Contraindications for Fenofibrate
Fenofibrate is absolutely contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73m²), including those on dialysis, active liver disease, preexisting gallbladder disease, nursing mothers, and those with known hypersensitivity to fenofibrate or fenofibric acid. 1
Absolute Contraindications
The FDA drug label explicitly lists the following absolute contraindications 1:
- Severe renal impairment (eGFR <30 mL/min/1.73m²), including patients receiving dialysis 2, 3, 1
- Active liver disease, including primary biliary cirrhosis and unexplained persistent liver function abnormalities 1
- Preexisting gallbladder disease 4, 1
- Nursing mothers 1
- Known hypersensitivity to fenofibrate or fenofibric acid 1
The American College of Cardiology reinforces that fenofibrate must be discontinued if eGFR persistently decreases to <30 mL/min/1.73m² during treatment 2. The KDOQI guidelines emphasize that fenofibrate should not be used in kidney transplant recipients 2.
High-Risk Situations Requiring Extreme Caution or Avoidance
Combination with Statins
- Gemfibrozil plus statin is absolutely contraindicated due to markedly increased risk of rhabdomyolysis 2, 5
- Fenofibrate plus statin combination carries increased risk of muscle toxicity and should only be considered with low- or moderate-intensity statins if benefits clearly outweigh risks 2
- The American Diabetes Association states statin-fibrate combination therapy has not shown cardiovascular benefit and is generally not recommended 2
- Case reports document severe rhabdomyolysis with creatine kinase levels exceeding 90,000 IU/L when fenofibrate is added to statin therapy 5
Moderate Renal Impairment (eGFR 30-59 mL/min/1.73m²)
- Dose must be reduced to maximum 54 mg/day in patients with moderate renal impairment 2, 3, 1
- Intensive monitoring is mandatory: assess renal function before initiation, within 3 months, and then every 6 months 2, 3
- Despite dose reduction requirements, research suggests fenofibrate can be used safely in moderate renal impairment with appropriate monitoring 6
Chronic Kidney Disease
- The KDIGO guidelines recommend against using fibric acid derivatives to reduce cardiovascular risk in CKD patients due to insufficient evidence of net clinical benefit 3
- Fenofibrate may only be considered for markedly elevated triglycerides (>1000 mg/dL) to prevent acute pancreatitis, not for cardiovascular risk reduction 3
- The National Kidney Foundation recommends against combining fenofibrate with statins in CKD patients due to increased rhabdomyolysis risk 4, 3
Critical Monitoring Requirements
Renal Function Monitoring
- Assess both serum creatinine and eGFR before starting fenofibrate 2
- Recheck within 3 months of initiation 2, 3
- Monitor every 6 months thereafter 2, 3
- Discontinue if eGFR persistently decreases to <30 mL/min/1.73m² 2
Important caveat: Fenofibrate increases serum creatinine by 10-20% through increased metabolic production of creatinine, not through true renal function deterioration 7, 8, 9. This increase occurs within 2 weeks, is reversible, and does not reflect actual GFR decline when measured by gold-standard methods (inulin clearance) 7, 8. However, clinical monitoring should still use eGFR thresholds as specified above 2.
Hepatic Function Monitoring
- Obtain baseline hepatic transaminases before initiation 2
- Monitor liver function tests as clinically indicated during treatment 2
- Discontinue if persistent ALT elevations ≥3 times upper limit of normal occur 2
Gallbladder Monitoring
- Obtain baseline ultrasound before initiating fibrate therapy to document absence of stones 4
- Use with caution in patients with history of gallstones 4
Special Populations
Elderly Patients
- Dose selection should be based on renal function 1
- Extreme caution is necessary when using combination therapy with statins 4
- Increased age is a risk predictor for fenofibrate-associated creatinine elevation 9