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  • CLASSES

    Bile Acid Sequestrants and Ion-exchange Resins

    DEA CLASS

    Rx

    DESCRIPTION

    Oral, non-absorbed hydrogel polymer
    Used for diabetes mellitus or hypercholesterolemia in adults and familial hypercholesterolemia in boys and postmenarchal girls
    Used as monotherapy or with a statin for hypercholesterolemia

    COMMON BRAND NAMES

    WelChol

    HOW SUPPLIED

    Colesevelam/Colesevelam Hydrochloride/WelChol Oral Pwd F/Recon: 3.75g
    Colesevelam/Colesevelam Hydrochloride/WelChol Oral Tab: 625mg

    DOSAGE & INDICATIONS

    For the treatment of primary hypercholesterolemia.
    For use as adjunctive therapy to diet and exercise for the reduction of elevated LDL cholesterol in patients with primary hyperlipoproteinemia as monotherapy or in combination with an HMG-CoA reductase inhibitor.
    Oral dosage (625 mg tablets)
    Adults

    Initially, 3 tablets (1.875 g/dose) orally twice daily or 6 tablets (3.75 g/dose) orally once daily; administer with liquid and a meal.  Doses of 4 to 6 tablets per day have been shown to be safe and effective when coadministered with an HMG-CoA reductase inhibitor. Colesevelam may be taken at the same time as or administered separately from the HMG-CoA reductase inhibitor without affecting the clinical response. Lipid concentrations should be analyzed within 4 to 6 weeks following initiation of colesevelam therapy.[30812]

    Oral dosage (oral suspension)
    Adults

    One 3.75-g packet orally once daily. Dissolve each packet in 8 ounces of water, fruit juice, or diet soda, and administer with a meal. To avoid esophageal distress, do not take in dry form. Lipid concentrations should be analyzed within 4 to 6 weeks following initiation of colesevelam therapy.

    For use as monotherapy or in combination with an HMG-CoA reductase inhibitor to reduce LDL cholesterol (LDL-C) in pediatric patients with heterozygous familial hypercholesterolemia (FH).
    NOTE: Colesevelam is indicated after an adequate trial of diet therapy for patients with FH who have LDL-C greater than or equal to 190 mg/dL or LDL-C greater than or equal to 160 mg/dL and have a positive family history of premature cardiovascular disease or 2 or more other CVD risk factors.
    Oral dosage (oral suspension)

    NOTE: Due to tablet size, the manufacturer recommends that colesevelam oral suspension be used for children.

    Children and Adolescents 10 to 17 years (females should be postmenarchal)

    One 3.75-g packet orally once daily. Dissolve each packet in 8 ounces of water, fruit juice, or diet soda, and administer with a meal. To avoid esophageal distress, do not take in dry form. Lipid concentrations should be analyzed within 4 to 6 weeks following initiation of colesevelam therapy.

    For use as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.
    Oral dosage (625 mg tablets)
    Adults

    Recommended dose is 3 tablets (1.875 g/dose) orally twice daily or 6 tablets (3.75 g/dose) orally once daily. Administer with liquid and a meal.

    Oral dosage (oral suspension)
    Adults

    One 3.75-g packet PO once daily. Dissolve each dose in 8 ounces of water, fruit juice, or diet soda, and administer with a meal. To avoid esophageal distress, do not take in dry form.

    MAXIMUM DOSAGE

    Adults

    3.75 g/day PO.

    Geriatric

    3.75 g/day PO.

    Adolescents

    3.75 g/day PO powder for oral suspension.

    Children

    10 years or more, including postmenarchal females: 3.75 g/day PO powder for oral suspension.
    Less than 10 years and pre-menarchal females: Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is needed; the drug is not systemically absorbed.

    Renal Impairment

    No dosage adjustment is needed; the drug is not systemically absorbed.
     
    Intermittent hemodialysis
    No dosage adjustment is needed; the drug is not systemically absorbed.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Tablets: Administer with meals and full glass of water or other liquid.[30812]

    Oral Liquid Formulations

    Powder for oral suspension:
    To prepare, empty the entire contents of one packet of colesevelam powder into a glass or cup. Add 1 cup (8 ounces or 240 mL) of water, fruit juice, or diet soda. Stir well and drink. Administer with meals.
    To avoid esophageal distress, do not take in dry form.

    STORAGE

    WelChol:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Biliary obstruction, cholelithiasis

    Use colesevelam with caution in patients with cholelithiasis or complete biliary obstruction. In these conditions, secretion of bile acids into the GI tract is impaired.

    Constipation, dysphagia, gastroparesis, GI obstruction, hemorrhoids, ileus, surgery

    Colesevelam is contraindicated in patients with GI obstruction because the drug causes constipation. Colesevelam is not recommended in patients with severe gastrointestinal motility disorders (e.g., ileus), gastroparesis, or previous major gastrointestinal tract surgery. Patients with preexisting constipation are at increased risk of developing fecal impaction. Hemorrhoids may be aggravated if constipation develops while taking colesevelam. Due to the size of the tablets, colesevelam may cause dysphagia or esophageal obstruction. Colesevelam suspension should be used for patients with difficulty swallowing tablets. To avoid esophageal distress, do not take oral suspension in its dry form.

    Coagulopathy, malabsorption syndrome, vitamin A deficiency, vitamin D deficiency, vitamin K deficiency

    Colesevelam may decrease the absorption of fat-soluble vitamins A, D, E, and K and should be used cautiously in patients with a susceptibility to vitamin K or fat-soluble vitamin deficiencies (e.g., vitamin A deficiency, vitamin D deficiency), such as patients on warfarin therapy, with malabsorption syndrome, or with another pre-existing coagulopathy. Studies to evaluate the effects of colesevelam on the absorption of fat-soluble vitamins have not been conducted; animal data suggest that it is possible to develop hemorrhage due to vitamin K deficiency induced by colesevelam therapy. Patients taking oral vitamin supplements should take their vitamins at least 4 hours before taking colesevelam.[30812]

