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  • CLASSES

    Bile Acid Sequestrants and Ion-exchange Resins

    DEA CLASS

    Rx

    DESCRIPTION

    Oral, non-absorbed hydrogel polymer for hypercholesterolemia in adults and familial hypercholesterolemia (FH) in boys and postmenarchal girls, ages 10 to 17 years; used as monotherapy or with a statin.

    COMMON BRAND NAMES

    WelChol

    HOW SUPPLIED

    WelChol Oral Pwd F/Recon: 3.75g
    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 hypercholesterolemia (Fredrickson Type IIa hyperlipoproteinemia) as monotherapy or in combination with an HMG-CoA reductase inhibitor.
    Oral dosage (625 mg tablets)
    Adults, including the Geriatric

    Initially, 3 tablets (1.875 g/dose) PO twice daily or 6 tablets (3.75 g/dose) PO once daily; administer with liquid and a meal. The dose may be increased to 7 tablets/day, depending upon the desired therapeutic effect. 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 or administered separately from the HMG-CoA reductase inhibitor without affecting clinical response.

    Oral dosage (oral suspension)
    Adults, including the Geriatric

    One 1.875 gram packet PO twice daily or one 3.75 gram packet PO once daily. Dissolve each packet in 4 to 8 ounces of water, fruit juice, or diet soda, and administer with a meal.

    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 for patients with FH who have LDL-C >= 190 mg/dL or LDL-C >= 160 mg/dL after an adequate trial of diet therapy and have a positive family history of premature cardiovascular disease or two 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.

    Females (postmenarchal and >= 10 years) and Males >= 10 years

    One 1.875 gram packet PO twice daily or one 3.75 gram packet PO once daily. Dissolve each packet in 4 to 8 ounces of water, fruit juice, or diet soda, and administer with a meal.

    For use as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.
    NOTE: Colesevelam has been studied in combination with other antidiabetic agents; however, use with dipeptidyl peptidase 4 inhibitors has not been studied.
    Oral dosage (625 mg tablets)
    Adults, including the Geriatric

    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, including the Geriatric

    One 1.875-g packet orally twice daily or one 3.75-g packet PO once daily. Dissolve each dose in 4 to 8 ounces of water, fruit juice, or diet soda, and administer with a meal.

    MAXIMUM DOSAGE

    Adults

    7 tablets/day (4.375 g/day) PO; 3.75 g/day PO powder for oral suspension.

    Elderly

    7 tablets/day (4.375 g/day) PO; 3.75 g/day PO powder for oral suspension.

    Adolescents

    3.75 g/day PO powder for oral suspension.

    Children

    >= 10 years, including postmenarchal females: 3.75 g/day PO powder for oral suspension.
    < 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

    Administer with meals and with a full glass of water or other liquid.

    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 one-half to 1 cup (4 to 8 ounces or 120 to 240 mL) of water, fruit juice, or diet soda. Stir well and drink. To avoid esophageal distress, do not take in dry form.

    STORAGE

    WelChol:
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Diabetes mellitus

    Before initiating therapy with colesevelam for primary hypercholesterolemia (Fredrickson Type IIa hyperlipoproteinemia), secondary causes of hypercholesterolemia (i.e., poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism) should be excluded, and a lipid profile obtained.

    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. Patients with preexisting constipation are at increased risk of developing fecal impaction. Hemorrhoids may be aggravated if constipation develops while taking colesevelam. Because of the tablet size, colesevelam can cause dysphagia or esophageal obstruction. Use colesevelam with caution in patients with dysphagia, swallowing disorders, severe gastrointestinal motility disorders (e.g., ileus), gastroparesis, or major gastrointestinal tract surgery.

    Coagulopathy, vitamin K deficiency

    Colesevelam should be used cautiously in patients with a susceptibility to vitamin K or fat soluble vitamin deficiencies or other 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 prior to taking colesevelam.

