VA Class:CV350
Colestipol hydrochloride is a bile acid sequestrant antilipemic agent.
Colestipol is used as an adjunct to dietary therapy to decrease elevated serum total and low-density lipoprotein (LDL)-cholesterol concentrations in the treatment of primary hypercholesterolemia (type IIa hyperlipoproteinemia).
The 2018 American Heart Association (AHA)/American College of Cardiology (ACC) cholesterol management guideline emphasizes lifestyle modification as the foundation of atherosclerotic cardiovascular disease (ASCVD) risk reduction.400 If pharmacologic therapy is needed, hydroxymethyl-glutaryl-CoA (HMG-CoA) reductase inhibitor (statin) therapy is recommended.400 Statins are considered the first-line drugs of choice for reducing LDL cholesterol, the lipoprotein fraction found to be a major cause of ASCVD.400 The addition of a nonstatin drug (e.g., ezetimibe, bile acid sequestrants, PCSK9 inhibitor) may be considered in certain circumstances such as in patients with very severe elevations of LDL-cholesterol concentrations who are not achieving adequate LDL lowering with maximally tolerated statin therapy.400 For additional details on prevention of ASCVD, see the HMG-CoA Reductase Inhibitors General Statement 24:06.08.
Dietary management often is relatively effective in young children (2-5 years of age) with heterozygous familial hypercholesterolemia; however, older children with this disorder usually require the addition of drug therapy.120 Bile acid sequestrants (e.g., colestipol) or statins generally are considered the initial drugs of choice for the management of dyslipidemia or primary prevention of coronary heart disease (CHD) in selected children and adolescents (i.e., those 10 years of age and older with higher risk of developing CHD) in whom initial nonpharmacologic therapy (i.e., a 6- to 12-month trial of therapeutic lifestyle changes) does not provide adequate response. A bile acid sequestrant combined with a statin may be useful in hypercholesterolemic patients in whom initial drug therapy does not provide an adequate response or is not tolerated.357 Children with homozygous familial hypercholesterolemia usually respond poorly to combined dietary management and drug (e.g., combined bile acid sequestrant and niacin) therapy.130, 144, 145, 146, 147, 148, 149, 150, 151 More radical forms of therapy (e.g., plasma exchange,124, 125, 127, 131, 136, 149, 154, 155, 156, 157, 163 portacaval shunt,123, 126, 128, 136, 153, 163 liver transplantation)130, 136, 150, 163 combined with adjuvant drug therapy (e.g., bile acid sequestrants and niacin) and dietary management may be necessary in homozygous patients, but specialists should be consulted.120, 121, 129, 132, 149, 150, 153, 154, 155, 156, 157, 163
Colestipol, in conjunction with dietary therapy, has been shown to be more effective than diet alone or placebo in the treatment of hypercholesterolemia. However, in some patients, serum cholesterol concentrations may return to or exceed baseline concentrations during colestipol therapy. Colestipol and cholestyramine are equally effective in lowering plasma cholesterol concentrations. The choice of bile acid sequestrant generally is individualized based on patient tolerance, including palatability and taste preference, and cost.136, 163 Patients with heterozygous familial type II hyperlipoproteinemia (familial hypercholesterolemia) who do not respond adequately to colestipol therapy and dietary management may benefit from the addition of niacin to the therapeutic regimen.100, 111, 112, 113, 114, 136 Combined colestipol and niacin therapy in these patients has been reported to further reduce serum total cholesterol and LDL-cholesterol, to increase serum high-density lipoprotein (HDL)-cholesterol, and to decrease serum triglyceride concentrations.111, 112, 113, 114, 136 This combination has also reduced xanthomas and the progression of coronary arterial lesions in these patients.111, 113, 114 There is some evidence that combined therapy with colestipol, niacin, and lovastatin (an HMG-CoA reductase inhibitor) provides complementary effects in reducing LDL-cholesterol, since reductions were greater with triple-drug therapy than with various two-drug combinations in a limited number of patients with severe familial (heterozygous or homozygous) hypercholesterolemia; additional study is necessary.143
In the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT), long-term administration of cholestyramine resin to men with type II hyperlipoproteinemia who received dietary management was shown to reduce the risk of CHD.101, 102, 103, 107, 108, 109, 110 There was a 19% reduction in the combined incidence of CHD death and nonfatal myocardial infarction in this study.100, 101, 103, 107, 108, 109, 110, 167 (See Uses: Dyslipidemias, in Cholestyramine Resin 24:06.04.) It is likely that similar effects would be produced by other bile acid sequestrants, such as colestipol, that have similar effects on serum cholesterol concentrations through the same general mechanism.101, 102, 104
For further information on the role of antilipemic therapy in the treatment of lipoprotein disorders, the prevention of cardiovascular events, and other conditions, see General Principles of Antilipemic Therapy in the HMG-CoA Reductase Inhibitors General Statement 24:06.08.
