for long periods of time, concomitant supplementation with water-miscible (or parenteral) forms of fat-soluble vitamins should be considered. since cholestyramine 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 cholestyramine (or at as great an interval as possible) to avoid impeding their absorption.

. prior to initiating therapy with cholestyramine, 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 cholestyramine 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 therapy. the therapy should be continued to sustain cholesterol reduction. if adequate cholesterol reduction is not attained, increasing the dosage of cholestyramine or adding other lipid-lowering agents in combination with cholestyramine 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) cholestyramine monotherapy has been demonstrated to retard the rate of progression 2,3 and increase the rate of regression 3 of coronary atherosclerosis. 2) cholestyramine for oral suspension is indicated for the relief of pruritus associated with partial biliary obstruction. cholestyramine for oral suspension 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.

o minimize the risk of developing fecal impaction. in patients with pre-existing constipation, the starting dose should be 1 packet 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.

stration 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 may be administered in 1 to 6 doses per day. cholestyramine should not be taken in its dry form. always mix cholestyramine 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 the drug interactions subsection of the precautions section for recommendations on administering concomitant therapy. preparation the color of cholestyramine 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 cholestyramine 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 cholestyramine for oral suspension usp 2-6 ounces per dose cholestyramine for oral suspension usp, light 2-6 ounces per dose stir to a uniform consistency and drink. cholestyramine may also be mixed with highly fluid soups or pulpy fruits with a high moisture content such as applesauce or crushed pineapple.

ation 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 cholestyramine resin. 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. miscellaneous—weight loss, weight gain, increased libido, swollen glands, edema, dental bleeding, dental caries, erosion of tooth enamel, tooth discoloration.

for long periods of time, concomitant supplementation with water-miscible (or parenteral) forms of fat-soluble vitamins should be considered. since cholestyramine 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 cholestyramine (or at as great an interval as possible) to avoid impeding their absorption.

ith partial biliary obstruction, the reduction of serum bile acid levels by cholestyramine reduces excess bile acids deposited in the dermal tissue with resultant decrease in pruritus. clinical studies in a large, placebo-controlled, multi-clinic study, lrc-cppt 1 , hypercholesterolemic subjects treated with cholestyramine had mean reductions in total and low-density lipoprotein cholesterol (ldl-c) which exceeded those for diet and placebo treatment by 7.2% and 10.4 %, respectively. over the seven-year study period the cholestyramine group experienced a 19% reduction (relative to the incidence in the placebo group) in the combined rate of coronary heart disease death plus non-fatal myocardial infarction (cumulative incidences of 7% cholestyramine and 8.6% placebo). the subjects included in the study were men aged 35-59 with serum cholesterol levels above 265 mg/dl and no previous history of heart disease. it is not clear to what extent these findings can be extrapolated to females and other segments of the hypercholesterolemic population. (see also precautions: carcinogenesis, mutagenesis, impairment of fertility. ) two controlled clinical trials have examined the effects of cholestyramine monotherapy upon coronary atherosclerotic lesions using coronary arteriography. in the nhlbi type ii coronary intervention trial 2, 116 patients (80% male) with coronary artery disease (cad) documented by arteriography were randomized to cholestyramine or placebo for five years of treatment. final study arteriography revealed progression of coronary artery disease in 49% of placebo patients compared to 32% of the cholestyramine group (p<0.05). in the st. thomas atherosclerosis regression study (stars) 3 , 90 hypercholesteroleic men with cad were randomized to three blinded treatments: usual care, lipid-lowering diet, and lipid-lowering diet plus cholestyramine. after 36 months, follow-up coronary arteriography revealed progression of disease in 46% of usual care patients, 15% of patients on lipid-lowering diet and 12% of those receiving diet plus cholestyramine (p<0.02). the mean absolute width of coronary segments decreased in the usual care group, increased slightly (0.003mm) in the diet group and increased by 0.103mm in the diet plus cholestyramine group (p<0.05). thus in these randomized controlled clinical trials using coronary arteriography, cholestyramine monotherapy has been demonstrated to slow progression 2,3 and promote regression 3 of atherosclerotic lesions in the coronary arteries of patients with coronary artery disease. the effect of intensive lipid-lowering therapy on coronary atherosclerosis has been assessed by arteriography in hyperlipidemic patients. in these randomized, controlled clinical trials, patients were treated for two to four years by either conventional measures (diet, placebo, or in some cases low dose resin), or intensive combination therapy using diet plus colestipol (an anion exchange resin with a mechanism of action and an effect on serum lipids similar to that of cholestyramine for oral suspension usp and cholestyramine for oral suspension usp, light) plus either nicotinic acid or lovastatin. when compared to conventional measures, intensive lipid-lowering combination therapy significantly reduced the frequency of progression and increased the frequency of regression of coronary atherosclerotic lesions in patients with or at risk for coronary artery disease.

, and in light of the animal experiments referred to above, a six-year post-trial follow-up of the lrc-cppt 5 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.