    Hypertriglyceridemia, pancreatitis

    In general, most patients with triglyceride levels greater than 300 mg/dL were excluded from clinical trials of colesevelam. Bile acid sequestrants can increase serum triglyceride concentrations. Colesevelam is contraindicated in patients with hypertriglyceridemia where triglycerides > 500 mg/dL and in patients with a history of hypertriglyceridemia-induced pancreatitis; 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 > 300 mg/dl and contraindicates its use in patients with triglycerides > 500 mg/dL, the NCEP guidelines indicate that bile acid resins are absolutely contraindicated in patients with a serum triglyceride concentration > 400 mg/dL and are relatively contraindicated in patients with a serum triglyceride concentration > 200 mg/dl. The NCEP also indicate that bile acid resins are contraindicated in patients with dysbetalipoproteinemia. In patients with diabetes mellitus, colesevelam in combination with sulfonylureas or insulin may increase triglyceride concentrations even greater than patients without diabetes. Additionally, the effects of colesevelam on LDL cholesterol in patients with diabetes may be attenuated because of the increase in triglycerides and a smaller decrease in non-HDL cholesterol as compared to the reduction in LDL cholesterol. Lipid parameters should be monitored prior to starting colesevelam and periodically thereafter. Discontinue colesevelam if triglyceride concentrations increase to > 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 classified as FDA pregnancy category B. There are no adequate and well-controlled studies in pregnant women. 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. According to the manufacturer, colesevelam should be used during pregnancy only if clearly needed.

    Breast-feeding

    According to the manufacturer, colesevelam hydrochloride is not expected to be excreted in human milk because the drug is not systemically absorbed ; for this reason, most experts consider nonabsorbable resins such as colesevelam the drugs of choice for breast-feeding mothers who require pharmacotherapy for cholesterol management. 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. 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 < 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.

