Can you take fenofibrate and rosuvastatin (Crestor) together?

Fenofibrate and Rosuvastatin Combination Therapy: Safety and Recommendations

Yes, fenofibrate and rosuvastatin can be taken together, but specific precautions should be followed to minimize risk of adverse effects. 1 This combination is considered safer than using gemfibrozil with statins, but still requires careful monitoring.

Evidence-Based Recommendations

The American Heart Association provides clear guidance on statin-fibrate combinations:

1. Preferred Fibrate Choice: Fenofibrate is the preferred fibrate to combine with statins (including rosuvastatin) due to a significantly lower risk of drug interactions compared to gemfibrozil 1

   • Data shows rhabdomyolysis reports are approximately 15 times lower with fenofibrate-statin combinations compared to gemfibrozil-statin combinations (0.58 vs 8.6 per million prescriptions) 1

2. Monitoring Requirements:

   • Check baseline renal function before starting therapy
   • Monitor for muscle symptoms (pain, weakness, tenderness)
   • Follow up liver enzymes and creatine kinase as indicated by symptoms 1

3. Clinical Indications:

   • This combination should be used when benefits outweigh risks
   • Particularly appropriate for patients with high triglycerides (≥500 mg/dL) alongside elevated LDL-C 1

Pharmacokinetic Considerations

The interaction between rosuvastatin and fenofibrate is minimal:

• Fenofibrate increases rosuvastatin exposure by only about 7% (AUC) and 21% (Cmax) 2
• This is considered a clinically insignificant interaction compared to gemfibrozil, which significantly increases statin levels 1

Safety Profile

Clinical studies support the relative safety of this combination:

• In the FIELD study with approximately 1,000 patients on statin-fenofibrate combination, no cases of rhabdomyolysis were reported 1
• The ACCORD study showed no significant differences in myositis, rhabdomyolysis, or liver enzyme elevations between simvastatin-fenofibrate combination and simvastatin alone 1

Potential Adverse Effects to Monitor

While generally safe, be aware of potential issues:

• Renal effects: Monitor kidney function as rare cases of acute renal failure have been reported 3
• Muscle symptoms: Watch for signs of myopathy or rhabdomyolysis
• Liver enzymes: Monitor for elevations, though studies show similar rates to statin monotherapy 4

FDA Labeling Considerations

The FDA drug label for rosuvastatin specifically addresses fenofibrate combinations:

• "Consider if the benefit of using fibrates concomitantly with rosuvastatin outweighs the increased risk of myopathy and rhabdomyolysis"
• "If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug" 5

Practical Algorithm for Management

1. Before starting combination:

   • Ensure patient truly needs both medications (high LDL-C plus triglycerides ≥500 mg/dL)
   • Check baseline renal function, liver enzymes, and CK levels
   • Review for drug interactions with other medications

2. Dosing recommendations:

   • Start with moderate doses of both medications
   • Consider rosuvastatin 5-10 mg daily with fenofibrate 135-145 mg daily
   • Avoid high-dose rosuvastatin in combination therapy

3. Monitoring schedule:

   • Follow up within 4-6 weeks of initiation
   • Check renal function, liver enzymes
   • Educate patient about reporting muscle pain, weakness or dark urine immediately

4. Contraindications:

   • Severe renal impairment
   • Active liver disease
   • History of statin-induced myopathy

In conclusion, the fenofibrate-rosuvastatin combination is reasonable when clinically indicated, with fenofibrate being the preferred fibrate to combine with any statin due to its more favorable safety profile compared to gemfibrozil.