Colestipol

Abstract

Colestipol¹ is an anion exchange resin with bile acid sequestering properties resembling those of cholestyramine, another lipid-lowering binding resin. In daily doses of 15 to 30g colestipol reduces total plasma cholesterol concentrations (primarily low density lipoprotein cholesterol) by about 15 to 30%, but plasma triglyceride concentrations may be unchanged or in some patients increased. Thus, like cholestyramine, colestipol is of benefit in patients with primary hypercholesterolaemia without associated hypertriglyceridaemia (type IIa hyperlipoproteinaemia). Colestipol is odourless and tasteless, and is said by some to be more readily tolerated by patients than cholestyramine, leading to improved compliance, but such data has not been documented in most studies. Side effects of colestipol treatment are primarily gastrointestinal in nature since the drug is essentially unabsorbed. As with cholestyramine, colestipol may bind with other concomitantly administered drugs reducing their absorption or enterohepatic recirculation; dosage intervals of other concurrent medications should be adjusted to minimise the potential for such an interaction. By binding with bile acids in the gut, colestipol results in their increased faecal excretion. The plasma concentration of low density lipoproteins and of total cholesterol is reduced during colestipol administration (the latter by about 20 to 30 % with a dose of 15 to 30g daily), but the concentration of lipids associated with very low density lipoproteins (i.e. primarily triglycerides) may be unchanged or may increase, especially in patients with elevated pretreatment triglyceride concentrations. The concentration of high density lipoprotein lipids does not appear to be significantly altered by colestipol. In a small number of patients studied to date, combined administration of colestipol and Clofibrate has produced a similar or slightly increased cholesterol lowering effect while usually reducing plasma triglyceride concentrations compared with colestipol treatment alone. As with cholestyramine, the mechanism of colestipol’s cholesterol lowering action is likely to be related to increased catabolism of low density lipoproteins. Colestipol’s cholesterol lowering action has been well studied in both open and controlled trials. A small number of patients have received continuous treatment for periods of up to 7 or 8 years without loss of effect, but most patients were treated for shorter durations (usually several months to 1 to 3 years). As in pharmacodynamic studies, colestipol (usually 5 or 10g 3 times daily) lowered total plasma cholesterol concentrations (primarily low density lipoprotein cholesterol) by about 15 to 30 % in most studies, while plasma triglyceride concentrations were unchanged or increased. In comparative studies with cholestyramine both drugs produced similar effects, lowering plasma cholesterol concentrations by about 15% more than that achieved with diet alone. In a single study in which patient compliance was recorded, colestipol seemed to be more readily acceptable to patients than cholestyramine, as is claimed by some to be the case due to its lack of odour and taste, but this aspect of treatment has not been documented in other studies. Small numbers of patients have been treated with combinations of colestipol and Clofibrate or colestipol and nicotinic acid, or β-sitosterol often with encouraging results, but further studies are needed to establish more clearly the effectiveness of such regimens. In a large multicentre study measuring mortality over a 3-year treatment period, total mortality and mortality due to cardiovascular disease were significantly lower in colestipol-treated men than in those receiving a placebo, but several difficulties with the trial design require that these reported effects on mortality be cautiously interpreted. Thus, further well designed studies are needed to establish whether treatment of elevated plasma lipid concentrations with colestipol (or other lipid-lowering drugs) reduces mortality due to coronary heart disease. The most frequent side effects during colestipol administration are gastrointestinal in nature, constipation occurring in about 10 % of patients and nausea, vomiting, abdominal pain, flatulence, etc. in about 5%. Infrequently, transient elevations in serum glutamic oxaloacetic transaminase and alkaline phosphatase have occurred, as have nonspecific complaints such as fatigue or weakness. Like other lipid-lowering drugs, colestipol is indicated as an adjunct to management of primary hypercholesterolaemia only when diet restriction alone is unsuccessful. Before initiating drug treatment adequate baseline studies should be performed, so that the subsequent response to the drug can be readily monitored. The recommended dosage is 15g to 30g daily, in 2 to 4 divided doses preferably shortly before meals, taken in water, juice or another suitable liquid. (Twice daily administration may be more acceptable to the patient, thus encouraging compliance). During treatment, plasma concentrations of cholesterol and triglycerides should be periodically monitored to ensure that the patient is responding adequately. If plasma triglyceride levels increase markedly, and remain elevated despite adequate dietary measures, colestipol should be discontinued. Like cholestyramine, the binding capability of colestipol may include concurrently administered anionic drugs. Although adequate documentation for individual drugs is relatively scarce, it appears that colestipol may reduce the absorption of enterohepatic recirculation of tetracycline, penicillin G and chlorothiazide or hydrochlorothiazide. It probably has no important effect on absorption of aspirin, tolbutamide, warfarin, Clofibrate or methyldopa. In cases of intoxication, colestipol appears to reduce the elimination half-life of digitoxin; however, disposition of digoxin, or of digitoxin in patients with therapeutic serum concentrations, may not be markedly altered by concurrent use of colestipol. Until conclusive data for more individual drugs are available, all concomitant drugs should be administered at least 1 hour before or 4 hours after colestipol administration to minimise the possibility of a clinically important interaction occurring.