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Colesevelam Hydrochloride - Dosage, Uses, and Side Effects

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Colesevelam hydrochloride is a drug used to treat primary hyperlipidemia. Read the article below to learn more about this medication.

Medically reviewed by

Dr. Rajesh Gulati

Published At April 17, 2024
Reviewed AtApril 18, 2024

Overview

Colesevelam hydrochloride is a medication used to reduce low-density lipoprotein cholesterol (LDL-C), as well as exercise and diet in adult patients with primary hyperlipidemia (high levels of fats in the blood). It can be used alone or with statins such as hydroxymethyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors. It was approved by the United States Food and Drug Administration (US FDA) on February 10, 2009, and by the European Medicines Agency (EMA) on May 26, 2000.

How Does Colesevelam Hydrochloride Work?

Colesevelam hydrochloride belongs to a class of medications called bile acid sequestrants. The body does not absorb the drug; it stays in the gut and works by attaching to bile acids and eliminating them from the body through the feces. Bile acids are not absorbed into the bloodstream, forcing the liver to produce more. The liver uses cholesterol to produce bile acids, thus lowering the level in the blood and reducing the risk of heart disease.

Indications of Colesevelam Hydrochloride

  • Colesevelam hydrochloride is indicated in adult patients with primary hyperlipidemia as an adjunct to diet and exercise to decrease low-density lipoprotein cholesterol (LDL-C).

  • It can also be used in heterozygous familial hypercholesterolemia (high levels of cholesterol in the blood) in boys and postmenarchal girls of 10 to 17 years of age as a monotherapy or in combination with a statin.

  • It is indicated in patients with coronary heart disease (CHD) (cholesterol deposits in the walls of the major blood vessels of the heart) or the presence of CHD risk factors.

  • It is also recommended for adult patients with type 2 diabetes mellitus (increased glucose level in the blood), along with exercise and diet, to improve glycemic control.

  • Colesevelam hydrochloride can improve stool consistency (non-FDA-approved use) in patients with irritable bowel syndrome (abdominal discomfort) and diarrhea, thus improving bowel function.

Contraindications of Colesevelam Hydrochloride

  • Colesevelam hydrochloride is contraindicated in the treatment of type I diabetes and diabetic ketoacidosis (high levels of ketones in the body).

  • It is not recommended for children below ten or premenarchal girls.

  • Colesevelam hydrochloride has not been studied in individuals with type 2 diabetes as monotherapy or along with a dipeptidyl peptidase four inhibitor or thiazolidinediones and in patients with Fredrickson type (Type I, III, IV, and V) dyslipidemias (increased levels of triglycerides).

  • It is also contraindicated in patients with a history of bowel obstruction, pancreatitis (inflammation of the pancreas) induced by hypertriglyceridemia, and if serum triglyceride (TG) concentrations are more than 500 mg/dL (milligram per deciliter).

Available Doses and Dose Forms

Colesevelam hydrochloride is available as 625 mg (milligrams) tablets and as a powder for oral suspension in single-dose packets of 3.75 grams or 1.875 grams.

The recommended dose of Colesevelam hydrochloride is:

  • As monotherapy or in combination with a statin, six tablets of Colesevelam hydrochloride must be taken once or three tablets twice daily with food.

  • Oral suspension must be prepared by emptying the entire contents of one packet into a cup or glass. About half to one cup of water (4 to 8 ounces), fruit juice, or any diet soft drinks are added and stirred well; this mixture must be taken with meals. Colesevelam hydrochloride can be taken at the same time as a statin, or both drugs can be dosed apart. Oral suspension powder must not be consumed in its dry form, as it can cause esophageal distress. Oral suspension can also be recommended for patients having difficulty swallowing the tablet due to its size.

Warnings and Precautions

  • Colesevelam hydrochloride can increase serum triglyceride concentration; therefore, care must be taken when treating patients whose triglyceride levels are above 300 mg/dL. Triglyceride and non-HDL-C levels must be obtained before beginning the treatment and periodically after that. Colesevelam hydrochloride must be discontinued if patients develop hypertriglyceridemia-induced pancreatitis if triglyceride levels increase more than 500 mg/dL.