    Hypertriglyceridemia, pancreatitis

    Bile acid sequestrants can increase serum triglyceride concentrations. Colesevelam is contraindicated in patients with hypertriglyceridemia where triglycerides are greater than 500 mg/dL and in patients with a history of hypertriglyceridemia-induced pancreatitis. Patients with a triglyceride level greater than 300 mg/dL may experience greater increases in triglycerides with colesevelam therapy and require increased monitoring. In trials in patients with hyperlipidemia, colesevelam increased serum triglyceride concentrations by approximately 5%. While the manufacturer cautions the use of colesevelam in patients with triglycerides greater than 300 mg/dL and contraindicates its use in patients with triglycerides greater than 500 mg/dL, the collaborative guidelines on the management of blood cholesterol indicate that bile acid resins should be avoided in patients with a serum triglyceride concentration greater than 300 mg/dL.[64068] The NCEP guidelines indicate that bile acid resins are contraindicated in patients with dysbetalipoproteinemia.[25994] In patients with type 2 diabetes mellitus, colesevelam monotherapy or in combination with pioglitazone, sulfonylureas, or insulin increased triglyceride levels by 9.7%, 11%, 18%, and 22%, respectively, compared to placebo. Lipid parameters, including triglycerides, should be monitored prior to starting colesevelam, 4 to 6 weeks after therapy initiation, and periodically thereafter. Discontinue colesevelam if triglyceride concentrations increase to greater than 500 mg/dL or if the patient develops hypertriglyceridemia-induced pancreatitis.

    Phenylketonuria

    Colesevelam oral suspension contains phenylalanine, it should be used with caution in patients with phenylketonuria.

    Pregnancy

    Colesevelam is not systemically absorbed, so fetal exposure to the drug is not expected with maternal use during pregnancy. There are no adequate and well-controlled studies in pregnant women. No evidence of maternal or fetal toxicity was found in reproduction studies on rats or rabbits. The effect of colesevelam on the absorption of fat-soluble vitamins has not been studied in pregnant women. However, bile acid sequestrants are known to interfere with the absorption of fat-soluble vitamins in pregnancy, which may lead to deficiencies even with supplementation. Maternal vitamin K deficiencies may lead to fetal deficiencies, resulting in coagulopathy and possible fetal death.[27402] Published guidelines state that bile acid sequestrants, such as colesevelam, may be administered to pregnant women and that vitamin K should be monitored during therapy. According to the manufacturer, patients should be informed of a lack of known clinical benefit to colesevelam treatment in pregnancy.[30812]

    Breast-feeding

    According to the manufacturer, colesevelam hydrochloride is not expected to be excreted in human milk because the drug is not systemically absorbed [30812]; for this reason, nonabsorbable resins, such as colesevelam, may be considered for breast-feeding mothers who require pharmacotherapy for cholesterol management.[63892] It should be noted, however, that prolonged use of colesevelam may result in decreased absorption of fat-soluble vitamins (A, D, E, and K) in the mother and could potentially reduce vitamin concentrations in maternal milk.[48286] The possible need for vitamin supplementation should be discussed with the infant's pediatrician. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Children, infants, neonates

    The safe and effective use of colesevelam in children less than 10 years, pre-menarchal girls, infants, and neonates has not been established. The effects of lowering cholesterol levels in children over the long-term have not been established. Due to tablet size, colesevelam oral suspension is recommended by the manufacturer for use in children.[30812]

    ADVERSE REACTIONS

    Severe

    pancreatitis / Delayed / Incidence not known
    GI obstruction / Delayed / Incidence not known
    bradycardia / Rapid / Incidence not known
    myocardial infarction / Delayed / Incidence not known

    Moderate

    hypertriglyceridemia / Delayed / 5.0-22.0
    constipation / Delayed / 6.5-11.0
    hypoglycemia / Early / 3.4-3.4
    hypertension / Early / 2.6-2.6
    dysphagia / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hemorrhoids / Delayed / Incidence not known
    folate deficiency / Delayed / Incidence not known

