Colesevelam

Primary Hyperlipidemia : Colesevelam hydrochloride, the active pharmaceutical ingredient, is a non-absorbed, lipid-lowering polymer that binds bile acids in the intestine, impeding their reabsorption. As the bile acid pool becomes depleted, the hepatic enzyme, cholesterol 7-α-hydroxylase, is upregulated, which increases the conversion of cholesterol to bile acids.

• Colesevelam hydrochloride is a bile acid sequestrant indicated as an adjunct to diet and exercise to: reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia ( 1.1 ). reduce LDL-C levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia (HeFH), unable to reach LDL-C target levels despite an adequate trial of diet and lifestyle modification ( 1.1 ).ICD-10: E78.00, E78.5

• Colesevelam hydrochloride is contraindicated in patients with: Serum TG concentrations >500 mg/dL [see Warnings and Precautions (5.1) ] History of hypertriglyceridemia-induced pancreatitis [see Warnings and Precautions (5.1) ] A history of bowel obstruction [see Warnings and Precautions (5.2) ] Patients with serum triglyceride levels >500 mg/dL ( 4 ) Patients with a history of hypertriglyceridemia-induced pancreatitis ( 4 ) Patients with a history of bowel obstruction ( 4 )contraindicated

Obtain lipid parameters, including serum triglyceride (TG) levels, before starting colesevelam hydrochloride ( 2.1 ). The recommended dosage for adults and for boys and postmenarchal girls aged 10 to 17 years with primary hyperlipidemia is 3.75 grams daily. The recommended dosage for adults with type 2 diabetes mellitus is 3.75 grams daily. Colesevelam hydrochloride should be taken as follows ( 2.2 , 2.4 ): Tablets Take 6 tablets once daily or 3 tablets twice daily with a meal and liquid. For Oral Suspension Take one packet once daily with a meal. To prepare, empty the entire contents of one packet into a glass or cup. Add 1 cup of water, fruit juice, or diet soft drinks. Stir well and drink. 2.1 Testing Prior to Initiation of Colesevelam Hydrochloride Obtain lipid parameters, including triglyceride (TG) levels, before starting colesevelam hydrochloride. Colesevelam hydrochloride is contraindicated in patients with TG levels >500 mg/dL [see Contraindications (4) and Warnings and Precautions (5.1) ] . 2.2 Recommended Dosage in Primary Hyperlipidemia and Type 2 Diabetes Mellitus The recommended dosage of colesevelam hydrochloride for adults and for boys and postmenarchal girls aged 10 to 17 years with primary hyperlipidemia is 3.75 grams daily. The recommended dosage of colesevelam hydrochloride for adults with type 2 diabetes mellitus is 3.75 grams daily. Colesevelam hydrochloride should be taken as follows: Tablets Take 6 tablets once daily or 3 tablets twice daily.

Hypertriglyceridemia and Pancreatitis: Colesevelam hydrochloride can increase TG. Hypertriglyceridemia can cause acute pancreatitis. Monitor lipids, including TG. Instruct patients to discontinue colesevelam hydrochloride and seek prompt medical attention if the symptoms of acute pancreatitis occur ( 5.1 ). Gastrointestinal Obstruction: Cases of bowel obstruction have occurred. Colesevelam hydrochloride is not recommended in patients with gastroparesis, other gastrointestinal motility disorders, and in those who have had major gastrointestinal tract surgery and who may be at risk for bowel obstruction ( 5.2 ). Vitamin K or Fat-Soluble Vitamin Deficiencies: Colesevelam hydrochloride may decrease absorption of fat-soluble vitamins. Patients with a susceptibility to deficiencies of vitamin K (e.g., patients on warfarin, patients with malabsorption syndromes) or other fat-soluble vitamins may be at increased risk. Patients on oral vitamin supplementation should take their vitamins at least 4 hours prior to colesevelam hydrochloride ( 5.3 ). Drug Interactions: Due to the potential for decreased absorption of other drugs that have not been tested for interaction, consider administering at least 4 hours prior to colesevelam hydrochloride ( 5.4 , 7 , 12.3 ). Risks in Patients with Phenylketonuria (PKU): Phenylalanine can be harmful to patients with phenylketonuria. Colesevelam hydrochloride for oral suspension contains 27 mg phenylalanine per 3.75 gram packet ( 5.5 , 11 ).

The following important adverse reactions are described below and elsewhere in the labeling: Hypertriglyceridemia and Pancreatitis [see Warnings and Precautions (5.1) ] Gastrointestinal Obstruction [see Warnings and Precautions (5.2) ] Vitamin K or Fat-Soluble Vitamin Deficiencies [see Warnings and Precautions (5.3) ] In clinical trials, the most common (incidence ≥2% and greater than placebo) adverse reactions with colesevelam hydrochloride included constipation, dyspepsia, and nausea ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Cosette Pharmaceuticals, Inc. at 1-800-922-1038 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in clinical studies of another drug and may not reflect the rates observed in practice. Primary Hyperlipidemia In 7 double-blind, placebo-controlled clinical trials, 807 patients with primary hyperlipidemia (age range 18-86 years, 50% women, 90% Caucasians, 7% Blacks, 2% Hispanics, 1% Asians) and elevated LDL-C were treated with colesevelam hydrochloride 1.5 g/day to 4.5 g/day from 4 to 24 weeks (total exposure 199 patient-years).

