Can fenofibrate and icosapent be used together?

Fenofibrate and Icosapent Ethyl Combination Therapy

Fenofibrate and icosapent ethyl can be used together safely when clinically indicated, particularly in patients with mixed dyslipidemia who have not achieved target lipid goals with monotherapy. 1, 2

Safety and Efficacy of Combination Therapy

• Fenofibrate can be safely combined with icosapent ethyl without significant drug-drug interactions, unlike the higher risk seen with gemfibrozil-statin combinations 1
• The combination may provide complementary effects on the lipid profile - fenofibrate primarily reduces triglycerides and increases HDL, while icosapent ethyl reduces cardiovascular events in patients with elevated triglycerides 3, 4
• In patients with nonalcoholic steatohepatitis and hypertriglyceridemia, the combination of fenofibrate with other medications has been shown to be well-tolerated with no discontinuations due to adverse events 5

Clinical Indications for Combination Therapy

• Consider combination therapy for patients with:

  • Persistent elevated triglycerides (135-499 mg/dL) despite statin therapy 3
  • Mixed dyslipidemia not adequately controlled with monotherapy 6
  • High cardiovascular risk with residual hypertriglyceridemia 4

• Icosapent ethyl (4g daily) has demonstrated a 25% relative risk reduction in cardiovascular events in the REDUCE-IT trial, particularly in patients with established cardiovascular disease or diabetes plus cardiovascular risk factors 3

Monitoring Recommendations

• Before initiating combination therapy:

  • Obtain baseline liver function tests and creatine kinase levels 1
  • Assess renal function, as impaired renal function increases risk of adverse effects 1

• During treatment:

  • Monitor for muscle symptoms including pain, tenderness, or weakness 1
  • Perform more frequent laboratory monitoring in patients with risk factors for myopathy 1
  • Check lipid parameters to assess efficacy 2

Risk Factors Requiring Closer Monitoring

• Advanced age (especially >80 years) 1
• Small body frame and frailty 1
• Chronic renal insufficiency 1
• Multiple medications 1
• Perioperative periods 1

Important Considerations and Caveats

• While fenofibrate-statin combinations have not shown improved cardiovascular outcomes in general populations, specific patient subgroups may benefit 3
• Icosapent ethyl has demonstrated cardiovascular benefit in the REDUCE-IT trial, with a number needed to treat of only 12 in patients with prior percutaneous coronary intervention 7
• Results from the REDUCE-IT trial should not be extrapolated to other omega-3 fatty acid products that contain both EPA and DHA 3
• Some patients have shown improved lipid profiles when switching from fenofibrate to icosapent ethyl while maintaining statin therapy, suggesting these agents may be used sequentially rather than concurrently if needed 2

Practical Approach to Combination Therapy

• Start with standard doses:
  • Fenofibrate 54-160 mg daily 8
  • Icosapent ethyl 2 g twice daily with food 3, 4
• Consider lower initial doses in elderly patients or those with renal impairment 1
• Evaluate response after 8-12 weeks of therapy 2
• Discontinue if inadequate response or intolerance develops 1