Cholestyramine for Oral Suspension

INDICATIONS AND USAGE 1) Cholestyramine 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 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 ( 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 NCEP4 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. Definite Atherosclerotic Disease * Two or More Other Risk Factors † LDL-Cholesterol mg/dL (mmol/L) Initiation Level Goal No No ≥ 190 (4.9) ≥ 60 (4.1) No Yes ≥ 160 (4.1) ≥ 130 (3.4) Yes Yes or No ≥ 130 (3.4) ≥ 100 (‐2.6) * Coronary heart disease or peripheral vascular disease (including symptomatic carotid artery disease). † Other risk factors for coronary heart disease (CHD) include: age (males 45 years; females: 55 years or premature menopause without estrogen replacement therapy); family history of premature CHD; current cigarette smoking; hypertension; confirmed HDL-C <35 mg/dL (<0.91 mmol/L); and diabetes mellitus. Subtract one risk factor if HDL-C is 60 mg/dL (1.6 mmol/L). Cholestyramine resin monotherapy has been demonstrated to retard the rate of progression 2,3 and increase the rate of regression 3 of coronary atherosclerosis. 2) Cholestyramine 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.

DOSAGE AND ADMINISTRATION The recommended starting adult dose for cholestyramine is 1 level scoopful (9 grams of Cholestyramine for Oral Suspension, USP powder contains 4 grams of anhydrous cholestyramine resin and 5.7 grams of Cholestyramine for Oral Suspension, USP Light powder contains 4 grams of anhydrous cholestyramine resin) once or twice a day. The recommended maintenance dose for cholestyramine is 2 to 4 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 scoopfuls of cholestyramine (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 may be administered in 1 to 6 doses per day. Cholestyramine powder should not be taken in its dry form. Always mix the dry powder with water or other fluids before ingesting. See Preparation Instructions. Concomitant Therapy Preliminary evidence suggests that the lipid-lowering effects of cholestyramine on total and LDL-cholesterol are enhanced when combined with a HMG-COA reductase inhibitor, e.g., pravastatin, lovastatin, simvastatin and fluvastatin. Additive effects on LDL-cholesterol are also seen with combined nicotinic acid/cholestyramine therapy. See PRECAUTIONS , Drug Interactions for recommendations on administering concomitant therapy. Preparation The color of cholestyramine for oral suspension products powder may vary somewhat from batch to batch but this variation does not affect the performance of the product. Place the contents of one level scoopful of cholestyramine for oral suspension products powder in a glass or cup. Add at least 2 to 3 ounces of water or the beverage of your choice. Stir to a uniform consistency. Cholestyramine for oral suspension products powder may also be mixed with highly fluid soups or pulpy fruits with a high moisture content such as applesauce or crushed pineapple.

Preparation The color of cholestyramine for oral suspension products powder may vary somewhat from batch to batch but this variation does not affect the performance of the product. Place the contents of one level scoopful of cholestyramine for oral suspension products powder in a glass or cup. Add at least 2 to 3 ounces of water or the beverage of your choice. Stir to a uniform consistency. Cholestyramine for oral suspension products powder may also be mixed with highly fluid soups or pulpy fruits with a high moisture content such as applesauce or crushed pineapple.

CONTRAINDICATIONS Cholestyramine for oral suspension and cholestyramine for oral suspension light 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.

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: Gastrointestinal GI-rectal bleeding, black stools, hemorrhoidal bleeding, bleeding from known duodenal ulcer, dysphagia, hiccups, ulcer attack, sour taste, pancreatitis, rectal pain, diverticulitis. Laboratory Test Changes Liver function abnormalities. Hematologic Prolonged prothrombin time, ecchymosis, anemia. 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 to urine, diuresis.

DESCRIPTION Cholestyramine, 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. Each 9 grams of Cholestyramine for Oral Suspension, USP powder contains 4 grams of cholestyramine resin. Each 5.7 grams of Cholestyramine for Oral Suspension, USP Light powder contains 4 grams of cholestyramine resin. It is represented by the following structural formula: Representation of structure of main polymeric groups Cholestyramine for Oral Suspension, USP inactive ingredients: citric acid anhydrous, pectin, propylene glycol alginate, sorbitol, sucrose, mono ammonium glycyrrhizinate, fructose, xanthan gum, artificial strawberry flavor, and D&C red No. 30 aluminum lake. Cholestyramine for Oral Suspension, USP Light inactive ingredients : aspartame, citric acid anhydrous, colloidal silicon dioxide, fructose, mannitol, mono ammonium glycyrrhizinate, pectin, propylene glycol alginate, sorbitol, xanthan gum, artificial strawberry flavor, and D&C red No. 30 aluminum lake. cholestyramine-structural-formula

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.

HOW SUPPLIED Cholestyramine for Oral Suspension, USP powder strawberry flavor is off white to pink in color and available in cans containing 378 grams. Nine grams of Cholestyramine for Oral Suspension, USP powder, contains 4 grams of anhydrous cholestyramine resin. NDC # 62135-008-56 Can, 378 g (containing a scoop that is not interchangeable with scoops from other products) Cholestyramine for Oral Suspension, USP Light powder strawberry flavor is off white to pink in color and available in cans containing 239.4 grams. Each 5.7 gram dose of Cholestyramine for Oral Suspension, USP Light powder contains 4 grams of anhydrous cholestyramine resin. NDC # 62135-937-54 Can, 239.4 g (containing a scoop that is not interchangeable with scoops from other products) Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Always replace plastic lid after using. KEEP OUT OF THE REACH OF CHILDREN.