    Mild

    dyspepsia / Early / 2.8-8.3
    headache / Early / 3.9-7.6
    nausea / Early / 2.6-4.2
    fatigue / Early / 3.9-3.9
    influenza / Delayed / 3.2-3.8
    asthenia / Delayed / 3.6-3.6
    rhinitis / Early / 2.3-3.2
    pharyngitis / Delayed / 3.2-3.2
    vomiting / Early / 2.3-2.3
    back pain / Delayed / 2.3-2.3
    myalgia / Early / 2.1-2.1
    infection / Delayed / Incidence not known
    rash / Early / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) Colesevelam may decrease the absorption of acebutolol if coadministered. To minimize potential for interactions, consider administering acebutolol at least 1 hour before or at least 4 hours after colesevelam; monitor drug response and/or serum drug concentrations.
    Acetohexamide: (Moderate) Colesevelam reduces the oral bioavailability of glyburide, glipizide, glimepiride and other sulfonylureas. Administer these drugs at least 4 hours before colesevelam to limit this interaction. Drug response, including glycemic control, should also be monitored. Additionally, in patients with type 2 diabetes mellitus receiving sulfonylureas, colesevelam increased serum triglyceride concentrations by 18% compared to placebo (p less than 0.001). Monitor patients taking these treatments together for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are more than 500 mg/dL or if hypertriglyceridemia-induced pancreatitis occurs.
    Alendronate; Cholecalciferol: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Alogliptin; Metformin: (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Amlodipine; Olmesartan: (Moderate) Colesevelam decreases the Cmax and AUC of olmesartan by approximately 28% and 39%, respectively. Administer olmesartan at least 4 hours before colesevelam.
    Ascorbic Acid, Vitamin C: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Atorvastatin; Ezetimibe: (Moderate) The oral absorption of ezetimibe may be decreased by the concomitant administration of the bile acid sequestrants; the incremental LDL-cholesterol reduction expected to occur by adding ezetimibe to bile acid sequestrant therapy may be reduced by this interaction. To limit a potential interaction, ezetimibe should be administered at least 2 hours before or 4 hours after administration of a bile acid sequestrant. In a study of 40 hypercholesterolemic adult subjects, concomitant cholestyramine (4 grams PO twice daily) administration decreased the mean AUC values of total ezetimibe (ezetimibe plus ezetimibe-glucuronide) and ezetimibe by approximately 55% and 80%, respectively. A similar effect might be expected to occur with the concomitant administration of colesevelam with ezetimibe; however, this potential interaction has not been studied.
    Atropine: (Moderate) Colesevelam may decrease the absorption of atropine if coadministered. To minimize potential for interactions, consider administering atropine at least 1 hour before or at least 4 hours after colesevelam; monitor drug response and/or serum drug concentrations.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Colesevelam may decrease the absorption of atropine if coadministered. To minimize potential for interactions, consider administering atropine at least 1 hour before or at least 4 hours after colesevelam; monitor drug response and/or serum drug concentrations.
    Atropine; Difenoxin: (Moderate) Colesevelam may decrease the absorption of atropine if coadministered. To minimize potential for interactions, consider administering atropine at least 1 hour before or at least 4 hours after colesevelam; monitor drug response and/or serum drug concentrations.
    Atropine; Edrophonium: (Moderate) Colesevelam may decrease the absorption of atropine if coadministered. To minimize potential for interactions, consider administering atropine at least 1 hour before or at least 4 hours after colesevelam; monitor drug response and/or serum drug concentrations.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Colesevelam may decrease the bioavailability of phenobarbital. To minimize potential for interactions, consider administering oral anticonvulsants such as phenobarbital at least 1 hour before or at least 4 hours after colesevelam.
    Bempedoic Acid; Ezetimibe: (Moderate) The oral absorption of ezetimibe may be decreased by the concomitant administration of the bile acid sequestrants; the incremental LDL-cholesterol reduction expected to occur by adding ezetimibe to bile acid sequestrant therapy may be reduced by this interaction. To limit a potential interaction, ezetimibe should be administered at least 2 hours before or 4 hours after administration of a bile acid sequestrant. In a study of 40 hypercholesterolemic adult subjects, concomitant cholestyramine (4 grams PO twice daily) administration decreased the mean AUC values of total ezetimibe (ezetimibe plus ezetimibe-glucuronide) and ezetimibe by approximately 55% and 80%, respectively. A similar effect might be expected to occur with the concomitant administration of colesevelam with ezetimibe; however, this potential interaction has not been studied.
    Bendroflumethiazide; Nadolol: (Moderate) Colesevelam may decrease the absorption of nadolol. To minimize potential for interactions, consider administering nadolol at least 1 hour before or at least 4 hours after colesevelam.
    Brimonidine; Timolol: (Moderate) Colesevelam may decrease the absorption of timolol. To minimize potential for interactions, consider administering timolol at least 1 hour before or at least 4 hours after colesevelam.
    Bupivacaine; Lidocaine: (Moderate) Colesevelam may decrease the absorption of lidocaine. To minimize potential for interactions, consider administering lidocaine at least 1 hour before or at least 4 hours after colesevelam.
    Calcium; Vitamin D: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Canagliflozin; Metformin: (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Carbamazepine: (Moderate) Colesevelam may decrease the bioavailability of carbamazepine. To minimize potential for interactions, consider administering oral drugs with a narrow therapeutic index such as carbamazepine at least 1 hour before or at least 4 hours after colesevelam.
    Chenodiol: (Moderate) Bile acid sequestrants, such as colesevelam, may interfere with the action of chenodiol by reducing its absorption. To minimize drug interactions, administer chenodiol at least 1 hour before or at least 4 hours after colesevelam.
    Chlorpropamide: (Moderate) Colesevelam reduces the oral bioavailability of glyburide, glipizide, glimepiride and other sulfonylureas. Administer these drugs at least 4 hours before colesevelam to limit this interaction. Drug response, including glycemic control, should also be monitored. Additionally, in patients with type 2 diabetes mellitus receiving sulfonylureas, colesevelam increased serum triglyceride concentrations by 18% compared to placebo (p less than 0.001). Monitor patients taking these treatments together for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are more than 500 mg/dL or if hypertriglyceridemia-induced pancreatitis occurs.
    Cholic Acid: (Moderate) Do not administer cholic acid simultaneously with bile acid binding resins such as cholestyramine, colestipol, or colesevelam because a reduction in cholic acid absorption will occur. Administer cholic acid at least 1 hour before or 4 to 6 hours (or the maximal interval possible) after a bile acid binding resin.
    Class IA Antiarrhythmics: (Moderate) Colesevelam may decrease the bioavailability of antiarrhythmics if coadministered. To minimize potential for interactions, consider administering oral antiarrhythmics at least 1 hour before or at least 4 hours after colesevelam.
    Clobazam: (Major) The manufacturer for colesevelam suggests monitoring serum drug concentrations and/or clinical effects for those drugs for which alterations in serum blood concentrations have a clinically significant effect on safety or efficacy. To minimize potential for interactions, consider administering oral anticonvulsants such as clobazam at least 4 hours before colesevelam.
    Clonazepam: (Moderate) The manufacturer for colesevelam suggests monitoring serum drug concentrations and/or clinical effects for those drugs for which alterations in serum blood concentrations have a clinically significant effect on safety or efficacy. To minimize potential for interactions, consider administering oral anticonvulsants such as clonazepam at least 4 hours before colesevelam.
