Rhabdomyolysis after Concomitant Use of Simvastatin and Voriconazole in an Allogeneic Stem Cell Transplant Patient

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Objective: To report a case of rhabdomyolysis after concomitant use of simvastatin and voriconazole. Case Summary: A 65-year-old white male, weight 66 kg, 79 months post allogeneic stem cell transplant for chronic lymphocytic leukemia, was on a stable medication regimen that included voriconazole. He was hospitalized with weakness and elevated creatine kinase a few weeks after initiation of simvastatin for treatment of hyperlipidemia. His symptoms resolved and creatine kinase level returned to within the normal range after fluid administration and discontinuation of simvastatin. Discussion: The use of statins has become a standard in the treatment and prevention of atherosclerotic disease. Most statins are metabolized via the cytochrome P450 enzyme system. For simvastatin, metabolism occurs specifically via the CYP3A4 isoenzyme. Drugs known to inhibit this isoenzyme, such as voriconazole, can increase the risk for toxicities, including rhabdomyolysis, when used concomitantly with simvastatin. This case represents a probable drug-drug interaction, based on the Horn Drug Interaction Probability Scale. Conclusions: Due to the broad use of statins for the treatment and prevention of atherosclerotic disease, as well as the need for azole antifungals in the stem cell transplant population, interactions between these agents are becoming an increasing possibility. Care should be taken to minimize these interactions and, when feasible, a change to an alternative agent may be warranted to avoid adverse effects.