Cholestyramine resin - a bile-acid binding resin.

Cholestyramine is an insoluble bile acid binding resin that inhibits the absorption of the bile acid-bound low-density lipoprotein complex resulting in its excretion. It is used to treat the following conditions:

  • As an adjunct to statins in the management of primary hypercholesterolemia and regression of arteriolosclerosis.
  • For the treatment of pruritus associated with cholestasis, as a result of partial biliary obstruction.

Off-Label Uses of cholestyramine in Adults include:

    • Chronic diarrhea resulting from the malabsorption of bile acids.
    • TO enhance the elimination of digoxin (in non-life threatening toxicity)
    • As adjunctive therapy in Graves disease.

Adult dose:

Cholestyramine Dosage:

Cholestyramine dose in dyslipidemia (in patients not achieving the target lipids with the maximally tolerated dose of statins and ezetimibe):

  • 4 gms orally once or twice daily.
  • The dose may be increased gradually to the usual maintenance dose of 8 - 16 gms/day and the maximum dose of 24 gms/day.

Off-label use in the treatment of chronic diarrhea due to bile acid malabsorption:

    • 4 gms once a day.
    • The dose may be increased by 4 gms weekly to the maximum dose of 36 gms/day in 1 - 4 divided doses.

Off-label use in the adjunctive therapy of Hyperthyroidism due to Graves disease:

    •  4 gms twice or thrice daily in combination with beta-blockers and anti-thyroid drugs.

Pruritus associated with cholestasis:

    • 4 gms once or twice a day.
    • The dose may be increased to 16 gms per day in two divided doses.

Dose in children:

Cholestyramine dose in Diaper dermatitis:

  • Infants and Children:

    • Prepare a 5% - 10% as a topical paste or an ointment in aquaphor, polyethylene glycol, or petrolatum and apply to the affected area with each diaper change.

Dose in Dyslipidemia:

  • Children older than 6 years and Adolescents:
    • 2 - 4 gms/day for one week to a maximum dose of 8 gms per day.
  • Children and Adolescents:
    • 240 mg/kg/day orally in three divided doses to the maximum daily dose of 8 gms/day.

Pruritus secondary to cholestasis:

  • Children less than 10 years:
    • 240 mg/kg/day in two or three divided doses administered after meals to a maximum daily dose of 4 g/day.
  • Children older than 10 years and Adolescents:
    • 240 mg/kg/day orally to a maximum daily dose of 8 g/day.

Diarrhea secondary to intestinal failure and short-bowel syndrome:

  • Children and Adolescents:
    • 240 mg/kg/day in three divided doses to a maximum daily dose of 8 gms/day.

 

Pregnancy Risk Factor C

  • It may be used in pregnant patients when required.
  • Lipid profile should be monitored during therapy.
  • Pregnant patients should also be given supplemental vitamin K.

Cholestyramine resin use during breastfeeding:

  • Since it is not systemically absorbed, it does not affect the breastfeeding infant. However, it may result in vitamins deficiency in the mother that may require supplementation.

 

Dose in Renal disease:

The manufacturer has not recommended any dose adjustment, however, it should be used with caution in patients with renal impairment. It may also cause hyperchloremic metabolic acidosis, especially in children.

Dose in liiver disease:

Dose adjustment is not necessary as it is not absorbed from the gastrointestinal tract.

Side effects:

Cholestyramine Side effects:

