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Class: Bile Acid Sequestrants
VA Class: CV350
Chemical Name: 2-Propen-1-amine polymer withN,N,N-trimethyl-6-(2-propenylamino)-1-hexanaminium chloride-(chloromethyl)oxirane and N-2-propenyl-1-decanamine hydrochloride
Molecular Formula: (C3H7N)m(C3H5ClO)n(C12H27ClN2)o(C13H27N)pxHCl
CAS Number: 182815-44-7
Brands: WelChol

Medically reviewed by Last updated on Oct 27, 2020.


Antilipemic agent (bile acid sequestrant).1 Adjunct antidiabetic agent for type 2 diabetes mellitus.1

Uses for Colesevelam

Primary Hypercholesterolemia

Adjunct to dietary therapy and exercise to decrease elevated serum LDL-cholesterol concentrations in the management of primary hypercholesterolemia (Frederickson type IIa).1 2 3 5 6

May be used alone or combined with a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (i.e., statin).1

Effect of colesevelam (alone or in combination with a statin on cardiovascular morbidity and mortality not established.1 2

Safety and efficacy of colesevelam for management of Fredrickson type I, III, IV, and V dyslipidemias not established.1 (See Hypertriglyceridemia under Cautions.)

ACC/AHA cholesterol management guideline states that nonstatin drugs (e.g., bile acid sequestrants) do not provide acceptable atherosclerotic cardiovascular disease (ASCVD) risk reduction benefits compared to their potential for adverse effects in the routine prevention of ASCVD.350 May be useful as adjuncts to statin therapy in high-risk patients (e.g., patients with ASCVD, LDL-cholesterol concentrations ≥190 mg/dL, or diabetes mellitus) who have a less-than-anticipated response to statins, are unable to tolerate even a less-than-recommended intensity of a statin, or are completely intolerant to statin therapy.350 Select nonstatin drug based on favorable benefit-risk ratio (i.e., demonstrated benefit of ASCVD risk reduction outweighs risks of adverse effects and drug interactions) and patient preferences.350 Current recommendations from ACC/AHA regarding prevention of ASCVD and lifestyle modifications to reduce cardiovascular risk are available at [Web] or [Web]352

Diabetes Mellitus

Used in combination with metformin, sulfonylurea, or insulin monotherapy or in combinations with these and other oral antidiabetic agents as an adjunct to diet and exercise for the management of type 2 diabetes mellitus.1 13

Safety and efficacy as monotherapy or in combination with a dipeptidyl peptidase-4 (DPP-4) inhibitor not established in type 2 diabetes mellitus; has not been studied extensively in combination with thiazolidinediones.1

Not effective as sole therapy for type 1 diabetes mellitus or diabetic ketoacidosis.1

Colesevelam Dosage and Administration


  • Institute standard lipid-lowering diet before initiation of colesevelam therapy; patient should remain on this diet during treatment with the drug.1 7 8 10

Monitoring during Antilipemic Therapy

  • Monitor serum lipoprotein concentrations periodically.1 15 ACC/AHA cholesterol management guideline recommends obtaining a fasting lipoprotein profile before initiating bile acid sequestrant therapy, after 3 months of therapy, and every 6–12 months thereafter.350

    Intensive control of hyperlipidemia warranted in addition to glycemic control in patients with diabetes mellitus.1


Oral Administration

Administer orally once or twice daily with a liquid at mealtime.1 2

May be administered simultaneously with a statin.1

Drugs known to interact with colesevelam or drugs that have not been evaluated in formal drug interaction studies with colesevelam, especially those with a narrow therapeutic index, (see Interactions), should be administered at least 4 hours prior to colesevelam.1 Alternatively, monitor blood concentrations of the co-administered drug.1


Available as colesevelam hydrochloride; dosage expressed in terms of colesevelam.1


Primary Hypercholesterolemia

Initially, 1.875 g (3 tablets) twice daily or 3.75 g (6 tablets) once daily.1 2 May increase dosage to 4.375 g (7 tablets) daily depending on desired therapeutic effect.1

Diabetes Mellitus

Oral: 1.875 g (3 tablets) twice daily or 3.75 g (6 tablets) once daily in combination with other antidiabetic agents (e.g., metformin, a sulfonylurea, insulin) in patients with type 2 diabetes mellitus.1 9

Therapeutic response usually occurs following 4–6 weeks of treatment and reaches maximal or near maximal after 12–18 weeks of therapy.1 13

Cautions for Colesevelam


  • Bowel obstruction.1

  • Serum triglyceride concentrations exceeding 500 mg/dL.1 12

  • History of hypertriglyceridemia-induced pancreatitis.1 12

  • Known hypersensitivity to colesevelam or any ingredient in the formulation.1


General Precautions


Increased serum triglyceride concentrations reported in patients with primary hypercholesterolemia or type 2 diabetes mellitus (particularly patients receiving concomitant insulin or sulfonylurea therapy).1 13 Severe hypertriglyceridemia can cause pancreatitis.1

