Cholestyramine

Brand Names: Cholybar, Questran

Clinical Names: Cholestyramine

Summary

generic name: Cholestyramine

trade name: Cholybar®, Questran®

type of drug: Bile acid sequestrant.

used to treat: High cholesterol, though less often used than in past.

overview of interactions:
• nutrients affected by drug: Vitamin A, Vitamin B12, Vitamin D, Vitamin E, Vitamin K, Folic Acid, and Beta-carotene

• nutrient affected by drug: Calcium

• nutrient affected by drug: Iron




Interactions

nutrients affected by drug: Vitamin A, Vitamin B12, Vitamin D, Vitamin E, Vitamin K, Folic Acid, and Beta-carotene

• mechanism: Bile acid sequestrants, such as cholestyramine, decrease lipid digestion and absorption, as well as absorption of the fat-soluble vitamins and other nutrients.
(Longnecker JB, Basu SG. Fed Proc. 24:375, 1965; Roe DA. 1985: 158-159; Watkins DW, et al. Dig Dis Sci 1985 May;30(5):477-482; Hathcock JN. Fed Proc. 1985 Jan;44(1 Pt 1):124-129; West RJ, Lloyd JK. Gut. 1975 Feb;16(2):93-98; Coronato A, Glass GB. Proc Soc Exp Biol Med 1973 Apr;142(4):1341-1344.)

• nutritional support: Regular use of a high-potency multiple vitamin/mineral formulation will replace the nutrients impeded by the drug.

nutrient affected by drug: Calcium

• mechanism: Calcium levels tend to be low due to lowered Vitamin D absorption.

• nutritional support: Supplemental calcium is recommended. A daily dosage of 1000 mg calcium is considered safe and is commonly used.

• nutritional concern: Cholestyramine may produce or worsen pre-existing constipation. Constipation may aggravate hemorrhoids.

• nutritional support: Individuals taking cholestyramine 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.

nutrient affected by drug: Iron

• mechanism: Cholestyramine binds iron and decreases its absorption.
(Watkins DW, et al. Dig Dis Sci 1985 May;30(5):477-482; Hathcock JN. Fed Proc. 1985 Jan;44(1 Pt 1):124-129.)


Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.



References

Bays HE, Dujovne CA.  Drug interactions of lipid-altering drugs. Drug Saf. 1998 Nov;19(5):355-371. (Review)

Coronato A, Glass GB. Depression of the intestinal uptake of radio-vitamin B 12 by cholestyramine. Proc Soc Exp Biol Med 1973 Apr;142(4):1341-1344.

Elinder LS, Hadell K, Johansson J, Molgaard J, Holme I, Olsson AG, Walldius G. Probucol treatment decreases serum concentrations of diet-derived antioxidants. Arterioscler Thromb Vasc Biol 1995 Aug;15(8):1057-1063.
Abstract: The effect of probucol, which is both a cholesterol-lowering drug and an antioxidant, on the serum concentrations of diet-derived antioxidants vitamin E, beta-carotene, lycopene, and vitamin A was studied in 303 hypercholesterolemic subjects. In a 3-year, double-blind, randomized trial we investigated to determine whether combined treatment with diet, cholestyramine, and probucol could reduce the progression of femoral atherosclerosis. Serum and lipoprotein antioxidant levels were measured by reverse-phase high-performance liquid chromatography. Cholestyramine significantly lowered serum concentrations of vitamin E by 7%, beta-carotene by 40%, and lycopene by 30% (all P < .001) due to impairment of gastrointestinal absorption and to serum cholesterol lowering. Probucol reduced serum vitamin E by 14% (P < .001) secondary to cholesterol and triglyceride lowering. The carotenoids were reduced by probucol by 30% to 40% (P < .001) most probably due to reductions in lipoprotein particle size and to competition with these substances for incorporation into VLDL during its assembly in the liver. This study shows that the use of a lipid-soluble antioxidant and cholesterol-lowering drug may have unfavorable effects on blood levels of diet-derived antioxidants.

