How to use fenofibrate for hypertriglyceridemia?

Fenofibrate for Hypertriglyceridemia: Dosing and Administration Guidelines

Fenofibrate should be administered at a dose of 54-160 mg once daily with meals for the treatment of hypertriglyceridemia, with the specific dose determined by the severity of triglyceride elevation and renal function. 1

Indications

Fenofibrate is indicated as:

• Adjunctive therapy to diet for treatment of severe hypertriglyceridemia (triglycerides ≥500 mg/dL)
• Adjunctive therapy to diet to reduce elevated LDL-C, total cholesterol, triglycerides, and apolipoprotein B, and to increase HDL-C in patients with primary hypercholesterolemia or mixed dyslipidemia 1

Dosing Recommendations

Based on Triglyceride Levels:

• Severe hypertriglyceridemia (≥500 mg/dL): 54-160 mg once daily, with dose individualized according to patient response 1
• Maximum dose: 160 mg once daily 1

Based on Renal Function:

• Normal or mild-moderate CKD (stages 1-2): 96 mg/day 2
• Moderate renal impairment (CKD stage 3): 48 mg/day 2
• eGFR 30-59 mL/min per 1.73 m²: Do not exceed 54 mg/day 2
• Severe renal impairment (CKD stages 4-5, eGFR <30 mL/min per 1.73 m²): Avoid use 2

Administration Guidelines

• Fenofibrate should be given with meals to optimize bioavailability 1
• The suprabioavailable tablet formulation has increased bioavailability compared to the micronized capsule formulation:
  • 54 mg tablet = 67 mg micronized capsule
  • 160 mg tablet = 200 mg micronized capsule 3
• Patients should be placed on an appropriate lipid-lowering diet before receiving fenofibrate and should continue this diet during treatment 1

Monitoring and Follow-up

1. Before Starting Therapy:

   • Assess baseline renal function
   • Obtain baseline lipid profile
   • Address contributing factors: excess body weight, alcohol intake, hypothyroidism, diabetes 1

2. During Treatment:

   • Monitor renal function within 3 months after initiation and every 6 months thereafter 2
   • Monitor lipid levels periodically (every 4-8 weeks initially) 1
   • Assess liver function regularly 3
   • Consider dose reduction if lipid levels fall significantly below target range 1
   • Discontinue if inadequate response after two months at maximum dose 1
   • Discontinue if eGFR decreases persistently to <30 mL/min per 1.73 m² 2

Special Considerations

Combination Therapy

• When combining with statins, use caution due to increased risk of myopathy 4
• Fenofibrate has a better safety profile for combination therapy with statins compared to gemfibrozil 2
• If statins and fenofibrate are used together:
  • Use lower statin doses 4
  • Take fenofibrate in the morning and statins in the evening to minimize peak dose concentrations 4
  • Monitor for muscle symptoms 4

Lifestyle Modifications

• Implement dietary modifications (reduce saturated fats to <7% of calories, cholesterol to <200 mg/day) 4
• Encourage weight reduction if obesity is present 4
• Promote regular physical activity 4
• Reduce or eliminate alcohol consumption, especially with severe hypertriglyceridemia 4
• Manage hyperglycemia in diabetic patients 4

Clinical Benefits

• Reduces triglyceride levels by approximately 36-46% 5, 6
• Decreases small LDL particles by approximately 40% 6
• Increases HDL cholesterol levels 7
• Reduces oxidative stress and inflammatory markers (VCAM-1, ICAM-1) 6
• Improves postprandial lipid metabolism 6

Common Adverse Effects

• Gastrointestinal symptoms (diarrhea, dyspepsia) 8
• Elevated liver enzymes 8
• Potential for myositis, especially when combined with statins 4

Important Limitations

Fenofibrate was not shown to reduce coronary heart disease morbidity and mortality in patients with type 2 diabetes mellitus 1