M. Kusus et al., Rhabdomyolysis and acute renal failure in a cardiac transplant recipient due to multiple drug interactions, AM J MED SC, 320(6), 2000, pp. 394-397
Citations number
21
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Background: The 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors
lovastatin and simvastatin have been associated with rhabdomyolysis in car
diac transplant recipients. Herein, we report a case of a 52-year-old male
recipient of a cardiac transplant who developed rhabdomyolysis and acute re
nal failure caused by simvastatin precipitated by multiple drug interaction
s. Methods: The patient had a history of cardiac transplantation (5 years b
efore) 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 d
iscontinued 2 months before admission. Two weeks before the onset of muscle
symptoms, digoxin and verapamil were started for new-onset atrial fibrilla
tion. Creatinine phosphokinase levels peaked at 950,000 IU with serum creat
inine 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 cont
aining cyclosporine and the episode of rhabdomyolysis. All of these drugs a
re cytochrome P450 3A4 and/or P-glycoprotein substrates that are known from
previous pharmacokinetic studies to individually produce substantial incre
ases in levels of simvastatin. Conclusion: We believe this case illustrates
that avoiding the use of drugs that are cytochrome P450 3A4 and/or P-glyco
protein substrates reduces the risk of rhabdomyolysis caused by 3-hydroxy-3
-methyl-glutaryl-coenzyme A reductase inhibitors.