Can you take atorvastatin (statin) and fenofibrate (fibrate) together?

Atorvastatin and Fenofibrate Combination Therapy

Yes, atorvastatin and fenofibrate can be safely used together, with fenofibrate being the strongly preferred fibrate option when combined with any statin due to significantly lower risk of myopathy compared to gemfibrozil. 1

Safety Profile of the Combination

The combination of atorvastatin and fenofibrate has been shown to be reasonably safe when used appropriately. The American Heart Association specifically recommends fenofibrate (or fenofibric acid) over gemfibrozil when statin-fibrate combination therapy is indicated 2. This recommendation is based on substantial evidence:

• FDA Adverse Event Reporting System data shows rhabdomyolysis reports were approximately 15 times lower for fenofibrate than for gemfibrozil when prescribed with statins (0.58 vs 8.6 cases per million prescriptions) 2, 1
• In the FIELD study (n=9,795), none of the approximately 1,000 patients on statin-fenofibrate combination experienced rhabdomyolysis 2
• The ACCORD study showed no statistically significant differences in myositis, rhabdomyolysis, or liver enzyme elevations between simvastatin-fenofibrate combination therapy and simvastatin monotherapy 2

Mechanism of Interaction

The key difference between fenofibrate and gemfibrozil lies in their interaction with statin metabolism:

• Fenofibrate does not significantly interfere with statin metabolism, making it much safer for combination therapy 1
• Gemfibrozil inhibits CYP2C8, OATP1B1/3-mediated hepatic uptake of statins, and statin glucuronidation, which can increase statin concentrations 2, 1
• Specifically with atorvastatin, gemfibrozil leads to significant increases in the area under the curve (AUC) of atorvastatin and its metabolites, while fenofibrate administration does not lead to clinically meaningful changes 3

Clinical Considerations

When using atorvastatin with fenofibrate:

1. Monitoring requirements:

   • Evaluate muscle symptoms and CK before starting therapy
   • Monitor for muscle soreness, tenderness, or pain at 6-12 weeks and follow-up visits
   • Check liver function tests initially, at 12 weeks, then annually or more frequently if indicated 2
   • Monitor renal function before starting therapy and periodically thereafter 1

2. Dosing considerations:

   • Standard dosing of atorvastatin (10-80 mg daily) can be used with fenofibrate
   • Fenofibrate requires dose adjustment in renal impairment:
     • eGFR 30-59 mL/min: ≤54 mg/day
     • eGFR <30 mL/min: Avoid use 1, 4

3. Contraindications:

   • Severe renal impairment
   • Active liver disease
   • Preexisting gallbladder disease 4

Efficacy of the Combination

The combination of atorvastatin and fenofibrate has shown superior efficacy compared to monotherapy with either agent:

• Combination therapy produces greater reductions in LDL-C, triglycerides, and total cholesterol, with greater increases in HDL-C compared to monotherapies 5, 6
• A fixed-dose combination of atorvastatin 40 mg and fenofibrate 100 mg demonstrated significantly greater triglyceride reduction (-49.1%) compared to either atorvastatin (-28.9%) or fenofibrate (-27.8%) alone 6

Important Caveats

• Despite the relative safety of the atorvastatin-fenofibrate combination, caution is still warranted as the risk of myopathy remains higher than with statin monotherapy
• Elderly patients, particularly older thin or frail women, should be monitored more carefully 2
• Patients with diabetes combined with chronic renal failure appear to be at higher risk for myopathy and require careful monitoring 2
• Consider temporarily withholding both medications during periods of major surgery 2

In conclusion, the atorvastatin-fenofibrate combination is an effective and relatively safe option for treating mixed dyslipidemia, particularly when both LDL-C lowering and triglyceride reduction are needed.