Colesevelam

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

Colesevelam is used in the treatment of Diabetes mellitus, type 2, and Hyperlipidemia (primary). It is also used to treat Diarrhea associated with bile acid malabsorption.

Colesevelam is not hydrolyzed by digestive enzymes and is not absorbed. An average of 0.05% of administered radioactivity from a single 14C-labeled colesevelam hydrochloride dose was excreted in the urine.

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

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

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

Colesevelam binds bile acids in the intestine and prevents their reabsorption. Colesevelam has not absorbed itself. The depletion of bile acid causes the upregulation of cholesterol 7-alpha-hydroxylase and the conversion of cholesterol to bile acid. This increases the production and activity of hydroxymethyl-glutaryl-coenzyme A (HMG-CoA) reductase in the liver, as well as an increase in the number of low-density lipoproteins (LDL) receptors. This process clears LDL cholesterol from the blood.

Colesevelam is available in the form of Granules for oral suspension And tablets.

Granules for oral suspension: Administer with the meal(s). The powder is not to be taken in dry form (to avoid esophageal distress).

Tablets: Administer with meal(s) and a liquid. Due to tablet size, it is recommended that any patient who has trouble swallowing tablets should use the oral suspension form.

Colesevelam is used in the treatment of Diabetes mellitus, type 2, and Hyperlipidemia (primary). It is also used to treat Diarrhea associated with bile acid malabsorption.

Colesevelam, a nonabsorbable hydrogel, binds w/ bile acids in the intestine to form a nonabsorbable complex that is excreted in the faeces. This results in increased conversion of cholesterol to bile acids in the liver causing a compensatory increase in hepatic uptake of circulating LDL cholesterol.

Colesevelam is approved for use in the following clinical indications

Diabetes mellitus, type 2: Improve glycemic control in adults with type 2 diabetes mellitus in conjunction with diet and exercise

Guideline recommendations: Colesevelam is not generally used in patients with type 2 diabetes but may be tried in specific situations .

Hyperlipidemia (primary):

Management of elevated LDL-C in adults with primary hyperlipidemia in conjunction with diet and exercise.

Management of heterozygous familial hypercholesterolemia (heFH) in adolescent patients (males and postmenarcheal females 10 to 17 years of age) who are unable to reach LDL-C target levels despite an adequate trial of dietary therapy and lifestyle modification.

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

Diarrhea associated with bile acid malabsorption.

Colesevelam is available in various strengths as 3.75 g, 625 mg

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.

Colesevelam is contraindicated in patients with

• History of bowel obstruction; serum TG concentrations of more than 500 mg/dL; history of hypertriglyceridemia-induced pancreatitis.

Disease-related concerns:

• Gastrointestinal disease: Use is not recommended in patients with gastroparesis, other severe GI motility disorders, a history of major GI tract surgery, or patients at risk for bowel obstruction. Use tablets with caution in patients with dysphagia or swallowing disorders; use the oral suspension form of colesevelam due to large tablet size and risk for esophageal obstruction. Discontinue if symptoms of bowel obstruction occur (eg, severe abdominal pain, severe constipation).

• Hypertriglyceridemia: Bile acid sequestrants can increase serum triglyceride concentrations; severely elevated triglycerides can cause acute pancreatitis. The manufacturer contraindicates use if triglycerides exceed 500 mg/dL and in patients with a history of hypertriglyceridemia-induced pancreatitis. The American College of Cardiology/American Heart Association recommends avoiding use in patients with baseline fasting triglyceride levels ≥300 mg/dL ). Use with caution in patients using insulin, thiazolidinediones, or sulfonylureas (may cause increased triglyceride concentrations). Discontinue if symptoms of acute pancreatitis occur (eg, severe abdominal pain with or without nausea and vomiting).

• Patients susceptible to fat-soluble vitamin deficiencies: Use with caution in patients susceptible to fat-soluble vitamin deficiencies. Absorption of fat soluble vitamins A, D, E, and K may be decreased; patients should take vitamins ≥4 hours before colesevelam

• Phenylketonuria: Some products may contain phenylalanine; use with caution.

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

Due to lack of systemic absorption, colesevelam 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, and therapy with colesevelam is preferred

Colesevelam is not absorbed systemically following oral administration and maternal use is not expected to result in fetal exposure to the drug.

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, and therapy with colesevelam is preferred.

Colesevelam (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.

May decrease absorption of fat-soluble vit A, D, E and K. May interfere w/ anticoagulant effect of warfarin. May reduce serum concentration of ciclosporin, phenytoin, glibenclamide, Ethinyl estradiol, norethindrone.

The common side effects of Colesevelam include the following

Common

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

Symptoms: Severe local GI effects (e.g., constipation).

Management: Location and degree of obstruction, presence or absence of normal gut motility would determine treatment.

Pharmacodynamic

Colesevelam binds with bile acids in the intestine to form an insoluble complex that is eliminated in feces. This increased excretion of bile acids results in an increased oxidation of cholesterol to bile acid and a lowering of the serum cholesterol.

Pharmacokinetics

• Absorption

Not hydrolyzed by digestive enzymes and is not absorbed. Not absorbed from the gastrointestinal tract following oral administration.

• Distribution

N.A.

• Metabolism

N.A.

• Excretion

In 16 healthy volunteers, an average of 0.05% of administered radioactivity from a single 14C-labeled colesevelam hydrochloride dose was excreted in the urine.

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