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Colesevelam


General


Pronunciation

(koh le SEV a lam)


Brand Names: U.S.

  • Welchol

Indications


Use: Labeled Indications

Diabetes mellitus, type 2: Improve glycemic control in adults with type 2 diabetes mellitus (noninsulin dependent, NIDDM) in conjunction with diet and exercise

Heterozygous familial hypercholesterolemia: Management of heterozygous familial hypercholesterolemia (heFH) in adolescent patients (males and postmenarcheal females 10-17 years of age) used alone or in combination with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor when after an adequate trial of dietary therapy patient continues to have low-density lipoprotein-cholesterol (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.

Hyperlipidemia:

U.S. labeling: Management of elevated LDL-C in adults with primary hyperlipidemia (Fredrickson type IIa) when used alone or in combination with an HMG-CoA reductase inhibitor in conjunction with diet and exercise

Canadian labeling (Lodalis): Adjunct to diet and lifestyle modifications in the management of primary hypercholesterolemia (Fredrickson type IIa) as monotherapy or in combination with an HMG-CoA reductase inhibitor

Limitations of use: Should not be used for the treatment of type 1 diabetes or diabetic ketoacidosis. Colesevelam has not been studied in Fredrickson Type I, III, IV, and V dyslipidemias; type 2 diabetes in combination with a dipeptidyl peptidase 4 inhibitor; pediatric patients with type 2 diabetes; children <10 years of age or in premenarchal girls. No effect on cardiovascular morbidity and mortality has been established. There is no evidence of macrovascular disease risk reduction with colesevelam use.


Contraindications


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

Canadian labeling: Hypersensitivity to colesevelam or any component of the formulation; bowel or biliary obstruction


Dosing and Administration


Dosing: Adult

U.S. labeling: Hyperlipidemia, type 2 diabetes mellitus: Oral:

Once-daily dosing: 3.75 g (oral suspension or 6 tablets)

Twice-daily dosing: 1.875 g (3 tablets)

Canadian labeling:Hyperlipidemia: Oral:

Combination therapy: 2.5 to 3.75 g (4 to 6 tablets) daily; maximum dose: 3.75 g (6 tablets) given once daily or 1.875 g (3 tablets) given twice daily

Monotherapy: Initial: 1.875 g (3 tablets) twice daily or 3.75 g (6 tablets) once daily; maximum dose: 4.375 g (7 tablets) daily


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Heterozygous familial hypercholesterolemia: Children 10 to 17 years (males and postmenarchal females): Oral: 3.75 g once daily (oral suspension). Note: Due to large tablet size, oral suspension is recommended in pediatric patients.


Dosing: Renal Impairment

No dosage adjustments necessary; not absorbed from the gastrointestinal tract.


Dosing: Hepatic Impairment

No dosage adjustments necessary; not absorbed from the gastrointestinal tract.


Reconstitution

Granules for oral suspension: 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.


Administration

Educate the patient on dietary guidelines.

Granules for oral suspension: Administer with meal(s). Powder is not to be taken in dry form (to avoid GI 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.


Dietary Considerations

Should be taken with meal(s) and a liquid. Follow dietary guidelines. Some products may contain phenylalanine.


Storage

Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Protect from moisture.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Packet, Oral, as hydrochloride:

Welchol: 3.75 g (30 ea) [sugar free; contains aspartame]

Tablet, Oral, as hydrochloride:

Welchol: 625 mg


Drug Interactions

Amiodarone: Bile Acid Sequestrants may decrease the bioavailability of Amiodarone. Consider therapy modification

AtorvaSTATin: Bile Acid Sequestrants may decrease the serum concentration of AtorvaSTATin. Monitor therapy

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. Consider therapy modification

Cholic Acid: Bile Acid Sequestrants may decrease the absorption of Cholic Acid. Management: Administer cholic acid at least 1 hour before or 4 to 6 hours after administration of any bile acid-binding products to minimize the potential for a significant interaction. 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. 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. Consider therapy modification

