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  • CLASSES

    Bile Acid Sequestrants and Ion-exchange Resins

    DEA CLASS

    Rx

    DESCRIPTION

    Oral bile acid resin; used to treat hypercholesterolemia or pruritis secondary to cholestasis.

    COMMON BRAND NAMES

    Locholest, Locholest Light, Prevalite, Questran, Questran Light

    HOW SUPPLIED

    Cholestyramine/Locholest/Locholest Light/Prevalite/Questran/Questran Light Oral Pwd F/Recon: 4g

    DOSAGE & INDICATIONS

    For treatment of hypercholesterolemia, especially elevated LDL cholesterol (type IIa and IIb hyperlipoproteinemia), and for pruritus associated with biliary stasis.
    Oral dosage (dried cholestyramine resin)
    Adults

    Initially, 4 g PO given 1 to 2 times daily before meals. Adjust dosage to attain NCEP goals. Maintenance dosage range is 4 to 16 g/day PO given in 2 divided doses. The maximum antihyperlipidemic dosage is 24 g/day. The maximum recommended antipruritic dosage is 16 g/day.

    Adolescents

    8 g/day PO, given in 2 divided doses, before meals, has been shown to be safe and effective. The safety and effects of long-term administration in maintaining lowered cholesterol levels are unknown.

    Children

    One source recommends 80 mg/kg PO or 2.35 g/m2 PO, given 3 times per day before meals. Alternatively, initiate therapy with 2 to 4 g PO twice daily. Increase dosage gradually according to response and tolerance, up to 8 g/day PO. The safety and effects of long-term administration in maintaining lowered cholesterol levels are unknown.

    For the treatment of diarrhea†.
    For the adjunctive treatment of diarrhea† associated with excess fecal bile acids.
    Oral dosage
    Adults

    2 to 4 g PO 2 to 4 times daily. Cholestyramine is not effective in severe cases.

    For control of diarrhea† secondary to AIDS-associated enteropathy.
    Oral dosage
    Adults

    Although no published studies exist on the effectiveness of nonspecific antidiarrheal agents in treating AIDS-associated diarrhea, cholestyramine may be an effective alternative. Doses of 4 to 16 g/day PO have been recommended.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    24 g/day PO for hypercholesterolemia; 16 g/day PO for pruritus.

    Geriatric

    24 g/day PO for hypercholesterolemia; 16 g/day PO for pruritus.

    Adolescents

    8 g/day PO for hypercholesterolemia.

    Children

    8 g/day PO for hypercholesterolemia.

    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

     
    NOTE: In the treatment of hypercholesterolemia, patients receiving cholestyramine should also be placed on a standard cholesterol-lowering diet, and this diet should be continued throughout therapy. Serum lipoprotein concentrations should be determined periodically and dosage adjusted according to individual response and established treatment guidelines.
     
    NOTE: Dosage of cholestyramine is expressed in terms of dried resin: Each 5.5 g of Prevalite, 9 g of Questran, or 5 g of Questran Light contains about 4 g dried resin. Specifically, 1000 mg of Questran powder contains 444 mg dried resin; 1000 mg of Questran Light contains 800 mg dried resin; and 1000 mg of Prevalite contains 727 mg dried resin.

    Oral Administration
    Oral Liquid Formulations

    Administer as a suspension. To avoid esophageal irritation or blockage or intestinal blockage, do not administer as a dry powder.
    To minimize drug interactions, administer other drugs at least 1 hour before or at least 4—6 hours after each dose.
    Mix the dose in 60—180 mL of water, milk, fruit juice, or other noncarbonated beverage and stir until completely mixed. Palatability and compliance may be increased if the entire next day's dose is mixed in the evening and then refrigerated. Complaints of consistency may be minimized by mixing in a heavy or pulpy fruit juice. If a carbonated beverage is used, foaming may be minimized by mixing slowly in a large glass.
    Alternatively, the powder may be mixed with a highly fluid soup or a pulpy fruit with a high moisture content (i.e., applesauce or crushed pineapple).
    To minimize excessive swallowing of air, advise patients to avoid rapid ingestion of suspensions.

    STORAGE

    Locholest :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Locholest Light:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Prevalite :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Questran:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Questran Light:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Biliary cirrhosis, biliary obstruction, cholelithiasis

    Cholestyramine is contraindicated in patients with complete biliary obstruction where bile is not secreted into the intestine. In addition, because secretion of bile acids into the GI tract is impaired in patients with cholelithiasis, cholestyramine should be used cautiously in these patients. Cholestyramine should also be used cautiously in patients with primary biliary cirrhosis because it can further raise serum cholesterol.

    Hypertriglyceridemia

    Bile acid resins have been reported to increase serum triglyceride concentrations and should be used with caution in patients with hypertriglyceridemia. Bile acid resins such as cholestyramine are 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. Bile acid resins are also contraindicated in patients with dysbetalipoproteinemia.

