What is the indication for cholestyramine?

Indications for Cholestyramine

Cholestyramine is primarily indicated as adjunctive therapy to diet for the reduction of elevated serum cholesterol in patients with primary hypercholesterolemia who do not respond adequately to diet, and for the relief of pruritus associated with partial biliary obstruction. 1

Primary Indications

1. Hypercholesterolemia Management

• Primary indication: Adjunct to diet for lowering LDL cholesterol in primary hypercholesterolemia 2, 1
• Dosage: 8-16 g/day orally divided into 2 doses 2
• Efficacy: Monotherapy reduces LDL-C by approximately 10.4% vs placebo 2
• Clinical outcomes: In the LRC-CPPT trial, cholestyramine demonstrated a 19% reduction in risk of definite CHD death and/or nonfatal MI in asymptomatic middle-aged men with primary hypercholesterolemia 2

2. Pruritus Relief

• Secondary indication: Relief of pruritus associated with partial biliary obstruction 1
• Mechanism: Binds bile acids in the intestine, reducing their circulation and associated pruritus
• Note: Has variable effect on serum cholesterol in patients with biliary obstruction 1

Mechanism of Action

Cholestyramine works through a non-absorbed, lipid-lowering mechanism:

1. Binds bile acids in intestine and prevents their reabsorption
2. As bile acid pool decreases, hepatic enzyme cholesterol 7-a-hydroxylase is upregulated
3. Increases conversion of cholesterol to bile acids
4. Creates increased demand for cholesterol in liver cells
5. Results in increased transcription/activity of HMG-CoA reductase and increased hepatic LDL receptors
6. Ultimately increases clearance of LDL-C from blood, decreasing serum LDL-C levels 2

Patient Selection and Considerations

Appropriate Candidates:

• Patients with primary hypercholesterolemia not responding to diet alone 1
• Patients with mild hypertriglyceridemia and elevated LDL-C 3
• Patients with pruritus from partial biliary obstruction 1, 3

Cautions:

• Not indicated when hypertriglyceridemia is the primary concern 1
• May increase or have no effect on triglyceride levels 2
• Avoid in patients with complete biliary obstruction 2
• Not recommended in Crohn's disease patients with extensive ileal involvement or resection due to risk of increased steatorrhea 2

Administration Considerations

• Timing: Most effective when administered 30 minutes before meals, particularly the evening meal 4
• Drug interactions: Other medications should be taken at least 1 hour before or 4 hours after cholestyramine to avoid impeding their absorption 2
• Dose titration: Start with low doses (2-4 g/day) and gradually titrate to minimize side effects 2

Adverse Effects

• Common: Constipation, dyspepsia, and nausea 2
• Potential complications: Bowel obstruction, dysphagia, esophageal obstruction, fecal impaction, hypertriglyceridemia, pancreatitis 2
• Drug interactions: May decrease absorption of medications including phenytoin, warfarin, and thyroid hormone replacement therapy 2

Pediatric Use

• Cholestyramine has been studied in children with familial hypercholesterolemia (FH)
• In children aged 6-11 years with FH, 8g daily reduced LDL by 17% 2
• Consider in boys and post-menarchal girls with LDL-C ≥190 mg/dL without family history of premature CVD, or LDL-C ≥160 mg/dL with family history 2

Emerging Uses

While not FDA-approved for these indications, research suggests potential benefit for:

• Management of diabetes mellitus 3
• Treatment of diarrhea from bile acid malabsorption 3

Cholestyramine remains a valuable option for specific hypercholesterolemia cases and pruritus management, particularly when statins are contraindicated or as part of combination therapy for enhanced LDL-C reduction.