Can you take fish oil and fenofibrate and statin (HMG-CoA reductase inhibitor) together?

Safety of Combining Fish Oil, Fenofibrate, and Statins

The combination of fish oil, fenofibrate, and a statin can be safely used together with appropriate monitoring, though fenofibrate is strongly preferred over other fibrates when combining with statins due to significantly lower risk of myopathy. 1

Safety of the Combination

Statin + Fenofibrate

• Fenofibrate is the preferred fibrate when combination therapy with a statin is needed 2
• The risk of rhabdomyolysis is significantly lower with fenofibrate-statin combinations compared to gemfibrozil-statin combinations (0.58 vs 8.6 cases per million prescriptions) 1
• Long-term studies have shown that fenofibrate with low-dose statins (pravastatin or simvastatin) is generally safe and effective for treating combined hyperlipidemia in patients with normal hepatic and renal function 3

Adding Fish Oil

• Fish oil can be safely added to fenofibrate and statin therapy 4
• Fish oil has no measurable effect on immunologic parameters or the pharmacokinetics of certain antiretrovirals, suggesting minimal drug interactions 4
• The American Heart Association guidelines indicate that fish oil may be reasonable for patients who continue to have elevated non-HDL-C while on adequate statin therapy 2

Efficacy of the Combination

Triglyceride Management

• For severe hypertriglyceridemia (≥500 mg/dL), combining therapies may be necessary to reduce the risk of pancreatitis 2
• Fish oil reduced triglycerides by a median of 46%, fenofibrate by 58%, and the combination therapy by 65.5% in one study 4
• Both fish oil and fenofibrate reduce several saturated triglyceride species that are associated with increased cardiovascular disease risk 5

Cardiovascular Outcomes

• While statin plus fibrate combination therapy has not been shown to improve atherosclerotic cardiovascular disease outcomes in general populations 2, it may be beneficial in specific subgroups
• In patients with ASCVD or other cardiovascular risk factors on a statin with controlled LDL cholesterol but elevated triglycerides (135-499 mg/dL), the addition of icosapent ethyl (a purified fish oil component) can be considered to reduce cardiovascular risk 2

Important Monitoring and Precautions

Potential Adverse Effects

• Monitor for:
  • Liver function abnormalities (10% of patients may have transitory isolated elevations in alanine aminotransferase) 3
  • Muscle symptoms and creatine kinase levels (risk of myopathy and rhabdomyolysis) 2
  • Renal function (fenofibrate requires dose adjustment in renal impairment) 1

Contraindications

• Avoid using gemfibrozil with any statin, particularly lovastatin, pravastatin, and simvastatin which are contraindicated 2
• Avoid fibrates in severe renal impairment (GFR <30 mL/min/1.73 m²) 1

Algorithm for Management

1. First, optimize statin therapy to achieve LDL-C goals
2. If triglycerides remain elevated (>150 mg/dL):
   • For moderate hypertriglyceridemia (150-499 mg/dL): Consider adding fenofibrate
   • For severe hypertriglyceridemia (≥500 mg/dL): Add fenofibrate to reduce pancreatitis risk 2
3. If triglycerides remain elevated despite statin + fenofibrate:
   • Consider adding fish oil (3-4g daily) 4
4. Monitor regularly:
   • Liver function tests
   • Creatine kinase levels if muscle symptoms develop
   • Renal function
   • Lipid profile

Conclusion

The triple combination of fish oil, fenofibrate, and a statin can be used safely in patients who require intensive lipid management, particularly those with severe hypertriglyceridemia or mixed dyslipidemia. Fenofibrate is the preferred fibrate when combining with statins, and appropriate monitoring should be implemented to ensure safety.