Colestipol hydrochloride is administered orally.
Colestipol hydrochloride tablets must be taken one at a time and promptly swallowed whole, using plenty of water or other appropriate liquid. The tablets must not be cut, crushed, or chewed. Patients should be instructed to take other drugs at least 1 hour before or 4 hours after taking colestipol tablets to minimize possible interference with absorption. (See Drug Interactions: Effects on GI Absorption of Drugs.)
To avoid accidental inhalation or esophageal distress, colestipol hydrochloride for suspension should not be taken in its dry form. The drug should be added to at least 90 mL of a liquid (e.g., fruit juice, water, milk, a soft drink) and stirred until completely mixed. Some clinicians suggest that palatability and compliance may be increased if the entire next-day's dose is mixed in one of these liquids in the evening and then refrigerated.121 Use of a heavy or pulpy fruit juice may minimize complaints about consistency of suspensions of the drug.135, 136 To minimize excessive swallowing of air, patients should be advised to avoid rapid ingestion of suspensions of the drug.136 If a carbonated beverage is used, excessive foaming can be minimized by mixing the powder slowly in a large glass; however, use of a carbonated beverage as a vehicle may be associated with adverse GI effects. After the mixture is ingested, the glass should be rinsed with a small amount of additional fluid and the remaining liquid should be ingested to ensure that the entire dose has been taken. Alternatively, colestipol may be mixed with cereals, a highly fluid soup, or pulpy fruit (e.g., crushed pineapple, pears, peaches, fruit cocktail).
Serum lipoprotein concentrations should be determined periodically and dosage adjusted accordingly to achieve the desired effect while avoiding excessive dosage.135, 136
For the management of primary hypercholesterolemia, the usual adult dosage of colestipol hydrochloride as the tablets is 2-16 g daily taken once or in divided doses. Therapy should be initiated at a dosage of 2 g once or twice daily. Dosage increases of 2 g once or twice daily should occur at 1- or 2-month intervals. If the desired therapeutic effect is not obtained using colestipol in the tablet formulation at a dosage of 2-16 g daily with good compliance and acceptable adverse effects, combined therapy or alternative treatment should be considered.
For the management of primary hypercholesterolemia, the usual adult dosage of colestipol hydrochloride as the suspension is 5-30 g (1-6 packets or level scoops) daily taken once or in divided doses.100 To optimize antilipemic effects while minimizing the risk of adverse GI effects, dosage should be adjusted carefully and titrated slowly.135, 136 Colestipol hydrochloride suspension therapy generally is initiated in adults with 5 g (1 packet or 1 level scoop) once or twice daily; if the initial dose is well tolerated, the dosage may be titrated upward as necessary in 5-g increments at 1- or 2-month intervals.100, 135, 136, 166 In patients with preexisting constipation, the initial dosage of colestipol suspension should be 5 g (1 packet or 1 scoop) daily for 5-7 days, increasing to 5 g twice daily with monitoring of constipation and of serum lipoprotein values, at least twice, 4-6 weeks apart.166 If the initial dosage is well tolerated, the dosage of the suspension may be increased as needed by one dose per day (at monthly intervals) with periodic monitoring of serum lipoprotein values.166 If constipation worsens or the desired effect is not achieved with acceptable adverse effects within the usual dosage range of 1-6 doses per day, substitution or addition of another antilipemic agent should be considered.135, 136, 166 When used in combination with niacin in adults with heterozygous familial hypercholesterolemia, a colestipol hydrochloride dosage of 30 g daily has been used; niacin dosage was gradually increased as tolerated to a total dosage of 3-8 g daily in divided doses.111, 112, 113, 114
Although pediatric dosage has not been established,100 colestipol hydrochloride dosages of 10-20 g or 500 mg/kg daily in 2-4 divided doses have been used in a limited number of children for the management of hypercholesterolemia†.115, 116, 118, 119 Lower dosages (e.g., 125-250 mg/kg daily) have also been used in some children when serum cholesterol concentrations were only 15-20% above normal after dietary management alone.117
As an adjunct in the management of digitoxin (no longer commercially available in the US) overdosage†, colestipol hydrochloride has been given in an initial dose of 10 g, followed by 5 g every 6-8 hours.