    Clorazepate: (Moderate) Colesevelam may decrease the bioavailability of clorazepate if coadministered. To minimize potential for interactions, consider administering oral anticonvulsants such as clorazepate at least 1 hour before or at least 4 hours after colesevelam.
    Cranberry, Vaccinium macrocarpon Ait.: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Cyanocobalamin, Vitamin B12: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Cyclosporine: (Moderate) Colesevelam decreases the Cmax and AUC of cyclosporine by 44% and 34%, respectively. The manufacturer recommends administration of cyclosporine at least 4 hours before colesevelam. Additionally, cyclosporine serum concentrations should be monitored.
    Dapagliflozin; Metformin: (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Deferasirox: (Major) The concomitant administration of deferasirox and colesevelam may result in decreased systemic exposure to deferasirox. Avoid the concomitant use if possible. If colesevelam and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox to 30 mg/kg. Monitor serum ferritin levels and clinical responses for further dose modification.
    Desogestrel; Ethinyl Estradiol: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Diazepam: (Moderate) Colesevelam may decrease the absorption of anticonvulsants. To minimize potential for interactions, consider administering oral anticonvulsants at least 1 hour before or at least 4 hours after colesevelam.
    Digoxin: (Moderate) Oral drugs with a narrow therapeutic range, with the potential for loss of efficacy with reduced absorption, include antiarrhythmics. The manufacturer recommends that when administering other drugs with a narrow therapeutic index, consideration should be given to separating the administration of the drug with colesevelam. Although not specifically studied, it may be prudent to administer antiarrhythmics at least 4 hours before colesevelam. Additionally, drug response and/or serum concentrations should also be monitored.
    Diltiazem: (Moderate) Colesevelam may decrease the absorption of diltiazem. To minimize potential for interactions, consider administering diltiazem at least 1 hour before or at least 4 hours after colesevelam.
    Diphenoxylate; Atropine: (Moderate) Colesevelam may decrease the absorption of atropine if coadministered. To minimize potential for interactions, consider administering atropine at least 1 hour before or at least 4 hours after colesevelam; monitor drug response and/or serum drug concentrations.
    Dorzolamide; Timolol: (Moderate) Colesevelam may decrease the absorption of timolol. To minimize potential for interactions, consider administering timolol at least 1 hour before or at least 4 hours after colesevelam.
    Drospirenone; Ethinyl Estradiol: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Empagliflozin; Linagliptin; Metformin: (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Empagliflozin; Metformin: (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Encainide: (Moderate) Colesevelam may decrease the bioavailability of encainide if coadministered. To minimize potential for interactions, consider administering oral antiarrhythmics such as encainide at least 1 hour before or at least 4 hours after colesevelam.
    Ertugliflozin; Metformin: (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Ethinyl Estradiol: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated. (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Ethinyl Estradiol; Norelgestromin: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Ethinyl Estradiol; Norgestrel: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Ethotoin: (Moderate) Colesevelam may decrease the bioavailability of the hydantoin anticonvulsants. To minimize potential for interactions, consider administering oral anticonvulsants at least 1 hour before or at least 4 hours after colesevelam. Although colesevelam was found to have no significant effect on the bioavailability of phenytoin in an in vivo pharmacokinetic study, there have been post-marketing reports of increased seizure activity or decreased phenytoin concentrations in patients receiving concomitant colesevelam therapy. Hydantoins should be administered at least 4 hours before colesevelam. The manufacturer recommends that when administering other drugs with a narrow therapeutic index, consideration should be given to separating the administration of the drug with colesevelam. Although not specifically studied, it may be prudent to administer other anticonvulsants at least 4 hours before colesevelam. Additionally, drug response and/or serum concentrations should also be monitored.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Etonogestrel; Ethinyl Estradiol: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Ezetimibe: (Moderate) The oral absorption of ezetimibe may be decreased by the concomitant administration of the bile acid sequestrants; the incremental LDL-cholesterol reduction expected to occur by adding ezetimibe to bile acid sequestrant therapy may be reduced by this interaction. To limit a potential interaction, ezetimibe should be administered at least 2 hours before or 4 hours after administration of a bile acid sequestrant. In a study of 40 hypercholesterolemic adult subjects, concomitant cholestyramine (4 grams PO twice daily) administration decreased the mean AUC values of total ezetimibe (ezetimibe plus ezetimibe-glucuronide) and ezetimibe by approximately 55% and 80%, respectively. A similar effect might be expected to occur with the concomitant administration of colesevelam with ezetimibe; however, this potential interaction has not been studied.
    Ezetimibe; Simvastatin: (Moderate) The oral absorption of ezetimibe may be decreased by the concomitant administration of the bile acid sequestrants; the incremental LDL-cholesterol reduction expected to occur by adding ezetimibe to bile acid sequestrant therapy may be reduced by this interaction. To limit a potential interaction, ezetimibe should be administered at least 2 hours before or 4 hours after administration of a bile acid sequestrant. In a study of 40 hypercholesterolemic adult subjects, concomitant cholestyramine (4 grams PO twice daily) administration decreased the mean AUC values of total ezetimibe (ezetimibe plus ezetimibe-glucuronide) and ezetimibe by approximately 55% and 80%, respectively. A similar effect might be expected to occur with the concomitant administration of colesevelam with ezetimibe; however, this potential interaction has not been studied.
    Fat soluble vitamins: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Felbamate: (Moderate) Colesevelam may decrease the bioavailability or felbamate if coadministered. To minimize potential for interactions, consider administering oral anticonvulsants such as felbamate at least 1 hour before or at least 4 hours after colesevelam.
    Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Flecainide: (Moderate) Colesevelam may decrease the bioavailability of flecainide if coadministered. To minimize potential for interactions, consider administering oral antiarrhythmics such as flecainide at least 1 hour before or at least 4 hours after colesevelam.
    Folic Acid, Vitamin B9: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Fosphenytoin: (Moderate) Colesevelam may decrease the bioavailability of the hydantoin anticonvulsants. To minimize potential for interactions, consider administering oral anticonvulsants at least 1 hour before or at least 4 hours after colesevelam. Although colesevelam was found to have no significant effect on the bioavailability of phenytoin in an in vivo pharmacokinetic study, there have been post-marketing reports of increased seizure activity or decreased phenytoin concentrations in patients receiving concomitant colesevelam therapy. Hydantoins should be administered at least 4 hours before colesevelam. The manufacturer recommends that when administering other drugs with a narrow therapeutic index, consideration should be given to separating the administration of the drug with colesevelam. Although not specifically studied, it may be prudent to administer other anticonvulsants at least 4 hours before colesevelam. Additionally, drug response and/or serum concentrations should also be monitored.
    Gabapentin: (Moderate) The manufacturer for colesevelam suggests monitoring serum drug concentrations and/or clinical effects for those drugs for which alterations in serum blood concentrations have a clinically significant effect on safety or efficacy. To minimize potential for interactions, consider administering oral anticonvulsants such as gabapentin at least 1 hour before or at least 4 hours after colesevelam.