Corticosteroids (Oral): Bile Acid Sequestrants may decrease the absorption of Corticosteroids (Oral). Monitor therapy

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. Consider therapy modification

Deferasirox: Bile Acid Sequestrants may decrease the serum concentration of Deferasirox. Management: Avoid combination when possible; if the combination must be used, consider a 50% increase in initial deferasirox dose, with monitoring of serum ferritin concentrations and clinical responses to guide further dosing. Consider therapy modification

Ethinyl Estradiol: Colesevelam may decrease the serum concentration of Ethinyl Estradiol. Consider therapy modification

Ezetimibe: Bile Acid Sequestrants may decrease the absorption of Ezetimibe. Management: Administer ezetimibe at least 2 hours before or 4 hours after any bile acid sequestrant. Consider therapy modification

Glimepiride: Colesevelam may decrease the serum concentration of Glimepiride. Management: Administer glimepiride at least 4 hours prior to colesevelam. Consider therapy modification

GlipiZIDE: Colesevelam may decrease the serum concentration of GlipiZIDE. Management: Administer glipizide at least 4 hours prior to colesevelam. Consider therapy modification

GlyBURIDE: Colesevelam may decrease the serum concentration of GlyBURIDE. Management: Administer glyburide at least 4 hours prior to colesevelam. 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. Consider therapy modification

Lomitapide: Bile Acid Sequestrants may decrease the absorption of Lomitapide. Management: Administer lomitapide at least 4 hours before or after administration of a bile acid sequestrant. Consider therapy modification

Loop Diuretics: Bile Acid Sequestrants may decrease the absorption of Loop Diuretics. Consider therapy modification

Methotrexate: Bile Acid Sequestrants may decrease the absorption of Methotrexate. Monitor therapy

Multivitamins/Fluoride (with ADE): Bile Acid Sequestrants may decrease the serum concentration of Multivitamins/Fluoride (with ADE). Management: Avoid concomitant administration of multivitamins and bile acid sequestrants (e.g., cholestyramine). Separate administration of these agents by several hours to minimize the risk of an interaction. Consider therapy modification

Multivitamins/Minerals (with ADEK, Folate, Iron): Bile Acid Sequestrants may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, bile acid sequestrants may impair the absorption of fat-soluble vitamins. Management: Avoid concomitant administration of multivitamins and bile acid sequestrants (e.g., cholestyramine). Separate administration of these agents by several hours to minimize the risk of an interaction. Consider therapy modification

Multivitamins/Minerals (with AE, No Iron): Bile Acid Sequestrants may decrease the serum concentration of Multivitamins/Minerals (with AE, No Iron). Management: Avoid concomitant administration of multivitamins and bile acid sequestrants (e.g., cholestyramine). Separate administration of these agents by several hours to minimize the risk of an interaction. Consider therapy modification

Mycophenolate: Bile Acid Sequestrants may decrease the serum concentration of Mycophenolate. Avoid combination

Niacin: Bile Acid Sequestrants may decrease the absorption of Niacin. Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents: Bile Acid Sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Consider therapy modification

Norethindrone: Colesevelam may decrease the serum concentration of Norethindrone. Consider therapy modification

Obeticholic Acid: Bile Acid Sequestrants may decrease the serum concentration of Obeticholic Acid. Management: Administer obeticholic acid at least 4 hours before or at least 4 hours after the administration of bile acid sequestrants. Consider therapy modification

Olmesartan: Colesevelam may decrease the serum concentration of Olmesartan. Management: Administer olmesartan at least 4 hours prior to colesevelam. Consider therapy modification

Phenytoin: Colesevelam may decrease the serum concentration of Phenytoin. Management: Administer phenytoin at least 4 hours prior to colesevelam. 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. Consider therapy modification

Propranolol: Bile Acid Sequestrants may decrease the serum concentration of Propranolol. Monitor therapy

Raloxifene: Bile Acid Sequestrants may decrease the absorption of Raloxifene. Consider therapy modification