    Constipation, dysphagia, GI obstruction, hemorrhoids, ileus

    Cholestyramine should be avoided 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 cholestyramine. The drug should also be used with caution in patients with dysphagia, swallowing disorders, severe gastrointestinal motility disorders (e.g., ileus), or major gastrointestinal tract surgery.

    Coagulopathy

    Because cholestyramine can bind with vitamin K, it is relatively contraindicated in patients with any preexisting coagulopathy (e.g., hemophilia).

    Phenylketonuria

    Cholestyramine Light products contain phenylalanine. Questran Light should not be used in patients with phenylketonuria.

    Hypothyroidism

    Because cholestyramine can bind with exogenous thyroid hormones if administered simultaneously, it is relatively contraindicated in patients with hypothyroidism.

    Renal disease

    Prolonged therapy with cholestyramine should be used with caution in patients with renal disease or renal failure because the cholestyramine resin releases chloride, which can increase the risk of developing hyperchloremic metabolic acidosis.

    Pregnancy

    Cholestyramine is classified as FDA pregnancy risk category C. Cholestyramine is not absorbed systemically and is therefore not expected to cause fetal harm during pregnancy. However, cholestyramine is 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. In general, cholestyramine should only be used for symptomatic relief of pruritus secondary to cholestasis in pregnancy; dyslipidemias should be controlled with diet. Monitor the patient's INR and supplement with vitamin K, if needed. In addition, other fat-soluble vitamins may need to be supplemented.

    Breast-feeding

    Cholestyramine is not systemically absorbed. It has no specific precautions for use in breast-feeding women. However, prolonged use of cholestyramine 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. 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

    There is limited data available on the use of cholestyramine in children. The effects of lowering cholesterol levels in children over the long-term have not been established.

    Geriatric

    The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities (LTCFs). According to OBRA, cholestyramine may reduce the absorption of certain other concurrent medications, such as diuretics, beta-blockers, corticosteroids, thyroid hormones, digoxin, valproic acid, NSAIDs, sulfonylureas, and warfarin; therefore, these medications should be administered 1 hour before or 4 hours after cholestyramine to avoid this interaction. In addition, cholestyramine may cause constipation, dyspepsia, nausea, vomiting, and abdominal pain.

    ADVERSE REACTIONS

    Severe

    GI obstruction / Delayed / 0-1.0
    night blindness / Delayed / 0-1.0
    peptic ulcer / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    uveitis / Delayed / Incidence not known

    Moderate

    osteoporosis / Delayed / 1.0-10.0
    cholelithiasis / Delayed / 0-1.0
    colic / Delayed / 0-1.0
    constipation / Delayed / 10.0
    dysphagia / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    prolonged bleeding time / Delayed / Incidence not known
    hypoprothrombinemia / Delayed / Incidence not known
    hyperchloremic acidosis / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    wheezing / Rapid / Incidence not known
    neuropathic pain / Delayed / Incidence not known
    hematuria / Delayed / Incidence not known
    dysuria / Early / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    edema / Delayed / Incidence not known
    folate deficiency / Delayed / Incidence not known

