What is the classification and typical dosing of fenofibrate (fibric acid derivative) for treating hypertriglyceridemia?

Fenofibrate Classification and Dosing

Fenofibrate is a fibric acid derivative (fibrate) typically dosed at 54-160 mg once daily, with the standard dose being 160 mg daily for patients with normal renal function, though patients with renal impairment require dose reduction starting at 54 mg daily. 1, 2

Drug Classification

• Fenofibrate belongs to the fibric acid derivative class of lipid-lowering agents 3, 4
• It functions as a peroxisome proliferator-activated receptor-alpha (PPAR-α) agonist 4
• Fenofibrate is indicated for primary hypercholesterolemia, mixed dyslipidemia (types IIa and IIb), and hypertriglyceridemia (types IV and V) 4, 5

Standard Dosing Regimens

Normal Renal Function

• Standard dose: 160 mg once daily 3, 2
• Alternative dosing: 54-160 mg daily range 3, 1
• The 200 mg micronized capsule formulation is equivalent to the 160 mg tablet formulation 2, 5
• Once-daily dosing is appropriate due to fenofibric acid's 20-hour half-life 2

Renal Impairment Dosing

• For mild to moderate renal impairment (eGFR 30-59 mL/min/1.73 m²): initiate at 54 mg daily and do not exceed this dose 1, 6, 2
• For severe renal impairment (eGFR <30 mL/min/1.73 m²): fenofibrate should be avoided entirely 6, 2
• Renal function must be assessed before initiation, within 3 months after starting, and every 6 months thereafter 1, 6
• If eGFR persistently decreases to <30 mL/min/1.73 m², discontinue fenofibrate 1

Administration Considerations

• Fenofibrate can be taken at any time of day without regard to meals (newer formulations) 1
• If combined with bile acid sequestrants, administer fenofibrate ≥2 hours before or ≥4 hours after the bile acid sequestrant to prevent absorption interference 1
• No dosage adjustment needed for elderly patients with normal renal function 2

Combination Therapy Dosing

• When combining fenofibrate with statins, use only low- or moderate-intensity statins due to increased risk of muscle symptoms and rhabdomyolysis 1, 6
• Fenofibrate has a safer profile than gemfibrozil when combined with statins, as it does not interfere with statin catabolism 3
• The ACCORD-Lipid trial used fenofibrate added to simvastatin 40 mg in patients with type 2 diabetes 3
• The FIELD trial used fenofibrate 200 mg daily (mean dose) as monotherapy 3

Alternative Fibrate Dosing

• Gemfibrozil: 600 mg twice daily before meals 3
• For patients with serum creatinine >2 mg/dL on gemfibrozil, decrease dose or consider alternative therapy 3
• Gemfibrozil should NOT be combined with statins due to significantly higher rhabdomyolysis risk compared to fenofibrate 6

Clinical Context from Major Trials

• The FIELD trial demonstrated that fenofibrate 200 mg daily reduced total cardiovascular events primarily through prevention of non-fatal MI and coronary revascularization, though the primary endpoint was not significantly reduced 3, 4
• The DAIS study used fenofibrate 200 mg daily and showed slowing of angiographic progression of coronary atherosclerosis in type 2 diabetes 3, 4
• Post-hoc analyses suggest potential benefit in patients with triglycerides ≥204 mg/dL and HDL-C ≥40 mg/dL 3

Important Safety Monitoring

• Monitor liver transaminases regularly, as fenofibrate can increase ALT levels 3, 5
• Monitor creatine phosphokinase (CPK) levels, especially when combined with statins 7
• Fenofibrate increases serum creatinine by 0.113-0.136 mg/dL on average 3
• Watch for muscle symptoms, though clinical myopathy risk is low with fenofibrate-statin combinations 3, 4