    Gemfibrozil: (Moderate) Separate the administration of gemfibrozil and colesevelam by at least 2 hours. Coadministration of bile acid resins such as colestipol resulted in a 30% reduction in gemfibrozil AUC; exposure to gemfibrozil was not significantly affected when the drugs were administed 2 hours apart.
    Glimepiride: (Moderate) Colesevelam reduces the oral bioavailability of glyburide, glipizide, glimepiride and other sulfonylureas. Administer these drugs at least 4 hours before colesevelam to limit this interaction. Drug response, including glycemic control, should also be monitored. Additionally, in patients with type 2 diabetes mellitus receiving sulfonylureas, colesevelam increased serum triglyceride concentrations by 18% compared to placebo (p less than 0.001). Monitor patients taking these treatments together for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are more than 500 mg/dL or if hypertriglyceridemia-induced pancreatitis occurs.
    Glimepiride; Rosiglitazone: (Moderate) Colesevelam reduces the oral bioavailability of glyburide, glipizide, glimepiride and other sulfonylureas. Administer these drugs at least 4 hours before colesevelam to limit this interaction. Drug response, including glycemic control, should also be monitored. Additionally, in patients with type 2 diabetes mellitus receiving sulfonylureas, colesevelam increased serum triglyceride concentrations by 18% compared to placebo (p less than 0.001). Monitor patients taking these treatments together for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are more than 500 mg/dL or if hypertriglyceridemia-induced pancreatitis occurs.
    Glipizide: (Moderate) Colesevelam reduces the oral bioavailability of glyburide, glipizide, glimepiride and other sulfonylureas. Administer these drugs at least 4 hours before colesevelam to limit this interaction. Drug response, including glycemic control, should also be monitored. Additionally, in patients with type 2 diabetes mellitus receiving sulfonylureas, colesevelam increased serum triglyceride concentrations by 18% compared to placebo (p less than 0.001). Monitor patients taking these treatments together for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are more than 500 mg/dL or if hypertriglyceridemia-induced pancreatitis occurs.
    Glipizide; Metformin: (Moderate) Colesevelam reduces the oral bioavailability of glyburide, glipizide, glimepiride and other sulfonylureas. Administer these drugs at least 4 hours before colesevelam to limit this interaction. Drug response, including glycemic control, should also be monitored. Additionally, in patients with type 2 diabetes mellitus receiving sulfonylureas, colesevelam increased serum triglyceride concentrations by 18% compared to placebo (p less than 0.001). Monitor patients taking these treatments together for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are more than 500 mg/dL or if hypertriglyceridemia-induced pancreatitis occurs. (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Glyburide: (Moderate) Colesevelam reduces the oral bioavailability of glyburide, glipizide, glimepiride and other sulfonylureas. Administer these drugs at least 4 hours before colesevelam to limit this interaction. Drug response, including glycemic control, should also be monitored. Additionally, in patients with type 2 diabetes mellitus receiving sulfonylureas, colesevelam increased serum triglyceride concentrations by 18% compared to placebo (p less than 0.001). Monitor patients taking these treatments together for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are more than 500 mg/dL or if hypertriglyceridemia-induced pancreatitis occurs.
    Glyburide; Metformin: (Moderate) Colesevelam reduces the oral bioavailability of glyburide, glipizide, glimepiride and other sulfonylureas. Administer these drugs at least 4 hours before colesevelam to limit this interaction. Drug response, including glycemic control, should also be monitored. Additionally, in patients with type 2 diabetes mellitus receiving sulfonylureas, colesevelam increased serum triglyceride concentrations by 18% compared to placebo (p less than 0.001). Monitor patients taking these treatments together for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are more than 500 mg/dL or if hypertriglyceridemia-induced pancreatitis occurs. (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Hydantoins: (Moderate) Colesevelam may decrease the bioavailability of the hydantoin anticonvulsants. To minimize potential for interactions, consider administering oral anticonvulsants at least 1 hour before or at least 4 hours after colesevelam. Although colesevelam was found to have no significant effect on the bioavailability of phenytoin in an in vivo pharmacokinetic study, there have been post-marketing reports of increased seizure activity or decreased phenytoin concentrations in patients receiving concomitant colesevelam therapy. Hydantoins should be administered at least 4 hours before colesevelam. The manufacturer recommends that when administering other drugs with a narrow therapeutic index, consideration should be given to separating the administration of the drug with colesevelam. Although not specifically studied, it may be prudent to administer other anticonvulsants at least 4 hours before colesevelam. Additionally, drug response and/or serum concentrations should also be monitored.
    Hydroxocobalamin: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Insulins: (Moderate) In patients with type 2 diabetes mellitus receiving insulins, colesevelam increased serum triglyceride concentrations by 22% compared to placebo. Monitor patients for increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 500 mg/dl or if hypertriglyceridemia-induced pancreatitis occurs.
    Lamotrigine: (Moderate) Colesevelam may decrease the bioavailability of lamotrigine. To minimize potential for interactions, consider administering oral anticonvulsants such as lamotrigine at least 1 hour before or at least 4 hours after colesevelam.
    Levetiracetam: (Moderate) Colesevelam may decrease the bioavailability of levetiracetam if coadministered. To minimize potential for interactions, consider administering oral anticonvulsants such as levetiracetam at least 1 hour before or at least 4 hours after colesevelam.
    Levonorgestrel; Ethinyl Estradiol: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Levothyroxine: (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of colesevelam. Colesevelam and other bile acid sequestrants have been shown to decrease the oral absorption of thyroid hormones. Monitor thyroid function periodically to ensure proper clinical management.
    Levothyroxine; Liothyronine (Porcine): (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of colesevelam. Colesevelam and other bile acid sequestrants have been shown to decrease the oral absorption of thyroid hormones. Monitor thyroid function periodically to ensure proper clinical management.
    Levothyroxine; Liothyronine (Synthetic): (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of colesevelam. Colesevelam and other bile acid sequestrants have been shown to decrease the oral absorption of thyroid hormones. Monitor thyroid function periodically to ensure proper clinical management.
    Lidocaine: (Moderate) Colesevelam may decrease the absorption of lidocaine. To minimize potential for interactions, consider administering lidocaine at least 1 hour before or at least 4 hours after colesevelam.
    Lidocaine; Prilocaine: (Moderate) Colesevelam may decrease the absorption of lidocaine. To minimize potential for interactions, consider administering lidocaine at least 1 hour before or at least 4 hours after colesevelam.
    Linagliptin; Metformin: (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Liothyronine: (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of colesevelam. Colesevelam and other bile acid sequestrants have been shown to decrease the oral absorption of thyroid hormones. Monitor thyroid function periodically to ensure proper clinical management.
    Lomitapide: (Moderate) Separate administration of lomitapide and bile acid sequestrants by at least 4 hours. Although this interaction has not been studied, bile acid sequestrants can interfere with the absorption of oral medications.