    Mild

    flatulence / Early / 1.0-10.0
    nausea / Early / 1.0-10.0
    vomiting / Early / 1.0-10.0
    eructation / Early / 1.0-10.0
    diarrhea / Early / 1.0-10.0
    steatorrhea / Delayed / 1.0-10.0
    anorexia / Delayed / 1.0-10.0
    abdominal pain / Early / 1.0-10.0
    hiccups / Early / Incidence not known
    weight loss / Delayed / Incidence not known
    stool discoloration / Delayed / Incidence not known
    weight gain / Delayed / Incidence not known
    dysgeusia / Early / Incidence not known
    dyspepsia / Early / Incidence not known
    ecchymosis / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    rash / Early / Incidence not known
    back pain / Delayed / Incidence not known
    skin irritation / Early / Incidence not known
    musculoskeletal pain / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    dizziness / Early / Incidence not known
    headache / Early / Incidence not known
    drowsiness / Early / Incidence not known
    vertigo / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    fatigue / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    syncope / Early / Incidence not known
    diuresis / Early / Incidence not known
    tooth discoloration / Delayed / Incidence not known
    dental caries / Delayed / Incidence not known
    libido increase / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Caffeine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Chlorpheniramine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Codeine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Dextromethorphan: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Diphenhydramine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Hydrocodone: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Oxycodone: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Pentazocine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Propoxyphene: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Acetaminophen; Pseudoephedrine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Alendronate; Cholecalciferol: (Moderate) Cholestyramine can decrease the intestinal absorption of fat and fat-soluble vitamins. If used concurrently, administration of the two agents should be staggered for the longest time interval possible.
    Alpha-glucosidase Inhibitors: (Moderate) It has been postulated that concomitant administration of acarbose or miglitol with cholestyramine may enhance the effects of acarbose. However, the clinical significance of such an interaction is unknown and co-use may also lead to an increased incidence of gastrointestinal side effects. Administer acarbose or miglitol at least 1 hour before or at least 4-6 hours after the administration of cholestyramine.
    Amiodarone: (Major) Cholestyramine can enhance amiodarone clearance presumably via reduced enterohepatic recirculation, thereby reducing amiodarone serum concentrations. This interaction between amiodarone and cholestyramine may be of benefit to temporarily reduce amiodarone serum concentrations prior to surgery and possibly limit the cardiac depressant effects of the drug in the immediate post-surgical period, although more data are needed before this recommendation can be made.
    Aspirin, ASA; Pravastatin: (Moderate) Administer pravastatin 1 hour before or 4 hours after a dose of cholestyramine if both agents are used together. Bile acid-sequestering agents, such as cholestyramine, have been shown to significantly reduce serum concentrations of pravastatin. Coadministration with cholestyramine decreases the AUC of pravastatin by about 40-50%.
    Atorvastatin; Ezetimibe: (Moderate) The oral absorption of ezetimibe may be decreased by the concomitant administration of the bile acid sequestrants, such as cholestyramine. 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.
    Bempedoic Acid; Ezetimibe: (Moderate) The oral absorption of ezetimibe may be decreased by the concomitant administration of the bile acid sequestrants, such as cholestyramine. 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.
    Benzhydrocodone; Acetaminophen: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Bexarotene: (Moderate) Cholestyramine can bind with and possibly decrease the oral absorption of bexarotene. To minimize drug interactions, administer other drugs at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Administer metronidazole at least 1 hour before or at least 4 to 6 hours after administration of cholestyramine. The oral bioavailability of metronidazole was reduced by 21% when given with cholestyramine.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Administer metronidazole at least 1 hour before or at least 4 to 6 hours after administration of cholestyramine. The oral bioavailability of metronidazole was reduced by 21% when given with cholestyramine.
    Bupivacaine; Meloxicam: (Minor) Pretreatment for four days with cholestyramine before IV meloxicam significantly increased the clearance of meloxicam by 50%. This interaction may occur via reduction of enterohepatic recycling of meloxicam in the gastrointestinal tract; the impact on oral dosing of meloxicam or overall clinical relevance is not established.
    Butalbital; Acetaminophen: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Calcifediol: (Moderate) Separate administration of calcifediol by 1 hour before or 4 hours after a cholestyramine dose to limit effects on oral absorption. Dose adjustment of calcifediol may be necessary during coadministration with cholestyramine. Additionally, serum 25-hydroxyvitamin D, intact PTH, and calcium concentrations should be closely monitored if a patient initiates or discontinues therapy with cholestyramine. Cholestyramine can decrease the intestinal absorption of fat-soluble vitamins like calcifediol.
    Calcitriol: (Moderate) Separate administration of calcitriol by 1 hour before or 4 hours after a cholestyramine dose to limit effects on oral absorption. Dose adjustment of calcitriol may be necessary during coadministration with cholestyramine. Additionally, serum 25-hydroxyvitamin D, intact PTH, and calcium concentrations should be closely monitored if a patient initiates or discontinues therapy with cholestyramine. Cholestyramine can decrease the intestinal absorption of fat-soluble vitamins like calcitriol.
    Calcium; Vitamin D: (Moderate) Cholestyramine can decrease the intestinal absorption of fat and fat-soluble vitamins. If used concurrently, administration of the two agents should be staggered for the longest time interval possible.
    Carbidopa; Levodopa; Entacapone: (Moderate) Entacapone should be given cautiously with drugs known to interfere with biliary excretion, glucuronidation, or intestinal beta-glucuronidation such as cholestyramine. Decreased biliary excretion of entacapone may occur if these agents are given concurrently.
