Colestipol

Colestipol comes as granules to take by mouth. It usually is taken two to four times a day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take colestipol exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Unless otherwise instructed, take all other medications at least 1 hour before or 4 hours after you take colestipol because colestipol can interfere with their absorption.

Continue to take colestipol even if you feel well. Do not stop taking colestipol without talking to your doctor.

Do not take the granules dry. Add them to at least 3 ounces (90 milliliters) of a liquid (e.g., fruit juice, water, milk, or soft drink) and stir until completely mixed. If you use a carbonated beverage, mix it slowly in a large glass to minimize foaming. After taking the dose, rinse the glass with a small amount of additional liquid and drink it to be sure that you receive the entire dose.

For convenience and to improve taste, mix your entire next-day's dose in a liquid in the evening and refrigerate it. Colestipol also may be mixed with hot or regular breakfast cereals, thin soups (e.g., tomato and chicken noodle), or pulpy fruit (e.g., crushed pineapple, pears, peaches, and fruit cocktail).

Colestipol comes as a tablet or granules to take by mouth.

Your dose will depend on your medical condition, age, response to treatment, and other factors.

Colestipol can interfere with the absorption of other medicines. Be sure to take all other medication at least one hour before, or four hours after, your dose of colestipol.

Follow the instructions on your prescription label carefully when taking this medicine. Don't use more or less colestipol than is recommended.

Colestipol granules

Colestipol granules are usually taken two to four times a day.

Add the granules to at least 3 ounces of liquid and mix completely. You can use water, milk, fruit juice, or a soft drink.

If you use a carbonated drink, mix it slowly in a large glass to reduce foaming.

Drink the colestipol mixture. Then, rinse the glass with a small amount of additional liquid and drink it, so that you receive the entire dose.

Colestipol granules can also be mixed with thin soups, hot or cold breakfast cereals, and certain pulpy fruits, such as pears, peaches, fruit cocktail, or crushed pineapple.

Talk to your doctor about how to properly mix the medication.

Don't take colestipol granules without mixing them with some type of liquid.

Colestipol tablets

Colestipol tablets can be taken with or without food. They're usually taken once or twice daily.

Swallow the tablet whole. Don't crush, chew, or split it.

Take one tablet at a time, and swallow it right away.

Take each colestipol tablet with a full glass of water or other liquid.

Colestipol Overdose

If you suspect an overdose, contact a poison control center or emergency room immediately. You can get in touch with a poison control center at 800-222-1222.

Missed Dose of Colestipol

If you miss a dose of colestipol, take it as soon as you remember. Then, take any remaining doses for that day at evenly spaced intervals.

Don't double up on a dose to make up for a missed one.

Colestipol is part of the drug class:

• Bile acid sequestrants

Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

Usual Adult Dose for Hyperlipoproteinemia:

Tablets:
-Initial dose: 2 g orally once or twice a day
-Maintenance dose: 2 to 16 g once a day or in divided doses

Comments:
-Dose increases of 2 g once or twice a day should occur at 1 to 2 month intervals.
-If desired therapeutic effect on low density lipoprotein (LDL) cholesterol is not obtained at a dose of 2 to 16 g per day with good compliance and acceptable side effects, combined therapy or alternate treatment should be considered.

Granules:
-Initial dose: 5 g (1 packet or 1 level scoop) orally once or twice a day
-Maintenance dose: 5 to 30 g (1 to 6 packets or level scoops) orally once a day or in divided doses

Comments:
-Incremental dose increases should occur at a rate of 1 dose per day at 1 to 2 month intervals.
-If desired therapeutic effect is not obtained at 1 to 6 doses per day with good compliance and acceptable side effects, combined therapy or alternate treatment should be considered.

Use: For use as adjunctive treatment to diet for the reduction of elevated serum total and low-density lipoprotein (LDL) cholesterol in patients with primary hypercholesterolemia (elevated LDL) who do not respond adequately to diet

In the U.S.

