What are the contraindications for Questran (cholestyramine) in patients with gastrointestinal disorders or those taking other medications like warfarin, digoxin, or thyroid hormones?

Contraindications for Questran (Cholestyramine)

Questran is absolutely contraindicated in patients with complete biliary obstruction and in those with a history of serious hypersensitivity to any component of the medication. 1

Absolute Contraindications

Complete Biliary Obstruction

• Cholestyramine cannot work when bile is not secreted into the intestine, making it both ineffective and contraindicated in complete biliary obstruction. 1
• This is the primary FDA-labeled contraindication based on the drug's mechanism of action—it requires bile acids in the intestinal lumen to bind and sequester. 1

Hypersensitivity

• Any documented serious hypersensitivity reaction to cholestyramine or its components is an absolute contraindication. 2, 1

Critical Precautions and Relative Contraindications

Gastrointestinal Disorders

Bowel Obstruction Risk

• Avoid cholestyramine in patients with gastroparesis, other GI motility disorders, or history of major GI tract surgery with risk for bowel obstruction, as it can cause or worsen GI obstruction. 2
• The medication can produce or severely worsen preexisting constipation and may lead to fecal impaction. 1
• In patients with symptomatic coronary artery disease, particular effort must be made to avoid constipation, as straining can precipitate cardiac events. 1

Hypertriglyceridemia

• Cholestyramine is contraindicated when triglycerides exceed 500 mg/dL due to risk of hypertriglyceridemia-induced pancreatitis. 2
• The drug may increase triglyceride levels, requiring baseline and periodic monitoring. 2, 1

Medication Interactions Requiring Extreme Caution

Warfarin

• Cholestyramine significantly increases bleeding risk in patients on warfarin through two mechanisms: direct binding that reduces warfarin absorption and vitamin K deficiency from fat-soluble vitamin malabsorption. 2, 1
• Warfarin must be taken at least 1 hour before or 4-6 hours after cholestyramine, with frequent INR monitoring during initiation and periodically thereafter. 2, 3, 1
• Chronic cholestyramine use causes hypoprothrombinemia from vitamin K deficiency, which usually responds to parenteral vitamin K₁. 1

Digoxin

• Cholestyramine decreases digoxin bioavailability and can reduce therapeutic levels, requiring dose adjustments and careful monitoring. 2, 1, 4
• Digoxin should be taken at least 1 hour before or 4-6 hours after cholestyramine. 2, 3, 1
• Discontinuing cholestyramine in a patient whose digoxin has been titrated while taking the resin poses a hazard, as digoxin levels will rise and may cause toxicity. 1

Thyroid Hormone Replacement

• Cholestyramine significantly impairs absorption of thyroid hormones (levothyroxine, thyroxine preparations), potentially causing hypothyroidism or inadequate replacement. 2, 1
• Thyroid medications must be taken at least 1 hour before or 4-6 hours after cholestyramine. 2, 3, 1
• TSH monitoring is essential if symptoms of hypothyroidism emerge. 5

Other High-Risk Drug Interactions

The following medications require strict timing separation (1 hour before or 4-6 hours after cholestyramine): 2, 3, 1

• Oral contraceptives (ethinyl estradiol/norethindrone)—risk of contraceptive failure 2, 5
• Phenytoin—risk of subtherapeutic anticonvulsant levels 2, 5
• Thiazide diuretics, propranolol, phenylbutazone, tetracycline, penicillin G, phenobarbital, estrogens, progestins—all have documented reduced absorption 1

Metabolic and Nutritional Concerns

Vitamin Deficiencies

• Long-term cholestyramine use causes deficiencies of fat-soluble vitamins (A, D, E, K) and folate. 2, 1
• Water-miscible or parenteral forms of fat-soluble vitamins should be supplemented during chronic therapy, taken at least 4 hours before cholestyramine. 2, 3, 1
• Folate supplementation should be considered with long-term use. 1

Hyperchloremic Acidosis

• Caution in younger/smaller patients, those with renal insufficiency, volume depletion, or concurrent spironolactone use, as cholestyramine may produce hyperchloremic acidosis. 1

Pregnancy and Lactation

• Use only if potential benefits outweigh risks to mother and child. 1
• While cholestyramine is not systemically absorbed, it interferes with fat-soluble vitamin absorption, making regular prenatal supplementation potentially inadequate. 1
• Exercise caution when administered to nursing mothers. 1

Practical Implementation Algorithm

Before prescribing cholestyramine, verify:

1. No complete biliary obstruction (check imaging, bilirubin levels) 1
2. Triglycerides <500 mg/dL 2
3. No history of bowel obstruction, gastroparesis, or major GI surgery 2
4. Review all concurrent medications for critical interactions 1
5. Establish medication timing schedule separating other drugs by 1 hour before or 4-6 hours after 3, 1

Common pitfall: Failing to adjust timing of narrow therapeutic index medications (warfarin, digoxin, thyroid hormone, phenytoin) leads to therapeutic failure or toxicity. 1