    Cephalexin: (Minor) Caution may be warranted with coadministration of cephalexin and cholestyramine as cephalexin absorption may be decreased. In a study comparing patients receiving cephalexin alone with cephalexin plus cholestyramine, cephalexin mean and peak plasma concentrations were significantly reduced in patients with malabsorption syndromes.
    Chenodiol: (Moderate) Bile acid sequestrants, such as cholestyramine, 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 cholestyramine.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Minor) As with other nonsteroidal anti-inflammatory drugs (NSAIDs), the absorption of ibuprofen can be delayed if cholestyramine is concomitantly administered. Staggering the administration times may minimize this interaction.
    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.
    Cranberry, Vaccinium macrocarpon Ait.: (Moderate) Cholestyramine can decrease the intestinal absorption of fat and fat-soluble vitamins. If used concurrently, administration of the two agents should be staggered for the longest time interval possible.
    Deferasirox: (Major) The concomitant administration of deferasirox and cholestyramine may result in decreased systemic exposure to deferasirox. In healthy volunteers, the administration of cholesytramine after a single dose of deferasirox resulted in a 45% decrease in deferasirox exposure (AUC). Avoid the concomitant use of cholestyramine with deferasirox if possible. If cholestyramine and deferasirox coadministration is necessary, consider increasing the initial dose of deferasirox. Monitor serum ferritin levels and clinical responses for further dose modification.
    Dexamethasone: (Moderate) Cholestyramine may increase the clearance of corticosteroids.
    Diclofenac: (Moderate) Limited data suggest that cholestyramine can substantially reduce the bioavailability of diclofenac. In a randomized cross-over study, six healthy subjects took a single oral dose of diclofenac with water, cholestyramine (8 g), or colestipol (10 g). Diclofenac AUC was reduced by 62% or 33%, respectively, during coadministration with cholestyramine or colestipol. Although the clinical implications of this pharmacokinetic interaction are uncertain, clinicians should be alert to loss of antiinflammatory or analgesic effect with diclofenac. Staggering the administration times may prevent this interaction.
    Diclofenac; Misoprostol: (Moderate) Limited data suggest that cholestyramine can substantially reduce the bioavailability of diclofenac. In a randomized cross-over study, six healthy subjects took a single oral dose of diclofenac with water, cholestyramine (8 g), or colestipol (10 g). Diclofenac AUC was reduced by 62% or 33%, respectively, during coadministration with cholestyramine or colestipol. Although the clinical implications of this pharmacokinetic interaction are uncertain, clinicians should be alert to loss of antiinflammatory or analgesic effect with diclofenac. Staggering the administration times may prevent this interaction.
    Digoxin: (Moderate) Cholestyramine has been shown to significantly interfere with the absorption of digoxin. The administration of cholestyramine twice daily (8 hours before and after digoxin administration) or the use of digoxin solution may minimize this interaction. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of cholestyramine. Continue monitoring during concomitant treatment and increase the digoxin dose by 20-40% as necessary. Parenteral digoxin does not seem to interact with cholestyramine.
    Dihydrotachysterol: (Moderate) Cholestyramine can decrease the intestinal absorption of fat and fat-soluble vitamins including dihydrotachysterol. If used concurrently, administration of the two agents should be staggered for the longest time interval possible.
    Diphenhydramine; Ibuprofen: (Minor) As with other nonsteroidal anti-inflammatory drugs (NSAIDs), the absorption of ibuprofen can be delayed if cholestyramine is concomitantly administered. Staggering the administration times may minimize this interaction.
    Diphenhydramine; Naproxen: (Minor) The absorption of NSAIDs can be delayed if cholestyramine is concomitantly administered.
    Doxercalciferol: (Moderate) Administer doxercalciferol at least 1 hour before or 4 to 6 hours after taking cholestyramine. Cholestyramine can decrease the intestinal absorption of fat or fat soluble vitamins including vitamin D analogs, such as oral doxercalciferol.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) L-methylfolate and cholestyramine should be used together cautiously. Cholestyramine administration may decrease L-methylfolate plasma concentrations. Patients taking both drugs should take L-methylfolate 1 hour before or 4 to 6 hours after a dose of cholestyramine.
    Entacapone: (Moderate) Entacapone should be given cautiously with drugs known to interfere with biliary excretion, glucuronidation, or intestinal beta-glucuronidation such as cholestyramine. Decreased biliary excretion of entacapone may occur if these agents are given concurrently.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Major) L-methylfolate and cholestyramine should be used together cautiously. Cholestyramine administration may decrease L-methylfolate plasma concentrations. Patients taking both drugs should take L-methylfolate 1 hour before or 4 to 6 hours after a dose of cholestyramine. (Moderate) Chronic administration of cholestyramine may interfere with folic acid, vitamin B9 oral absorption. Patients receiving both drugs should take folic acid 1 hour before or 4 to 6 hours after a dose of cholestyramine.
    Ezetimibe: (Moderate) The oral absorption of ezetimibe may be decreased by the concomitant administration of the bile acid sequestrants, such as cholestyramine. 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.
    Ezetimibe; Simvastatin: (Moderate) The oral absorption of ezetimibe may be decreased by the concomitant administration of the bile acid sequestrants, such as cholestyramine. 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.
    Famotidine; Ibuprofen: (Minor) As with other nonsteroidal anti-inflammatory drugs (NSAIDs), the absorption of ibuprofen can be delayed if cholestyramine is concomitantly administered. Staggering the administration times may minimize this interaction.
    Fat soluble vitamins: (Moderate) Cholestyramine can decrease the intestinal absorption of fat and fat-soluble vitamins. If used concurrently, administration of the two agents should be staggered for the longest time interval possible.
    Fenofibrate: (Minor) Cholestyramine can potentially reduce the oral bioavailability of fenofibrate if these agents are administered together. Patients should take fenofibrate at least 1 hour before or 4 to 6 hours after a bile acid resin to avoid affecting the bioavailability of fenofibrate.