• Colestid

Available Dosage Forms:

• Powder for Suspension
• Tablet

Therapeutic Class: Antihyperlipidemic

Pharmacologic Class: Bile Acid Sequestrant

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly to lower your cholesterol levels and to decide if you should continue to take it.

Do not stop taking colestipol without first checking with your doctor. When you stop taking colestipol, your blood cholesterol levels may increase again. Your doctor may want you to follow a special diet to help prevent this from happening.

Do not take any other medicine unless prescribed by your doctor since colestipol may interfere with other medicines.

Prior to initiating therapy with Colestipol hydrochloride tablets, 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 − [(Triglycerides/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 Colestipol hydrochloride tablets may not be indicated.

Because it sequesters bile acids, Colestipol hydrochloride may interfere with normal fat absorption and, thus, may reduce absorption of folic acid and fat soluble vitamins such as A, D, and K.

Chronic use of Colestipol hydrochloride may be associated with an increased bleeding tendency due to hypoprothrombinemia from vitamin K deficiency. This will usually respond promptly to parenteral vitamin K1 and recurrences can be prevented by oral administration of vitamin K1.

Serum cholesterol and triglyceride levels should be determined periodically based on NCEP guidelines to confirm a favorable initial and adequate long-term response.

Colestipol hydrochloride tablets may produce or severely worsen pre-existing constipation. The dosage should be increased gradually in patients to minimize the risk of developing fecal impaction. In patients with pre-existing constipation, the starting dose should be 2 grams once or twice a day. Increased fluid 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 a further 2 to 4 grams/day (at monthly intervals) with periodic monitoring of serum lipoproteins. If constipation worsens or the desired therapeutic response is not achieved at 2 to 16 grams/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 Colestipol hydrochloride tablets may aggravate hemorrhoids.

While there have been no reports of hypothyroidism induced in individuals with normal thyroid function, the theoretical possibility exists, particularly in patients with limited thyroid reserve.

Since Colestipol hydrochloride is a chloride form of an anion exchange resin, there is a possibility that prolonged use may lead to the development of hyperchloremia acidosis.

Carcinogenesis, Mutagenesis and Impairment of Fertility

In studies conducted in rats in which cholestyramine resin (a bile acid sequestering agent similar to Colestipol hydrochloride) was used as a tool to investigate the role of various intestinal factors, such as fat, bile salts, and microbial flora, in the development of intestinal tumors induced by potent carcinogens, the incidence of such tumors was observed to be greater in cholestyramine resin treated rats than in control rats.

The relevance of this laboratory observation from studies in rats with cholestyramine resin to the clinical use of Colestipol hydrochloride is not known. In the LRC-CPPT study referred to above, the total incidence of fatal and nonfatal neoplasms was similar in both treatment groups. When the many different categories of tumors are examined, various alimentary system cancers were somewhat more prevalent in the cholestyramine group. The small numbers and the multiple categories prevent conclusions from being drawn. Further follow-up of the LRC-CPPT participants by the sponsors of that study is planned for cause-specific mortality and cancer morbidity. When Colestipol hydrochloride was administered in the diet to rats for 18 months, there was no evidence of any drug related intestinal tumor formation. In the Ames assay, Colestipol hydrochloride was not mutagenic.

Use in Pregnancy

Since Colestipol hydrochloride is essentially not absorbed systemically (less than 0.17% of the dose), it is not expected to cause fetal harm when administered during pregnancy in recommended dosages. There are 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. The use of Colestipol hydrochloride tablets in pregnancy or by women of childbearing potential requires that the potential benefits of drug therapy be weighed against possible hazards to the mother or child.

Nursing Mothers

Caution should be exercised when Colestipol hydrochloride tablets are administered to a nursing mother. The possible lack of proper vitamin absorption described in the "Pregnancy" section may have an effect on nursing infants.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established.

