Can fenofibrate be taken together with statins (HMG-CoA reductase inhibitors)?

From the Guidelines

Fenofibrate can be taken together with statins, but this combination requires careful medical supervision due to an increased risk of muscle-related side effects, and should only be considered if the benefits from ASCVD risk reduction or triglyceride lowering outweigh the potential risk for adverse effects 1. The combination therapy is typically reserved for patients with mixed dyslipidemia (high triglycerides and LDL cholesterol) who don't achieve adequate control with a statin alone.

• Common statin medications that may be combined with fenofibrate include atorvastatin, rosuvastatin, and simvastatin.
• When taking this combination, patients should promptly report any unexplained muscle pain, tenderness, or weakness to their healthcare provider, as these could indicate a rare but serious condition called rhabdomyolysis.
• Regular blood tests to monitor liver function and muscle enzymes are essential when on this combination therapy.
• The combination works effectively because statins primarily lower LDL cholesterol while fenofibrate is particularly effective at reducing triglycerides and increasing HDL (good) cholesterol, providing complementary lipid-lowering effects through different mechanisms of action.
• It is also important to evaluate renal status before fenofibrate initiation, within 3 months after initiation, and every 6 months thereafter, as fenofibrate should not be used if moderate or severe renal impairment is present 1.
• Additionally, the dose of fenofibrate should not exceed 54 mg/day if the eGFR is between 30 and 59 mL/min per 1.73 m2, and fenofibrate should be discontinued if the eGFR decreases persistently to 30 mL/min per 1.73 m2 1.
• The FIELD trial demonstrated that fenofibrate treatment can reduce total cardiovascular events in patients with type 2 diabetes mellitus without prior cardiovascular disease, but also highlighted the need for careful monitoring of renal function and the potential risk of myositis and rhabdomyolysis when fibrates are used in combination with statins 1.

From the FDA Drug Label

The combined use of fenofibrate and HMG-CoA reductase inhibitors should be avoided unless the benefit of further alterations in lipid levels is likely to outweigh the increased risk of this drug combination Concomitant administration of fenofibrate (equivalent to fenofibrate 200 mg) and pravastatin (40 mg) once daily for 10 days increased the mean Cmax and AUC values for pravastatin by 36% (range from 69% decrease to 321% increase) and 28% (range from 54% decrease to 128% increase), respectively, and for 3α-hydroxy-iso-pravastatin by 55% (range from 32% decrease to 314% increase) and 39% (range from 24% decrease to 261% increase), respectively The combined use of fibric acid derivatives and HMG-CoA reductase inhibitors has been associated, in the absences of a marked pharmacokinetic interaction, in numerous case reports, with rhabdomyolysis, markedly elevated creatine kinase (CK) levels and myoglobinuria, leading in a high proportion of cases to acute renal failure

Fenofibrate can be taken together with statins (HMG-CoA reductase inhibitors), but the combination should be avoided unless the benefit of further alterations in lipid levels is likely to outweigh the increased risk of this drug combination. The use of fenofibrate with statins may increase the risk of rhabdomyolysis, elevated creatine kinase levels, and myoglobinuria, which can lead to acute renal failure. Patients taking this combination should be closely monitored for signs of muscle injury or renal dysfunction. 2 2

From the Research

Combination Therapy of Fenofibrate and Statins

• Fenofibrate can be prescribed concomitantly with an HMG-CoA reductase inhibitor (statin) to improve achievement of lipid goals in patients with atherogenic mixed hyperlipidaemia 3.
• The combination of fenofibrate and statins has been shown to be effective in reducing cardiovascular risk in patients with dyslipidemia, including those with low levels of HDL cholesterol and elevated levels of triglycerides and small, dense LDL 4.
• Studies have demonstrated that the combination of fenofibrate and statins is generally well tolerated, with a safety profile comparable to that of statin and fenofibrate monotherapies 3, 5, 6.

Safety Considerations

• There is a potential increased risk of myopathy when statins and fibrates are taken together, although fenofibrate is considered to be associated with a lower risk of myopathy than gemfibrozil 7, 4.
• The risk of muscle injury with statin-fibrate combination therapy can be increased by various factors, including pharmacokinetic, pharmacodynamic, metabolic, and pathophysiologic factors 4.
• Monitoring of patients taking combination therapy is necessary to minimize the risk of adverse effects, particularly muscle toxicity 7.

Efficacy of Combination Therapy

• Combination therapy with fenofibrate and statins has been shown to be more efficacious than monotherapy with individual drugs in reducing LDL, triglycerides, and total cholesterol, and increasing HDL 5, 6.
• The fixed-dose combination of fenofibrate and pravastatin has been demonstrated to be effective and well tolerated in patients with mixed hyperlipidaemia 3.
• The atorvastatin/fenofibrate fixed-dose combination tablet has been shown to be effective in improving lipid profiles and reducing cardiovascular risk in patients with dyslipidemia 6.