  • Cardiovascular:
    • Edema
    • Syncope
  • Central nervous system:
    • Anxiety
    • Dizziness
    • Drowsiness
    • Fatigue
    • Headache
    • Neuralgia
    • Paresthesia
    • Vertigo
  • Dermatologic:
    • Perianal skin irritation
    • Skin irritation
    • Skin rash
    • Urticaria
  • Endocrine & metabolic:
    • Hyperchloremic metabolic acidosis
    • Increased libido
    • Weight gain
    • Weight loss
  • Gastrointestinal:
    • Abdominal pain
    • Anorexia
    • Biliary colic
    • Constipation
    • Dental bleeding
    • Dental caries
    • Dental discoloration
    • Diarrhea
    • Diverticulitis
    • Duodenal ulcer with hemorrhage
    • Dysgeusia
    • Dysphagia
    • Eructation
    • Flatulence
    • Gallbladder calcification
    • Gastric ulcer
    • Gastrointestinal hemorrhage
    • Hemorrhoidal bleeding
    • Hiccups
    • Intestinal obstruction
    • Melena
    • Nausea
    • Pancreatitis
    • Rectal pain
    • Steatorrhea
    • Tongue irritation
    • Dental erosioin
    • Vomiting
  • Genitourinary:
    • Diuresis
    • Dysuria
    • Hematuria
  • Hematologic & oncologic:
    • Adenopathy
    • Anemia
    • Bruise
    • Hemorrhage
    • Hypoprothrombinemia
    • Prolonged prothrombin time
    • Rectal hemorrhage
  • Hepatic:
    • Abnormal hepatic function tests
  • Neuromuscular & skeletal:
    • Arthralgia
    • Arthritis
    • Back pain
    • Myalgia
    • Osteoporosis
  • Ophthalmic:
    • Nocturnal amblyopia
    • Uveitis
  • Otic:
    • Tinnitus
  • Respiratory:
    • Asthma
    • Dyspnea
    • Wheezing

 

Contraindication to cholestyramine resin include:

  • Allergic reactions to the drug or any component of the formulation
  • Biliary obstruction

Warnings & Precautions

  • Bleeding:
    • Prolonged therapy may result in vitamin K deficiency. This can cause bleeding problems.
    • Vitamin K supplementation may be necessary.
  • Constipation:
    • It should be initiated in a low dose as it may cause constipation and worsen hemorrhoids.
  • Hypertriglyceridemia:
    • Cholestyramine should be avoided in patients with a baseline fasting triglyceride levels of more than 300 mg/dL or type III hyperlipoproteinemia as severe triglyceride elevations may occur.
    • Patients with triglyceride levels 250 - 299 mg/dL should use it with caution and get the levels rechecked after 4 - 6 weeks of therapy.
    • Treatment should be discontinued if the triglyceride levels are more than 400 mg/dl.
  • Renal impairment:
    • Patients with renal impairment should use the drug with caution.

 

Cholestyramine resin: Drug Interaction

Note: Drug Interaction Categories:

  • Risk Factor C: Monitor When Using Combination
  • Risk Factor D: Consider Treatment Modification
  • Risk Factor X: Avoid Concomitant Use
    •  

    Risk Factor C (Monitor therapy)

    Cardiac Glycosides Bile Acid Sequestrants may decrease the absorption of Cardiac Glycosides.
    Corticosteroids (Oral) Bile Acid Sequestrants may decrease the absorption of Corticosteroids (Oral).
    Methotrexate Bile Acid Sequestrants may decrease the absorption of Methotrexate.
    Methylfolate Cholestyramine Resin may decrease the serum concentration of Methylfolate.
    Propranolol Bile Acid Sequestrants may decrease the serum concentration of Propranolol.
    Spironolactone Cholestyramine Resin may enhance the adverse/toxic effect of Spironolactone. Specifically, the risks of developing metabolic acidosis and hyperkalemia may be elevated with this combination.
    Vitamin K Antagonists (eg, warfarin) Bile Acid Sequestrants may decrease the absorption of Vitamin K Antagonists.

    Risk Factor D (Consider therapy modification)