Information for Patients

Colestipol hydrochloride tablets may be larger than pills you have taken before. If you have had swallowing problems or choking with food, liquids or other tablets or capsules in the past, you should discuss this with your doctor before taking Colestipol hydrochloride tablets.

It is important that you take Colestipol hydrochloride tablets correctly:

1. Always take one tablet at a time and swallow promptly.
2. Swallow each tablet whole. Do not cut, crush, or chew the tablets.
3. Colestipol hydrochloride tablets must be taken with water or another liquid that you prefer. Swallowing the tablets will be easier if you drink plenty of liquid as you swallow each tablet.

Difficulty swallowing and temporary obstruction of the esophagus (the tube between your mouth and stomach) have been rarely reported in patients taking Colestipol hydrochloride tablets. If a tablet does get stuck after you swallow it, you may notice pressure or discomfort. If this happens to you, you should contact your doctor. Do not take Colestipol hydrochloride tablets again without your doctor's advice.

If you are taking other medications, you should take them at least one hour before or four hours after taking Colestipol hydrochloride tablets.

DRUG INTERACTIONS

Since Colestipol hydrochloride is an anion exchange resin, it may have a strong affinity for anions other than the bile acids. In vitro studies have indicated that Colestipol hydrochloride binds a number of drugs. Therefore, Colestipol hydrochloride tablets may delay or reduce the absorption of concomitant oral medication. The interval between the administration of Colestipol hydrochloride tablets and any other medication should be as long as possible. Patients should take other drugs at least one hour before or four hours after Colestipol hydrochloride tablets to avoid impeding their absorption.

Repeated doses of Colestipol hydrochloride given prior to a single dose of propranolol in human trials have been reported to decrease propranolol absorption. However, in a follow-up study in normal subjects, single-dose administration of Colestipol hydrochloride and propranolol and twice-a-day administration for 5 days of both agents did not affect the extent of propranolol absorption, but had a small yet statistically significant effect on its rate of absorption; the time to reach maximum concentration was delayed approximately 30 minutes. Effects on the absorption of other beta-blockers have not been determined. Therefore, patients on propranolol should be observed when Colestipol hydrochloride tablets are either added or deleted from a therapeutic regimen.

Studies in humans show that the absorption of chlorothiazide as reflected in urinary excretion is markedly decreased even when administered one hour before Colestipol hydrochloride. The absorption of tetracycline, furosemide, penicillin G, hydrochlorothiazide, and gemfibrozil was significantly decreased when given simultaneously with Colestipol hydrochloride; these drugs were not tested to determine the effect of administration one hour before Colestipol hydrochloride.

No depressant effect on blood levels in humans was noted when Colestipol hydrochloride was administered with any of the following drugs: aspirin, clindamycin, clofibrate, methyldopa, nicotinic acid (niacin), tolbutamide, phenytoin or warfarin. Particular caution should be observed with digitalis preparations since there are conflicting results for the effect of Colestipol hydrochloride on the availability of digoxin and digitoxin. The potential for binding of these drugs if given concomitantly is present. Discontinuing Colestipol hydrochloride could pose a hazard to health if a potentially toxic drug that is significantly bound to the resin has been titrated to a maintenance level while the patient was taking Colestipol hydrochloride.

Bile acid binding resins may also interfere with the absorption of oral phosphate supplements and hydrocortisone.

A study has shown that cholestyramine binds bile acids and reduces mycophenolic acid exposure. As Colestipol also binds bile acids, Colestipol may reduce mycophenolic acid exposure and potentially reduce efficacy of mycophenolate mofetil.

Gastrointestinal

The most common adverse reactions are confined to the gastrointestinal tract. To achieve minimal GI disturbance with an optimal LDL-C lowering effect, a gradual increase of dosage starting with 2 grams, once or twice daily is recommended. Constipation is the major single complaint and at times is severe. Most instances of constipation are mild, transient, and controlled with standard treatment. Increased fluid intake and inclusion of additional dietary fiber should be the first step; a stool softener may be added if needed. Some patients require decreased dosage or discontinuation of therapy. Hemorrhoids may be aggravated.

