E levated levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C) are established risk factors for cardiovascular disease. 1 Lipid-lowering therapy has been shown to decrease the risk of cardiovascular events. 2,3 The statins (hydroxymethylglutaryl coenzyme A in- hibitors) are preferred as first-line drugs for treatment of hypercholesterolemia. However, target lipid concentrations sug- gested by the current guidelines may be difficult to achieve and may require com- bination therapy with statins and fibric acid derivatives. 4 Although combination therapy has complementary effects on lipid parameters, it also harbors the risk of myopathy and fatal rhabdomyolysis. The reported incidence of myopathy, generally defined clinically as creatine kinase levels more than 10 times the up- per limit of normal with accompanying muscle pain or weakness, is 0.1–0.2% in statin clinical trials. 5,6 The incidence is approximately 0.12% when statins are used in combination with fibric acid derivatives. 7 We present a case of serious hepatocel- lular injury and rhabdomyolysis, causing acute renal failure in a patient treated with fluvastatin–gem- fibrozil combination therapy. As of November 22, 2006, this is the first report of both hepatic and renal toxicity fol- lowing combination therapy with these agents. Case Report A 56-year-old woman with a history of hyperlipidemia presented with fatigue, weakness in her lower extremities, and red-colored urine. One month prior, she had started com- bination therapy with fluvastatin 80 mg/day and gemfibrozil 1200 mg/day. The dosages of the drugs had remained the same throughout therapy. She was not using any other medications. She had no history of smoking, alcohol con- Combined Organ Failure with Combination Antihyperlipidemic Treatment: A Case of Hepatic Injury and Acute Renal Failure Hadim Akoglu, Rahmi Yilmaz, Alper Kirkpantur, Mustafa Arici, Bulent Altun, and Cetin Turgan Author information provided at the end of the text. The Annals of Pharmacotherapy ■ 2007 January, Volume 41 ■ 143 www.theannals.com OBJECTIVE: To report a case of acute hepatic injury and acute renal failure secondary to rhabdomyolysis associated with fluvastatin–gemfibrozil combination therapy for hyperlipidemia. CASE SUMMARY : A 56-year-old woman with a history of hyperlipidemia presented with fatigue, weakness in her lower extremities, and red-colored urine. One month prior, she had started combination therapy of fluvastatin 80 mg/day and gemfibrozil 1200 mg/day. On physical examination, she had a serious loss of motor function in the upper and lower extremities. Her laboratory tests revealed severe liver enzyme elevation and abnormal renal function. Abdominal ultra- sound did not show hepatic cholestasis, renal parenchymal abnormality, or obstruction. DISCUSSION: Statins and fibric acid derivatives have complementary effects on mixed hyperlipidemia. However, such combination therapy increases the risk of myopathy, which may result in life-threatening rhabdomyolysis. Several reports have suggested that combination fluvastatin–gemfibrozil therapy is both effective and safe in mixed lipid disorders. In our patient, severe rhabdomyolysis with serious hepatocellular injury was observed one month after the combination antihyperlipidemic therapy was started. Assessment with the Naranjo probability scale determined that an adverse drug reaction was probable. The mechanism of this combined toxicity is difficult to clarify, although in vivo and in vitro studies to date have reported considerable data concerning antihyperlipidemic drug interactions. CONCLUSIONS: Clinicians should carefully consider the risks and benefits of treating dyslipidemia with fluvastatin–gemfibrozil combination therapy. KEY WORDS: acute renal failure, dyslipidemia, fluvastatin, gemfibrozil, hepatitis, statins. Ann Pharmacother 2007;41:143-7. Published Online, 5 Dec 2006, www.theannals.com, DOI 10.1345/aph.1H251 by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from