What is tablet fenofibrate used for in patients with hyperlipidemia?

Fenofibrate Tablet: Primary Uses and Indications

Fenofibrate is FDA-approved as adjunctive therapy to diet for treating severe hypertriglyceridemia (to prevent acute pancreatitis) and mixed dyslipidemia in adults, with its primary therapeutic role being triglyceride reduction (30-50%) rather than LDL cholesterol lowering. 1, 2

FDA-Approved Indications

Severe Hypertriglyceridemia

• Initiate fenofibrate 54-160 mg daily immediately for triglyceride levels ≥500 mg/dL to prevent acute pancreatitis, regardless of LDL-C levels or cardiovascular risk. 2, 1
• Markedly elevated triglycerides (>2,000 mg/dL) carry a 14% risk of acute pancreatitis, making fenofibrate first-line therapy in this setting. 2, 1
• The initial dose ranges from 54-160 mg daily, with dosage individualized based on lipid response at 4-8 week intervals. 1

Primary Hypercholesterolemia or Mixed Dyslipidemia

• Fenofibrate reduces elevated LDL-C (10-28%), total cholesterol, triglycerides, and apolipoprotein B while increasing HDL-C (6-12%) in adults with primary hypercholesterolemia or mixed dyslipidemia. 1, 3, 4
• The standard dose is 160 mg once daily for this indication. 1
• However, statins remain first-line therapy when LDL reduction is the primary goal, as they provide superior LDL lowering with proven cardiovascular outcomes benefit. 5, 6

Moderate Hypertriglyceridemia (200-499 mg/dL)

• Consider fenofibrate when triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications (weight loss, increased physical activity, reduced alcohol, dietary changes), particularly in patients with low HDL-C (<40 mg/dL) or additional cardiovascular risk factors. 2, 7
• This represents a Class IIb, Level C recommendation from the American College of Cardiology. 2
• For diabetic patients with marked hypertriglyceridemia (≥200 mg/dL) and low HDL-C (≤40 mg/dL), fenofibrate showed significant reduction in cardiovascular disease events. 2, 7

Critical Pre-Treatment Requirements

Lifestyle Optimization First

• Do not initiate fenofibrate without first optimizing lifestyle modifications and addressing secondary causes of hypertriglyceridemia (hypothyroidism, diabetes mellitus, estrogen therapy, thiazide diuretics, beta-blockers, excess alcohol). 2, 1
• Patients must be placed on an appropriate lipid-lowering diet before receiving fenofibrate and continue this diet during treatment. 1
• Improving glycemic control in diabetic patients with fasting chylomicronemia will usually obviate the need for pharmacologic intervention. 1

Renal Function Assessment

• Evaluate renal status (eGFR) before fenofibrate initiation, within 3 months after initiation, and every 6 months thereafter. 2, 7
• Do NOT use fenofibrate if eGFR <30 mL/min/1.73 m² (severe renal impairment). 2, 1
• If eGFR is 30-59 mL/min/1.73 m², limit the dose to 54 mg/day maximum. 2, 1
• If eGFR decreases persistently to <30 mL/min/1.73 m² during follow-up, discontinue fenofibrate immediately. 2

Administration and Monitoring

Dosing Instructions

• Administer fenofibrate with meals to optimize bioavailability. 1
• Monitor lipid levels 4-12 weeks after initiation and every 3-12 months thereafter. 7
• Withdraw therapy in patients who do not have an adequate response after two months of treatment with the maximum recommended dose of 160 mg once daily. 1

Safety Monitoring

• Monitor liver function tests regularly, as fenofibrate can cause transient increases in serum aminotransferase levels. 5, 3
• Monitor for muscle symptoms and obtain baseline and follow-up creatine kinase levels, especially when combining with statins. 2
• A transient rise in serum creatinine may occur but is reversible upon discontinuation. 5

Combination Therapy with Statins

When to Consider Combination

• For patients already on statin therapy with controlled LDL-C but persistent triglycerides 135-499 mg/dL, icosapent ethyl should be considered before fenofibrate. 7
• If combination therapy is necessary, use fenofibrate (NOT gemfibrozil) with lower statin doses (e.g., atorvastatin 10-20 mg maximum) to minimize myopathy risk. 2, 7

Critical Safety Warnings

• Do NOT combine fenofibrate with gemfibrozil due to significantly increased rhabdomyolysis risk. 5
• Fenofibrate has a better safety profile than gemfibrozil when combined with statins because it does not inhibit statin glucuronidation. 2
• Gemfibrozil should NOT be initiated in patients on statin therapy (Class III: Harm recommendation). 2
• Use particular caution in patients >65 years or with renal disease when combining fenofibrate with statins. 2, 7

Important Cardiovascular Outcomes Limitation

• Fenofibrate at 160 mg daily was NOT shown to reduce coronary heart disease morbidity and mortality in large randomized controlled trials (FIELD, ACCORD) of patients with type 2 diabetes mellitus. 1, 6, 5
• However, fenofibrate reduced nonfatal myocardial infarction by 24% and showed benefits in microvascular outcomes (reduced albuminuria progression and retinopathy requiring laser treatment). 6
• Subgroup analyses suggest potential benefit in patients with both high baseline triglycerides and low HDL-C. 6

Special Populations

Diabetic Patients

• Optimize glycemic control as the first priority before initiating fenofibrate. 7, 6
• Fenofibrate increases HDL cholesterol without adversely affecting glycemic control and may improve insulin resistance. 7
• For diabetic patients with combined hyperlipidemia, improved glycemic control plus high-dose statin is the first choice, followed by improved glycemic control plus statin plus fenofibrate (with caution due to myositis risk). 7

Chronic Kidney Disease

• Fibrates should generally NOT be used in patients with CKD and high triglyceride levels, as most randomized trials excluded individuals with eGFR <45 mL/min/1.73 m². 2
• Fibrate use was associated with increased risk of hospitalization due to increased serum creatinine. 2