Other, less frequent gastrointestinal complaints consist of abdominal discomfort (abdominal pain and cramping), intestinal gas (bloating and flatulence), indigestion and heartburn, diarrhea and loose stools, and nausea and vomiting. Bleeding hemorrhoids and blood in the stool have been infrequently reported. Peptic ulceration, cholecystitis, and cholelithiasis have been rarely reported in patients receiving Colestipol hydrochloride granules, and are not necessarily drug related.

Difficulty swallowing and transient esophageal obstruction have been rarely reported in patients taking Colestipol hydrochloride tablets.

Transient and modest elevations of aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT) and alkaline phosphatase were observed on one or more occasions in various patients treated with Colestipol hydrochloride.

The following nongastrointestinal adverse reactions have been reported with generally equal frequency in patients receiving Colestipol hydrochloride tablets, Colestipol granules, or placebo in clinical studies:

Cardiovascular

Chest pain, angina, and tachycardia have been infrequently reported.

Hypersensitivity

Rash has been infrequently reported. Urticaria and dermatitis have been rarely noted in patients receiving Colestipol hydrochloride granules.

Musculoskeletal

Musculoskeletal pain, aches and pains in the extremities, joint pain and arthritis, and backache have been reported.

Neurologic

Headache, migraine headache, and sinus headache have been reported. Other infrequently reported complaints include dizziness, light-headedness, and insomnia.

Miscellaneous

Anorexia, fatigue, weakness, shortness of breath, and swelling of the hands or feet, have been infrequently reported.

1. Summary of the Second Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 1993; 269(23):3015–3023.
2. Lipid Metabolism-Atherogenesis Branch, National Heart, Lung, and Blood Institute, Bethesda, MD: The Lipid Research Clinics Coronary Primary Prevention Trial Results. I. Reduction in Incidence of Coronary Heart Disease. JAMA 1984; 251:351–364.
3. Parra HJ, et al. Differential electroimmunoassay of human LpA-I lipoprotein particles on ready-to-use plates. Clin. Chem. 1990; 36(8):1431–1435.
4. Barbaras R, et al. Cholesterol efflux from cultured adipose cells is mediated by LpAI particles but not by LpAI:AII particles. Biochem. Biophys. Res. Comm. 1987; 142(1):63–69.
5. Kane JP, et al. Normalization of low-density-lipoprotein levels in heterozygous familial hypercholesterolemia with a combined drug regimen. N Engl. J. Med. 1981; 304:251–258.
6. Illingworth DR, et al. Colestipol plus nicotinic acid in treatment of heterozygous familial hypercholesterolemia. Lancet 1981; 1:296–298.
7. Kuo PT, et al. Familial type II hyperlipoproteinemia with coronary heart disease: Effect of diet-Colestipol-nicotinic acid treatment. Chest 1981; 79:286–291.
8. Blankenhorn DH, et al. Beneficial Effects of Combined Colestipol-Niacin Therapy on Coronary Atherosclerosis and Coronary Venous Bypass Grafts. JAMA 1987; 257(23):3233–3240.
9. Cashin-Hemphill L, et al. Beneficial Effects of Colestipol-Niacin on Coronary Atherosclerosis: A 4-Year Follow-up. JAMA 1990; 264:3013–3017.
10. Brown G. et al. Regression of Coronary Artery Disease as a Result of Intensive Lipid-Lowering Therapy in Men with High Levels of Apolipoprotein B. N. Engl. J. Med. 1990; 323:1289–1298.
11. Kane JP, et al. Regression of Coronary Atherosclerosis During Treatment of Familial Hypercholesterolemia with Combined Drug Regimens. JAMA 1990; 264:3007–3012.

