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Pronunciation
(koh le SEV a lam)
Generic Available (U.S.)
No
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of elevated LDL in primary hypercholesterolemia (Fredrickson type IIa) when used alone or in combination with an HMG-CoA reductase inhibitor; management of heterozygous familial hypercholesterolemia (heFH) in adolescent patients (males and postmenarcheal females 10-17 years of age) when used alone or in combination with an HMG-CoA reductase inhibitor, in patients who after an adequate trial of dietary therapy have LDL-C ≥190 mg/dL or LDL-C ≥160 mg/dL with positive family history of premature cardiovascular disease (CVD) or with two or more CVD risk factors; improve glycemic control in type 2 diabetes mellitus (noninsulin dependent, NIDDM) in conjunction with diet, exercise, and insulin or oral antidiabetic agents
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse effects have not been observed in animal reproduction studies. Colesevelam is not absorbed systemically, but may interfere with vitamin absorption; therefore, regular supplementation may not be adequate.
Lactation
Does not enter breast milk/use caution
Breast-Feeding Considerations
Due to lack of systemic absorption, colesevelam is not expected to be excreted in breast milk; however, the tendency of colesevelam to interfere with the vitamin absorption may have an effect on the nursing infant.
Contraindications
History of bowel obstruction; serum triglyceride concentration >500 mg/dL; history of hypertriglyceridemia-induced pancreatitis
Warnings/Precautions
Disease-related concerns:
• Gastrointestinal disease: Use in patients with gastroparesis, other severe GI motility disorders, or a history of major GI tract surgery is not recommended due to constipating effects of colesevelam. Patients with dysphagia or swallowing disorders should use the oral suspension form of colesevelam due to large tablet size and risk for esophageal obstruction.
• Hypertriglyceridemia: Use with caution in patients with serum triglyceride concentrations >300 mg/dL and in patients using insulin or sulfonylureas (may cause increased concentrations). Discontinue if triglyceride concentrations exceed 500 mg/dL or hypertriglyceridemia-induced pancreatitis occurs.
• 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.
Concurrent drug therapy issues:
• Decreased absorption (orally administered drugs): Not to be taken simultaneously with many other medicines (decreased absorption).
Dosage form specific issues:
• Phenylalanine: Some products may contain phenylalanine
Other warnings/precautions:
• Appropriate use in diabetes mellitus: Colesevelam is not indicated for the management of type 1 diabetes mellitus (insulin dependent, IDDM), particularly in the acute management (eg, DKA). It is also not indicated in type 2 diabetes mellitus as monotherapy and must be used as an adjunct to diet, exercise, and glycemic control with insulin or oral antidiabetic agents. Combination with dipeptidyl peptidase 4 inhibitors or thiazolidinediones has not been studied extensively.
• Appropriate use in hyperlipidemia: Secondary causes of hyperlipidemia should be ruled out prior to therapy. Minimal effects are seen on HDL-C and triglyceride concentrations. Colesevelam has not been studied in Fredrickson Type I, III, IV, or V dyslipidemias.
Adverse Reactions
Actual frequency may be dependent upon indication. Unless otherwise noted, frequency of adverse effects is reported for adult patients.
>10%: Gastrointestinal: Constipation (9% to 11%)
1% to 10%:
Cardiovascular: Hypertension (3%)
Central nervous system:Headache (children 4% to 8%), fatigue (children 4%)
Endocrine & metabolic: Hypertriglyceridemia (4% to 5%), hypoglycemia (3%), CPK increased (children 2%)
Gastrointestinal: Dyspepsia (4% to 8%), nausea (3%), vomiting (children 2%)
Neuromuscular & skeletal: Weakness (4%), myalgia (2%)
Respiratory: Nasopharyngitis (children 5% to 6%), upper respiratory tract infection (children 5%), pharyngitis (3%), rhinitis (children 2%)
Miscellaneous: Flu-like syndrome (children 4%)
<1%, postmarketing, and/or case reports: Abdominal distension, bowel obstruction, diarrhea, dysphagia, esophageal obstruction, fecal impaction, flatulence, hemorrhoid exacerbation, infection, pancreatitis, transaminases increased
Metabolism/Transport Effects
None known.