    Fenofibric Acid: (Moderate) Based on reported interactions with gemfibrozil, cholestyramine can potentially reduce the oral bioavailability of fenofibric acid if these agents are administered together. Although the presence of a drug interaction is uncertain, patients should take fenofibric acid at least 1 hour before or 4 to 6 hours after cholestyramine to avoid affecting the bioavailability of fenofibric acid.
    Ferric Maltol: (Moderate) Concurrent administration of cholestyramine and oral iron supplements may reduce the oral absorption of iron. To avoid any oral absorption interference, administration of other drugs is recommended 1 hour before or at least 4 to 6 hours after cholestyramine administration.
    Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Cholestyramine can decrease the intestinal absorption of fat and fat-soluble vitamins. If used concurrently, administration of the two agents should be staggered for the longest time interval possible.
    Fluvastatin: (Moderate) Concomitant administration of cholestyramine with fluvastatin (immediate-release capsules) significantly reduces fluvastatin serum concentrations (reduces AUC by 89%). Cholestyramine produces a complex with fluvastatin that is unavailable for absorption. However, administration of fluvastatin 4 hours after cholestyramine resulted in a clinically significant additive effect compared with that achieved with either component drug. If a patient is to receive both medications, administration times should be staggered by at least 4 hours to avoid impairing fluvastatin bioavailability.
    Folic Acid, Vitamin B9: (Moderate) Chronic administration of cholestyramine may interfere with folic acid, vitamin B9 oral absorption. Patients receiving both drugs should take folic acid 1 hour before or 4 to 6 hours after a dose of cholestyramine.
    Furosemide: (Moderate) In a study of 6 healthy volunteers, concurrent administration of cholestyramine with oral furosemide reduced the bioavailability of furosemide by 95% and reduced the diuretic response by 77%. Concomitant administration with colestipol reduced furosemide bioavailability by 80% and the diuretic response by 58%. The manufacturer of colestipol recommends administering other drugs at least 1 hour before or at least 4-6 hours after the administration of colestipol and that the interval between the administration of colestipol and other drugs should be as long as possible.
    Gemfibrozil: (Moderate) According to the manufacturer of gemfibrozil, the administration times of gemfibrozil and bile acid sequestrants should be separated by at least 2 hours. Coadministration with a bile acid resin resulted in a 30% reduction in gemfibrozil AUC; exposure to gemfibrozil was not significantly affected when the drugs were administed two hours apart.
    Glipizide: (Moderate) Cholestyramine has been shown to reduce the bioavailability of glipizide, but appears to have no effect on tolbutamide absorption. The effect of cholestyramine on the bioavailability of other oral sulfonylureas is unknown.
    Glipizide; Metformin: (Moderate) Cholestyramine has been shown to reduce the bioavailability of glipizide, but appears to have no effect on tolbutamide absorption. The effect of cholestyramine on the bioavailability of other oral sulfonylureas is unknown.
    Hydrocodone; Ibuprofen: (Minor) As with other nonsteroidal anti-inflammatory drugs (NSAIDs), the absorption of ibuprofen can be delayed if cholestyramine is concomitantly administered. Staggering the administration times may minimize this interaction.
    Hydrocortisone: (Moderate) Cholestyramine has been shown to bind to hydrocortisone. To minimize drug interactions, the manufacturer recommends to administer other drugs at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
    Ibuprofen: (Minor) As with other nonsteroidal anti-inflammatory drugs (NSAIDs), the absorption of ibuprofen can be delayed if cholestyramine is concomitantly administered. Staggering the administration times may minimize this interaction.
    Ibuprofen; Oxycodone: (Minor) As with other nonsteroidal anti-inflammatory drugs (NSAIDs), the absorption of ibuprofen can be delayed if cholestyramine is concomitantly administered. Staggering the administration times may minimize this interaction.
    Ibuprofen; Pseudoephedrine: (Minor) As with other nonsteroidal anti-inflammatory drugs (NSAIDs), the absorption of ibuprofen can be delayed if cholestyramine is concomitantly administered. Staggering the administration times may minimize this interaction.
    Imipramine: (Moderate) Cholestyramine has been shown to decrease the serum concentration of imipramine by 23% in six depressed patients; plasma concentrations of the desipramine metabolite were marginally decreased. Cholestyramine should be used with caution in patients stabilized on imipramine. It is not known if staggering the times of administration will minimize an interaction.
    Iron Salts: (Moderate) Concurrent administration of cholestyramine and oral iron supplements may reduce the oral absorption of iron. To avoid any oral absorption interference, administration of other drugs is recommended 1 hour before or at least 4 to 6 hours after cholestyramine administration.
    Iron: (Moderate) Concurrent administration of cholestyramine and oral iron supplements may reduce the oral absorption of iron. To avoid any oral absorption interference, administration of other drugs is recommended 1 hour before or at least 4 to 6 hours after cholestyramine administration.
    Isotretinoin: (Moderate) Cholestyramine can bind with and possibly decrease the oral absorption of isotretinoin. To minimize drug interactions, administer other drugs at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
    Lansoprazole; Naproxen: (Minor) The absorption of NSAIDs can be delayed if cholestyramine is concomitantly administered.
    Leflunomide: (Major) Cholestyramine can bind with leflunomide and enhance its clearance from the systemic circulation via intestinal trapping. Because the active metabolite of leflunomide, M1, has a prolonged half-life, staggering the administration times of each agent will not prevent this drug interaction. After 24 hours of cholestyramine administration, the levels of M1, the active metabolite of leflunomide, are reduced by approximately 40%. This effective means of 'gastrointestinal dialysis' has actually been used therapeutically in patients with leflunomide toxicity. Cholestyramine is the key agent in the drug elimination procedure for leflunomide.
    Levomefolate: (Major) L-methylfolate and cholestyramine should be used together cautiously. Cholestyramine administration may decrease L-methylfolate plasma concentrations. Patients taking both drugs should take L-methylfolate 1 hour before or 4 to 6 hours after a dose of cholestyramine.
    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.
