Colestid®

WARNINGS AND PRECAUTIONS Prior to initiating therapy with COLESTID 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). 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. COLESTID Tablets may produce or severely worsen pre-existing constipation. The dosage should be increased gradually in patients to minimize the risk of constipation. 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 relieve constipation and a stool softener may occasionally be indicated. If the initial dose is well tolerated, the dose may be increased as needed by 2 grams once or twice daily (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. 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 hyperchloremic acidosis. 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. In a large clinical study, the LRC-CPPT, the total incidence of fatal and nonfatal neoplasms was similar in both treatment groups. When colestipol hydrochloride was administered 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. 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 though the drug itself is not absorbed. Caution should be exercised when COLESTID Tablets are administered to a nursing mother. The possible lack of proper vitamin absorption may have an effect on nursing infants. Safety and effectiveness in the pediatric population have not been established. Patients should always take one tablet at a time and swallow promptly. Swallow each tablet whole. Do not cut, crush, or chew the tablets. Tablets should be taken with water or another liquid. Difficulty swallowing and temporary obstruction of the esophagus have been rarely reported. Since colestipol hydrochloride is an anion exchange resin, it may have a strong affinity for anions other than the bile acids. Therefore, colestipol hydrochloride resin may delay or reduce the absorption of concomitant oral medication. Drugs that have been reported to have decreased absorption when given with colestipol hydrochloride include chlorothiazide, tetracycline, furosemide, penicillin G, hydrochlorothiazide, and gemfibrozil. The interval between the administration of COLESTID 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 taking COLESTID Tablets to avoid impeding their absorption. Particular caution should be observed with digitalis preparations since conflicting results have been reported for the effect of colestipol hydrochloride on the availability of digoxin and digitoxin. The potential for binding of these drugs to colestipol hydrochloride is present. Colestipol hydrochloride may also interfere with the absorption of oral phosphate supplements and hydrocortisone. Concomitant use of colestipol hydrochloride may reduce mycophenolic acid exposure and potentially reduce efficacy of mycophenolate mofetil.