From the Guidelines
The combination of fibrates and statins should be used with caution due to increased risk of muscle toxicity and liver damage, and fenofibrate is the preferred fibrate to combine with statins rather than gemfibrozil, which significantly increases statin blood levels and toxicity risk. This combination therapy is generally reserved for patients with severe mixed dyslipidemia who haven't responded adequately to monotherapy. When prescribed together, patients on this combination should be monitored closely with regular liver function tests and creatine kinase measurements, especially during the first few months of treatment, as suggested by 1. Patients should be educated to immediately report muscle pain, weakness, or brown urine. Lower statin doses are typically recommended when initiating combination therapy, with pravastatin, rosuvastatin, or fluvastatin generally considered safer options due to their different metabolic pathways, as noted in 1. The increased risk occurs because both drug classes can independently cause myopathy, and fibrates (particularly gemfibrozil) inhibit statin metabolism and transport, leading to higher statin concentrations. Patients with renal impairment, advanced age, small body frame, hypothyroidism, or those taking multiple medications face higher risks and require more careful monitoring, as highlighted in 1.
Some key considerations when using fibrates with statins include:
- Monitoring for muscle toxicity and liver damage
- Using fenofibrate instead of gemfibrozil to minimize the risk of myopathy
- Starting with lower statin doses and adjusting as needed
- Regularly checking liver function tests and creatine kinase measurements
- Educating patients on the signs and symptoms of myopathy and the importance of reporting them promptly
It's also important to note that the combination of statin plus fibrate is accompanied by an increased danger of myopathy, but the use of moderate statin doses combined with fibrate appears to have a relatively low incidence of myopathy, especially when used in persons without multisystem disease or multiple medications, as stated in 1. Additionally, fibrates, particularly fenofibrate, may be useful not only for decreasing high triglyceride concentrations and increasing low HDL cholesterol but can further lower LDL cholesterol when applied together with a statin, as mentioned in 1.
From the Research
Risks and Considerations of Using Fibrates with Statins
- The combination of fibrates and statins can increase the risk of myopathy and rhabdomyolysis, particularly with gemfibrozil 2, 3, 4, 5, 6
- Gemfibrozil interferes with statin glucuronidation, which may increase the risk of myopathy due to elevations in statin serum levels 4, 5, 6
- Fenofibrate appears to be a more appropriate choice than gemfibrozil when combined with statins due to less myopathic potential 4, 5, 6
- Patients with hypothyroidism, renal insufficiency, and those taking cytochrome P450 inhibitors are at increased risk of fibrate/statine myopathy 3
- Clinicians should consider pharmacokinetic, pharmacodynamic, metabolic, pathophysiologic, and other factors that can increase the systemic exposure of statins and/or fibrates and hence heighten the risk of toxic effects on muscles 5
- Routine monitoring of creatinine is not required, but if a patient has a clinically important increase in creatinine, and other potential causes of creatinine increase have been excluded, consideration should be given to discontinuing fibrate therapy or reducing the dose 6
Clinical Considerations
- Combination therapy with a fibrate and a statin is a potentially useful therapy for patients with atherogenic lipid profiles 4, 5
- Clinicians should measure serum creatinine before fibrate use and adjust the dose accordingly for renal impairment 6
- Patients should be regularly monitored with regard to clinical and laboratory alterations, including signs of myopathy such as proximal myalgias, stiffness, weakness, and dark urine 3