QUESTRAN

INDICATIONS AND USAGE 1) QUESTRAN (Cholestyramine for Oral Suspension USP), 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. QUESTRAN 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 QUESTRAN 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 (<4.5 mmol/L), LDL-C can be estimated using the following equation: 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 QUESTRAN 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 QUESTRAN therapy. The therapy should be continued to sustain cholesterol reduction. If adequate cholesterol reduction is not attained, increasing the dosage of QUESTRAN or adding other lipid-lowering agents in combination with QUESTRAN should be considered. Since the goal of treatment is to lower LDL-C, the NCEP 4 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. *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). LDL-Cholesterol mg/dL (mmol/L) Definite Atherosclerotic Disease * Two or More Other Risk Factors ** Initiation Level Goal NO NO ≥190 (≥4.9) <160 (<4.1) NO YES ≥160 (≥4.1) <130 (<3.4) YES YES or NO ≥130 (≥3.4) ≤100 (≤2.6) QUESTRAN monotherapy has been demonstrated to retard the rate of progression 2,3 and increase the rate of regression 3 of coronary atherosclerosis. 2) QUESTRAN is indicated for the relief of pruritus associated with partial biliary obstruction. QUESTRAN 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 all QUESTRAN powdered products (QUESTRAN Powder and QUESTRAN LIGHT) is one packet or one level scoopful once or twice a day. The recommended maintenance dose for all QUESTRAN powdered products is 2 to 4 packets or scoopfuls daily (8 to 16 grams anhydrous cholestyramine resin) divided into two doses. Four grams of anhydrous cholestyramine resin is contained in each measured dose of QUESTRAN as follows: QUESTRAN Powder 9 grams QUESTRAN LIGHT 5 grams 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 six packets or scoopfuls of QUESTRAN (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, QUESTRAN may be administered in 1 to 6 doses per day. QUESTRAN should not be taken in its dry form. Always mix QUESTRAN with water or other fluids before ingesting. See Preparation Instructions. Concomitant Therapy Preliminary evidence suggests that the lipid-lowering effects of QUESTRAN 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 /QUESTRAN therapy. See the Drug Interactions subsection of the PRECAUTIONS section for recommendations on administering concomitant therapy. PREPARATION The color of QUESTRAN may vary somewhat from batch to batch but this variation does not affect the performance of the product. Place the contents of one single-dose packet or one level scoopful of QUESTRAN in a glass or cup. Add an amount of water or other non-carbonated beverage of your choice depending on the product being used: Product Formula Amount of Water or other Non-Carbonated Liquid QUESTRAN Powder 2 to 6 ounces per dose QUESTRAN LIGHT 2 to 6 ounces per dose Stir to a uniform consistency and drink. QUESTRAN may also be mixed with highly fluid soups or pulpy fruits with a high moisture content such as applesauce or crushed pineapple.

CONTRAINDICATIONS QUESTRAN 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.

WARNINGS PHENYLKETONURICS: QUESTRAN LIGHT CONTAINS 14.0 mg PHENYLALANINE PER 5 gram DOSE.

Drug Interactions QUESTRAN (Cholestyramine for Oral Suspension USP) 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. QUESTRAN may interfere with the pharmacokinetics of drugs that undergo enterohepatic circulation. The discontinuance of QUESTRAN 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 QUESTRAN. Because cholestyramine binds bile acids, QUESTRAN 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 QUESTRAN is given for long periods of time, concomitant supplementation with water-miscible (or parenteral) forms of fat-soluble vitamins should be considered. SINCE QUESTRAN MAY BIND OTHER DRUGS GIVEN CONCURRENTLY, IT IS RECOMMENDED THAT PATIENTS TAKE OTHER DRUGS AT LEAST ONE HOUR BEFORE OR 4 TO 6 HOURS AFTER QUESTRAN (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 and/or pain, flatulence, nausea, vomiting, diarrhea, eructation, anorexia, and 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 QUESTRAN 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 QUESTRAN. 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 QUESTRAN 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. Miscellaneous—Weight loss, weight gain, increased libido, swollen glands, edema, dental bleeding, dental caries, erosion of tooth enamel, tooth discoloration.

Pregnancy Pregnancy Category C There are no adequate and well controlled studies in pregnant women. The use of QUESTRAN in pregnancy or lactation or by women of childbearing age requires that the potential benefits of drug therapy be weighed against the possible hazards to the mother and child. QUESTRAN 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 ).