8.1 Pregnancy Risk Summary Colesevelam hydrochloride is not absorbed systemically following oral administration, and maternal use is not expected to result in fetal exposure to the drug. Limited available data on the use of colesevelam hydrochloride are insufficient to determine a drug-associated risk of major congenital malformations or miscarriage. In animal reproduction studies, no evidence of either maternal or fetal toxicity was found in rats or rabbits exposed to colesevelam hydrochloride during the period of fetal organogenesis at 8 and 5 times, respectively, the maximum recommended human dose (MRHD) of 3.75 g/day, based on body surface area (mg/m 2 ). No adverse effects on offspring survival and development were observed in rats administered 5 times the MRHD (see Data ). Colesevelam hydrochloride may decrease the absorption of fat-soluble vitamins [see Warnings and Precautions (5.3) ]. There are no data available on the effect of colesevelam hydrochloride on the absorption of fat-soluble vitamins in pregnant women. If the patient becomes pregnant while taking colesevelam hydrochloride, the patient should be advised of the lack of known clinical benefit with continued use during pregnancy. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

Metabolism

Absorption Colesevelam hydrochloride is a hydrophilic, water-insoluble polymer that is not hydrolyzed by digestive enzymes and is not absorbed. Distribution Colesevelam hydrochloride is not absorbed, and therefore, its distribution is limited to the gastrointestinal tract.

Colesevelam hydrochloride is not absorbed and the risk of systemic toxicity is low. Excessive doses of colesevelam hydrochloride may cause more severe local gastrointestinal effects (e.g., constipation).

• May 26, 2000NDANDA021176Cosette
• Oct 2, 2009NDANDA022362Cosette
• May 16, 2018ANDAANDA091600Impax Labs Inc
• May 18, 2018ANDAANDA203480Glenmark Pharms Ltd
• Jul 16, 2018ANDAANDA202190Glenmark Pharms Ltd
• Oct 5, 2018ANDAANDA209038Alkem Labs Ltd
• Oct 5, 2018ANDAANDA210889Dr Reddys
• May 6, 2019ANDAANDA210316Alkem Labs Ltd

1. 1Off Label Use1,44814%
2. 2No Adverse Event9229.1%
3. 3Diarrhoea8188.1%
4. 4Nausea5735.7%
5. 5Fatigue5645.6%
6. 6Drug Ineffective5455.4%
7. 7Constipation4134.1%
8. 8Dyspnoea4124.1%
9. 9Headache4064.0%
10. 10Muscle Spasms3633.6%
11. 11Pain3583.6%
12. 12Arthralgia3473.4%
13. 13Weight Decreased3263.2%
14. 14Dizziness3223.2%
15. 15Myalgia3043.0%

Recent PubMed references pinned to Colesevelam as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• IMpact of therapY using coleSevelam treatment reducing bile acids in patients with fonTan cIrCulation (MYSTIC): Rationale and study design.
  American heart journal · 2026 · Shah AH, Armstrong HK, Mittal I, et al.
  PMID 40840821DOI 10.1016/j.ahj.2025.08.011
• Liraglutide and Colesevelam Change Serum and Fecal Bile Acid Levels in a Randomized Trial With Patients With Bile Acid Diarrhea.
  Clinical and translational gastroenterology · 2024 · Ellegaard AM, Kårhus ML, Krych L, et al.
  PMID 39602188DOI 10.14309/ctg.0000000000000772
• The Effect of Colesevelam on the Microbiome in Postoperative Crohn's Disease.
  Inflammatory bowel diseases · 2025 · Kumar A, Quraishi MN, Al-Hassi HO, et al.
  PMID 39422655DOI 10.1093/ibd/izae230
• Colesevelam Reduces Ethanol-Induced Liver Steatosis in Humanized Gnotobiotic Mice.
  Cells · 2021 · Cabré N, Duan Y, Llorente C, et al.
  PMID 34198609DOI 10.3390/cells10061496
• A Meta-Analysis Assessing Additional LDL-C Reduction from Addition of a Bile Acid Sequestrant to Statin Therapy.
  The American journal of medicine · 2020 · Alder M, Bavishi A, Zumpf K, et al.
  PMID 32416177DOI 10.1016/j.amjmed.2020.03.056
• Colesevelam in the management of type 2 diabetes.
  JPMA. The Journal of the Pakistan Medical Association · 2020 · Kalra S, Priya G, Aggarwal S, et al.
  PMID 32400758
• IW-3718 Reduces Heartburn Severity in Patients With Refractory Gastroesophageal Reflux Disease in a Randomized Trial.
  Gastroenterology · 2020 · Vaezi MF, Fass R, Vakil N, et al.
  PMID 32092310DOI 10.1053/j.gastro.2020.02.031
• Colesevelam enhances the beneficial effects of brown fat activation on hyperlipidaemia and atherosclerosis development.
  Cardiovascular research · 2020 · Zhou E, Hoeke G, Li Z, et al.
  PMID 31589318DOI 10.1093/cvr/cvz253