    Lorazepam: (Moderate) Colesevelam may decrease the absorption of anticonvulsants. To minimize potential for interactions, consider administering oral anticonvulsants at least 1 hour before or at least 4 hours after colesevelam.
    Lovastatin; Niacin: (Moderate) In vitro studies have shown that bile acid sequestrants bind niacin. Roughly 98% of niacin was bound to colestipol, and 10 to 30% of niacin was bound to cholestyramine. These results suggest that at least 4 to 6 hours should elapse between the ingestion of bile-acid-binding resins and the administration of niacin.
    Maralixibat: (Moderate) Take maralixibat at least 4 hours before or 4 hours after taking a bile acid sequestrant. Bile acid sequestrants may bind maralixibat in the gut, which may reduce its efficacy.
    Mephobarbital: (Moderate) Colesevelam may decrease the bioavailability of mephobarbital if coadminsitered. To minimize potential for interactions, consider administering oral anticonvulsants such as mephobarbital at least 1 hour before or at least 4 hours after colesevelam.
    Mestranol; Norethindrone: (Moderate) Administer oral contraceptives containing mestranol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Mestranol is a prodrug for EE, the therapeutically active moeity. Patients should separate times of administration and clinicians should be alert for evidence of an interaction.
    Metformin: (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Metformin; Repaglinide: (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Metformin; Rosiglitazone: (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Metformin; Saxagliptin: (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Metformin; Sitagliptin: (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Mexiletine: (Moderate) Colesevelam may decrease the bioavailability of mexiletine if coadministered. To minimize potential for interactions, consider administering oral antiarrhythmics such as mexiletine at least 1 hour before or at least 4 hours after colesevelam.
    Moricizine: (Moderate) Colesevelam may decrease the bioavailability of moricizine if coadministered. To minimize potential for interactions, consider administering oral antiarrhythmics such as moricizine at least 1 hour before or at least 4 hours after colesevelam.
    Mycophenolate: (Major) Bile acid sequestrants can interrupt enterohepatic recirculation and thus, reduce mycophenolic acid systemic exposure. Concurrent use of colesevelaml and mycophenolate mofetil is not recommended.
    Nadolol: (Moderate) Colesevelam may decrease the absorption of nadolol. To minimize potential for interactions, consider administering nadolol at least 1 hour before or at least 4 hours after colesevelam.
    Niacin, Niacinamide: (Moderate) In vitro studies have shown that bile acid sequestrants bind niacin. Roughly 98% of niacin was bound to colestipol, and 10 to 30% of niacin was bound to cholestyramine. These results suggest that at least 4 to 6 hours should elapse between the ingestion of bile-acid-binding resins and the administration of niacin.
    Niacin; Simvastatin: (Moderate) In vitro studies have shown that bile acid sequestrants bind niacin. Roughly 98% of niacin was bound to colestipol, and 10 to 30% of niacin was bound to cholestyramine. These results suggest that at least 4 to 6 hours should elapse between the ingestion of bile-acid-binding resins and the administration of niacin.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Norethindrone; Ethinyl Estradiol: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Norgestimate; Ethinyl Estradiol: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Obeticholic Acid: (Moderate) Bile acid binding resins such as colesevelam absorb and reduce bile acid absorption and may reduce the absorption, systemic exposure, and efficacy of obeticholic acid. If used together, take obeticholic acid at least 4 hours before or 4 hours after taking the bile acid resin, or at as great an interval as possible.
    Odevixibat: (Moderate) Take odevixibat at least 4 hours before or 4 hours after taking a bile acid sequestrant. Bile acid sequestrants may bind odevixibat in the gut, which may reduce its efficacy.
    Olmesartan: (Moderate) Colesevelam decreases the Cmax and AUC of olmesartan by approximately 28% and 39%, respectively. Administer olmesartan at least 4 hours before colesevelam.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Colesevelam decreases the Cmax and AUC of olmesartan by approximately 28% and 39%, respectively. Administer olmesartan at least 4 hours before colesevelam.
    Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Colesevelam decreases the Cmax and AUC of olmesartan by approximately 28% and 39%, respectively. Administer olmesartan at least 4 hours before colesevelam.
    Oxcarbazepine: (Moderate) Colesevelam may decrease the bioavailability of oxcarbazepine. To minimize potential for interactions, consider administering oral anticonvulsants such as oxcarbazepine at least 1 hour before or at least 4 hours after colesevelam.
    Pentobarbital: (Moderate) Colesevelam may decrease the absorption of anticonvulsants. To minimize potential for interactions, consider administering oral anticonvulsants at least 1 hour before or at least 4 hours after colesevelam.
    Phenobarbital: (Moderate) Colesevelam may decrease the bioavailability of phenobarbital. To minimize potential for interactions, consider administering oral anticonvulsants such as phenobarbital at least 1 hour before or at least 4 hours after colesevelam.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Colesevelam may decrease the absorption of atropine if coadministered. To minimize potential for interactions, consider administering atropine at least 1 hour before or at least 4 hours after colesevelam; monitor drug response and/or serum drug concentrations. (Moderate) Colesevelam may decrease the bioavailability of phenobarbital. To minimize potential for interactions, consider administering oral anticonvulsants such as phenobarbital at least 1 hour before or at least 4 hours after colesevelam.
    Phenytoin: (Moderate) Colesevelam may decrease the bioavailability of the hydantoin anticonvulsants. To minimize potential for interactions, consider administering oral anticonvulsants at least 1 hour before or at least 4 hours after colesevelam. Although colesevelam was found to have no significant effect on the bioavailability of phenytoin in an in vivo pharmacokinetic study, there have been post-marketing reports of increased seizure activity or decreased phenytoin concentrations in patients receiving concomitant colesevelam therapy. Hydantoins should be administered at least 4 hours before colesevelam. The manufacturer recommends that when administering other drugs with a narrow therapeutic index, consideration should be given to separating the administration of the drug with colesevelam. Although not specifically studied, it may be prudent to administer other anticonvulsants at least 4 hours before colesevelam. Additionally, drug response and/or serum concentrations should also be monitored.
    Phytonadione, Vitamin K1: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Pioglitazone; Glimepiride: (Moderate) Colesevelam reduces the oral bioavailability of glyburide, glipizide, glimepiride and other sulfonylureas. Administer these drugs at least 4 hours before colesevelam to limit this interaction. Drug response, including glycemic control, should also be monitored. Additionally, in patients with type 2 diabetes mellitus receiving sulfonylureas, colesevelam increased serum triglyceride concentrations by 18% compared to placebo (p less than 0.001). Monitor patients taking these treatments together for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are more than 500 mg/dL or if hypertriglyceridemia-induced pancreatitis occurs.
    Pioglitazone; Metformin: (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Primidone: (Moderate) Colesevelam may decrease the bioavailability of primidone if coadministered. To minimize potential for interactions, consider administering oral anticonvulsants such as primidone at least 1 hour before or at least 4 hours after colesevelam.
    Propafenone: (Moderate) Colesevelam may decrease the bioavailability of propafenone if coadministered. To minimize potential for interactions, consider administering oral antiarrhythmics such as propafenone at least 1 hour before or at least 4 hours after colesevelam.