    Loperamide: (Moderate) Cholestyramine may inhibit the effect of loperamide, which may be the result of binding in the GI tract. A causal relationship has not been established; however, loperamide should be administered at least 2 hours apart from cholestyramine until the significance of this interaction is known.
    Loperamide; Simethicone: (Moderate) Cholestyramine may inhibit the effect of loperamide, which may be the result of binding in the GI tract. A causal relationship has not been established; however, loperamide should be administered at least 2 hours apart from cholestyramine until the significance of this interaction is known.
    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.
    Meloxicam: (Minor) Pretreatment for four days with cholestyramine before IV meloxicam significantly increased the clearance of meloxicam by 50%. This interaction may occur via reduction of enterohepatic recycling of meloxicam in the gastrointestinal tract; the impact on oral dosing of meloxicam or overall clinical relevance is not established.
    Methotrexate: (Major) The bile-acid sequestrant cholestyramine is well-known to cause drug interactions by binding and decreasing the oral administration of many drugs. Cholestyramine enhances the clearance of methotrexate from the systemic circulation. This interaction has been used therapeutically in patients with methotrexate toxicity. To minimize drug interactions, administer other drugs at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
    Methylprednisolone: (Moderate) The absorption of oral corticosteroids, such as methylprednisolone, may be reduced during concurrent administration with cholestyramine. In a study of 10 healthy subjects, reductions in plasma cortisol concentrations and delays in peak concentrations were observed when cholestyramine 4 g was given prior to a single dose of another corticosteroid. When given with cholestyramine, the AUC of the corticosteroid decreased by approximately one-third and time to peak plasma cortisol concentrations was reached 50 +/- 22 minutes later than controls. It is recommended that other drugs be taken at least 1 hour before or 4 to 6 hours after cholestyramine (or as great an interval as possible) to avoid absorption interference.
    Metronidazole: (Moderate) Administer metronidazole at least 1 hour before or at least 4 to 6 hours after administration of cholestyramine. The oral bioavailability of metronidazole was reduced by 21% when given with cholestyramine.
    Mycophenolate: (Major) Avoid administration of mycophenolate mofetil with cholestyramine. Coadministration of mycophenolate mofetil with cholestyramine decreases the bioavailability of mycophenolate mofetil. Cholestyramine decreases the AUC of mycophenolate by about 40%.
    Naproxen: (Minor) The absorption of NSAIDs can be delayed if cholestyramine is concomitantly administered.
    Naproxen; Esomeprazole: (Minor) The absorption of NSAIDs can be delayed if cholestyramine is concomitantly administered.
    Naproxen; Pseudoephedrine: (Minor) The absorption of NSAIDs can be delayed if cholestyramine is concomitantly administered.
    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) Concurrent administration of cholestyramine and oral iron supplements may reduce the oral absorption of iron. To avoid any oral absorption interference, administration of other drugs is recommended 1 hour before or at least 4 to 6 hours after cholestyramine administration.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Concurrent administration of cholestyramine and oral iron supplements may reduce the oral absorption of iron. To avoid any oral absorption interference, administration of other drugs is recommended 1 hour before or at least 4 to 6 hours after cholestyramine administration.
    Obeticholic Acid: (Moderate) Bile acid binding resins such as cholestyramine 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.
    Paricalcitol: (Moderate) Cholestyramine can decrease the intestinal absorption of fat soluble vitamins including vitamin D analogs, such as oral paricalcitol. If a patient must receive treatment with both of these drugs, separate administration of paricalcitol by 1 hour before or 4 to 6 hours after a cholestyramine dose to help limit absorption interactions.
    Penicillin G Benzathine: (Moderate) Cholestyramine can bind with and possibly decrease the oral absorption of penicillin G. To minimize drug interactions, administer penicillin at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
    Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Cholestyramine can bind with and possibly decrease the oral absorption of penicillin G. To minimize drug interactions, administer penicillin at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
    Penicillin G Procaine: (Moderate) Cholestyramine can bind with and possibly decrease the oral absorption of penicillin G. To minimize drug interactions, administer penicillin at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
    Penicillin G: (Moderate) Cholestyramine can bind with and possibly decrease the oral absorption of penicillin G. To minimize drug interactions, administer penicillin at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
    Phytonadione, Vitamin K1: (Moderate) Cholestyramine can decrease the intestinal absorption of fat and fat-soluble vitamins. If used concurrently, administration of the two agents should be staggered for the longest time interval possible.
    Piroxicam: (Moderate) Cholestyramine has been shown to enhance the oral clearance and decrease the half-life of piroxicam. The clinical implications of this pharmacokinetic interaction are uncertain. To minimize this interaction, it is prudent to administer piroxicam at least 2 hours before or 6 hours after cholestyramine.
    Polysaccharide-Iron Complex: (Moderate) Concurrent administration of cholestyramine and oral iron supplements may reduce the oral absorption of iron. To avoid any oral absorption interference, administration of other drugs is recommended 1 hour before or at least 4 to 6 hours after cholestyramine administration.
    Pravastatin: (Moderate) Administer pravastatin 1 hour before or 4 hours after a dose of cholestyramine if both agents are used together. Bile acid-sequestering agents, such as cholestyramine, have been shown to significantly reduce serum concentrations of pravastatin. Coadministration with cholestyramine decreases the AUC of pravastatin by about 40-50%.
    Prednisone: (Moderate) Cholestyramine may increase the clearance of corticosteroids, such as prednisone.
    Propranolol: (Moderate) Absorption of propranolol may be reduced by concurrent administration with colestipol or cholestyramine. To minimize drug interactions, administer other drugs at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Absorption of propranolol may be reduced by concurrent administration with colestipol or cholestyramine. To minimize drug interactions, administer other drugs at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