The 10 most recently updated of 58 ClinicalTrials.gov registrations naming Colesevelam as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Use of Bile Acid Binding Resins to Decrease PFAS Levels Via Colesevalem in Veterans Study
  Not yet recruiting · Phase 2 · Interventional · 50 enrolled · University of Rhode Island
  NCT07592858updated 2026-05-18
• Examining a Novel Gastrointestinal Intervention to Negate Environmental Toxicants (ENGINE)
  Recruiting · Phase 1 · Phase 2 · Interventional · 50 enrolled · University of California, San Francisco
  NCT07226440updated 2026-04-24
• A Study of Colesevelam for Lenalidomide-Associated Diarrhea
  Completed · Phase 2 · Interventional · 25 enrolled · Memorial Sloan Kettering Cancer Center
  NCT03767257updated 2025-10-21
• Prospective German Very High Cardiovascular Risk Patients Dyslipidemia Treatment Indication Registry
  Completed · Observational · 1,695 enrolled · GWT-TUD GmbH
  NCT03110432updated 2025-05-09
• Metabolic Effects of Endogenous Bile Acids After Gastric Bypass Surgery
  Recruiting · Early phase 1 · Interventional · 18 enrolled · Hvidovre University Hospital
  NCT06925997updated 2025-04-13
• Three Antidiarrheal Strategies in HER2+/HR+ Early Breast Cancer Patients Treated With Extended Adjuvant Neratinib
  Active not recruiting · Phase 2 · Interventional · 177 enrolled · Spanish Breast Cancer Research Group
  NCT05252988updated 2025-04-01
• Impact of Therapy Using Colesevelam Treatment Reducing Bile Acids in Patients With Fontan Circulation.
  Unknown · Phase 1 · Phase 2 · Interventional · 50 enrolled · St. Boniface Hospital
  NCT06197763updated 2024-04-17
• A Study of Colesevelam in Fecal Incontinence
  Completed · Phase 3 · Interventional · 88 enrolled · Mayo Clinic
  NCT02628626updated 2023-06-22
• Effect of the Sequestrant Colesevelam in Bile Acid Diarrhoea
  Completed · Phase 4 · Interventional · 255 enrolled · Lars Kristian Munck
  NCT03876717updated 2022-08-23
• Evaluate Carotid Artery Plaque Composition by Magnetic Resonance Imaging in People Receiving Cholesterol Medication
  Completed · Phase 4 · Interventional · 217 enrolled · University of Washington
  NCT00715273updated 2022-06-07

Frequently asked questions

How does Colesevelam work?

Primary Hyperlipidemia : Colesevelam hydrochloride, the active pharmaceutical ingredient, is a non-absorbed, lipid-lowering polymer that binds bile acids in the intestine, impeding their reabsorption. As the bile acid pool becomes depleted, the hepatic enzyme, cholesterol 7-α-hydroxylase, is upregulated, which increases the conversion of cholesterol to bile acids.

What is Colesevelam used for?

According to FDA labeling, Colesevelam carries indications including: Colesevelam hydrochloride is a bile acid sequestrant indicated as an adjunct to diet and exercise to: reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia ( 1.1 ). reduce LDL-C levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia (HeFH), unable to reach LDL-C target levels despite an adequate trial of diet and lifestyle modification ( 1.1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Colesevelam?

Colesevelam is classified as Bile acid sequestrants, Bile Acid Sequestrant, Bile-acid Binding Activity, Decreased Cholesterol Absorption.

What are the brand names for Colesevelam?

Colesevelam is marketed under brand names including Welchol.

What are the contraindications for Colesevelam?

Colesevelam labeling lists contraindications including: Colesevelam hydrochloride is contraindicated in patients with: Serum TG concentrations >500 mg/dL [see Warnings and Precautions (5.1) ] History of hypertriglyceridemia-induced pancreatitis [see Warnings and Precautions (5.1) ] A history of bowel obstruction [see Warnings and Precautions (5.2) ] Patients with serum triglyceride levels >500 mg/dL ( 4 ) Patients with a history of hypertriglyceridemia-induced pancreatitis ( 4 ) Patients with a history of bowel obstruction ( 4 ). Always consult the full prescribing information and a clinician.