Farmer JA, Gotto AM Jr. Antihyperlipidaemic agents. Drug interactions of clinical significance. Drug Saf 1994 Nov;11(5):301-309.
Abstract: 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 agents. Although the incidence is low, nicotinic acid may cause hepatic necrosis and so should not be used with drugs that adversely affect hepatic structure or function. With the HMG-CoA reductase inhibitors, relatively new agents for which clinical data are still being accumulated, the major problems appears to be rhabdomyolysis, associated with the concomitant use of cyclosporin, fibric acid derivatives or erythromycin, and mild, intermittent hepatic abnormalities that may be potentiated by other hepatotoxic drugs. Fibrates also have the potential to cause rhabdomyolysis, although generally only in combination with HMG-CoA reductase inhibitors, and are subject to binding by concomitantly administered bile acid sequestrants. The major interaction involving probucol is a possible additive effect with drugs or clinical conditions that alter the prolongation of the QTc interval, increasing the potential for polymorphic ventricular tachycardia.

Farmer JA, Gotto AM Jr. Choosing the right lipid-regulating agent. A guide to selection. Drugs 1996 Nov;52(5):649-661.

Hathcock JN. Metabolic mechanisms of drug-nutrient interactions. Fed Proc. 1985 Jan;44(1 Pt 1):124-129. (Review)

Hoogwerf BJ, Hibbard DM, Hunninghake DB. Effects of long-term cholestyramine administration on vitamin D and parathormone levels in middle-aged men with hypercholesterolemia. J Lab Clin Med 1992 Apr;119(4):407-411.
Abstract: The objective of this study was to evaluate possible adverse effects of long-term bile acid-binding resin (cholestyramine) treatment on vitamin D, parathyroid hormone, and calcium levels in middle-aged men. A double-blind randomized clinical trial was carried out over a period of 7 to 10 years at the University of Minnesota's Lipid Research Clinic as part of the Lipid Research Clinic's Coronary Primary Prevention Trial. Two hundred and sixty-eight men aged 42 to 68 years who had been previously randomized in the CPPT to cholestyramine or placebo and who had taken at least 75% of the prescribed study medication (6 packets or 24 gm/day) as determined by packet counts for the duration of the Coronary Primary Prevention Trial including the last 4 months of the trial were studied: one group (n = 124) received cholestyramine and the other group (n = 144) received a corresponding dose of placebo. Serum samples were obtained at the time of the final study visit in cholestyramine and placebo groups. (Results are reported as mean +/- SD in SI units). There were no differences in plasma levels of calcium (2.3 +/- 0.1 mmol/L vs 2.3 +/- 0.1 mmol/L), phosphorus (0.99 +/- 0.14 mmol/L vs 0.98 +/- 0.12 mmol/L), albumin (45 +/- 3 gm/L vs 46 +/- 0.6 gm/L), calcifediol (62.6 +/- 29.2 nmol/L vs 63.4 +/- 28.4), 25(OH)D2 (14 +/- 11 nmol/L vs 12 +/- 10 nmol/L) or calcitriol (99 +/- 190 pmol/L vs 91 +/- 56 pmol/L).

Ismail F, Corder CN, Epstein S, Barbi G, Thomas S. Effects of pravastatin and cholestyramine on circulating levels of parathyroid hormone and vitamin D metabolites. Clin Ther 1990 Sep-Oct;12(5):427-430.
Abstract: The subjects were 40 hypercholesterolemic patients (mean age, 58 years) receiving a low-fat diet and randomly assigned to treatment with placebo for eight weeks or 40 or 80 mg of pravastatin, 24 gm of cholestyramine, or 40 mg of pravastatin plus 24 gm of cholestyramine daily for 24 weeks. After eight weeks of active treatment, levels of total and low-density lipoprotein cholesterol were significantly reduced and the decline was maintained for the remaining 16 weeks. Parathyroid hormone levels and levels of the vitamin D metabolites 1,25(OH)2D3 and 25(OH)D3 did not change during treatment. The results indicate that 24 weeks of treatment with pravastatin and cholestyramine does not affect calcium metabolism.

Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987 Jan;2(1):10-32.
Abstract: 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 observed. Continued administration along with dietary manipulation (e.g. addition of dietary fibre) and/or stool softeners results in diminished complaints during long term therapy. Large doses of cholestyramine (greater than 32 g/day) may be associated with malabsorption of fat-soluble vitamins. Most significantly, osteomalacia and, on rare occasions, haemorrhagic diathesis are reported with cholestyramine impairment of vitamin D and vitamin K absorption, respectively. Paediatric patients have been reported to experience hyperchloraemic metabolic acidosis or gastrointestinal obstruction. Concurrent administration of acidic drugs may result in their reduced bioavailability. Serious adverse reactions to clofibrate will probably limit its role in the future. Of particular concern are ventricular arrhythmias, induction of cholelithiasis and cholecystitis, and the potential for promoting gastrointestinal malignancy which far outweigh the reported benefits in preventing new or recurrent myocardial infarction, cardiovascular death and overall death. Patients with renal disease are particularly prone to myositis, secondary to alterations in protein binding and impaired renal excretion of clofibrate. Drug interactions with coumarin anticoagulants and sulphonylurea compounds may produce bleeding episodes and hypoglycaemia, respectively. Nicotinic acid produces frequent adverse effects, but they are usually not serious, tend to decrease with time, and can be managed easily. Dermal and gastrointestinal reactions are most common. Truncal and facial flushing are reported in 90 to 100% of treated patients in large clinical trials. Significant elevations of liver enzymes, serum glucose, and serum uric acid are occasionally seen with nicotinic acid therapy. Liver enzyme elevations are more common in patients given large dosage increases over short periods of time, and in patients treated with sustained release formulations.

Longnecker JB, Basu SG. Effects of cholestyramine on absorption of amino acids and vitamin A in man. Fed Proc. 24:375, 1965.

Roe DA. Drug-induced Nutritional Deficiencies. 2nd ed. Westport, CT: Avi Publishing, 1985: 158-159.

Roe DA. Risk factors in drug-induced nutritional deficiencies. In: Roe DA, Campbell T, eds. Drugs and Nutrients: The Interactive Effects. New York: Marcel Decker, 1984: 505-523.

Threlkeld DS, ed. Diuretics and Cardiovasculars, Antihyperlipidemic Agents, Bile Acid Sequestrants. In: Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Feb 1997, 171i-171l.

Watkins DW, Khalafi R, Cassidy MM, Vahouny GV. Alterations in calcium, magnesium, iron, and zinc metabolism by dietary cholestyramine. Dig Dis Sci 1985 May;30(5):477-482.
Abstract: Cholestyramine is an effective drug for the reduction of plasma cholesterol because of its ability to sequester intestinal bile acids. Since metabolic alterations, including diminished intestinal absorption of vitamin D and osteomalacia have been reported with long-term use of this resin, the influence of cholestyramine on dietary balance of four mineral elements has been investigated. Wistar-strain rats were fed either a 2% cholestyramine or control diet for one month. Dietary intakes and fecal and urinary excretions of calcium, magnesium, iron, and zinc were determined using atomic absorption spectrophotometry during three, 3-day balance periods. Cholestyramine-fed rats had a net negative balance for calcium and a lower net positive balance for magnesium, iron, and zinc than the controls. Other effects of cholestyramine were an increased urinary excretion of calcium and magnesium, a decreased urinary zinc, and an alkalinization of urine. Blood and tissue cation content was unchanged except for a reduction in serum magnesium with resin feeding. Alterations in calcium, magnesium, and zinc metabolism might be explained by inadequate vitamin D absorption from the intestine followed by an increased secretion of parathyroid hormone. A diminished iron absorption due to resin binding could account for the reported disturbance in iron balance.

Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997, 221-222. (Review).

West RJ, Lloyd JK. The effect of cholestyramine on intestinal absorption. Gut. 1975 Feb;16(2):93-98.
Abstract: Cholestyramine in a mean dosage of 0-6 g/kg/day has been given to 18 children with familial hypercholesterolaemia for between one and two and a half years. With prolonged treatment folate deficiency occurred, as evidenced by a fall in the mean serum folate concentration from 7-7 ng/ml before treatment to 4-4 ng/ml for patients on treatment for over one year; a corresponding lowering of red cell folate was also seen. Oral folic acid 5 mg daily overcame this depletion, and should be given to all patients on long-term anion exchange resins. Prothrombin time has remained normal in all patients; there has been a significant decrease in the mean serum concentrations of vitamins A and E and of inorganic phosphorus over the first two years of treatment, although values remain within the normal range. The routine administration of fat-soluble vitamins appears unnecessary but it is prudent to measure prothrombin time and serum vitamins A and E at intervals. In children who were having a normal intake of dietary fat five out of seven tested had faecal fat of over 5 g/day while on cholestyramine. No child has developed diarrhoea, and growth has been normal. The concentrations of serum iron, vitamin B12, plasma calcium, and protein did not change significantly in any patient.