  • Colesevelam hydrochloride is not recommended in patients with gastrointestinal motility disorders or gastroparesis (a delay in food movement from stomach to intestine), patients who have undergone gastrointestinal tract surgery, or at risk for bowel obstruction. Colesevelam hydrochloride tablets can cause dysphagia or esophageal obstruction; therefore, they must be used with caution in patients with swallowing disorders.

  • Bile acid-sequestrant drugs can reduce the absorption of fat-soluble vitamins such as A, D, E, and K. Therefore, patients taking oral supplements must take them at least four hours before Colesevelam hydrochloride. Care must be taken in patients prone to vitamin K deficiencies and malabsorption syndromes, as well as patients on Warfarin.

  • The effect of Colesevelam hydrochloride on cardiovascular morbidity and mortality has not been established.

  • Colesevelam hydrochloride has the potential to reduce the gastrointestinal absorption of certain drugs. Therefore, the drugs that interact with Colesevelam hydrochloride or drugs with a narrow therapeutic index must be administered four hours before, or the doctor must monitor the levels of the co-administered drug.

  • Care must be taken while recommending Colesevelam hydrochloride in people with phenylketonuria (PKU), as the oral suspension contains 24 mg of phenylalanine per 1.875 g and 48 mg of phenylalanine per 3.75 g packets of the drug.

Adverse Effects of Colesevelam Hydrochloride

Some of the adverse effects of Colesevelam hydrochloride include:

  • Nausea and vomiting.

  • Headache.

  • Abdominal pain.

  • Diarrhea.

  • Muscle pain.

  • Weakness.

  • Constipation.

For Patients

What Is Primary Hyperlipidemia?

Hyperlipidemia is a condition in which lipid levels (organic compounds such as fats, fat-soluble vitamins, waxes, etc.) are elevated due to genetic or acquired disorders. It is further classified into primary and secondary hyperlipidemia. Primary hyperlipidemia occurs due to genetic causes, and secondary (acquired) hyperlipidemia can occur due to various underlying causes such as an unhealthy diet or lifestyle, hypothyroidism, uncontrolled diabetes (increased blood glucose levels), and medications.

Primary hyperlipidemia is characterized by a severe form of hypercholesterolemia (increased cholesterol level) or hypertriglyceridemia (increased triglyceride levels) in early life and an increased risk of cardiovascular disorders or recurrent pancreatitis (inflammation of the pancreas). It may not be associated with symptoms in most individuals; however, after several years, it can lead to coronary artery disease, which causes chest pain, nausea, difficulty breathing, and other symptoms. Primary hyperlipidemia can be managed by medications, regular exercise, consuming a healthy diet, quitting smoking and alcohol, and weight management.

What Is Colesevelam Hydrochloride?

Colesevelam hydrochloride is a prescription for hyperlipidemia, regular exercise, a healthy diet, and weight loss programs. It can be prescribed alone or in combination with other medications. It can also be used in boys and post-menarchal girls aged 10 to 17 years with familial hypercholesterolemia. It can be recommended for use in tablets, oral suspension, or chewable bars. It must be taken exactly as prescribed and should not be discontinued without the doctor’s consent. Colesevelam hydrochloride controls the condition but does not completely cure it.

How Effective Is Colesevelam Hydrochloride?

Colesevelam hydrochloride belongs to a group of drugs called bile acid sequestrants and works by binding bile acids to the intestine to form a product that is eliminated from the body through feces. Various studies have demonstrated that the drug is well tolerated at all doses and lacks the constipating effect, a characteristic factor of other bile acid sequestrants. It is an effective alternative to similar drugs for individuals requiring a moderate reduction in low-density lipoprotein levels. It helps achieve beneficial reductions in lipid levels with minimal gastrointestinal side effects.

How Should Colesevelam Hydrochloride Be Taken?

Colesevelam hydrochloride tablets must be taken orally once or twice daily as prescribed with food. The chewable bars or oral suspension must be taken daily with a meal. The contents of one packet must be emptied into a glass, and eight ounces of water, diet soft drink, or fruit juice must be added to it and stirred well. The mixture must be consumed immediately. However, the powder must be kept in its dry form.

What Are the Side Effects of Colesevelam Hydrochloride?

Some of the side effects of Colesevelam hydrochloride include:

  • Nausea and vomiting.

  • Gas.

  • Diarrhea.

  • Abdominal pain.

  • Constipation.

  • Muscle pain.

  • Headache.

  • Weakness.

What Must the Patient Inform the Doctor Before Taking Colesevelam Hydrochloride?

  • Before starting the treatment, patients must tell the doctor if they are allergic to Colesevelam hydrochloride, its components, or other medications.

  • Female patients must inform the doctor if they are pregnant, breastfeeding, or planning to become pregnant before taking Colesevelam hydrochloride.

  • Patients must inform the healthcare provider if they take cyclosporine, oral contraceptives, vitamins or herbal supplements, over-the-counter (OTC) drugs, or any other medications before taking Colesevelam hydrochloride.

What Are the Precautionary Measures to Be Followed While Taking Colesevelam Hydrochloride?

  • Patients must inform the doctor if they have or previously had a blockage in the stomach or intestine, swelling of the pancreas, any digestive problems, or high levels of triglycerides before starting treatment with Colesevelam hydrochloride.

  • Before starting the treatment, patients must inform the doctor if they have had any gastrointestinal surgery, problems with swallowing, or other stomach problems.

  • Patients with phenylketonuria (increased levels of phenylalanine in the blood) must be aware that the oral suspension powder contains aspartame, which forms phenylalanine.

  • A low-fat or low-cholesterol diet and regular exercise must be followed during the treatment with Colesevelam hydrochloride.

Dietary Considerations

During treatment with Colesevelam hydrochloride, a low-fat, low-cholesterol diet and other doctor-recommended diets must be followed, along with regular exercise.

Missed Dose

Colesevelam hydrochloride must be taken regularly and exactly as the doctor prescribes. However, if a dose is missed, it must be taken as soon as remembered, but if it is almost time for the next dose, the missed dose can be skipped, and the regular dosing schedule must be followed. A double dose must not be taken to compensate for the missed dose.

Overdose

In the event of an overdose, or if severe adverse effects are observed, the doctor must be consulted immediately.

Storage

Colesevelam hydrochloride tablets and oral suspension powder must be stored at 25 degrees Celsius (77 degrees Fahrenheit), away from excess heat and moisture.

For Doctors

Pharmacological Aspects of Colesevelam Hydrochloride

Mechanism of Action

Colesevelam hydrochloride is a non-absorbed lipid-lowering polymer that binds bile acids in the intestine and impedes their reabsorption. As the bile acid pool is reduced, the hepatic enzymes get upregulated and increase the conversion of cholesterol to bile acids. This increases the demand for cholesterol in the liver cells, results in a dual effect, and increases the transcription and activity of HMG-CoA reductase and LDL receptors. These effects result in increased clearance of LDL-C from the blood and decreased serum LDL-C levels; serum triglyceride levels can increase or remain unaffected.

Pharmacodynamics

The maximum therapeutic response to lipid-lowering was achieved within two weeks of treatment with Colesevelam hydrochloride and maintained during long-term therapy. In diabetes clinical studies, a reduction in hemoglobin A1C was observed as a therapeutic response. It was observed following four to six weeks of treatment and reached a maximum effect after 12 to 18 weeks.

Pharmacokinetics

  • Absorption: Colesevelam hydrochloride is a hydrophilic agent and a water-insoluble polymer not hydrolyzed by the digestive system's enzymes; hence, the drug is not absorbed.

  • Distribution: As Colesevelam hydrochloride is not absorbed, its distribution to the gastrointestinal tract (GIT) is limited.

  • Metabolism: Colesevelam hydrochloride is not metabolized in the body and does not interfere with systemic enzymes such as cytochrome P-450.

  • Excretion: In healthy volunteers, approximately 0.05 percent of Colesevelam hydrochloride (a single C-labeled radioactive) administered was excreted in the urine.

Drug Interactions

Colesevelam hydrochloride can interact with certain drugs; therefore, close monitoring is required.

These include:

  • Cyclosporine.

  • Levothyroxine.

  • Metformin.

  • Glimepiride.

