Colestipol

Colestipol is a bile acid sequestrant belonging to the Hyperlipidemia class.

Colestipol is used in the treatment of Adjunctive therapy to diet in patients with primary hypercholesterolemia. It is also used to treat Pruritus with primary biliary cholangitis.

Colestipol is hydrophilic, but it is virtually water-insoluble (99.75%). This water insolubility, combined with the high molecular weight polymer in colestipol, means the agent and the complexes it forms when it binds with bile acids are not absorbed.

Colestipol shows common side effects like Headache, dizziness, diarrhea, sore throat, runny nose, sneezing, joint pain, etc.

Colestipol is available in the form of an Oral Tablet and Granules.

Colestipol is available in India, Germany, Italy, France, USA

Colestipol releases Cl ions and binds w/ bile acids in the intestine to form a nonabsorbable complex excreted in the feces, resulting in partial removal of bile acids from the enterohepatic circulation, thereby increasing the bile salt-bound LDL cholesterol.

Colestipol is available in the form of Oral Granules And tablets.

Granules: Do not administer in dry form (to avoid esophageal distress or accidental inhalation). After mixing and administration of granules, rinse the glass with a small amount of liquid and ingest it to ensure all medication is taken.

Tablets: Administer tablets one at a time, swallow whole, with plenty of liquid. Do not cut, crush, or chew tablets.

Colestipol is a lipid-lowering polymer that binds with bile acids in the intestine, forming a complex that is excreted in the feces. This non-systemic action results in a continuous, partial removal of bile acids from the enterohepatic circulation preventing their reabsorption . This increased fecal loss of bile acids due to colestipol hydrochloride administration leads to increased oxidation of cholesterol to bile acids . This results in an increase in the number of hepatic low-density lipoprotein (LDL) receptors, and consequently an increased uptake of LDL and a decrease in serum/plasma beta lipoprotein or total and LDL cholesterol levels. Although hydrochloride produces an increase in the hepatic synthesis of cholesterol in man, serum cholesterol levels fall.

Colestipol is approved for use in the following clinical indications

Primary hypercholesterolemia: Adjunctive therapy to diet in patients with primary hypercholesterolemia.

Although not approved there have been certain off label use documented for Colestipol which includes:

• Pruritus with primary biliary cholangitis

Colestipol is available in various strengths as

• Tablets : 1g
• Granules : 5g

Colestipol is available in the form of Oral Granules and tablets.

• Dosage Adjustment for Pediatric Patients:
• Dyslipidemia: Limited data available: Note: Bile acid sequestrant therapy should not be used in pediatric patients with hypertriglyceridemia. Statins are recommended as the primary agent for the management of hypercholesterolemia, particularly those in high-risk categories. Multivitamin supplementation recommended due to potential folic acid and cholecalciferol malabsorption .
• Fixed dosing: Children ≥8 years and Adolescents: Oral: Reported range: 2 to 12 g/day; in one trial, both the 10 g once daily and 5 g twice daily were shown to produce significant lowering of serum cholesterol (McCrindle 2002; Tonstad 1996); doses <10 g suggested to maximize tolerability.

• Weight-directed dosing: Children ≥3 years and Adolescents: Very limited data available: 125 to 250 mg/kg/day has been used in patients 3 to 24 years of age (mean age: 13.7 years) with familial hypercholesterolemia .

Note: Although colestipol has been used in patients down to 3 years of age, experts recommend the initiation of drug therapy for the management of hypercholesterolemia in pediatric patients who are older (eg ≥10 years) 

Hypercholesterolemia: Reducing the amount of saturated and trans fats in the diet to lower cholesterol and heart disease risk. To reduce levels of “bad” cholesterol, limit the intake of the following foods, which contain high levels of saturated and trans fats: fatty meat, such as lamb and pork.

