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.


CONCLUSIONS
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.
Kusus
M
M
Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Stapleton
D D
DD
Lertora
J J
JJ
Simon
E E
EE
Dreisbach
A W
AW
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects*; D004077:Digoxin / Q000008:administration & dosage / Q000009:adverse effects*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D016027:Heart Transplantation; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012206:Rhabdomyolysis / Q000139:chemically induced*; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects*; D014700:Verapamil / Q000008:administration & dosage / Q000009:adverse effects*
D000889:Anti-Arrhythmia Agents; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D004077:Digoxin; D016572:Cyclosporine; D019821:Simvastatin; D014700:Verapamil