Rx only

LAB-0359-4.0
July 2017

Some products may contain phenylalanine.

Amiodarone: Bile Acid Sequestrants may decrease the bioavailability of Amiodarone. Consider therapy modification

AtorvaSTATin: Bile Acid Sequestrants may decrease the serum concentration of AtorvaSTATin. Monitor therapy

Cardiac Glycosides: Bile Acid Sequestrants may decrease the absorption of Cardiac Glycosides. Monitor therapy

Chenodiol: Bile Acid Sequestrants may decrease the serum concentration of Chenodiol. Management: Administration of chenodiol 5 hours or more after bile acid sequestrants may reduce chenodiol adsorption in the gastrointestinal tract. Monitor for decreased therapeutic effects of chenodiol in patients receiving bile acid sequestrants. Consider therapy modification

Cholic Acid: Bile Acid Sequestrants may decrease the absorption of Cholic Acid. Management: Administer cholic acid at least 1 to 4 hours before or 4 to 6 hours after administration of any bile acid-binding products to minimize the potential for a significant interaction. Consider therapy modification

Contraceptives (Estrogens): Bile Acid Sequestrants may decrease the serum concentration of Contraceptives (Estrogens). Management: Administer estrogen-based oral contraceptives at least 1 to 4 hours prior to or 4 to 6 hours after administration of a bile acid sequestrant. Consider therapy modification

Contraceptives (Progestins): Bile Acid Sequestrants may decrease the serum concentration of Contraceptives (Progestins). Management: Administer oral progestin-containing contraceptives at least 1 to 4 hours prior to or 4 to 6 hours after administration of a bile acid sequestrant. Consider therapy modification

Corticosteroids (Oral): Bile Acid Sequestrants may decrease the absorption of Corticosteroids (Oral). Monitor therapy

Deferasirox: Bile Acid Sequestrants may decrease the serum concentration of Deferasirox. Management: Avoid combination when possible; if the combination must be used, consider a 50% increase in initial deferasirox dose, with monitoring of serum ferritin concentrations and clinical responses to guide further dosing. Consider therapy modification

DilTIAZem: Colestipol may decrease the absorption of DilTIAZem. Monitor therapy

Ezetimibe: Bile Acid Sequestrants may decrease the absorption of Ezetimibe. Management: Administer ezetimibe at least 2 hours before or 4 hours after any bile acid sequestrant. Consider therapy modification

Fibric Acid Derivatives: Bile Acid Sequestrants may decrease the absorption of Fibric Acid Derivatives. Management: Separate doses by at least 2 hours to minimize this interaction; fenofibric acid labeling recommends administration one hour prior to or 4-6 hours after a bile acid sequestrant. Consider therapy modification

Leflunomide: Bile Acid Sequestrants may decrease serum concentrations of the active metabolite(s) of Leflunomide. Management: Unless using this combination to intentionally enhance leflunomide elimination, consider an alternative to the bile acid sequestrants when possible. Separating drug administration is not likely to be effective at avoiding this interaction. Consider therapy modification

Lomitapide: Bile Acid Sequestrants may decrease the absorption of Lomitapide. Management: Administer lomitapide at least 4 hours before or after administration of a bile acid sequestrant. Consider therapy modification

Loop Diuretics: Bile Acid Sequestrants may decrease the absorption of Loop Diuretics. Consider therapy modification

Methotrexate: Bile Acid Sequestrants may decrease the absorption of Methotrexate. Monitor therapy

Methylfolate: Colestipol may decrease the serum concentration of Methylfolate. Monitor therapy

Multivitamins/Fluoride (with ADE): Bile Acid Sequestrants may decrease the serum concentration of Multivitamins/Fluoride (with ADE). Management: Avoid concomitant administration of multivitamins and bile acid sequestrants (eg, cholestyramine). Separate administration of these agents by several hours to minimize the risk of an interaction. Consider therapy modification

