Colestipol

INDICATIONS & 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 tablets are indicated as adjunctive therapy to diet for the reduction of elevated serum total and LDL-C in patients with primary hypercholesterolemia (elevated LDL-C) who do not respond adequately to diet. Generally, colestipol hydrochloride tablets have no clinically significant effect on serum triglycerides, but with their 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; female: ≥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).

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 Edenbridge Pharmaceuticals at 1-877-381-3336 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.