Rhabdomyolysis in a patient receiving atorvastatin and fluconazole

Abstract

The hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used hypolipidemic agents which decrease cardiovascular morbidity and mortality in both primary and secondary prevention. Lovastatin, simvastatin, atorvastatin, fluvastatin, pravastatin and rosuvastatin are globally available. In general, statins are well tolerated, and serious adverse effects are rare. The most important adverse effect of statins is myopathy [1–3]. Clinically relevant myopathy is often defined as a proximal or generalised pain and/or weakness in skeletal muscles, and a creatine phosphokinase (CK) value higher than ten times the upper limit of the normal range. Statin-associated myopathy may also occur with normal CK levels [4]. Statin myopathy can progress to necrosis of muscle cells (rhabdomyolysis) which may lead to myoglobinuria and acute renal failure [1–3]. CYP3A4 catalyses the biotransformation of lovastatin, simvastatin and atorvastatin [5]. Erythromycin, clarithromycin, itraconazole and ketoconazole are examples of widely used drugs that inhibit CYP3A4. The concomitant use of these drugs with lovastatin, simvastatin or atorvastatin leads to increased bioavailability and reduced elimination of the statin, thereby greatly increasing the potential for myotoxicity [2, 5, 6]. One case of rhabdomyolysis after concomitant use of fluconazole and simvastatin has been reported [7], but, to our knowledge, there are no reported cases of rhabdomyolysis associated with concomitant intake of fluconazole and atorvastatin. We describe a fatal case of rhabdomyolysis in a 76-year-old male after use of this drug combination.