The most common adverse effects of colestipol involve the GI tract; constipation is the major single complaint.173 In addition, colestipol may increase the severity of preexisting constipation. Although constipation is usually mild, transient, and controllable with standard treatment, it may occasionally be severe. A high-fiber diet and increased fluid intake may reduce constipation;111, 114, 121, 136, 173 a stool softener can be added if necessary.135, 136 In addition, dosage should be adjusted carefully and titrated slowly to minimize the risk of GI disturbances.135 (See Dosage and Administration: Dosage.) Fecal impaction or aggravation of hemorrhoids has occasionally occurred in association with constipation. Obstruction of the GI tract is the principal potential hazard of colestipol overdosage. In patients with preexisting constipation and in those who develop constipation during colestipol therapy, dosage should be reduced; complete withdrawal of the drug is occasionally necessary. Particular effort should be made to avoid constipation in patients with symptomatic coronary heart disease. Difficulty swallowing and transient esophageal obstruction have been reported rarely in patients receiving colestipol tablets. Other less common adverse GI effects of colestipol are abdominal discomfort (including pain, cramping, and distention), bloating, belching, flatulence, indigestion, heartburn, nausea, vomiting, and diarrhea or loose stools.100, 167 Bleeding hemorrhoids and blood in the stool have been reported infrequently. Peptic ulceration, cholecystitis, and cholelithiasis have been reported rarely but were not definitely drug related.100, 167
Adverse nervous system effects of colestipol include headache, migraine headache, and sinus headache.100, 167 Other infrequently reported adverse nervous system effects include dizziness, light-headedness, insomnia, anxiety, vertigo, and drowsiness.100, 167
Rash, urticaria, dermatitis, muscle and joint pain, arthritis, backache, anorexia, fatigue, weakness, shortness of breath, and swelling of the hands or feet have been reported occasionally in patients receiving colestipol.100, 167 Transient and modest increases in serum AST, serum ALT, and alkaline phosphatase concentrations have also occurred in patients receiving the drug. Increases in serum phosphorus and chloride concentrations associated with a concomitant decrease in serum sodium and potassium concentrations have also occurred. Hyperchloremic acidosis potentially can occur during prolonged therapy. (See Cautions: Precautions and Contraindications.) Chest pain, angina, and tachycardia have been reported infrequently in patients receiving colestipol but have not been directly attributed to the drug.
Precautions and Contraindications
Prior to institution of colestipol therapy, a vigorous attempt should be made to control serum cholesterol by appropriate dietary regimens and the treatment of any underlying disorder that may be the cause of the hypercholesterolemia. In addition, the potential contribution of existing drug therapy to the patient's lipoprotein profile should be considered;135 however, drug-induced increases in lipoprotein concentrations do not necessarily preclude their continuance when such therapy is indicated.161 Instead, the potential risks and benefits of such therapy should be carefully weighed.161 Serum cholesterol and triglyceride concentrations should be determined prior to and regularly during colestipol therapy.
Colestipol should be used with caution in patients with GI dysfunction such as constipation. (See Cautions: GI Effects.) Dosage should be adjusted carefully and titrated slowly to minimize the risk of producing fecal impaction, particularly in patients with preexisting constipation.135 (See Dosage and Administration: Dosage.)
Colestipol may interfere with the absorption of folic acid and fat-soluble vitamins, and prolonged use of colestipol may be associated with an increased bleeding tendency as a result of hypoprothrombinemia secondary to vitamin K deficiency. (See Drug Interactions: Vitamins.)
Although colestipol-induced hypothyroidism has not been reported in patients with normal thyroid function receiving the drug, the theoretical risk for the development of hypothyroidism, especially in patients with limited thyroid reserve, should be considered.
Because colestipol is the chloride form of an anion-exchange resin, the possibility that hyperchloremic acidosis could develop during prolonged therapy should be considered.135
Individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine should be warned that Flavored Colestid® granules for oral suspension contain aspartame (NutraSweet®), which is metabolized in the GI tract following oral administration, to provide 18.2 mg of phenylalanine per 7.5-g packet.
Colestipol is contraindicated in patients who are hypersensitive to the drug or any ingredient in its formulation.
