Rhabdomyolysis and acute renal failure in a cardiac transplant recipient due to multiple drug interactions

Background: The 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors lovastatin and simvastatin have been associated with rhabdomyolysis in cardiac transplant recipients. Herein, we report a case of a 52-year-old male recipient of a cardiac transplant who developed rhabdomyolysis and acute renal failure caused by simvastatin precipitated by multiple drug interactions. Methods: The patient had a history of cardiac transplantation (5 years before) and presented with a 2-day history of dark urine preceded by 2 weeks of diffuse myalgias. He had been maintained on cyclosporine throughout the entire post-transplant period. Simvastatin was added and pravastatin was discontinued 2 months before admission. Two weeks before the onset of muscle symptoms, digoxin and verapamil were started for new-onset atrial fibrillation. Creatinine phosphokinase levels peaked at 950,000 IU with serum creatinine of 3.3 mg/dL (baseline, 1.8 mg/dL). Results: Review of the medication history indicates a temporal association between the addition of 3 drugs (simvastatin, verapamil, and digoxin) to the medication regimen already containing cyclosporine and the episode of rhabdomyolysis. All of these drugs are cytochrome P450 3A4 and/or P-glycoprotein substrates that are known from previous pharmacokinetic studies to individually produce substantial increases in levels of simvastatin. Conclusion: We believe this case illustrates that avoiding the use of drugs that are cytochrome P450 3A4 and/or P-glycoprotein substrates reduces the risk of rhabdomyolysis caused by 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors.