Patients with severe lipid abnormalities may require high-dose statin therapy, at times used in combination with additional agents. A report of a case of fatal rhabdomyolysis caused by the combination of simvastatin and gemfibrozil. Clinicians should be aware of risk factors for rhabdomyolysis, which include underlying renal insufficiency, high-dose statin therapy, and combination therapy with a fibrate.
– South Med J 2001 Oct;94(10):1023-6 — Fatal rhabdomyolysis caused by lipid-lowering therapy. — Federman DG, Hussain F, Walters AB.



Concomitant use of fibrates with statins has been associated with an increased risk of myopathy, but the underlying mechanism of this adverse reaction remains unclear. Gemfibrozil markedly increased the plasma concentrations of lovastatin acid, without affecting those of the parent lovastatin compared with placebo. The increased risk of myopathy observed during concomitant treatment with statins and fibrates may be partially of a pharmacokinetic origin. The risk of developing myopathy during concomitant therapy with lovastatin and a fibrate may be smaller with bezafibrate than with gemfibrozil.
– Clin Pharmacol Ther 2001 May;69(5):340-5 — Plasma concentrations of active lovastatin acid are markedly increased by gemfibrozil but not by bezafibrate. — Kyrklund C, Backman JT, Kivisto KT, Neuvonen M, Laitila J, Neuvonen PJ.



It has been clearly established that lipid-lowering treatments such as fibrates can reduce cardiovascular events. Potentially more serious adverse effects, which are more clearly related to drug treatment and are probably dose-dependent, include elevations in hepatic transaminase levels and myopathy; however, these effects are uncommon and generally resolve rapidly when treatment is stopped. The risk of myopathy with fibrate treatment is increased in patients with renal impairment. Lipid-lowering drugs should be administered with extra caution to elderly patients.
– Drugs Aging 2001;18(9):665-83 — How well tolerated are lipid-lowering drugs? — Tomlinson B, Chan P, Lan W.



An interaction with oral anticoagulants was observed.
– Artery 1980;7(1):73-82 — Hypolipidemic and hypouricemic action of fenofibrate in various types of hyperlipoproteinemias. — Harvengt C, Heller F, Desager JP.



Concomitant use of gemfibrozil with statins, particularly with cerivastatin, increases the risk of rhabdomyolysis, but the mechanism of this potentially fatal drug interaction remains unclear.
– Clin Pharmacol Ther 2002 Dec;72(6):685-91 — Gemfibrozil greatly increases plasma concentrations of cerivastatin. — Backman JT, Kyrklund C, Neuvonen M, Neuvonen PJ.