Primary Evaluation and Management of Statin Therapy Complications

Dean A. Seehusen, MD, MPH, FAAFP; Chad A. Asplund, MD; Dawn R. Johnson, DO; Kevin Horde, A. DO


South Med J. 2006;99(3):250-254. 

In This Article

Cotherapy with Fibric Acids

The most recent ATP III goals for triglyceride levels make combination therapy very appealing.[5,27] However, adding fibric acid therapy, in particular gemfibrozil, to statin therapy may increase the incidence of significant muscle toxicity. Although some studies have found minimal risk,[8,28] others have found rates of significant myopathy as high as 5% with fibrate-statin combination therapy.[4] Graham et al1[1] found greater than a 10-fold increase in the incidence of hospitalized rhabdomyolysis when a fibrate was added to statin therapy. Manufacturer package inserts have started indicating that statins should be used at a low dose when combined with gemfibrozil.[3] Patients on combination therapy need to be counseled more extensively and should be monitored more closely for signs and symptoms of muscle problems.[4]

Although the reason for the increased rate of adverse effects with combination therapy is not clear, one possible explanation is that gemfibrozil increases serum concentrations of active statin acids.[29] In comparison, fenofibrate does not seem to increase serum statin concentrations, and may therefore pose a less significant risk than gemfibrozil when combined with a statin. An evaluation using the United States Food and Drug Administration's Adverse Event Reporting System revealed a 15-fold lower rate of reported cases of rhabdomyolysis in patients using fenofibrate combined with a statin compared with those taking gemfibrozil and a statin.[30]