The manufacturer states that safety and efficacy of colestipol have not been established in pediatric patients.100, 167
Colestipol, combined with dietary management, has been used in a limited number of children for the management of hypercholesterolemia† (see Uses: Dyslipidemias), but the potential effect of the resin on vitamin absorption should be considered.115, 116, 117, 163 (See Drug Interactions: Vitamins.)
Since colestipol is essentially unabsorbed systemically (less than 0.17% of the dose), the drug is not expected to cause fetal harm when administered during pregnancy in recommended dosages. However, safe use of colestipol during pregnancy has not been established and the drug should be used in women who are or may become pregnant only when the potential benefits justify the possible risks. The known interference of colestipol with absorption of fat-soluble vitamins may be detrimental even in the presence of supplementation. (See Drug Interactions: Vitamins.) Currently, most experts recommend that dyslipidemias in pregnant women be managed with dietary measures;104, 136 consultation with a lipid specialist may be indicated for pregnant women with severe forms of dyslipidemia.136
Caution should be exercised when colestipol is administered to nursing women since the possible lack of proper vitamin absorption associated with colestipol therapy may have an effect on nursing infants.
Effects on GI Absorption of Drugs
Since colestipol is an anion-exchange resin, it is capable of binding to a number of drugs in the GI tract and may delay or reduce their absorption. Although the clinical importance of these potential interactions has not been determined, patients should be instructed to allow as long a time interval as possible between ingestion of other drugs and colestipol. The manufacturer recommends that other drugs be administered at least 1 hour before or 4 hours after colestipol.
Colestipol has been reported to substantially decrease absorption of tetracycline and penicillin G when the resin was given simultaneously with either of these antibiotics. Colestipol may decrease absorption of chenodiol (no longer commercially available in the US) and interfere with its action. Decreased absorption of chlorothiazide, hydrochlorothiazide, furosemide, and gemfibrozil also has occurred in patients receiving colestipol.100, 167
Colestipol may bind digoxin in the GI tract and impair its absorption.
Concomitant administration of colestipol and propranolol decreases and/or delays GI absorption of propranolol,133, 134, 135, 166 but the effect of the anion-exchange resin on absorption of other β-adrenergic blocking agents has not been fully determined.134, 135 Pending further accumulation of data, patients receiving colestipol and propranolol concomitantly should be monitored closely whenever colestipol therapy is initiated or discontinued;133, 135, 166 dosage adjustment of propranolol may be necessary.133, 134 The effect of separating administration of these drugs remains to be evaluated.133, 134
Bile acid binding resins may interfere with the absorption of oral phosphate supplements.
The possibility that discontinuance of colestipol in patients stabilized on potentially toxic drugs that bind to the resin may lead to toxicity and that administration of colestipol to patients stabilized on other drugs may reduce the effect of these drugs should be kept in mind.
Because colestipol sequesters bile acids, the drug may interfere with absorption of folic acid and fats and thus may prevent absorption of fat-soluble vitamins such as A, D, E, and K. If colestipol is to be given for a prolonged period, supplemental administration of vitamins A and D should be considered. If bleeding occurs in patients receiving colestipol, parenteral administration of phytonadione is usually valuable in promptly restoring normal clotting time, and oral administration of phytonadione can be used for the prevention of recurrent bleeding.
In one study in hypercholesterolemic children 5-17 years of age who received 15-20 g of colestipol hydrochloride daily combined with dietary management, mean serum vitamin A and E concentrations decreased from predrug levels of 68 mcg/dL and 14 mcg/mL, respectively, to 35 mcg/dL and 11 mcg/mL, respectively, after 18-24 months of therapy with the drug; clinical manifestations of vitamin deficiency were not present.116 Substantial changes in serum 25-hydroxycholecalciferol or folate concentration or in prothrombin time (indirect measure of vitamin K activity) did not occur, although serum folate was 2.8 ng/mL (normal: 3-15 ng/mL) after 36 months of colestipol therapy in one child.116 In another study in children 7-20 years of age who received 10-15 g of colestipol hydrochloride daily combined with dietary management, mean plasma 25-hydroxycholecalciferol decreased from predrug levels of 32.6 ng/mL to 18.5 ng/mL after 18-20 months of therapy with the drug; there was no consistent accompanying effect on plasma calcium or phosphate concentrations and plasma 25-hydroxycholecalciferol concentrations returned toward normal levels during continued therapy.119 However, the long-term effect of this change on optimal growth and development is not known.119 It has been recommended that serum concentrations of folate and fat-soluble vitamins be monitored annually in children receiving colestipol†, and that their diet be supplemented accordingly.116
In one study in a limited number of diabetic patients receiving phenformin and an oral sulfonylurea antidiabetic agent, colestipol failed to lower elevated plasma cholesterol concentrations, possibly as a result of the effects of the antidiabetic agents on lipid metabolism. In contrast, cholesterol concentrations were reduced in insulin-treated diabetic patients with hypercholesterolemia which was treated with colestipol.
