Can fenofibrate and icosapent (ethyl eicosapentaenoic acid, EPA) be administered concomitantly?

From the Guidelines

Fenofibrate and icosapent ethyl can be administered concomitantly, but with careful consideration of the potential risks and benefits, particularly in patients with renal impairment or those at high risk for myopathy. The combination of fenofibrate and icosapent ethyl may be beneficial for patients with mixed dyslipidemia, as fenofibrate works by activating peroxisome proliferator-activated receptor alpha (PPAR-α) to reduce triglycerides and increase HDL cholesterol, while icosapent ethyl (a purified form of the omega-3 fatty acid EPA) specifically lowers triglycerides through different mechanisms 1. When using this combination, standard dosing typically applies: fenofibrate 48-145 mg daily (depending on the formulation) and icosapent ethyl 2 grams twice daily with food. Patients should be monitored for potential side effects, including muscle pain, as there is a small increased risk of myopathy with combination therapy, and liver function tests should be checked periodically, especially in the first year of treatment 1. It is essential to evaluate renal status before initiating fenofibrate, as it should not be used in patients with moderate or severe renal impairment, defined as eGFR <30 mL/min per 1.73 m2, and the dose should not exceed 54 mg/day if eGFR is between 30 and 59 mL/min per 1.73 m2 1. The most recent study on the use of icosapent ethyl, the REDUCE-IT trial, demonstrated a significant reduction in cardiovascular events in patients with elevated triglycerides, but it is crucial to note that the results should not be extrapolated to other n-3 fatty acid products 1. In clinical practice, the decision to use fenofibrate and icosapent ethyl concomitantly should be based on individual patient needs and risk factors, weighing the potential benefits against the potential risks, and careful monitoring is necessary to minimize adverse effects. Key considerations include:

• Monitoring for muscle pain and myopathy
• Regular liver function tests
• Renal function evaluation and dose adjustment as necessary
• Careful consideration of the potential benefits and risks in individual patients.

From the Research

Administration of Fenofibrate and Icosapent

• Fenofibrate and icosapent (ethyl eicosapentaenoic acid, EPA) can be administered concomitantly, as shown in a study where the combination of prescription omega-3 fatty acids (P-OM3) and fenofibrate (FENO) resulted in a significant reduction in triglyceride (TG) levels 2.
• The concomitant use of P-OM3 and FENO was found to be safe and effective in reducing TG levels in patients with very high TG levels (> or =500 mg/dL) 2.
• Another study found that fenofibrate was effective in mitigating hypertriglyceridemia in patients with nonalcoholic steatohepatitis (NASH) treated with cilofexor and firsocostat, and icosapent ethyl (Vascepa) was also used in this study 3.
• The combination of fenofibrate and omega-3 fatty acids has been shown to have complementary benefits in the atherogenic lipid profile, and is well tolerated 4, 5.

Efficacy and Safety

• The combination of fenofibrate and omega-3 fatty acids has been found to be effective in reducing triglycerides, non-HDL cholesterol, and apolipoprotein B, and improving insulin sensitivity and flow-mediated dilation 5.
• The safety and efficacy of icosapent ethyl and fenofibrate have been evaluated in patients with NASH, and both treatments were found to be well tolerated 3.
• The use of fenofibrate and omega-3 fatty acids in combination has been found to be beneficial in patients with hypertriglyceridemia, and may provide a considerable clinical benefit in patients with high risk and mixed atherogenic dyslipidemia 4, 5.

Clinical Implications

• The concomitant administration of fenofibrate and icosapent may be a useful treatment strategy for patients with hypertriglyceridemia and high cardiovascular risk 2, 3.
• The combination of fenofibrate and omega-3 fatty acids may provide additional benefits in reducing triglycerides and improving insulin sensitivity, and may be considered in patients who do not achieve optimal lipid levels with a single agent 5.
• Further studies are needed to fully understand the effects of omega-3 fatty acids on cardiovascular disease, and to determine the optimal dose and type of omega-3 fatty acids to use in clinical practice 6.