Not systematically studied in patients with triglyceride concentrations >300 mg/dL.1 Use with caution in patients with baseline triglyceride concentrations of 250–299 mg/dL; monitor lipoprotein concentrations periodically during therapy.1 350 Manufacturer recommends discontinuing therapy if serum triglyceride concentrations exceed 500 mg/dL or if hypertriglyceridemia-induced pancreatitis occurs;1 however, ACC/AHA cholesterol management guideline recommends discontinuing therapy if serum triglyceride concentrations exceed 400 mg/dL.350

Do not use in patients with baseline fasting triglyceride concentrations ≥300 mg/dL or in those with primary dysbetalipoproteinemia (Fredrickson type III).350

Fat-soluble Vitamin Deficiency

Bile acid sequestrants may decrease absorption of fat-soluble vitamins A, D, E, and K.1 Effects of colesevelam on co-administered dietary or supplemental vitamin therapy, including such use in pregnant women, not established.1

Hemorrhage from vitamin K deficiency reported in rats receiving relatively high doses (30 times the usual human dosage).1 Clinically important effects on absorption of fat-soluble vitamins not observed in clinical trials.1 2 3 Use caution in patients susceptible to vitamin K deficiency (e.g., concomitant warfarin therapy, malabsorption syndromes) or other fat-soluble vitamin deficiency.1 (See Interactions.)

GI Disorders

Large tablet size of colesevelam may cause dysphagia or esophageal obstruction; use caution in patients with dysphagia or swallowing disorders.1

Not recommended in patients with gastroparesis, other GI motility disorders, or those who have undergone major GI tract surgery and who may be at risk for bowel obstruction.1

Combination Therapy

When used in combination with metformin, a sulfonylurea, or insulin, consider the cautions, precautions, and contraindications associated with the concomitant agent(s).1

Specific Populations


Category B.1

Requirements for vitamins and other nutrients increased during pregnancy.1 (See Fat-soluble Vitamin Deficiency under Cautions.)


Colesevelam is not expected to distribute into milk.9

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 9 Not recommended in pediatric patients because of large tablet size.1

Geriatric Use

No overall differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1

Renal Impairment

In patients with type 2 diabetes mellitus, no overall differences in safety or efficacy observed between patients with moderate renal insufficiency (Clcr <50 mL/minute) and those with mild renal insufficiency (Clcr ≥50 mL/minute).1

Common Adverse Effects

Patients with primary hypercholesterolemia: Constipation,1 2 3 5 dyspepsia,1 2 3 5 nausea,1 3 5 accidental injury,1 5 asthenia,1 pharyngitis,1 5 flu-like syndrome,1 5 rhinitis,1 5 myalgia.1 2 5

Patients with type 2 diabetes mellitus: Constipation,1 13 nasopharyngitis,1 13 dyspepsia,1 hypoglycemia,1 13 nausea,1 13 hypertension.1 13

Interactions for Colesevelam

If administered with a drug with a narrow therapeutic index (i.e., alterations in blood concentrations associated with clinically important effect on efficacy and/or safety) that has not been evaluated in formal drug interaction studies, administer drug at least 4 hours prior to colesevelam, or consider monitoring drug concentrations.1

Increased serum triglyceride concentrations observed in clinical studies with concomitant sulfonylurea or insulin therapy.1 13

Specific Drugs





Pharmacokinetic interaction unlikely1


Pharmacokinetic interaction unlikely1


Pharmacokinetic interaction unlikely1

Fat-soluble vitamins (i.e., vitamins A, D, E, K)

Potential decreased absorption of fat-soluble vitamins A, D, E, K1 (see Fat-soluble Vitamin Deficiency under Cautions)

Administer at least 4 hours prior to colesevelam1


Additive effects in reducing total and LDL cholesterol1

HMG-CoA reductase inhibitors (statins)

Additive antilipemic effects1 2 5

Lovastatin: Pharmacokinetic interaction unlikely1

Used to therapeutic advantage1


Potential decreased peak plasma concentration and AUC of glyburide1

Administer at least 4 hours prior to colesevelam1


Pharmacokinetic interaction unlikely1


Pharmacokinetic interaction unlikely1

Oral contraceptives (ethinyl estradiol combined with norethindrone)

Decreased peak blood concentrations of ethinyl estradiol and norethindrone, decreased AUC of ethinyl estradiol1

Administer at least 4 hours prior to colesevelam1


Potential decreased blood phenytoin concentrations; potential for increased seizure activity1

Administer at least 4 hours prior to colesevelam1

Thyroid agents (e.g., levothyroxine)

Increased TSH concentrations; decreased peak blood levothyroxine concentrations and AUC1

Administer at least 4 hours prior to colesevelam1

Valproic acid

Pharmacokinetic interaction unlikely1

Verapamil (extended-release)

Pharmacokinetic interaction unlikely1


Potential reduced INR; pharmacokinetic interaction unlikely1

Monitor INR prior to colesevelam therapy and subsequently to ensure no appreciable alteration in INR; once INR is stable, monitor periodically at recommended intervals for warfarin therapy1

Colesevelam Pharmacokinetics



Not absorbed from the GI tract.1 2 4 5


Maximum therapeutic response usually occurs within 2 weeks and is maintained during long-term (≥50 weeks) therapy.1 2 3 9