Multivitamins/Minerals (with ADEK, Folate, Iron): Bile Acid Sequestrants may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, bile acid sequestrants may impair the absorption of fat-soluble vitamins. Management: Avoid concomitant administration of multivitamins and bile acid sequestrants (eg, cholestyramine). Separate administration of these agents by several hours to minimize the risk of an interaction. Consider therapy modification

Multivitamins/Minerals (with AE, No Iron): Bile Acid Sequestrants may decrease the serum concentration of Multivitamins/Minerals (with AE, No Iron). Management: Avoid concomitant administration of multivitamins and bile acid sequestrants (e.g., cholestyramine). Separate administration of these agents by several hours to minimize the risk of an interaction. Consider therapy modification

Mycophenolate: Bile Acid Sequestrants may decrease the serum concentration of Mycophenolate. Avoid combination

Niacin: Bile Acid Sequestrants may decrease the absorption of Niacin. Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents: Bile Acid Sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Consider therapy modification

Obeticholic Acid: Bile Acid Sequestrants may decrease the serum concentration of Obeticholic Acid. Management: Administer obeticholic acid at least 4 hours before or at least 4 hours after the administration of bile acid sequestrants. Consider therapy modification

Pravastatin: Bile Acid Sequestrants may decrease the serum concentration of Pravastatin. Management: Administer pravastatin at least 1 hour before or 4 hours after administration of bile-acid resins (eg, cholestyramine, colestipol, colesevelam) to minimize the risk for any significant interaction. Consider therapy modification

Propranolol: Bile Acid Sequestrants may decrease the serum concentration of Propranolol. Monitor therapy

Raloxifene: Bile Acid Sequestrants may decrease the absorption of Raloxifene. Consider therapy modification

Teriflunomide: Bile Acid Sequestrants may decrease the serum concentration of Teriflunomide. Management: Unless using this combination to intentionally enhance teriflunomide elimination, consider an alternative to the bile acid sequestrants when possible. Separating drug administration is unlikely to be effective at avoiding the interaction. Consider therapy modification

Tetracycline Derivatives: Bile Acid Sequestrants may decrease the absorption of Tetracycline Derivatives. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Bile Acid Sequestrants may decrease the absorption of Thiazide and Thiazide-Like Diuretics. The diuretic response is likewise decreased. Consider therapy modification

Thyroid Products: Bile Acid Sequestrants may decrease the serum concentration of Thyroid Products. Management: Administer oral thyroid products at least 4 h prior to colesevelam, and at least 1 h before or 4-6 h after cholestyramine. Specific recommendations for colestipol are not available. Monitor for decreased concentrations/effects of the thyroid product. Consider therapy modification

Ursodiol: Bile Acid Sequestrants may decrease the serum concentration of Ursodiol. Management: Administer ursodiol 5 hours or more after bile acid sequestrants to minimize ursodiol adsorption in the gastrointestinal tract. Monitor for decreased therapeutic effects of ursodiol in patients receiving bile acid sequestrants. Consider therapy modification

Vancomycin: Bile Acid Sequestrants may diminish the therapeutic effect of Vancomycin. Management: Avoid concurrent administration of oral vancomycin and bile acid sequestrants when possible. If use of both agents is necessary, consider separating doses by at least 2 hours to minimize the significance of the interaction. Consider therapy modification

Vitamin D Analogs: Bile Acid Sequestrants may decrease the serum concentration of Vitamin D Analogs. More specifically, bile acid sequestrants may impair absorption of Vitamin D Analogs. Management: Avoid concomitant administration of vitamin D analogs and bile acid sequestrants (eg, cholestyramine). Separate administration of these agents by several hours to minimize the potential risk of interaction. Monitor plasma calcium concentrations. Exceptions: Calcipotriene; Calcitriol (Topical); Tacalcitol. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Bile Acid Sequestrants may decrease the absorption of Vitamin K Antagonists. Monitor therapy