Colestipol
side effects, nutrient depletions, herbal interactions and health notes:
Data provided by Applied Health
• Colestipol, by design, reduces fat absorption and hence interferes with absorption of fat-souble nutrients1
• This interaction raises serious questions given the accumulating experimental, epidemiological, and clinical evidence of an association between anti-oxidant vitamin intake (especially vitamin E) and reduced risk of coronary heart disease. Hodis et al have reported an association between supplementary vitamin E intake and angiographically demonstrated reduction in coronary artery lesion progression. Tonstad et al conducted a study of 37 boys and 29 girls aged 10-16 years with familial hypercholesterolemia first in an eight week double blind, placebo controlled protocol, then in open treatment for 44-52 weeks. They found that levels of serum folate, vitamin E, and carotenoids were reduced in the colestipol group. After one year of colestipol, those who took 80% or more of the prescribed dose had a greater decrease in serum 25-hydroxyvitamin D levels than those who took less than 80%.2
• While supplementary Vitamin E has been found to be effective in treating high cholesterol by reducing progression of carotid arterial wall intima-media thickness, there has been no confirmation that the addition of moderate doses of Vitamin E along with colestipol will enhance the effectiveness of the therapy in reducing the progression of atherosclerosis.3
• Colestipol lowers vitamin D absorption and hence adversely effects calcium metabolism. Some research indicates that colestipol can bind calcium and thereby further decrease absorption.4
• An iron deficiency can result from long-term use of colestipol.5
• Bile acid sequestrants, such as colestipol, often cause adverse effects such as abdominal bloating and may produce or worsen pre-existing constipation. Constipation may aggravate hemorrhoids.Individuals taking colestipol would most likely benefit from increased fluid and fiber intake alleviate the constipation. Psyllium seed husk could be particularly beneficial, but only with proportionately increased water intake.: Research by Spence et al suggests that adding psyllium to half the usual dose of bile acid sequestrant resins maintains the efficacy and improves the tolerability of these resins.6
• Effect of supplementary antioxidant vitamin intake on carotid arterial wall intima-media thickness in a controlled clinical trial of cholesterol lowering.7
• The available antihyperlipidaemic drugs are generally safe and effective, and major systemic adverse effects are uncommon. However, because of their complex mechanisms of action, careful monitoring is required to identify and correct potential drug interactions. Bile acid sequestrants are the most difficult of these agents to administer concomitantly, because their nonspecific binding results in decreased bioavailability of a number of other drugs, including thiazide diuretics, digitalis preparations, beta-blockers, coumarin anticoagulants, thyroid hormones, fibric acid derivatives and certain oral antihyperglycaemia agents8
• Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis9
• Cholestyramine, colestipol, clofibrate, gemfibrozil, nicotinic acid (niacin), probucol, neomycin, and dextrothyroxine are the most commonly used drugs in the treatment of hyperlipoproteinaemic disorders. While adverse reaction data are available for all of them, definitive data regarding the frequency and severity of potential adverse effects from well-controlled trials using large numbers of patients (greater than 1000) are available only for cholestyramine, clofibrate, nicotinic acid and dextrothyroxine. In adult patients treated with cholestyramine, gastrointestinal complaints, especially constipation, abdominal pain and unpalatability are most frequently observed10
• The ability of cholestyramine and colestipol, two hypocholesterolaemic resins, to bind in vitro several compounds such as vitamin B12, vitamin B12-intrinsic factor complex, folic acid, iron citrate and calcium chloride was investigated. Both resins bound to a high extent vitamin B12-intrinsic factor complex, folic acid and iron citrate; in addition, cholestyramine also caused appreciable binding of calcium. Throughout a large range of pH, there was no change in the binding capacity; however, at pH 2, cholestyramine exhibited a marked drop in the binding of tested substances (with exception of folic acid).11
• Serum total carotenoid (STC) and vitamin A levels were done as part of the biochemical screening in comparative studies of lipid lowering agents in type Ila hyperlipoproteinemic patients. STC levels were reduced following bile acid sequestering agent administration (colestipol 30 g/d) by 30% (P less than 0.01). Clofibrate and avicel placebo had inconsistent and nonsignificant effects on the STC levels. Serum vitamin A levels were not significantly altered by any of the test agents. The STC level changes were not correlated with concomitant changes in low-density lipoprotein-cholesterol (LDL-C) during any of the treatment regimens. It is suggested that STC level changes are related to alterations in the absorption of carotenoids during bile acid sequestrant administration.12
• Longterm treatment for 5 years of young patients with familial hypercholesterolemia was accompanied by monitoring of plasma levels of calcium, iron, sodium, parathyroid hormone and water- and fat soluble vitamins, since interference of the ion exchange resin with absorption of numerous substances as well as abnormal plasma levels of some of the above had been described in several studies. Treatment was effective in the group with good compliance (lowering of plasma cholesterol at the end of 5 years by 19% and, compared to the control group, by 23%). Adverse drug effects with respect to the above parameters were not found. Plasma levels of carotinoides and vitamin E were elevated in the patients according to elevated concentrations of lipoproteins which are carriers of these vitamins.13