Elimination Route

Binds to bile acids in the intestine and forms a nonabsorbable complex that is excreted in feces.1 2 3 4





25°C (may be exposed to 15–30°C).1 Protect from moisture.1


  • Binds to bile acids in the intestine and forms a nonabsorbable complex.1 2 3 4 Partial removal of bile acids from enterohepatic circulation results in increased conversion of cholesterol to bile acids in the liver.1 2 4 5 This causes an increased demand for cholesterol in liver cells, resulting in a compensatory increase in hepatic uptake (and thus systemic clearance) of circulating LDL-cholesterol.1 2

  • Reduces serum total cholesterol, LDL-cholesterol, and apolipoprotein B (apo B), and increases HDL-cholesterol concentrations.1 2 3 4 5 Serum triglyceride concentrations may remain unchanged or increase slightly (5–10%).1 3 5 6

    The mechanism by which colesevelam improves glycemic control is unknown.1 14

Advice to Patients

  • Risk of increased serum triglyceride concentrations in diabetic patients receiving colesevelam with a sulfonylurea or insulin; long-term effect of hypertriglyceridemia on CAD risk uncertain.1

  • Importance of informing a clinician of high triglyceride concentrations (i.e., >300 mg/dL) before starting colesevelam therapy.1 12

  • Importance of adherence to prescribed directions for use.1

  • Importance of taking certain other drugs (e.g., glyburide, thyroid agents, oral contraceptives, warfarin, phenytoin, fat-soluble vitamins) at least 4 hours before colesevelam.1

  • Importance of adhering to nondrug therapies and measures (i.e., lifestyle modifications, including dietary management, weight control, physical activity, and management of potentially contributory disease [e.g., diabetes mellitus]).1

  • Importance of instructing diabetic patients regarding self-monitoring of blood glucose, adherence to meal planning, and regular physical exercise.1

  • Importance of discontinuing colesevelam and seeking medical advice if severe abdominal pain or severe constipation occurs.1

  • Importance of discontinuing colesevelam and seeking medical advice if symptoms of acute pancreatitis (e.g., severe abdominal pain with or without nausea, vomiting) occur.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., glyburide, levothyroxine, oral contraceptives) and OTC (e.g., vitamins) drugs, as well as any concomitant illnesses (e.g., stomach or intestinal disease, including gastroparesis, abnormal contractions of the digestive system, or major GI surgery; vitamin A, D, E, or K deficiencies; difficulty swallowing).1 12

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)


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.

Colesevelam Hydrochloride


Dosage Forms


Brand Names




625 mg


Daiichi Sankyo

AHFS DI Essentials™. © Copyright 2021, Selected Revisions November 6, 2014. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.


1. Daiichi-Sankyo Inc. WelChol (colesevelam hydrochloride) tablets prescribing information. Parsippany, NJ; 2008 Jan.

2. Anon. Colesevelam (WelChol) for hypercholesterolemia. Med Lett Drugs Ther. 2000; 42:102-4.

3. Davidson MH, Dillon MA, Gordon B et al. Colesevelam hydrochloride (cholestagel). Arch Intern Med. 1999; 159:1893-900.

4. Rosenbaum DP, Petersen JS, Ducharme S et al. Absorption, distribution and excretion of GT31-104, a novel bile acid sequestrant, in rats and dogs after acute and subchronic administration. J Pharm Sci. 1997; 86:591-5.

5. Davidson MH, Dicklin MR, Maki KC et al. Colesevelam hydrochloride: a non-absorbed, polymeric cholesterol-lowering agent. Exp Opin Invest Drugs. 2000; 9:2663-71.

6. Insull W, Toth P, Mullican W et al. Cholestagel, a novel, highly potent, polymeric bile acid sequestrant significantly lowers LDL cholesterol. J Am Coll Cardiol. 2000; 35(suppl A): 258A.

7. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993;269:3015-23.

8. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Bethesda, MD: National Institutes of Health. (NIH publication No. 01-3670.)

9. Sankyo Pharmaceuticals, Parsippany, NJ: Personal communication.

10. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Adult Treatment Panel III Report. From AHA web site.

12. Daiichi-Sankyo Inc. Important information about Welchol. Parsippany, NJ; 2008. Available from website. Accessed 2008 May 30.

13. Fonseca VA, Rosenstock J, Wang AC et al. Colesevelam HCl improves glycemic control and reduces LDL-cholesterol in patients with type 2 diabetes inadequately controlled on sulfonylurea-based therapy. Diabetes Care. 2008 May 5 (Epub ahead of print). DOI: 10.2337/dc08-0283.

14. Bays HE, Goldberg RB. The ’forgotten’ bile acid sequestrants: is now a good time to remember?. Am J Ther. 2007 Nov-Dec; 14:567-80.

15. Grundy SM, Cleeman JI, Bairey Merz CN et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004; 110: 227-39.

350. Stone NJ, Robinson J, Lichtenstein AH et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013; :.

352. Eckel RH, Jakicic JM, Ard JD et al. 2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014; 63:2960-84.