    ADVERSE REACTIONS

    Severe

    GI obstruction / Delayed / Incidence not known
    pancreatitis / 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
    hemorrhoids / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    dysphagia / 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 (unspecified) / 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.
    Acetazolamide: (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.
    Acetohexamide: (Moderate) Colesevelam has been found to have an effect on the bioavailability of glyburide, glipizide, and glimepiride. Administer these drugs at least 4 hours before colesevelam. Drug response 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<0.001). In patients taking metformin, serum triglyceride concentrations only increased by 5%. Similarly, in patients taking colesevelam for hyperlipidemia, serum triglyceride concentrations increased by 5%. Monitor patients for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 500 mg/dl or if hypertriglyceridemia-induced pancreatitis occurs.
    Adenosine: (Moderate) Colesevelam may decrease the absorption of adenosine if coadministered. To minimize potential for interactions, consider administering adenosine at least 1 hour before or at least 4 hours after colesevelam; monitor drug response and/or serum drug concentrations.
    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) Colesevelam increases the Cmax and AUC of extended-release metformin (metformin ER) by approximately 8% and 44%, respectively. According to the manufacturer of colesevelam, the clinical response to metformin ER should be monitored in patients receiving concomitant therapy. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Colesevelam decreases the Cmax and AUC of olmesartan by approximately 28% and 39%, respectively. Administer olmesartan at least 4 hours before colesevelam.
    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.
    Atenolol: (Moderate) Colesevelam may decrease the absorption of atenolol if coadministered. To minimize potential for interactions, consider administering atenolol at least 1 hour before or at least 4 hours after colesevelam; monitor drug response and/or serum drug concentrations.
    Atenolol; Chlorthalidone: (Moderate) Colesevelam may decrease the absorption of atenolol if coadministered. To minimize potential for interactions, consider administering atenolol at least 1 hour before or at least 4 hours after colesevelam; monitor drug response and/or serum drug concentrations.
    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; Diphenoxylate: (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.
    Atropine; Hyoscyamine; Phenobarbital; 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.
    Azelaic Acid; Copper; Folic Acid; Nicotinamide; Pyridoxine; Zinc: (Major) In vitro studies have shown that bile acid sequestrants bind niacin. The results suggest that at least 4 to 6 hours should elapse between the ingestion of bile-acid-binding resins and the administration of 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. (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.
    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.
    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) Colesevelam increases the Cmax and AUC of extended-release metformin (metformin ER) by approximately 8% and 44%, respectively. According to the manufacturer of colesevelam, the clinical response to metformin ER should be monitored in patients receiving concomitant therapy. 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 has been found to have an effect on the bioavailability of glyburide, glipizide, and glimepiride. Administer these drugs at least 4 hours before colesevelam. Drug response 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<0.001). In patients taking metformin, serum triglyceride concentrations only increased by 5%. Similarly, in patients taking colesevelam for hyperlipidemia, serum triglyceride concentrations increased by 5%. Monitor patients for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 500 mg/dl or if hypertriglyceridemia-induced pancreatitis occurs.
    Cholecalciferol, Vitamin D3: (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.
    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.
    Chondroitin; Glucosamine: (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.
    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.
    Class III Antiarrhythmics: (Moderate) Colesevelam may decrease the absorption of oral antiarrhythmics. 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.
    Cod Liver Oil: (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.
    Co-Enzyme Q10, Ubiquinone: (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.
    Collagenase: (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.
    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) Colesevelam increases the Cmax and AUC of extended-release metformin (metformin ER) by approximately 8% and 44%, respectively. According to the manufacturer of colesevelam, the clinical response to metformin ER should be monitored in patients receiving concomitant therapy. 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.
    Desiccated Thyroid: (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 drugs with a narrow therapeutic index, such as liothyronine, at least 4 hours before colesevelam. There have been rare reports of elevated thyroid stimulating hormone (TSH) concentrations in patients who have received colesevelam coadministered with thyroid hormone replacement therapy.
    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.
    Diclofenac: (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.
    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.
    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) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    Empagliflozin; Metformin: (Moderate) Colesevelam increases the Cmax and AUC of extended-release metformin (metformin ER) by approximately 8% and 44%, respectively. According to the manufacturer of colesevelam, the clinical response to metformin ER should be monitored in patients receiving concomitant therapy. 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.
    Ergocalciferol, Vitamin D2: (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: (Moderate) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    Ethinyl Estradiol; Desogestrel: (Moderate) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Moderate) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    Ethinyl Estradiol; Etonogestrel: (Moderate) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    Ethinyl Estradiol; Levonorgestrel: (Moderate) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam. (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) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    Ethinyl Estradiol; Norethindrone: (Moderate) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    Ethinyl Estradiol; Norgestimate: (Moderate) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    Ethinyl Estradiol; Norgestrel: (Moderate) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    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.