The manufacturer states that there has been no experience to date with acute overdosage of colestipol.100 The principal risk of acute overdosage of the drug is expected to be GI obstruction.100 Specific measures for management would depend on the degree and location of obstruction and GI motility,100 and experts should be consulted for specific recommendations.
The pharmacologic actions of colestipol are similar to those of cholestyramine. Following oral administration, colestipol binds bile acids in the intestine, forming a nonabsorbable complex which is excreted in feces. This results in partial removal of bile acids from the enterohepatic circulation. A compensatory increase in the oxidation of cholesterol to bile acids and in hepatic cholesterol production accompanies increased fecal excretion of bile acids; however, the amount of cholesterol in the rapidly turning over cholesterol body pool remains unchanged. In spite of increased production of cholesterol, plasma cholesterol and low-density lipoprotein (LDL) concentrations fall in patients with primary type II hyperlipoproteinemia, possibly secondary to an increased rate of clearance of LDL from the plasma. Decreases in plasma cholesterol concentrations may occur within 24-48 hours following initiation of colestipol therapy; most patients respond maximally to therapy within 1 month. Patients with the highest initial plasma cholesterol concentrations experience the greatest reduction. Cholesterol concentrations return to baseline within 1 month when the drug is discontinued. A reduction in the frequency of progression and an increase in the frequency of regression of coronary atherosclerotic lesions has been reported in patients with coronary atherosclerosis who have received long-term therapy (e.g., 2-4 years) with colestipol plus either niacin or lovastatin. In some patients with hypercholesterolemia, a decrease in the size of xanthomas has been associated with long-term colestipol therapy. Plasma triglyceride concentrations may increase during colestipol therapy, partly due to increases in very low-density lipoprotein (VLDL) concentrations. Increases in VLDL triglyceride concentrations are especially evident in patients with type IV and type V hyperlipoproteinemia receiving the drug.
Since colestipol is an anion-exchange resin, it may bind other substances, usually those with a greater affinity for the resin than the chloride ion. (See Drug Interactions.)
Colestipol hydrochloride is a bile acid sequestrant antilipemic agent. The drug is a high molecular weight basic anion-exchange resin. Colestipol hydrochloride is a copolymer of diethylenetriamine and 1-chloro-2,3-epoxypropane that contains secondary and tertiary amines with approximately 1 out of 5 amine nitrogens protonated with chloride; in contrast, cholestyramine contains quaternary ammonium groups protonated with chloride ions. In vitro, each gram of colestipol hydrochloride binds about 938 µmol of taurocholate and 825 µmol of glycocholate; an equal amount of cholestyramine binds about 1100 µmol of taurocholate and 913 µmol of glycocholate. Each gram of colestipol hydrochloride unflavored granules for oral suspension (Colestid®) binds 1.1-1.6 mEq of sodium cholate, calculated as the cholate binding capacity.
Colestipol hydrochloride occurs as light yellow to orange, water-insoluble beads which are hygroscopic and swell when placed in aqueous fluids. The commercially available unflavored granules for oral suspension (Colestid®) contains 0.2% colloidal silicon dioxide as a flow-promoting agent; Flavored Colestid® granules for oral suspension contains aspartame and other inactive ingredients. Each 7.5-g packet of Flavored Colestid® granules for oral suspension (orange-flavored) contains 5 g of colestipol hydrochloride. Each Colestid® tablet contains 1 g of micronized colestipol hydrochloride. A 10% (w/w) aqueous suspension of colestipol hydrochloride has a pH of 6-7.5.
Commercially available preparations of colestipol hydrochloride for oral suspension should be stored in tight containers at a temperature of 20-25°C. Colestipol hydrochloride tablets should be stored at a temperature of 20-25°C.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | For suspension | 5 g/packet or calibrated scoop* | Colestid® Granules | |
5 g/7.5 g packet or calibrated scoop | Colestid® Flavored Granules | Pfizer | ||
Tablets (micronized) | 1 g | Colestid® | Pfizer |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
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