What is the role of bile acid-binding resins in the treatment of pediatric lipid disorders?

Updated: Jun 27, 2019
  • Author: Henry J Rohrs, III, MD; Chief Editor: Stuart Berger, MD  more...
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Answer

The 1991 NCEP recommendations for children advised using bile acid–binding resins as the drugs of choice to treat type IIA HLP in children. [16] However, bile acid–binding resins can lead to elevations in TG levels. Therefore, they are indicated in the treatment of type IIA HLP, but are not routinely indicated for type IIB HLP.

Bile acid–binding resins block bile acid reabsorption from the gut, resulting in bile acid excretion in the stool. Compensatory hepatocyte bile acid synthesis increases, which increases hepatocyte LDL-R expression. Increased LDL-R expression on the hepatocyte surface increases LDL clearance, resulting in a decrease in LDL-C concentrations. Bile acid–binding resins available in the United States include cholestyramine and colestipol.

Cholestyramine and colestipol are insoluble and must be mixed with water or juice to avoid the development of intestinal obstruction. The resins are taken with meals (when bile acids are secreted) and are dosed in scoops or packets of 4-5 g each. Therapy begins with 1-2 packets or scoops per day, given in orange juice or water. The dose is divided between breakfast and dinner and is increased every month to achieve an LDL-C level of less than 130 mg/dL or until maximum dosage is reached (see dosing information below).

Lack of palatability is a major factor limiting their use. The poor palatability may be compounded by the gritty texture of some resin preparations, which can be disguised with a high-pulp juice (eg, pineapple juice). Poor compliance has been reported in more than 50% of patients in some studies. To try to improve compliance, cholestyramine has been packaged into bars (Cholybar) and pills. Again, water must be ingested following the bars or pills to decrease the risk of intestinal obstruction. Reductions in TC and LDL-C levels of 10-40% have been described.

Stein et al observed a significant improvement in LDL-cholesterol from baseline when colesevelam was administered to children aged 10-17 years with heterozygous familial hypercholesterolemia. [24] Additionally, significant improvement was observed for total cholesterol and HDL-cholesterol. The study included patients who were statin-naive or on a stable statin regimen.

The dosing information is summarized below

Cholestyramine (Questran, Questran Lyte, LoCHOLEST, LoCHOLEST Light, Prevalite)

  • One scoop or pouch equals 4 g of cholestyramine.

  • Begin with 1 scoop or pouch mixed with water or juice; advance slowly to 8-16 g/d (usually divided twice daily immediately before major meals; dosage frequency ranges from 1-6 doses/d), not to exceed 24 g/d.

  • The maximal doses refer to adult-sized adolescents.

  • Optimal dosage for children has not been established, but standard texts list a usual pediatric dosage of 240 mg/kg/d divided in 2-3 doses, not to exceed 8 g/d.

  • When calculating pediatric doses of anhydrous cholestyramine resin, 80 mg is contained in 110 mg of Prevalite, 44.4 mg is contained in 100 mg of Questran powder, and 62.7 mg is contained in 100 mg of Questran Light.

Colestipol (Colestid, Flavored Colestid)

  • This agent is available as a 1-g tablet or granules for oral suspension (5 g per packet).

  • For adults, the starting tablet dose is 2 g once or twice daily, with increases of 2 g once or twice daily over periods of 1-2 months.

  • The maximum recommended dose is 16 g/d.

  • The granule starting dose for adults is 5 g orally every day to twice daily.

  • The dose may be increased by 5-g increments every 1-2 months.

  • Depending on the size of the child, these doses need to be reduced by one half to three quarters. Certainly, adult-sized children or adolescents could be dosed as adult levels.

  • The granules are convenient to administer but must not be taken dry. To administer, mix with liquids, soups, cereals, or pulpy fruits (eg, crushed pineapple, pears, peaches).

Use of bile acid–binding resins may lead to a decline in serum folate, carotinoid, and 25-hydroxyvitamin D concentrations. Fat malabsorption may occur. Children treated with bile acid–binding resins should receive supplementation with multivitamins including folate. Approximately 10% of children treated with cholestyramine have elevations in AST levels, lactate dehydrogenase (LD) levels, or both, which is surprising because these agents are not systemically absorbed.

Bile acid–binding resins bind drugs in addition to bile acids and vitamins; therefore, other drugs should be taken at least one hour before or 3 hours after consumption of bile acid–binding resins. No adverse effects on growth have been noted using bile-acid binding resins.


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