What are the side effects of Fenofibrate?

Fenofibrate Side Effects

Fenofibrate can cause serious adverse effects including renal impairment, hepatotoxicity, myopathy, and gallstones, requiring careful monitoring of renal function, liver enzymes, and muscle symptoms during treatment. 1

Major Side Effects

Renal Effects

• Elevations in serum creatinine are common with fenofibrate therapy 2, 1
• Monitoring requirements:
  • Evaluate renal status before starting fenofibrate
  • Recheck within 3 months after initiation
  • Continue monitoring every 6 months thereafter
  • Use both serum creatinine and eGFR for assessment 2
• Dosing restrictions:
  • Fenofibrate is contraindicated in moderate to severe renal impairment (eGFR <30 mL/min/1.73 m²)
  • For eGFR between 30-59 mL/min/1.73 m², dose should not exceed 54 mg/day
  • Discontinue fenofibrate if eGFR decreases persistently to <30 mL/min/1.73 m² 2

Hepatotoxicity

• Can cause transient elevations in liver enzymes 1, 3
• Rare cases of severe hepatitis with substantially elevated transaminases have been reported 4, 5
• In one case report, liver injury occurred within 48 hours of first administration 5
• Monitor liver function tests regularly
• Discontinue if persistent ALT elevations >3 times upper limit of normal occur 1

Musculoskeletal Effects

• Risk of myopathy and rhabdomyolysis, especially when combined with statins 1
• Gemfibrozil has higher risk than fenofibrate when combined with statins 2
• Mild to moderate decreases in hemoglobin, hematocrit, and white blood cell counts may occur 1
• Periodic monitoring of blood counts recommended during first 12 months of treatment 1

Gastrointestinal Effects

• Common side effects include gastrointestinal disturbances 4, 3
• Risk of pancreatitis 1
• Increased risk of gallstones due to increased cholesterol excretion into bile 1
• Discontinue therapy if gallstones are found 1

Other Important Side Effects

Cardiovascular Effects

• Increased risk of venothromboembolic disease:
  • Higher rates of pulmonary embolism (1% vs 0.7% with placebo)
  • Higher rates of deep vein thrombosis (1% vs 0.7% with placebo) 1

Hypersensitivity Reactions

• Acute reactions: anaphylaxis and angioedema (can be life-threatening)
• Delayed reactions: Severe cutaneous adverse reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS syndrome 1

Drug Interactions

• Potentiates effects of coumarin anticoagulants - requires frequent monitoring of PT/INR 1
• Increased risk of myopathy when combined with colchicine 1
• May be used with low or moderate-intensity statins only when benefits outweigh risks 2

Paradoxical HDL Decreases

• Severe decreases in HDL cholesterol (as low as 2 mg/dL) have been reported
• Can occur within 2 weeks to years after starting therapy
• Monitor HDL-C within first few months of treatment
• If severe decrease detected, withdraw therapy and monitor until HDL-C returns to baseline 1

Monitoring Recommendations

1. Before starting fenofibrate:

   • Baseline renal function (serum creatinine and eGFR)
   • Baseline liver function tests
   • Baseline lipid panel
   • Consider baseline CBC

2. After starting fenofibrate:

   • Renal function: within 3 months, then every 6 months
   • Liver function: periodically as clinically indicated
   • CBC: periodically during first 12 months
   • HDL-C: within first few months

3. When to discontinue:

   • If eGFR decreases to <30 mL/min/1.73 m²
   • If persistent ALT elevations >3 times ULN
   • If gallstones develop
   • If severe hypersensitivity reactions occur
   • If severe decreases in HDL-C are detected

Common Pitfalls

1. Failing to assess renal function before starting therapy
2. Not adjusting dose in patients with mild-to-moderate renal impairment
3. Combining with gemfibrozil and statins (higher risk than fenofibrate with statins)
4. Inadequate monitoring of liver function and blood counts
5. Not recognizing early signs of hypersensitivity reactions
6. Overlooking drug interactions, especially with anticoagulants

Fenofibrate can provide benefits for patients with hypertriglyceridemia and mixed dyslipidemia, but requires careful patient selection and monitoring to minimize the risk of serious adverse effects.