Teriflunomide: Bile Acid Sequestrants may decrease the serum concentration of Teriflunomide. Management: Unless using this combination to intentionally enhance teriflunomide elimination, consider an alternative to the bile acid sequestrants when possible. Separating drug administration is unlikely to be effective at avoiding the interaction. Consider therapy modification

Tetracycline Derivatives: Bile Acid Sequestrants may decrease the absorption of Tetracycline Derivatives. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Bile Acid Sequestrants may decrease the absorption of Thiazide and Thiazide-Like Diuretics. The diuretic response is likewise decreased. Consider therapy modification

Thyroid Products: Bile Acid Sequestrants may decrease the serum concentration of Thyroid Products. Management: Administer oral thyroid products at least 4 h prior to colesevelam, and at least 1 h before or 4-6 h after cholestyramine. Specific recommendations for colestipol are not available. Monitor for decreased concentrations/effects of the thyroid product. Consider therapy modification

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. 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. 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. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Bile Acid Sequestrants may decrease the absorption of Vitamin K Antagonists. Monitor therapy


Monitoring Parameters

Fasting lipid profile before initiating treatment, 3 months after initiation (within 4-6 weeks if baseline fasting triglycerides of 250-299 mg/dL), and every 6-12 months thereafter (ACC/AHA [Stone, 2013])


Lab Test Interferences


Test Interactions

Increased prothrombin time


Adverse Reactions


Actual frequency may be dependent upon indication. Unless otherwise noted, frequency of adverse effects is reported for adult patients.

>10%: Gastrointestinal: Constipation (3% to 11%)

1% to 10%:

Cardiovascular: Cardiovascular toxicity (2%, including myocardial infarction, aortic stenosis, bradycardia), hypertension (2% to 3%)

Central nervous system: Headache (children and adults 4% to 8%), fatigue (children 4%)

Endocrine & metabolic: Hypertriglyceridemia (4% to 5%; >500 mg/dL: <1%; >1,000 mg/dL: <1%), hyperglycemia (3%), hypoglycemia (3%)

Gastrointestinal: Dyspepsia (3% to 8%), diarrhea (4%), nausea (children and adults 3% to 4%), gastroesophageal reflux disease (2%), periodontal abscess (2%), vomiting (children 2%)

Hematologic & oncologic: C-reactive protein increased (3%)

Neuromuscular & skeletal: Weakness (4%), back pain (2%), increased creatine phosphokinase (children and adults 2%), myalgia (2%)

Respiratory: Nasopharyngitis (children 5% to 6%), upper respiratory tract infection (children and adults 3% to 5%), flu-like symptoms (children 4%), pharyngitis (3%), rhinitis (children 2%)

<1% (Limited to important or life-threatening): Dysphagia, esophageal obstruction, fecal impaction, worsening of hemorrhoids, increased serum transaminases, infection, intestinal obstruction, pancreatitis, unstable angina pectoris


Warnings/Precautions


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.

- Hypertriglyceridemia: Use with caution in patients with serum triglyceride concentrations >300 mg/dL and in patients using insulin, thiazolidinediones, or sulfonylureas (may cause increased concentrations). Discontinue if triglyceride concentrations exceed 500 mg/dL or hypertriglyceridemia-induced pancreatitis occurs. The American College of Cardiology/American Heart Association recommends to avoid use in patients with baseline fasting triglyceride levels ≥300 mg/dL or type III hyperlipoproteinemia since severe triglyceride elevations may occur. Use bile acid sequestrants with caution in patients with triglyceride levels 250-299 mg/dL and evaluate a fasting lipid panel in 4-6 weeks after initiation; discontinue use if triglycerides are >400 mg/dL (Stone, 2013).

- 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:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

- Phenylalanine: Some products may contain phenylalanine


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.


Actions


Pharmacology

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.


Absorption

None


Excretion

Urine (0.05%)


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


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience headache, heartburn, back pain, or rhinitis. Have patient report immediately to prescriber signs pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), severe constipation, severe abdominal pain, or dysphagia (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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