Is it safe to prescribe Crestor (rosuvastatin) 20 mg with TRICor (fenofibrate) 48 mg?

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Last updated: December 5, 2025View editorial policy

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Safety of Crestor 20 mg with TRICor 48 mg

Yes, it is safe to prescribe Crestor (rosuvastatin) 20 mg with TRICor (fenofibrate) 48 mg—this combination is reasonable when clinically indicated and is associated with significantly lower rates of muscle toxicity compared to gemfibrozil-statin combinations. 1

Evidence Supporting Safety

The American Heart Association's 2016 scientific statement explicitly states that "combination therapy with fenofibrate/fenofibric acid and any statin is reasonable when clinically indicated" and that fenofibrate is the preferred fibrate when statin-fibrate combination therapy is needed. 1

Clinical Trial Safety Data

  • In the FIELD study (n=9,795), approximately 1,000 patients received statin-fenofibrate combination therapy and none experienced rhabdomyolysis. 1

  • The ACCORD study demonstrated no statistically significant differences in the incidence of myositis, rhabdomyolysis, or hepatic transaminase elevations with simvastatin-fenofibrate combination therapy compared to simvastatin monotherapy in patients with type 2 diabetes. 1

  • FDA Adverse Event Reporting System data show that rhabdomyolysis reports per 1 million prescriptions were approximately 15 times lower for fenofibrate (0.58 per million) than for gemfibrozil (8.6 per million) when prescribed with statins. 1

Clinical Indications for This Combination

The 2013 ACC/AHA cholesterol guideline states that fenofibrate may be considered concomitantly with a low- or moderate-intensity statin only if the benefits from ASCVD risk reduction or triglyceride lowering when triglycerides are ≥500 mg/dL are judged to outweigh the potential risk for adverse effects. 1

When to Consider This Combination:

  • Patients with mixed dyslipidemia requiring both LDL-C reduction and triglyceride lowering 1
  • Patients with triglycerides ≥500 mg/dL at risk for pancreatitis 1
  • Patients with triglycerides ≥204 mg/dL and HDL-C ≥40 mg/dL may experience additional cardiovascular benefit 1

Required Monitoring

Renal Function Monitoring (Critical)

Renal status must be evaluated before fenofibrate initiation, within 3 months after initiation, and every 6 months thereafter using both serum creatinine and eGFR. 1

  • Fenofibrate should not be used if eGFR <30 mL/min per 1.73 m² (moderate or severe renal impairment) 1
  • If eGFR is 30-59 mL/min per 1.73 m², fenofibrate dose should not exceed 54 mg/day 1
  • If eGFR decreases persistently to ≤30 mL/min per 1.73 m² during follow-up, discontinue fenofibrate 1

Muscle Toxicity Monitoring

  • Obtain baseline creatine kinase (CK) before initiating combination therapy 1
  • Educate patients to immediately report muscle pain, tenderness, weakness, or dark urine 1
  • Check CK levels if any muscle symptoms develop 1
  • Monitor for muscle symptoms at 6-12 weeks after starting therapy and at each follow-up visit 1

Hepatic Monitoring

  • Obtain baseline hepatic transaminases before initiation 1
  • Monitor ALT/AST approximately 12 weeks after starting therapy, then annually or more frequently if indicated 1
  • Discontinue if persistent ALT elevations ≥3 times upper limit of normal occur 1

Lipid Monitoring

  • Obtain fasting lipid panel within 4-12 weeks after initiation or dose adjustment 1
  • Continue monitoring every 3-12 months thereafter 1

Important Caveats

Creatinine Elevation

Fenofibrate is associated with increases in serum creatinine (average 0.113-0.136 mg/dL or 10-12 mmol/L). 1 This is typically reversible upon discontinuation but requires monitoring as outlined above. 1

Limited Cardiovascular Benefit in Some Populations

While safe, the ACCORD trial showed that fenofibrate-simvastatin did not reduce cardiovascular events compared to simvastatin alone in the overall trial population or in those with or without clinical CVD. 1 However, patients with triglycerides ≥204 mg/dL and HDL-C ≥40 mg/dL may have experienced cardiovascular benefit. 1

Avoid Gemfibrozil

Gemfibrozil should not be initiated in patients on statin therapy due to significantly increased risk for muscle symptoms and rhabdomyolysis. 1 The combination of gemfibrozil with rosuvastatin should be avoided per FDA labeling. 1

Practical Implementation

When prescribing this combination:

  1. Verify baseline eGFR is ≥30 mL/min per 1.73 m² 1
  2. Obtain baseline CK, ALT/AST, and lipid panel 1
  3. Educate patient about muscle symptom reporting 1
  4. Schedule renal function monitoring at 3 months, then every 6 months 1
  5. Schedule hepatic and lipid monitoring at 12 weeks, then periodically 1
  6. Adjust fenofibrate dose if eGFR 30-59 mL/min per 1.73 m² 1

This combination represents a guideline-supported approach with robust safety data when appropriate monitoring is implemented. 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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