  • Norethindrone.

  • Levonorgestrel.

  • Olmesartan.

  • Phenytoin.

  • Vitamin D.

  • Warfarin.

Clinical Studies

Colesevelam hydrochloride was studied in nine clinical trials, all of which were multicentered, randomized, double-blind, and placebo-controlled, except for one uncontrolled, open-label study and a long-term extension study. In all these studies, approximately 1600 patients were studied, and the duration of treatment ranged from 4 to 50 weeks.

Study results demonstrated a reduction in total cholesterol (TC), LDL-C, apolipoprotein B (Apo B), and non-HDL-C as early as two weeks. Colesevelam hydrochloride was administered twice a day in divided doses along with meals in the morning and evening to patients with elevated LDL-C ranging from 130 mg/dl to 220 mg/dl with a mean of 158 mg/dl. The study conducted for 24 weeks demonstrated a reduction in LDL-C by 15 percent on the administration of 3.8 g (grams) of Colesevalem; this increased to 18 percent when the dose was increased to 4.8 g. Total cholesterol showed a reduction of 7 percent and 10 percent on administration of similar doses. Apo-B was reduced by 12 percent, HDL-C was increased by 3 percent, and the study also demonstrated an increase in triglycerides by 9 to 10 percent.

In another study, in three different trials, Colesevelam hydrochloride was co-administered with stains such as Atorvastatin, Lovastatin, or Simvastatin. The combination demonstrated additive effects in reducing LDL-C levels by adding Colesevelam hydrochloride 2.3 g, reducing LDL-C by 8 percent, and increasing the dose to 3.8 g, further reducing LDL-C by 16 percent in addition to the reduction achieved by statins. The reduction achieved by the combination was statistically significant compared to monotherapy with either Colesevalem or statins.

An eight-week, randomized, multicenter, placebo-controlled, double-masked, and parallel-group study conducted to assess the safety and efficacy of Colesevalem in pediatric patients demonstrated a significant reduction in LDL-C, non-HDL-C, TC, and Apo-B on administration of 3.8 g/day (grams per day) of Colesevalem hydrochloride.

The efficacy of Colesevelam hydrochloride in diabetes mellitus was evaluated in three placebo-controlled, double-blind, add-on therapy trials in 1018 patients with HbA1C ranging from 7.5 to 9.5 percent. The administration of a 3.8 g/day dose of Colesevelam hydrochloride in these trials demonstrated a significant reduction in HbA1C up to 0.5 percent compared to placebo when administered alone or as an add-on therapy to standard anti-diabetic drugs. Along with HbA1C, it significantly affected the lipid profile, but there was no effect on body weight.

Nonclinical Toxicology

  • Carcinogenicity studies conducted in male and female mice at doses of Colesevelam hydrochloride up to 3 g/kg/day (gram per kilogram per day) showed no significant drug-induced tumor findings. However, a statistically significant increase in pancreatic acinar cell adenoma was observed in male rats at doses greater than 1.2 g/kg/day, and an increase in thyroid C-cell adenoma was observed in female rats at doses of 2.4 g/kg/day.

  • Colesevelam hydrochloride and its degradants were evaluated for mutagenicity in the Ames and chromosomal aberration tests.

  • Colesevelam hydrochloride did not affect fertility in rats at doses up to 3 g/kg/day, which is approximately 50 times the maximum dose in humans.

Specific Considerations

  • Pregnancy: Animal studies have reported no evidence of fetal harm. However, adequate and well-controlled studies of Colesevelam hydrochloride have not been performed in pregnant females.

  • Lactation: Colesevelam hydrochloride is not excreted in breast milk as the drug is not absorbed from the gastrointestinal tract.

  • Pediatric Use: The safety and effectiveness of Colesevelam hydrochloride have not been determined in children below ten years of age and pre-menarchal girls.

  • Geriatric Use: No significant differences were observed in individuals above 75 and younger adults.

  • Hepatic and Renal Impairment: Dosage adjustments are not required in patients with hepatic or renal impairment.

Source Article IclonSourcesSource Article Arrow
Dr. Rajesh Gulati
Dr. Rajesh Gulati

Family Physician

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hyperlipidemia
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