Colestipol is contraindicated in patients with

• Hypersensitivity to bile acid sequestering resins or any component of the formulation; complete biliary obstruction

Concerns related to adverse effects:

• Acidosis: Chronic use may lead to the development of hyperchloremic acidosis.

• Bleeding: Chronic use may be associated with bleeding problems due to hypoprothrombinemia from vitamin K deficiency; may be prevented with the use of vitamin K therapy.

• Constipation: May produce or exacerbate constipation; fecal impaction may occur; initiate therapy at a reduced dose and increase gradually in patients with a history of constipation. Encourage increased fluid and fiber intake; a stool softener may also be indicated. Hemorrhoids may be worsened.

• Hypothyroidism: There is a theoretical risk of developing hypothyroidism, particularly in patients with limited thyroid reserve. Use with caution.

Disease-related concerns:

• Hypertriglyceridemia: Bile acid sequestrants can increase serum triglyceride concentrations. The American College of Cardiology/American Heart Association recommends avoiding use in patients with fasting triglyceride levels ≥300 mg/dL

Colestipol may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Due to lack of systemic absorption (<0.17%), colestipol is not expected to be present in breast milk.

When treatment for hypercholesterolemia in breastfeeding women is needed, therapy with bile acid sequestrants may be considered . However, because use may interfere with maternal vitamin absorption, the manufacturer recommends caution be used if administered to breastfeeding women.

Lipid concentrations increase during pregnancy as required for normal fetal development. When increases are greater than expected, supervised dietary intervention should be initiated. Bile acid sequestrants are recommended when treatment is needed.

Colestipol is not absorbed systemically (<0.17%), but may interfere with maternal vitamin absorption; therefore, regular prenatal supplementation may not be adequate.

Colestipol (especially high doses or long-term therapy) may decrease the absorption of folic acid, calcium, fat-soluble vitamins (vitamins A, D, E, and K), and iron. Management: Supplementation of folic acid, calcium, fat-soluble vitamins (vitamins A, D, E, and K), and iron may be necessary.

• Common Adverse effects

Constipation, faecal impaction, aggravation of haemorrhoids, abdominal discomfort or pain, heartburn, flatulence, nausea, vomiting, diarrhoea

• Less Common Adverse effects:

Increased bleeding tendency (chronic use), steatorrhoea (high doses), skin rashes, Pruritus of the tongue, skin and perianal region; hyperchloraemic acidosis

• Rare Adverse effects

Night blindness secondary vit A deficiency, Vit D deficiency.

• It may interfere w/ absorption of folic acid, oral phosphate supplements, and fats, preventing absorption of fat-soluble vit. Decreased absorption of tetracycline, penicillin G, hydrochlorothiazide, furosemide or gemfibrozil. May bind digoxin in the GI tract and impair its absorption. Decreased and/or delayed GI absorption of propranolol. May decrease the serum concentration of mycophenolic acid.

The common side effects of Colestipol include the following

Common

● Constipation, diarrhea, Heartburn, pain in the back, arm, or legs, Headache, joint pain.

Symptoms: GI obstruction.

Management: Dependent on the degree and location of obstruction and GI motility. Expert opinion is required.

Pharmacodynamic

Colestipol , as well as some of its metabolites, are pharmacologically active in humans. The liver is the primary site of action and the Principal site of cholesterol synthesis and LDL clearance. Drug dosage, rather than systemic drug concentration, correlates better with LDL-C reduction. Individualization of drug dosage should be based on therapeutic response

Pharmacokinetics

• Absorption

Not absorbed from the gastrointestinal tract following oral administration.

• Distribution

N.A.

• Metabolism

N.A.

• Excretion

Colestipol resin adsorbs and combines with the bile acids in the intestine to form an insoluble complex which is excreted in the feces.

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
2. https://reference.medscape.com/drug/colestid-colestipol-342452
3. https://go.drugbank.com/drugs/DB00375
4. https://www.sciencedirect.com/topics/medicine-and-dentistry/colestipol
5. https://europepmc.org/article/med/6988203