What are the contraindications for fenofibrate?

Fenofibrate Contraindications

Fenofibrate is absolutely contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73m²), active liver disease, preexisting gallbladder disease, nursing mothers, and those with known hypersensitivity to fenofibrate or fenofibric acid. 1

Absolute Contraindications

Renal Contraindications

• Severe renal impairment (eGFR <30 mL/min/1.73m²) including patients on dialysis 1
• The American College of Cardiology explicitly states fenofibrate must be discontinued if eGFR persistently decreases to <30 mL/min/1.73m² during treatment 2
• The KDOQI guidelines emphasize that fenofibrate is contraindicated in advanced CKD and should not be used in kidney transplant recipients 2

Hepatic Contraindications

• Active liver disease of any etiology 1
• Primary biliary cirrhosis 1
• Unexplained persistent liver function abnormalities 1
• Note: Recent evidence suggests fenofibrate may be tolerated in mild hepatic impairment with dose adjustment, but this does not change the FDA contraindication for active disease 3

Gallbladder Disease

• Preexisting gallbladder disease is an absolute contraindication 1
• Fenofibrate increases the biliary lithogenic index, raising the theoretical risk of gallstone formation 4

Other Absolute Contraindications

• Nursing mothers - fenofibrate is contraindicated during breastfeeding 1
• Known hypersensitivity to fenofibrate or fenofibric acid 1

Relative Contraindications and High-Risk Situations

Combination with Statins

• Gemfibrozil plus statin is absolutely contraindicated due to markedly increased risk of rhabdomyolysis 2
• Fenofibrate may be considered with low- or moderate-intensity statins only if benefits outweigh risks, but this combination carries increased risk of muscle toxicity 2
• The American Diabetes Association states statin-fibrate combination therapy has not shown cardiovascular benefit and is generally not recommended 2

Moderate Renal Impairment (eGFR 30-59 mL/min/1.73m²)

• Not an absolute contraindication, but requires mandatory dose reduction to maximum 54 mg/day 2, 5
• Requires intensive monitoring: renal function assessment before initiation, within 3 months, then every 6 months 2, 6

Critical Monitoring Requirements When Not Contraindicated

Renal Monitoring

• Assess both serum creatinine and eGFR before starting fenofibrate 2
• Recheck within 3 months of initiation 2, 6
• Continue monitoring every 6 months thereafter 2, 6
• An acute creatinine rise of approximately 0.13 mg/dL is expected and reversible, not representing true nephrotoxicity 5, 7, 8

Hepatic Monitoring

• Obtain baseline hepatic transaminases before initiation 2
• Monitor liver function tests as clinically indicated during treatment 2, 6
• Discontinue if persistent ALT elevations ≥3 times upper limit of normal occur 2

Common Pitfalls to Avoid

• Do not confuse the expected creatinine rise with true renal toxicity - fenofibrate increases creatinine production without impairing GFR 7, 8
• Do not use fenofibrate in patients already on gemfibrozil - this combination is never appropriate 2
• Do not continue fenofibrate if eGFR drops below 30 mL/min/1.73m² even if it was initiated at higher eGFR 2, 5
• Do not overlook dose adjustment in moderate renal impairment - failure to reduce dose increases adverse event risk 2, 5