• In summary: (1) Colestipol therapy plus diet reduced total cholesterol 19 +/- 3% in 11 hypercholesterolemic children after two months and 13 +/- 5% after two years in five children. (2) Diet therapy did not significantly reduce serum concentration of any of the fat-soluble vitamins or folate. (3) During 24 months of colestipol therapy plus diet serum vitamin A and E concentrations did decrease in the five patients with good drug adherence (vitamin A, 68 +/- 11 vs 35 +/- 4 microgram/100 ml, P less than .005) (vitamin E, 14 +/- 1 vs 11 +/- 1 microgram/ml, P less than .05). However, those concentrations remained within normal limits. (4) Colestipol therapy plus diet had no effect on prothrombin time, serum 25-hydroxycholecalciferol, folate, or calcium metabolism (as studied by sequential determination of serum total and ionized calcium phosphorus, alkaline phosphatase, and parathyroid hormone).14
• OBJECTIVE: To test whether combining psyllium mucilloid with half the usual dose of colestipol reduces the adverse effects associated with colestipol and maintains or increases its efficacy in the treatment of hyperlipidemia. This strategy might make bile acid sequestrants, which are seldom used because they cause adverse effects such as bloating and constipation, more tolerable and less expensive. DESIGN: A randomized, parallel-group, double-blind, controlled trial.15
• The effects of orange flavoured colestipol granules, 10 g/day, in 37 boys and 29 girls aged 10-16 years with familial hypercholesterolaemia were examined first in an eight week double blind, placebo controlled protocol, then in open treatment for 44-52 weeks. All patients were on a low fat diet. Low density lipoprotein cholesterol levels were reduced by 19.5% by colestipol v 1.0% by placebo. Levels of serum folate, vitamin E, and carotenoids were reduced in the colestipol group, but not the vitamin E/cholesterol and carotenoid/cholesterol ratios or serum concentrations of vitamins A and D. After one year of colestipol, two thirds of the participants remained in the study, of whom half took > or = 80% of the prescribed dose. Those who took > or = 80% of the dose had a greater decrease in serum 25-hydroxyvitamin D levels than those who took < 80%. No adverse effects on weight gain or linear growth velocity were observed. Although low dose colestipol effectively reduces low density lipoprotein cholesterol levels, only a minority of adolescents adhered to the new formulation for one year. Folate and possibly vitamin D supplementation is recommended.16
• There are no Herbal considerations at this time17
References1 Tonstad S, et al. Arch Dis Child 1996 Feb;74(2):157-160
1 Tsang RC, Roginsky MS, Mellies MJ, Glueck CJ. Plasma 25-hydroxy-vitamin D in familial hypercholesterolemic children receiving colestipol resin. Pediatr Res. 1978 Oct;12(10):980-982.
1 Werbach, MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 224, 1997. (Review)
2 Hodis HN, et al. JAMA 1995 Jun 21;273(23):1849-1854; Tonstad S, et al. Arch Dis Child 1996 Feb;74(2):157-160
3 Azen SP, et al. Circulation 1996 Nov 15;94(10):2369-2372; Schlierf G, et al. Klin Wochenschr. 1985 Sep 2;63(17):802-8026
3 Schwarz KB, et al. Pediatrics. 1980 Feb;65(2):243-250;
3 Leonard JP, et al. Arzneimittelforschung 1979;29(7):979-981
3 Tsang RC, et al. Pediatr Res. 1978 Oct;12(10):980-982
4 Leonard JP, et al. Arzneimittelforschung 1979;29(7):979-981
5 Leonard JP, et al. Arzneimittelforschung 1979;29(7):979-981
5 Schlierf G, et al. Klin Wochenschr. 1985 Sep 2;63(17):802-806
6 Spence JD, et al. Ann Intern Med 1995 Oct 1;123(7):493-499.
7 Azen SP, Qian D, Mack WJ, Sevanian A, Selzer RH, Liu CR, Liu CH, Hodis Circulation 1996 Nov 15;94(10):2369-2372.
8 Farmer JA, Gotto AM Jr. Antihyperlipidaemic agents. Drug interactions of clinical significance. Drug Saf 1994 Nov;11(5):301-309.
9 Hodis HN, Mack WJ, LaBree L, Cashin-Hemphill L, Sevanian A, Johnson R, Azen SP. JAMA 1995 Jun 21;273(23):1849-1854
10 Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987 Jan;2(1):10-32
11 Leonard JP, Desager JP, Beckers C, Harvengt Arzneimittelforschung 1979;29(7):979-981
12 Probstfield JL, Lin TL, Peters J, Hunninghake DB. Carotenoids and vitamin A: the effect of hypocholesterolemic agents on serum levels. Metabolism 1985 Jan;34(1):88-91.
13 Schlierf G, Vogel G, Kohlmeier M, Vuilleumier JP, Huppe R, Schmidt-Gayk H. [Long-term therapy of familial hypercholesterolemia in young patients with colestipol: availability of minerals and vitamins]. Klin Wochenschr. 1985 Sep 2;63(17):8020-806. [Article in German]
14 Schwarz KB, Goldstein PD, Witztum JL, Schonfeld G. Fat-soluble vitamin concentrations in hypercholesterolemic children treated with colestipol. Pediatrics. 1980 Feb;65(2):243-250.
15 Spence JD, Huff MW, Heidenheim P, Viswanatha A, Munoz C, Lindsay R, Wolfe B, Mills D. Combination therapy with colestipol and psyllium mucilloid in patients with hyperlipidemia. Ann Intern Med 1995 Oct 1;123(7):493-499.
16 Tonstad S, Sivertsen M, Aksnes L, Ose L. Low dose colestipol in adolescents with familial hypercholesterolaemia. Arch Dis Child 1996 Feb;74(2):157-160.
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Disclaimers
The information in Drug Watch is provided as a courtesy to NewsTarget readers by Applied Health Solutions in cooperation with Healthway Solutions. Although the information is presented with scientific references, we do not wish to imply that this represents a comprehensive list of considerations about any specific drug, herb or nutrient. Nor should this information be considered a substitute for the advice of your doctor, pharmacist, or other healthcare practitioner. Please read the disclaimer about the intentions and limitations of the information provided on these pages. It is important to tell your doctor and pharmacist about all other drugs and nutritional supplements that you are taking if they are recommending a new medication. Copyright © 2007 by Applied Health Solutions, Inc. All rights reserved.
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