    Amiodarone Bile Acid Sequestrants may decrease the bioavailability of Amiodarone.
    Chenodiol Bile Acid Sequestrants may decrease the serum concentration of Chenodiol. Management: Administration of chenodiol 5 hours or more after bile acid sequestrants may reduce chenodiol adsorption in the gastrointestinal tract. Monitor for decreased therapeutic effects of chenodiol in patients receiving bile acid sequestrants.
    Cholic Acid Bile Acid Sequestrants may decrease the absorption of Cholic Acid. Management: Administer cholic acid at least 1 to 4 hours before or 4 to 6 hours after administration of any bile acid-binding products to minimize the potential for a significant interaction.
    Deferasirox Bile Acid Sequestrants may decrease the serum concentration of Deferasirox. Management: Avoid combination when possible; if the combination must be used, consider a 50% increase in initial deferasirox dose, with monitoring of serum ferritin concentrations and clinical responses to guide further dosing.
    Estrogen Derivatives (Contraceptive) Bile Acid Sequestrants may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Administer estrogen-based oral contraceptives at least 1 to 4 hours prior to or 4 to 6 hours after administration of a bile acid sequestrant.
    Ezetimibe Bile Acid Sequestrants may decrease the absorption of Ezetimibe. Management: Administer ezetimibe at least 2 hours before or 4 hours after any bile acid sequestrant.
    Fibric Acid Derivatives Bile Acid Sequestrants may decrease the absorption of Fibric Acid Derivatives. Management: Separate doses by at least 2 hours to minimize this interaction; fenofibric acid labeling recommends administration one hour prior to or 4-6 hours after a bile acid sequestrant.
    Fluvastatin Cholestyramine Resin may decrease the serum concentration of Fluvastatin. Management: Administer fluvastatin at least 1 hour or greater (particularly with extended-releaseform) before, or at least 4 hours after cholestyramine to minimize the risk for any significant interaction.
    Leflunomide Bile Acid Sequestrants may decrease serum concentrations of the active metabolite(s) of Leflunomide. Management: Unless using this combination to intentionally enhance leflunomide elimination, consider an alternative to the bile acid sequestrants when possible. Separating drug administration is not likely to be effective at avoiding this interaction.
    Lomitapide Bile Acid Sequestrants may decrease the absorption of Lomitapide. Management: Administer lomitapide at least 4 hours before or after administration of a bile acid sequestrant.
    Loop Diuretics Bile Acid Sequestrants may decrease the absorption of Loop Diuretics.
    Multivitamins/Fluoride (with ADE) Bile Acid Sequestrants may decrease the serum concentration of Multivitamins/Fluoride (with ADE). Management: Avoid concomitant administration of multivitamins and bile acid sequestrants (eg, cholestyramine). Separate administration of these agents by several hours to minimize the risk of an interaction.
    Multivitamins/Minerals (with ADEK, Folate, Iron) Bile Acid Sequestrants may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, bile acid sequestrants may impair the absorption of fat-soluble vitamins. Management: Avoid concomitant administration of multivitamins and bile acid sequestrants (eg, cholestyramine). Separate administration of these agents by several hours to minimize the risk of an interaction.
    Multivitamins/Minerals (with AE, No Iron) Bile Acid Sequestrants may decrease the serum concentration of Multivitamins/Minerals (with AE, No Iron). Management: Avoid concomitant administration of multivitamins and bile acid sequestrants (e.g., cholestyramine). Separate administration of these agents by several hours to minimize the risk of an interaction.
    Niacin Bile Acid Sequestrants may decrease the absorption of Niacin.
    Nonsteroidal Anti-Inflammatory Agents Bile Acid Sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents.
    Obeticholic Acid Bile Acid Sequestrants may decrease the serum concentration of Obeticholic Acid. Management: Administer obeticholic acid at least 4 hours before or at least 4 hours after the administration of bile acid sequestrants.
    PHENobarbital Cholestyramine Resin may decrease the serum concentration of PHENobarbital. Management: Administer phenobarbital at least 1 hour before or 4-6 hours after administration of cholestyramine in order to minimize the risk for any significant interaction.
    Pravastatin Bile Acid Sequestrants may decrease the serum concentration of Pravastatin. Management: Administer pravastatin at least 1 hour before or 4 hours after administration of bile-acid resins (eg, cholestyramine, colestipol, colesevelam) to minimize the risk for any significant interaction.
    Progestins (Contraceptive) Bile Acid Sequestrants may decrease the serum concentration of Progestins (Contraceptive). Management: Administer oral progestin-containing contraceptives at least 1 to 4 hours prior to or 4 to 6 hours after administration of a bile acid sequestrant.
    Raloxifene Bile Acid Sequestrants may decrease the absorption of Raloxifene.
    Rosiglitazone Cholestyramine Resin may decrease the serum concentration of Rosiglitazone. Management: Administer rosiglitazone at least 2 hours prior to cholestyramine in order to minimize the likelihood of an interaction, and monitor patients closely for evidence of reduced rosiglitazone effectiveness.
    Sincalide Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction.
    Teriflunomide Bile Acid Sequestrants may decrease the serum concentration of Teriflunomide. Management: Unless using this combination to intentionally enhance teriflunomide elimination, consider an alternative to the bile acid sequestrants when possible. Separating drug administration is unlikely to be effective at avoiding the interaction.
    Tetracyclines Bile Acid Sequestrants may decrease the absorption of Tetracyclines. Exceptions: Eravacycline.
    Thiazide and Thiazide-Like Diuretics Bile Acid Sequestrants may decrease the absorption of Thiazide and Thiazide-Like Diuretics. The diuretic response is likewise decreased.
    Thyroid Products Bile Acid Sequestrants may decrease the serum concentration of Thyroid Products. Management: Administer oral thyroid products at least 4 h prior to colesevelam, and at least 1 h before or 4-6 h after cholestyramine. Specific recommendations for colestipol are not available. Monitor for decreased concentrations/effects of the thyroid product.
    Ursodiol Bile Acid Sequestrants may decrease the serum concentration of Ursodiol. Management: Administer ursodiol 2 to 4 hours before or at least 2 to 5 hours after bile acid sequestrants to minimize the potential for any significant interaction. Monitor for decreased therapeutic effects of ursodiol in patients receiving bile acid sequestrants.
    Valproic Acid and Derivatives Cholestyramine Resin may decrease the serum concentration of Valproic Acid and Derivatives. Management: Separate administration of valproic acid and cholestyramine by at least 3 hours whenever possible in order to minimize the potential for a significant interaction.
    Vancomycin Bile Acid Sequestrants may diminish the therapeutic effect of Vancomycin. Management: Avoid concurrent administration of oral vancomycin and bile acid sequestrants when possible. If use of both agents is necessary, consider separating doses by at least 2 hours to minimize the significance of the interaction.
    Vitamin D Analogs Bile Acid Sequestrants may decrease the serum concentration of Vitamin D Analogs. More specifically, bile acid sequestrants may impair absorption of Vitamin D Analogs.Management: Avoid concomitant administration of vitamin D analogs and bile acid sequestrants (eg, cholestyramine). Separate administration of these agents by several hours to minimize the potential risk of interaction. Monitor plasma calcium concentrations. Exceptions: Calcipotriene; Calcitriol (Topical); Tacalcitol.