    Raloxifene: (Moderate) A single dose of cholestyramine causes a 60% reduction in the absorption and enterohepatic cycling of raloxifene. The coadministration of cholestyramine and raloxifene is not recommended.
    Rosuvastatin; Ezetimibe: (Moderate) The oral absorption of ezetimibe may be decreased by the concomitant administration of the bile acid sequestrants, such as cholestyramine. 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.
    Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Concurrent administration of cholestyramine and oral iron supplements may reduce the oral absorption of iron. To avoid any oral absorption interference, administration of other drugs is recommended 1 hour before or at least 4 to 6 hours after cholestyramine administration.
    Spironolactone: (Moderate) Use caution if spironolactone is administered concurrently with cholestyramine. Hyperkalemic metabolic acidosis has been reported in patients given spironolactone concurrently with cholestyramine.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Use caution if spironolactone is administered concurrently with cholestyramine. Hyperkalemic metabolic acidosis has been reported in patients given spironolactone concurrently with cholestyramine.
    Sulfinpyrazone: (Moderate) Cholestyramine can bind with and possibly delay the absorption of sulfinpyrazone. It is recommended that sulfinpyrazone be administered at least 1 hour before or 4 to 6 hours after cholestyramine.
    Sumatriptan; Naproxen: (Minor) The absorption of NSAIDs can be delayed if cholestyramine is concomitantly administered.
    Teriflunomide: (Major) Cholestyramine can bind with teriflunomide and enhance its clearance from the systemic circulation via intestinal trapping. Because teriflunomide has a prolonged half-life, staggering the administration times of each agent will not prevent this drug interaction. After 11 days of cholestyramine administration, teriflunomide concentrations are reduced by approximately 98%. Cholestyramine is used to facilitate teriflunomide elmination from the body when clinically necessary.
    Tetracyclines: (Major) Colestipol has been shown to reduce tetracycline absorption by roughly 50%. It is likely this is enough to cause a clinically significant effect. Although no data are available for other tetracyclines, or for cholestyramine, it should be assumed that any tetracycline antibiotic may be affected similarly by either cholestyramine or colestipol. Staggering oral doses of each agent is recommended to minimize this pharmacokinetic interaction. To minimize drug interactions, administer tetracyclines at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine. Since doxycycline undergoes enterohepatic recirculation, it may be even more susceptible to this drug interaction than the other tetracyclines.
    Thiazide diuretics: (Moderate) Cholestyramine, an ion exchange resin, binds hydrochlorothiazide and reduces its absorption from the gastrointestinal tract by up to 85% when co-administered as single doses. Although the manufacturer for Questran recommends that other medicines be taken at least 1 hour before or 4-6 hours after cholestyramine, it has been recommended that thiazides be administered at least 4 hours before or after cholestyramine to minimize the reduction in absorption. By administering hydrochlorothiazide at least 4 hours before cholestyramine, the decrease in absorption of hydrochlorothiazide is approximately 30-35%.
    Thyroid hormones: (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of cholestyramine. Cholestyramine 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.
    Tinidazole: (Moderate) Administer tinidazole at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine. Separate dosing of cholestyramine and tinidazole to minimize any potential effect on the bioavailability of tinidazole. Cholestyramine was shown to decrease the bioavailability of another nitroimidazole by 21%.
    Torsemide: (Minor) Cholestyramine inhibits the oral bioavailability of torsemide. Simultaneous use of torsemide and cholestyramine is not recommended. Stagger the administration times of cholestyramine and oral torsemide by several hours to avoid the possibility of this interaction.
    Tramadol; Acetaminophen: (Moderate) Cholestyramine has been shown to decrease the absorption of acetaminophen by roughly 60%. Experts have recommended that cholestyramine not be given within 1 hour of acetaminophen if analgesic or antipyretic effect is to be achieved.
    Tretinoin, ATRA: (Moderate) Cholestyramine can bind with and possibly decrease the oral absorption of tretinoin. To minimize drug interactions, administer other drugs at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
    Ursodeoxycholic Acid, Ursodiol: (Moderate) Cholestyramine 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 to 6 hours after the bile acid sequestering agents.
    Valproic Acid, Divalproex Sodium: (Major) One small study in 6 healthy volunteers suggested that cholestyramine can impair the oral bioavailability of valproic acid, divalproex sodium. Concurrent administration reduced valproic acid plasma concentrations by a mean of 14%, however, intersubject variability was large. Separating the dosing of valproic acid, divalproex sodium and cholestyramine by 3 hours may lessen the interaction.
    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 1 hour before or 4 to 6 hours after cholestyramine (or as great an interval as possible). Cholestyramine can bind other drugs, such as oral vancomycin, when given concurrently.
    Vitamin A: (Moderate) Cholestyramine can decrease the intestinal absorption of fat and fat-soluble vitamins. If used concurrently, administration of the two agents should be staggered for the longest time interval possible.
    Vitamin D: (Moderate) Cholestyramine can decrease the intestinal absorption of fat and fat-soluble vitamins. If used concurrently, administration of the two agents should be staggered for the longest time interval possible.
    Vitamin E: (Moderate) Cholestyramine can decrease the intestinal absorption of fat and fat-soluble vitamins. If used concurrently, administration of the two agents should be staggered for the longest time interval possible.
    Warfarin: (Major) Cholestyramine can either increase or decrease the hypoprothrombinemic actions of warfarin. Cholestyramine can bind with vitamin K in the diet, impairing vitamin K absorption, which, in turn, may increase warfarin's hypoprothrombinemic effect. Conversely, cholestyramine can bind with warfarin directly and impair warfarin bioavailability. To prevent altering warfarin pharmacokinetics, doses of warfarin and cholestyramine should be staggered by at least 4 to 6 hours. Cholestyramine should be prescribed cautiously to any patient receiving warfarin since cholestyramine may enhance systemic warfarin clearance.