Drug Interactions
Amiodarone: Bile Acid Sequestrants may decrease the bioavailability of Amiodarone. Risk D: Consider therapy modification
Antidiabetic Agents (Thiazolidinedione): Bile Acid Sequestrants may decrease the absorption of Antidiabetic Agents (Thiazolidinedione). Risk D: Consider therapy modification
Chenodiol: Bile Acid Sequestrants may decrease the serum concentration of Chenodiol. Management: Administration of chenodiol 5 hours or more after bile acid sequestrants may reduce chenodiol adsorption in the gastrointestinal tract. Monitor for decreased therapeutic effects of chenodiol in patients receiving bile acid sequestrants. Risk D: Consider therapy modification
Contraceptives (Estrogens): Bile Acid Sequestrants may decrease the serum concentration of Contraceptives (Estrogens). Management: Administer estrogen-based oral contraceptives at least 1-4 hours prior to or 4-6 hours after administration of a bile acid sequestrant. Risk D: Consider therapy modification
Contraceptives (Progestins): Bile Acid Sequestrants may decrease the serum concentration of Contraceptives (Progestins). Management: Administer oral progestin-containing contraceptives at least 1-4 hours prior to or 4-6 hours after administration of a bile acid sequestrant. Risk D: Consider therapy modification
Corticosteroids (Oral): Bile Acid Sequestrants may decrease the absorption of Corticosteroids (Oral). Risk C: Monitor therapy
CycloSPORINE: Colesevelam may decrease the serum concentration of CycloSPORINE. Management: Administer cyclosporine at least 4 hours prior to colesevelam. Monitor for decreased cyclosporine concentrations during concomitant colesevelam therapy. Risk D: Consider therapy modification
CycloSPORINE (Systemic): Colesevelam may decrease the serum concentration of CycloSPORINE (Systemic). Management: Administer cyclosporine at least 4 hours prior to colesevelam. Monitor for decreased cyclosporine concentrations during concomitant colesevelam therapy. Risk D: Consider therapy modification
Ethinyl Estradiol: Colesevelam may decrease the serum concentration of Ethinyl Estradiol. Risk D: Consider therapy modification
Ezetimibe: Bile Acid Sequestrants may decrease the absorption of Ezetimibe. Risk C: Monitor therapy
GlyBURIDE: Colesevelam may decrease the serum concentration of GlyBURIDE. Risk D: Consider therapy modification
Leflunomide: Bile Acid Sequestrants may decrease serum concentrations of the active metabolite(s) of Leflunomide. Management: Unless using this combination to intentionally enhance leflunomide elimination, consider an alternative to the bile acid sequestrants when possible. Separating drug administration is not likely to be effective at avoiding this interaction. Risk D: Consider therapy modification
Loop Diuretics: Bile Acid Sequestrants may decrease the absorption of Loop Diuretics. Risk D: Consider therapy modification
Methotrexate: Bile Acid Sequestrants may decrease the absorption of Methotrexate. Risk C: Monitor therapy
Niacin: Bile Acid Sequestrants may decrease the absorption of Niacin. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: Bile Acid Sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Risk D: Consider therapy modification
Norethindrone: Colesevelam may decrease the serum concentration of Norethindrone. Risk D: Consider therapy modification
Phenytoin: Colesevelam may decrease the serum concentration of Phenytoin. Risk D: Consider therapy modification
Pravastatin: Bile Acid Sequestrants may decrease the serum concentration of Pravastatin. Management: Administer pravastatin at least 1 hour before or 4 hours after administration of bile-acid resins (eg, cholestyramine, colestipol, colesevelam) to minimize the risk for any significant interaction. Risk D: Consider therapy modification
Propranolol: Bile Acid Sequestrants may decrease the serum concentration of Propranolol. Risk C: Monitor therapy
Raloxifene: Bile Acid Sequestrants may decrease the absorption of Raloxifene. Risk D: Consider therapy modification
Tetracycline Derivatives: Bile Acid Sequestrants may decrease the absorption of Tetracycline Derivatives. Risk D: Consider therapy modification
Thiazide Diuretics: Bile Acid Sequestrants may decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification
Thyroid Products: Bile Acid Sequestrants may decrease the absorption of Thyroid Products. Risk C: Monitor therapy
Ursodiol: Bile Acid Sequestrants may decrease the serum concentration of Ursodiol. Management: Administer ursodiol 5 hours or more after bile acid sequestrants to minimize ursodiol adsorption in the gastrointestinal tract. Monitor for decreased therapeutic effects of ursodiol in patients receiving bile acid sequestrants. Risk D: Consider therapy modification
Vancomycin: Bile Acid Sequestrants may diminish the therapeutic effect of Vancomycin. Management: Avoid concurrent administration of oral vancomycin and bile acid sequestrants when possible. If use of both agents is necessary, consider separating doses by at least 2 hours to minimize the significance of the interaction. Risk D: Consider therapy modification
Vitamin D Analogs: Bile Acid Sequestrants may decrease the serum concentration of Vitamin D Analogs. More specifically, bile acid sequestrants may impair absorption of Vitamin D Analogs. Management: Avoid concomitant administration of vitamin D analogs and bile acid sequestrants (e.g., cholestyramine). Separate administration of these agents by several hours to minimize the potential risk of interaction. Monitor plasma calcium concentrations. Exceptions: Calcipotriene. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Bile Acid Sequestrants may decrease the absorption of Vitamin K Antagonists. Risk C: Monitor therapy
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.
Mechanism of Action
Cholesterol is the major precursor of bile acid. 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.