    Pyridoxine, Vitamin B6: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Rosuvastatin; Ezetimibe: (Moderate) The oral absorption of ezetimibe may be decreased by the concomitant administration of the bile acid sequestrants; the incremental LDL-cholesterol reduction expected to occur by adding ezetimibe to bile acid sequestrant therapy may be reduced by this interaction. To limit a potential interaction, ezetimibe should be administered at least 2 hours before or 4 hours after administration of a bile acid sequestrant. In a study of 40 hypercholesterolemic adult subjects, concomitant cholestyramine (4 grams PO twice daily) administration decreased the mean AUC values of total ezetimibe (ezetimibe plus ezetimibe-glucuronide) and ezetimibe by approximately 55% and 80%, respectively. A similar effect might be expected to occur with the concomitant administration of colesevelam with ezetimibe; however, this potential interaction has not been studied.
    Secobarbital: (Moderate) Colesevelam may decrease the absorption of anticonvulsants. To minimize potential for interactions, consider administering oral anticonvulsants at least 1 hour before or at least 4 hours after colesevelam.
    Segesterone Acetate; Ethinyl Estradiol: (Moderate) Administer oral contraceptives containing ethinyl estradiol at least 4 hours prior to a colesevelam dose to avoid an interaction and reduce the potential for loss of contraceptive efficacy. Colesevelam has been shown to significantly decrease the AUC of ethinyl estradiol (EE) in oral contraceptives by about 24% when the drugs are administered at the same time. When the 2 drug products were given 4 hours apart, the drug interaction risk was lessened. Patients should separate times of administration and clinicians should be alert for evidence of an interaction. Consider alternative therapy if indicated.
    Succinimides: (Moderate) Colesevelam may decrease the bioavailability of succinimides if coadministered. To minimize potential for interactions, consider administering oral anticonvulsants at least 1 hour before or at least 4 hours after colesevelam.
    Sulfonylureas: (Moderate) Colesevelam reduces the oral bioavailability of glyburide, glipizide, glimepiride and other sulfonylureas. Administer these drugs at least 4 hours before colesevelam to limit this interaction. Drug response, including glycemic control, should also be monitored. Additionally, in patients with type 2 diabetes mellitus receiving sulfonylureas, colesevelam increased serum triglyceride concentrations by 18% compared to placebo (p less than 0.001). Monitor patients taking these treatments together for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are more than 500 mg/dL or if hypertriglyceridemia-induced pancreatitis occurs.
    Tetracyclines: (Moderate) Colesevelam may decrease the bioavailability of tetracyclines. To minimize potential for interactions, consider administering oral tetracyclines at least 4 hours before colesevelam. The manufacturer for colesevelam suggests monitoring serum drug concentrations and/or clinical effects for those drugs for which alterations in serum blood concentrations have a clinically significant effect on safety or efficacy.
    Theophylline, Aminophylline: (Moderate) Colesevelam may decrease the absorption of oral aminophylline. To minimize potential for interactions, consider administering oral aminophylline at least 1 hour before or at least 4 hours after colesevelam. (Moderate) Colesevelam may decrease the absorption of oral theophylline. To minimize potential for interactions, consider administering oral theophylline at least 1 hour before or at least 4 hours after colesevelam.
    Thyroid hormones: (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of colesevelam. Colesevelam and other bile acid sequestrants have been shown to decrease the oral absorption of thyroid hormones. Monitor thyroid function periodically to ensure proper clinical management.
    Tiagabine: (Moderate) Colesevelam may decrease the bioavailability of tiagabine if coadministered. To minimize potential for interactions, consider administering oral anticonvulsants such as tiagabine at least 1 hour before or at least 4 hours after colesevelam.
    Timolol: (Moderate) Colesevelam may decrease the absorption of timolol. To minimize potential for interactions, consider administering timolol at least 1 hour before or at least 4 hours after colesevelam.
    Tocainide: (Moderate) Colesevelam may decrease the bioavailability of tocainide. To minimize potential for interactions, consider administering oral antiarrhythmics such as tocainide at least 1 hour before or at least 4 hours after colesevelam.
    Tolazamide: (Moderate) Colesevelam reduces the oral bioavailability of glyburide, glipizide, glimepiride and other sulfonylureas. Administer these drugs at least 4 hours before colesevelam to limit this interaction. Drug response, including glycemic control, should also be monitored. Additionally, in patients with type 2 diabetes mellitus receiving sulfonylureas, colesevelam increased serum triglyceride concentrations by 18% compared to placebo (p less than 0.001). Monitor patients taking these treatments together for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are more than 500 mg/dL or if hypertriglyceridemia-induced pancreatitis occurs.
    Tolbutamide: (Moderate) Colesevelam reduces the oral bioavailability of glyburide, glipizide, glimepiride and other sulfonylureas. Administer these drugs at least 4 hours before colesevelam to limit this interaction. Drug response, including glycemic control, should also be monitored. Additionally, in patients with type 2 diabetes mellitus receiving sulfonylureas, colesevelam increased serum triglyceride concentrations by 18% compared to placebo (p less than 0.001). Monitor patients taking these treatments together for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are more than 500 mg/dL or if hypertriglyceridemia-induced pancreatitis occurs.
    Trandolapril; Verapamil: (Moderate) Colesevelam may significantly decrease the Cmax and AUC of sustained-release verapamil. The clinical significance of this interaction is not known since verapamil bioavailability is highly variable.
    Ursodeoxycholic Acid, Ursodiol: (Moderate) Colesevelam may interfere with the action of ursodeoxycholic acid, ursodiol by reducing its absorption. To minimize drug interactions, administer ursodiol at least 1 hour before or at least 4 hours after the bile acid sequestering agents.
    Valproic Acid, Divalproex Sodium: (Moderate) Colesevelam may decrease the bioavailability of valproic acid. To minimize potential for interactions, consider administering oral anticonvulsants such as valproic acid or divalproex sodium at least 1 hour before or at least 4 hours after colesevelam.
    Vancomycin: (Major) The concurrent use of anion-exchange resins and oral vancomycin is contraindicated by clinical practice guidelines. Per FDA-approved labeling, administer other drugs at least 4 hours before colesevelam. Colesevelam can bind other drugs, such as oral vancomycin, when given concurrently.
    Verapamil: (Moderate) Colesevelam may significantly decrease the Cmax and AUC of sustained-release verapamil. The clinical significance of this interaction is not known since verapamil bioavailability is highly variable.
    Vitamin A: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Vitamin D: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Vitamin E: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Warfarin: (Moderate) Cholestyramine can decrease warfarin absorption. Staggering the doses of cholestyramine and warfarin is recommended but this may not completely avoid a drug interaction. Cholestyramine has also been shown to enhance the clearance of IV warfarin. Thus, it is theoretically possible that cholestyramine may interfere with the actions of warfarin after warfarin has been absorbed. Colestipol may be an acceptable alternative to cholestyramine in patients receiving warfarin, although, both cholestyramine and colestipol can decrease vitamin K absorption from the gut, which may indirectly affect the clinical response to warfarin. Colesevelam may also decrease vitamin K absorption from the gut and interfere with the clinical effects of warfarin.
    Zonisamide: (Major) The manufacturer for colesevelam suggests monitoring serum drug concentrations and/or clinical effects for those drugs for which alterations in serum blood concentrations have a clinically significant effect on safety or efficacy. To minimize potential for interactions, consider administering oral anticonvulsants such as zonisamide at least 1 hour before or at least 4 hours after colesevelam.

