartburn, anorexia, dyspepsia and steatorrhea, bleeding tendencies due to hypoprothrombinemia (vitamin K deficiency) as well as vitamin A (night blindness has been reported rarely) and D deficiencies, hyperchloremic acidosis in children, osteoporosis, rash and irritation of the skin, tongue and perianal area.

Occasional calcified material has been observed in the biliary tree, including calcification of the gallbladder, in patients to whom cholestyramine resin has been given. This may be a manifestation of the liver disease and not drug related.

One patient experienced biliary colic on each of 3 occasions on which he took cholestyramine. One patient diagnosed with acute abdominal symptom complex was found to have a “pasty mass” in the transverse colon x-ray.

Other adverse reactions (not necessarily drug related) reported in patients taking cholestyramine resin include: Gastrointestinal: gastrointestinal-rectal bleeding, black stools, hemorrhoidal bleeding, bleeding from known duodenal ulcer, dysphagia, hiccups, ulcer attack, sour taste, pancreatitis, rectal pain, diverticulitis, eructation.

Laboratory Test Changes: liver function abnormalities.

Hematologic: decreased or increased prothrombin time, ecchymosis, anemia, dental bleeding.

Hypersensitivity: urticaria, asthma, wheezing, shortness of breath.

Musculoskeletal: backache, muscle and joint pains, arthritis.

Neurologic: headache, anxiety, vertigo, dizziness, fatigue, tinnitus, syncope, drowsiness, femoral nerve pain, paresthesia.

Eye: uveitis.

Renal: hematuria, dysuria, burnt odor of urine, diuresis.

Miscellaneous: weight loss, weight gain, increased libido, swollen glands, edema, dental caries.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: One case of overdosage with cholestyramine resin has been reported in a patient taking 150% of the maximum recommended daily dosage for several weeks. No ill effects were observed.

Should 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.

Dosage And Administration: To familiarize the patient with cholestyramine resin and to minimize gastrointestinal side effects, it is desirable to begin all therapy with one dose daily. Dosage is then increased within a day or two to the desired level for effective control.

Motivation of the patient to continue the prescribed regimen in spite of gastrointestinal problems is important. Physician’s encouragement and supervision are essential for successful management.

The recommended adult dose is 4 g of cholestyramine resin, 1 to 6 times daily. Dosage may be adjusted as required to meet the patient’s needs. A pediatric dosage schedule has not been established.

Cholestyramine resin should not be taken in its dry form. Always mix the powder with water or other fluids before ingesting (see Preparation Instructions).

Preparation Instructions: The color of cholestyramine resin may vary somewhat from batch to batch but this variation does not affect the performance of the product. Mix contents of 1 packet or 1 level scoop of Questran with 120 to 180 mL to 180 mL of a preferred beverage (water, milk, fruit juice or other noncarbonated beverage).

Mix contents of 1 packet of Questran Light with 60 to 90 mL of a preferred beverage (water, milk, fruit juice or other noncarbonated beverage).

Cholestyramine resin may also be mixed with highly fluid soups or pulpy fruits with high moisture content such as applesauce or crushed pineapple.

Availability And Storage: Questran: Each packet (1 dose) of powder contains: anhydrous cholestyramine resin 4 g. Nonmedicinal ingredients: acacia, citric acid, D&C yellow No. 10, FD&C yellow No. 6, flavor, polysorbate 80, propylene glycol alginate and sucrose. Energy: 53.5 kJ (12.8 kcal)/9 g. Sodium- and tartrazine-free. Cartons of 30 packets. Cans of 378 g (42 doses).

Questran Light: Each packet (1 dose) of powder contains: anhydrous cholestyramine resin 4 g. Nonmedicinal ingredients: aspartame, citric acid, D&C yellow No. 10, FD&C red No. 40, flavor, propylene glycol alginate, silicon dioxide, sucrose and xanthan gum. Energy: 6.7 kJ (1.6 kcal). Sodium- and tartrazine-free. Cartons of 30 packets.

Store at room temperature (15 to 30°C). Protect from temperatures above 30°C. Protect from moisture. (Shown in Product Recognition Section)

QUESTRAN® QUESTRAN® LIGHT Bristol Cholestyramine Resin Antidiarrheal – Antihypercholesterolemic

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