    PREGNANCY AND LACTATION

    Pregnancy

    Cholestyramine is classified as FDA pregnancy risk category C. Cholestyramine is not absorbed systemically and is therefore not expected to cause fetal harm during pregnancy. However, cholestyramine is 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. In general, cholestyramine should only be used for symptomatic relief of pruritus secondary to cholestasis in pregnancy; dyslipidemias should be controlled with diet. Monitor the patient's INR and supplement with vitamin K, if needed. In addition, other fat-soluble vitamins may need to be supplemented.

    Cholestyramine is not systemically absorbed. It has no specific precautions for use in breast-feeding women. However, prolonged use of cholestyramine 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. 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

    Cholestyramine resin releases chloride and combines with bile acids in the intestine to form insoluble, nonabsorbable complexes that are excreted in the feces along with unchanged resin. Bile acids undergo enterohepatic circulation. Since cholesterol is the precursor of bile acids, interference with reuptake of bile acids actually stimulates cholesterol synthesis via an increase in the activity of HMG-CoA reductase. Plasma cholesterol levels do not rise, however, since the newly formed cholesterol is shunted into the bile acid-synthesis pathway. In addition, the hepatocyte responds to this change in plasma cholesterol by intensifying uptake of low-density lipoprotein (LDL) cholesterol, thereby decreasing plasma cholesterol. Plasma cholesterol and LDL concentrations fall in patients with primary type II hyperlipoproteinemia. Plasma cholesterol concentrations decrease by 20—50% when these patients receive 12—32 g of cholestyramine resin daily.

    PHARMACOKINETICS

    Since cholestyramine is not absorbed orally, serum concentrations and half-life parameters do not apply. Reduction of plasma cholesterol usually is seen within the first month of therapy and returns to pretreatment levels within 1 month of discontinuation. Relief of pruritus associated with biliary stasis usually takes 1—3 weeks.