    PREGNANCY AND LACTATION

    Pregnancy

    Colesevelam is not systemically absorbed, so fetal exposure to the drug is not expected with maternal use during pregnancy. There are no adequate and well-controlled studies in pregnant women. No evidence of maternal or fetal toxicity was found in reproduction studies on rats or rabbits. The effect of colesevelam on the absorption of fat-soluble vitamins has not been studied in pregnant women. However, bile acid sequestrants are known to interfere with the absorption of fat-soluble vitamins in pregnancy, which may lead to deficiencies even with supplementation. Maternal vitamin K deficiencies may lead to fetal deficiencies, resulting in coagulopathy and possible fetal death.[27402] Published guidelines state that bile acid sequestrants, such as colesevelam, may be administered to pregnant women and that vitamin K should be monitored during therapy. According to the manufacturer, patients should be informed of a lack of known clinical benefit to colesevelam treatment in pregnancy.[30812]

    According to the manufacturer, colesevelam hydrochloride is not expected to be excreted in human milk because the drug is not systemically absorbed [30812]; for this reason, nonabsorbable resins, such as colesevelam, may be considered for breast-feeding mothers who require pharmacotherapy for cholesterol management.[63892] It should be noted, however, that prolonged use of colesevelam may result in decreased absorption of fat-soluble vitamins (A, D, E, and K) in the mother and could potentially reduce vitamin concentrations in maternal milk.[48286] The possible need for vitamin supplementation should be discussed with the infant's pediatrician. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Colesevelam binds with bile acids in the intestine thereby impeding their reabsorption. As the bile acid pool is depleted, the hepatic enzyme, cholesterol 7-alpha-hydroxylase, is upregulated, which increases the conversion of cholesterol to bile acids. Hepatic demand for cholesterol is raised resulting in two effects: 1) increased transcription and activity of hydroxymethyl-glutaryl-coenzyme A (HMG-CoA) reductase, the cholesterol biosynthetic enzyme and 2) increased number of hepatic low-density lipoprotein (LDL) receptors. These effects increase clearance of LDL cholesterol from the blood, thereby decreasing serum LDL-C levels. Overall, colesevelam reduces total cholesterol, LDL cholesterol, and apolipoprotein B levels, and increases HDL cholesterol in patients with primary hypercholesterolemia. The mechanism of colesevelam in the reduction in fasting plasma glucose and A1C in patients with type 2 diabetes is unknown.

    PHARMACOKINETICS

    Colesevelam is administered orally. Colesevelam is a hydrophilic, water-insoluble polymer that is not absorbed or hydrolyzed by digestive enzymes. Since colesevelam is not absorbed, distribution is limited to the gastrointestinal tract and it does not undergo systemic metabolism. Less than 0.05% of a dose is excreted renally.[30812]
     
    Maximum therapeutic response to lipid-lowering effects in clinical trials was achieved within 2 weeks and maintained during long-term therapy. In diabetes trials, initial reduction in A1C was observed after 4 to 6 weeks of therapy and maximum or near-maximum effect after 12 to 16 weeks of treatment.[30812]