Pharmacodynamics/Kinetics
Onset of action:
Lipid lowering: Therapeutic: ~2 weeks
Reduction of hemoglobin A1C (Type II diabetes): 4-6 weeks initial onset; 12-18 weeks maximal effect
Absorption: None
Excretion: Urine (0.05%)
Dosage
Oral:
Children 10-17 years (males and postmenarchal females): Dyslipidemia (heterozygous familial hypercholesterolemia):
Once-daily dosing: 3.75 g (oral suspension or 6 tablets)
Twice-daily dosing: 1.875 g (3 tablets)
Note: Due to large tablet size, oral suspension is recommended in pediatric patients.
Adults: Dyslipidemia, type 2 diabetes (combination therapy with insulin or oral antidiabetic agents):
Once-daily dosing: 3.75 g (oral suspension or 6 tablets)
Twice-daily dosing: 1.875 g (3 tablets)
Elderly: Refer to adult dosing.
Dosage adjustment in renal impairment: No dosage adjustment necessary; not absorbed from the gastrointestinal tract.
Dosage adjustment in hepatic impairment: No dosage adjustment necessary; not absorbed from the gastrointestinal tract.
Administration: Oral
Educate the patient on dietary guidelines.
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.
Granules for oral suspension: Administer with meal(s). Empty 1 packet into a glass; add 1/2-1 cup (4-8 ounces) of water, fruit juice, or a diet soft drink and mix well. Powder is not to be taken in dry form (to avoid GI distress).
Monitoring Parameters
Serum cholesterol, LDL, and triglyceride levels should be obtained before initiating treatment and periodically thereafter (in accordance with NCEP guidelines)
Test Interactions
Increased prothrombin time
Dietary Considerations
Should be taken with meal(s) and a liquid. Follow dietary guidelines. Some products may contain phenylalanine.
Patient Education
Many other medications should be taken 1 hour before or 4 hours after colesevelam. You may experience constipation. Report persistent GI upset, skeletal or muscle pain or weakness, or respiratory difficulties.
Geriatric Considerations
The definition of and, therefore, when to treat hyperlipidemia in elderly is a controversial issue. The National Cholesterol Education Program recommends that all adults maintain a plasma cholesterol <160 mg/dL. Elderly with one additional risk factor, goal LDL would be <130 mg/dL. It is the authors' belief that pharmacologic treatment be reserved for those who are unable to obtain a desirable plasma cholesterol concentration by diet alone and for whom the benefits of treatment are believed to outweigh the potential adverse effects, drug interactions, and cost of treatment.
Cardiovascular Considerations
Colesevelam may be 4-6 times as potent as traditional bile acid sequestrants, perhaps because of its greater binding affinity for glycocholic acid (Steinmetz, 2002). Unlike cholestyramine and colestipol, colesevelam appears to reduce LDL cholesterol in a dose-dependent manner. No trials are available comparing colesevelam to cholestyramine or colestipol. Colesevelam does not interfere with intestinal absorption of fat-soluble vitamins. Colesevelam alone or when combined with a statin is effective in lowering cholesterol. The effect of colesevelam on cardiovascular morbidity and mortality has not been established. Colesevelam may increase triglycerides; therefore, it should be used with caution or avoided in patients with triglyceride levels ≥200 mg/dL. Systemic toxicity is low since the drug is not absorbed.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
Constipation is common, concurrent use with psychotropic agents may exacerbate this effect
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Granules for suspension, oral, as hydrochloride:
Welchol®: 3.75 g/packet (30s) [contains phenylalanine 48 mg/packet; citrus flavor]
Tablet, oral, as hydrochloride:
Welchol®: 625 mg
Pricing: U.S. (www.drugstore.com)
Pack (Welchol)
3.75 g (30): $249.99
Tablets (Welchol)
625 mg (30): $48.99
References
Davidson MH, Dillon MA, Gordon B, et al, “Colesevelam Hydrochloride (Cholestagel): A New, Potent Bile Acid Sequestrant Associated With a Low Incidence of Gastrointestinal Side Effects,” Arch Intern Med, 1999, 159(16):1893-900.
“Executive 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),” JAMA, 2001, 285(19):2486-97.
Rodbard HW, Jellinger PS, Davidson JA, et al, “Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology Consensus Panel on Type 2 Diabetes Mellitus: An Algorithm for Glycemic Control,” Endocr Pract, 2009, 15(6):540-59.
Smith SC Jr, Benjamin EJ, Bonow RO, et al, “AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update: A Guideline From the American Heart Association and American College of Cardiology Foundation,” Circulation, 2011, 124(22):2458-73.
Staels B and Kuipers F, “Bile Acid Sequestrants and the Treatment of Type2 Diabetes Mellitus,” Drugs, 2007, 67(10):1383-92.
Steinmetz KL, “Colesevelam Hydrochloride,” Am J Health Syst Pharm, 2002, 59:932-9.
Zieve FJ, Kalin MF, Schwartz SL, et al, “Results of the Glucose-Lowering Effect of WelChol Study (GLOWS): A Randomized, Double-Blind, Placebo-Controlled Pilot Study Evaluating the Effect of Colesevelam Hydrochloride on Glycemic Control in Subjects With Type 2 Diabetes,” Clin Ther, 2007, 29(10):74-83,
International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
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