Label: CHOLESTYRAMINE powder, for suspension

Cholestyramine for oral suspension USP, light 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  is not absorbed from the digestive tract. Each 5.7 grams of  cholestyramine for oral suspension USP, light contain 4 grams of cholestyramine resin. It is represented by the following structural formula:

Representation of structure of main polymeric groups

Inactive Ingredients: aspartame, citric acid anhydrous, colloidal silicon dioxide, fructose, pectin, propylene glycol alginate, sorbitol, xanthan gum, Mafco Magnasweet MM 185, Orange flavor 501071AP0554, D&C yellow No. 10 aluminum lake and FD&C yellow No. 6 aluminum lake.

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  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 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  reduces excess bile acids deposited in the dermal tissue with resultant decrease in pruritus.

In a large, placebo-controlled, multi-clinic study, LRC-CPPT1, 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 to 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 Trial2, 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 hypercholesterolemic 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 (0.003 mm) in the diet group and increased by 0.103 mm 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 progression2,3 and promote regression3 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 methods (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 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.

1) Cholestyramine for oral suspension USP, light 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, light 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 , 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 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.

 
*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 progression2,3 and increase the rate of regression3 of coronary atherosclerosis.
2) Cholestyramine for oral suspension USP, light, is indicated for the relief of pruritus associated with partial biliary obstruction. Cholestyramine  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 for oral suspension USP, 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.

PHENYLKETONURICS: CHOLESTYRAMINE FOR ORAL SUSPENSION USP, LIGHT CONTAINS 22.4 mg PHENYLALANINE PER 5.7 GRAM DOSE.

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 resin 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.

Miscellaneous: Weight loss, weight gain, increased libido, swollen glands, edema, dental bleeding, dental caries, erosion of tooth enamel, tooth discoloration.

Overdosage of cholestyramine  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.

The recommended starting adult dose for cholestyramine for oral suspension USP, light is one pouch or one level scoopful once or twice a day. The recommended maintenance dose for cholestyramine for oral suspension USP, light is 2 to 4 pouches or scoopfuls daily (8 to 16 grams anhydrous cholestyramine) 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, light (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, light may be administered in 1 to 6 doses per day.

Cholestyramine for oral suspension USP, light 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 the PRECAUTIONS, Drug Interactionsfor recommendations on administering concomitant therapy.

Preparation

The color of cholestyramine for oral suspension USP, light 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 pouch or one level scoopful of cholestyramine for oral suspension USP, light in a glass or cup. Add at least 2 to 6 ounces of water or other noncarbonated beverage of your choice. Stir to a uniform consistency and drink.

Cholestyramine for oral suspension USP, light may also be mixed with highly fluid soups or pulpy fruits with a high moisture content such as applesauce or crushed pineapple.

Cholestyramine for oral suspension USP, light orange flavor is available in cartons of 42 and 60 pouches of 5.7 gram each and in Jar containing 239.4
grams. Each 5.7 gram dose of cholestyramine for oral suspension USP, light contains 4 gram of anhydrous cholestyramine resin.

NDC # 33342-319-72 Carton of 42 single-dose pouches, each containing 4 grams cholestyramine
NDC # 33342-319-70 Carton of 60 single-dose pouches, each containing 4 grams cholestyramine
NDC # 33342-319-83 Jar, 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) excursions permitted to 15° to 30°C (59 ° to 86 °F) [see USP Controlled Room Temperature].

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. JAMA. 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. Circulation 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). Lancet 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). Circulation 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. Arch Intern Med 1992; 152:1399-1410.

6. Behrman RE et al (eds): Nelson, Textbook of Pediatrics, ed 15. Philadelphia, PA, WB Saunders Company, 1996.

7. Takemoto CK et al (eds): Pediatric Dosage Handbook, ed 3. Cleveland/Akron, OH, Lexi-Comp, Inc., 1996-1997.

To report SUSPECTD ADVERSE REACTIONS, contact Macleods Pharma USA, Inc. at 1-888-943-3210 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Manufactured for :
Macleods Pharma USA, Inc.
Princeton, NJ 08540

Manufactured by:
Macleods Pharmaceuticals Ltd.
At Oxalis Labs
Baddi, Himachal Pradesh-174101 INDIA

Revision date: January 2025

PRINCIPAL DISPLAY PANEL
NDC 33342-319-72
Cholestyramine for oral suspension USP, light
Rx only 
42 Measured Doses


PRINCIPAL DISPLAY PANEL
NDC 33342-319-70
Cholestyramine for oral suspension USP, light
Rx only 
60 Single Dose Pouches

PRINCIPAL DISPLAY PANEL
NDC 33342-319-01
Cholestyramine for oral suspension USP, light
Rx only 
Single Dose