Can atorvastatin (lipitor) and fenofibrate (tricor) be prescribed together?

From the Guidelines

Atorvastatin and fenofibrate can be prescribed together, but with caution and close monitoring due to the increased risk of muscle-related side effects and rhabdomyolysis. This combination, known as statin-fibrate therapy, is sometimes used for patients with mixed dyslipidemia who have both elevated LDL cholesterol and high triglycerides, particularly when either medication alone doesn't adequately control both issues 1. The risk of rhabdomyolysis is lower when statins are combined with fenofibrate than gemfibrozil, as indicated by data from the FDA Adverse Event Reporting System, which showed that the number of reports of rhabdomyolysis per 1 million prescriptions was ≈15 times lower for fenofibrate than for gemfibrozil when prescribed with statins other than cerivastatin 1.

Some key points to consider when prescribing this combination include:

• Starting with lower doses of both medications and monitoring patients more closely for muscle-related side effects and liver function tests 1
• Checking liver function tests and muscle enzyme levels periodically
• Patients taking this combination should promptly report any unexplained muscle pain, tenderness, or weakness to their healthcare provider
• The combination works effectively because statins primarily lower LDL cholesterol by inhibiting cholesterol production in the liver, while fibrates mainly reduce triglycerides and modestly increase HDL cholesterol through different mechanisms involving gene activation

It's also important to note that the expert panel of the 2013 American College of Cardiology/American Heart Association blood cholesterol guideline recommended 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. However, the FDA-approved product labeling recommends that the combined use of gemfibrozil with lovastatin, fluvastatin, pravastatin, pitavastatin, atorvastatin, and rosuvastatin should be avoided 1.

From the FDA Drug Label

Data from observational studies indicate that the risk for rhabdomyolysis is increased when fibrates, in particular gemfibrozil, are co-administered with a statin 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 [see Clinical Pharmacology (12. 3)].

The use of atorvastatin and fenofibrate together may increase the risk of myopathy and rhabdomyolysis. This combination should be avoided unless the potential benefits outweigh the increased risk.

• Key considerations:
  • The risk of serious muscle toxicity appears to be increased in elderly patients and in patients with diabetes, renal insufficiency, or hypothyroidism.
  • Patients should be advised to report promptly unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.
  • CPK levels should be assessed in patients reporting these symptoms, and fenofibrate therapy should be discontinued if markedly elevated CPK levels occur or myopathy/myositis is suspected or diagnosed 2.

From the Research

Combination Therapy of Atorvastatin and Fenofibrate

• Atorvastatin (Lipitor) and fenofibrate (Tricor) can be prescribed together for the management of dyslipidemia, particularly in patients with mixed hyperlipidemia 3, 4, 5.
• The combination of a statin and a fibrate may raise the risk of myopathy and rhabdomyolysis, but fenofibrate appears to be a more appropriate choice due to less myopathic potential compared to gemfibrozil 3.
• Studies have shown that combination therapy with atorvastatin and fenofibrate can improve vascular reactivity and lipid profiles in patients with combined hyperlipidemia 6, 5.
• However, there have been reports of severe rhabdomyolysis and acute renal failure associated with the combination treatment of statin and fenofibrate, highlighting the need for careful monitoring and caution when prescribing these medications together 7.
• To minimize the risk of adverse effects, combination therapy should be hospital-based, reserved for high-risk patients, and conducted with regular monitoring of liver function and creatine kinase levels 4.

Key Considerations

• Patients should have normal renal, liver, and thyroid function tests and should not be receiving therapy with cyclosporine, protease inhibitors, or drugs metabolized through cytochrome P450 (especially 3A4) 4.
• Fibrates should be prescribed in the morning and statins at night to minimize peak dose interactions, and both drug classes should be progressively titrated from low doses 4.
• Regular monitoring of liver function and creatine kinase is required, and patients should be carefully monitored for signs of myopathy and rhabdomyolysis 7, 4.