Colestipol for Lipid Metabolism Disorders

INDICATIONS AND USAGE Since no drug is innocuous, strict attention should be paid to the indications and contraindications, particularly when selecting drugs for chronic long-term use. Colestipol hydrochloride for oral suspension is indicated as adjunctive therapy to diet for the reduction of elevated serum total and low-density lipoprotein (LDL) cholesterol in patients with primary hypercholesterolemia (elevated low density lipoproteins [LDL] cholesterol) who do not respond adequately to diet. Generally, colestipol hydrochloride for oral suspension has no clinically significant effect on serum triglycerides, but with its use triglyceride levels may be raised in some patients. 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 (see NCEP guidelines). A minimum of six months of intensive dietary therapy and counseling should be carried out prior to initiation of drug therapy. Shorter periods may be considered in patients with severe elevations of LDL-C or with definite CHD. According to the NCEP guidelines, the goal of treatment is to lower LDL-C, and LDL-C is to be used to initiate and assess treatment response. Only if LDL-C levels are not available, should the Total-C be used to monitor therapy. The NCEP treatment guidelines are shown below. 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) * 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).

DOSAGE AND ADMINISTRATION One dose (1 packet or 1 level teaspoon) of COLESTID Granules contains 5 grams of colestipol hydrochloride. One dose (1 packet or 1 level scoopful) of FLAVORED COLESTID Granules is approximately 7.5 grams powder which contains 5 grams of colestipol hydrochloride. The recommended daily adult dose is one to six packets or level scoopfuls given once or in divided doses. Treatment should be started with one dose once or twice daily with an increment of one dose/day at one- or two-month intervals. Appropriate use of lipid profiles as per NCEP guidelines including LDL-cholesterol and triglycerides is advised so that optimal, but not excessive doses are used to obtain the desired therapeutic effect on LDL-cholesterol level. If the desired therapeutic effect is not obtained at one to six doses/day with good compliance and acceptable side effects, combined therapy or alternate treatment should be considered. To avoid accidental inhalation or esophageal distress, COLESTID and FLAVORED COLESTID should not be taken in its dry form. COLESTID and FLAVORED COLESTID should always be mixed with water or other fluids before ingesting. Patients should take other drugs at least one hour before or four hours after COLESTID or FLAVORED COLESTID to minimize possible interference with their absorption. (See PRECAUTIONS, Drug Interactions .) Before COLESTID or FLAVORED COLESTID Administration 1. Define the type of hyperlipoproteinemia, as described in NCEP guidelines. 2. Institute a trial of diet and weight reduction. 3. Establish baseline serum total and LDL-cholesterol and triglyceride levels. During COLESTID or FLAVORED COLESTID Administration 1. The patient should be carefully monitored clinically, including serum cholesterol and triglyceride levels. Periodic determinations of serum cholesterol levels as outlined in the NCEP guidelines should be done to confirm a favorable initial and longer-term response. 2. Failure of total or LDL-cholesterol to fall within the desired range should lead one to first examine dietary and drug compliance. If these are deemed acceptable, combined therapy or alternate treatment should be considered. 3. Significant rise in triglyceride level should be considered as indication for dose reduction, drug discontinuation, or combined or alternate therapy. Mixing and Administration Guide COLESTID and FLAVORED COLESTID should always be mixed in a liquid such as water or the beverage of your choice. It may also be taken in soups or with cereals or pulpy fruits. COLESTID or FLAVORED COLESTID should never be taken in its dry form. FLAVORED COLESTID is an orange-flavored product. Although it may be mixed with a variety of liquids or foods, the selection should be based on patient preference. With Beverages 1. Add the prescribed amount of COLESTID or FLAVORED COLESTID to a glassful (three ounces or more) of water or the beverage of your choice. A heavy or pulpy juice may minimize complaints relative to consistency. 2. Stir the mixture until the medication is completely mixed. (COLESTID and FLAVORED COLESTID will not dissolve in the liquid.) COLESTID and FLAVORED COLESTID may also be mixed with carbonated beverages, slowly stirred in a large glass; however, this mixture may be associated with GI complaints. Rinse the glass with a small amount of additional beverage to make sure all the medication is taken. With cereals, soups, and fruits COLESTID and FLAVORED COLESTID may be taken mixed with milk in hot or regular breakfast cereals, or even mixed in soups that have a high fluid content. It may also be added to fruits that are pulpy such as crushed pineapple, pears, peaches, or fruit cocktail.

WARNINGS TO AVOID ACCIDENTAL INHALATION OR ESOPHAGEAL DISTRESS, COLESTID GRANULES AND FLAVORED COLESTID GRANULES SHOULD NOT BE TAKEN IN ITS DRY FORM. ALWAYS MIX COLESTID AND FLAVORED COLESTID WITH WATER OR OTHER FLUIDS BEFORE INGESTING. PHENYLKETONURICS: FLAVORED COLESTID CONTAINS 18.2 MG PHENYLALANINE PER 7.5-GRAM DOSE.

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 for oral suspension resin may delay or reduce the absorption of concomitant oral medication. The interval between the administration of colestipol hydrochloride for oral suspension 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 for oral suspension 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 30 minutes. Effects on the absorption of other beta-blockers have not been determined. Therefore, patients on propranolol should be observed when colestipol hydrochloride for oral suspension is 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.

ADVERSE REACTIONS 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. To report SUSPECTED ADVERSE REACTIONS, contact Ingenus Pharmaceuticals, LLC at 1-877-748-1970 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.