    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 has been found to have an effect on the bioavailability of glyburide, glipizide, and glimepiride. Administer these drugs at least 4 hours before colesevelam. Drug response 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<0.001). In patients taking metformin, serum triglyceride concentrations only increased by 5%. Similarly, in patients taking colesevelam for hyperlipidemia, serum triglyceride concentrations increased by 5%. Monitor patients for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 500 mg/dl or if hypertriglyceridemia-induced pancreatitis occurs.
    Glimepiride; Pioglitazone: (Moderate) Colesevelam has been found to have an effect on the bioavailability of glyburide, glipizide, and glimepiride. Administer these drugs at least 4 hours before colesevelam. Drug response 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<0.001). In patients taking metformin, serum triglyceride concentrations only increased by 5%. Similarly, in patients taking colesevelam for hyperlipidemia, serum triglyceride concentrations increased by 5%. Monitor patients for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 500 mg/dl or if hypertriglyceridemia-induced pancreatitis occurs.
    Glimepiride; Rosiglitazone: (Moderate) Colesevelam has been found to have an effect on the bioavailability of glyburide, glipizide, and glimepiride. Administer these drugs at least 4 hours before colesevelam. Drug response 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<0.001). In patients taking metformin, serum triglyceride concentrations only increased by 5%. Similarly, in patients taking colesevelam for hyperlipidemia, serum triglyceride concentrations increased by 5%. Monitor patients for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 500 mg/dl or if hypertriglyceridemia-induced pancreatitis occurs.
    Glipizide: (Moderate) Colesevelam has been found to have an effect on the bioavailability of glyburide, glipizide, and glimepiride. Administer these drugs at least 4 hours before colesevelam. Drug response 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<0.001). In patients taking metformin, serum triglyceride concentrations only increased by 5%. Similarly, in patients taking colesevelam for hyperlipidemia, serum triglyceride concentrations increased by 5%. Monitor patients for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 500 mg/dl or if hypertriglyceridemia-induced pancreatitis occurs.
    Glipizide; Metformin: (Moderate) Colesevelam has been found to have an effect on the bioavailability of glyburide, glipizide, and glimepiride. Administer these drugs at least 4 hours before colesevelam. Drug response 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<0.001). In patients taking metformin, serum triglyceride concentrations only increased by 5%. Similarly, in patients taking colesevelam for hyperlipidemia, serum triglyceride concentrations increased by 5%. Monitor patients for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 500 mg/dl or if hypertriglyceridemia-induced pancreatitis occurs. (Moderate) Colesevelam increases the Cmax and AUC of extended-release metformin (metformin ER) by approximately 8% and 44%, respectively. According to the manufacturer of colesevelam, the clinical response to metformin ER should be monitored in patients receiving concomitant therapy. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Glyburide: (Moderate) Colesevelam has been found to have an effect on the bioavailability of glyburide, glipizide, and glimepiride. Administer these drugs at least 4 hours before colesevelam. Drug response 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<0.001). In patients taking metformin, serum triglyceride concentrations only increased by 5%. Similarly, in patients taking colesevelam for hyperlipidemia, serum triglyceride concentrations increased by 5%. Monitor patients for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 500 mg/dl or if hypertriglyceridemia-induced pancreatitis occurs.
    Glyburide; Metformin: (Moderate) Colesevelam has been found to have an effect on the bioavailability of glyburide, glipizide, and glimepiride. Administer these drugs at least 4 hours before colesevelam. Drug response 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<0.001). In patients taking metformin, serum triglyceride concentrations only increased by 5%. Similarly, in patients taking colesevelam for hyperlipidemia, serum triglyceride concentrations increased by 5%. Monitor patients for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 500 mg/dl or if hypertriglyceridemia-induced pancreatitis occurs. (Moderate) Colesevelam increases the Cmax and AUC of extended-release metformin (metformin ER) by approximately 8% and 44%, respectively. According to the manufacturer of colesevelam, the clinical response to metformin ER should be monitored in patients receiving concomitant therapy. 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.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Colesevelam decreases the Cmax and AUC of olmesartan by approximately 28% and 39%, respectively. Administer olmesartan at least 4 hours before colesevelam.
    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.
    Iron Salts: (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.
    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.
    Levomefolate; Mecobalamin; Pyridoxal-5-phosphate: (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.
    Levothyroxine: (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 drugs with a narrow therapeutic index, such as liothyronine, at least 4 hours before colesevelam. There have been rare reports of elevated thyroid stimulating hormone (TSH) concentrations in patients who have received colesevelam coadministered with thyroid hormone replacement therapy.
    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.
    Linagliptin; Metformin: (Moderate) Colesevelam increases the Cmax and AUC of extended-release metformin (metformin ER) by approximately 8% and 44%, respectively. According to the manufacturer of colesevelam, the clinical response to metformin ER should be monitored in patients receiving concomitant therapy. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Liothyronine: (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 drugs with a narrow therapeutic index, such as liothyronine, at least 4 hours before colesevelam. There have been rare reports of elevated thyroid stimulating hormone (TSH) concentrations in patients who have received colesevelam coadministered with thyroid hormone replacement therapy.