    Risk Factor X (Avoid combination)

    Mycophenolate Cholestyramine Resin may decrease the serum concentration of Mycophenolate.

Monitoring parameters:

Lipid profile should be checked prior to starting therapy, 4 - 12 weeks after its initiation, and at 3 - 12 months intervals therafter. 

 

How to administer cholestyramine resin?

It is administered as an oral suspension when prepared. The powder should not be ingested directly, snipped, or held in the mouth for a prolonged period of time (as it may result in tooth decay and discoloration).

It should be administered with meals twice daily.

 

Mechanism of action of cholestyramine resin:

It increases the excretion of bile salts via feces by inhibiting its reuptake. It forms a nonabsorbable complex with bile acids in the intestine thereby increases the excretion of bile salt-bound low-density lipoprotein cholesterol. The peak effect of cholestyramine is seen in about three weeks. It is not absorbed when ingested orally and is excreted via feces as an insoluble complex with bile acids.

 

Cholestyramine International Brand Names:

  • Cholestyramine-ODAN
  • DOM-Cholestyramine
  • NOVO-Cholamine
  • Novo-Cholestyramine Light
  • Olestyr
  • Olestyr Light
  • Choles
  • Cholestran
  • Colestiramina
  • Colestrol
  • Efensol
  • Kolestran
  • Lipramina
  • Olipo
  • Quantalan
  • Quantalan
  • Zuckerfrei
  • Quantanash
  • Questran
  • Questran Light
  • Questran Lite
  • Questran Loc
  • Resincolestiramina
  • Semide
  • Sequest
  • Vasosan P-Granulat
  • Vasosan S-Granulat

 

Cholestyramine brands in Pakistan:

Questran sachet (4.0 gms per sachet) - Bristol-Myers Squibb

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