    Liotrix: (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 drugs with a narrow therapeutic index, such as liothyronine, at least 4 hours before colesevelam. There have been rare reports of elevated thyroid stimulating hormone (TSH) concentrations in patients who have received colesevelam coadministered with thyroid hormone replacement therapy.
    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.
    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) Colesevelam has been found to have an effect on the bioavailability of oral contraceptives containing ethinyl estradiol and norethindrone. Although not specifically studied, it may be prudent to administer all oral contraceptives at least 4 hours before colesevelam.
    Metformin: (Moderate) Colesevelam increases the Cmax and AUC of extended-release metformin (metformin ER) by approximately 8% and 44%, respectively. According to the manufacturer of colesevelam, the clinical response to metformin ER should be monitored in patients receiving concomitant therapy. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Metformin; Pioglitazone: (Moderate) Colesevelam increases the Cmax and AUC of extended-release metformin (metformin ER) by approximately 8% and 44%, respectively. According to the manufacturer of colesevelam, the clinical response to metformin ER should be monitored in patients receiving concomitant therapy. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Metformin; Repaglinide: (Moderate) Colesevelam increases the Cmax and AUC of extended-release metformin (metformin ER) by approximately 8% and 44%, respectively. According to the manufacturer of colesevelam, the clinical response to metformin ER should be monitored in patients receiving concomitant therapy. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Metformin; Rosiglitazone: (Moderate) Colesevelam increases the Cmax and AUC of extended-release metformin (metformin ER) by approximately 8% and 44%, respectively. According to the manufacturer of colesevelam, the clinical response to metformin ER should be monitored in patients receiving concomitant therapy. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Metformin; Saxagliptin: (Moderate) Colesevelam increases the Cmax and AUC of extended-release metformin (metformin ER) by approximately 8% and 44%, respectively. According to the manufacturer of colesevelam, the clinical response to metformin ER should be monitored in patients receiving concomitant therapy. Colesevelam has no significant effect on the bioavailability of immediate-release metformin.
    Metformin; Sitagliptin: (Moderate) Colesevelam increases the Cmax and AUC of extended-release metformin (metformin ER) by approximately 8% and 44%, respectively. According to the manufacturer of colesevelam, the clinical response to metformin ER should be monitored in patients receiving concomitant therapy. 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.
    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.
    Olmesartan: (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.
    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.
    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.
    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.
    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 has been found to have an effect on the bioavailability of glyburide, glipizide, and glimepiride. Administer these drugs at least 4 hours before colesevelam. Drug response 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<0.001). In patients taking metformin, serum triglyceride concentrations only increased by 5%. Similarly, in patients taking colesevelam for hyperlipidemia, serum triglyceride concentrations increased by 5%. Monitor patients for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 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) 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 drugs with a narrow therapeutic index, such as liothyronine, at least 4 hours before colesevelam. There have been rare reports of elevated thyroid stimulating hormone (TSH) concentrations in patients who have received colesevelam coadministered with thyroid hormone replacement therapy.
    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 has been found to have an effect on the bioavailability of glyburide, glipizide, and glimepiride. Administer these drugs at least 4 hours before colesevelam. Drug response 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<0.001). In patients taking metformin, serum triglyceride concentrations only increased by 5%. Similarly, in patients taking colesevelam for hyperlipidemia, serum triglyceride concentrations increased by 5%. Monitor patients for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 500 mg/dl or if hypertriglyceridemia-induced pancreatitis occurs.
    Tolbutamide: (Moderate) Colesevelam has been found to have an effect on the bioavailability of glyburide, glipizide, and glimepiride. Administer these drugs at least 4 hours before colesevelam. Drug response 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<0.001). In patients taking metformin, serum triglyceride concentrations only increased by 5%. Similarly, in patients taking colesevelam for hyperlipidemia, serum triglyceride concentrations increased by 5%. Monitor patients for an increase in triglyceride concentrations. Discontinue colesevelam if triglyceride concentrations are > 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 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 classified as FDA pregnancy category B. There are no adequate and well-controlled studies in pregnant women. 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. According to the manufacturer, colesevelam should be used during pregnancy only if clearly needed.

    According to the manufacturer, colesevelam hydrochloride is not expected to be excreted in human milk because the drug is not systemically absorbed ; for this reason, most experts consider nonabsorbable resins such as colesevelam the drugs of choice for breast-feeding mothers who require pharmacotherapy for cholesterol management. 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. 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 HbA1C in patients with type 2 diabetes is unknown.

    PHARMACOKINETICS

    Colesevelam is administered orally. Less than 0.05% of a dose is excreted renally. Colesevelam is not hydrolyzed by digestive enzymes.

    Oral Route

    Colesevelam is not significantly absorbed. In clinical trials, maximum therapeutic response was achieved within 2 weeks and was maintained during long-term therapy.