Rhabdomyolysis after concomitant use of cyclosporine, simvastatin, gemfibrozil, and itraconazole.
OBJECTIVE
To report a case of rhabdomyolysis in a patient receiving cyclosporine, simvastatin, gemfibrozil, and itraconazole.


METHODS
Rhabdomyolysis occurring in transplant patients receiving both cyclosporine and the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin has been well documented. The exact mechanism by which this interaction leads to rhabdomyolysis is unknown. Experience with newer agents of the statin drug class in transplant patients is limited. Since the interaction between cyclosporine and HMG-CoA reductase inhibitors involves the CYP3A4 enzyme system, the possibility of amplifying this interaction exists when other drugs affecting the same enzyme system are coprescribed. We describe a case in which a heart transplant recipient stable on a drug regimen that included cyclosporine, simvastatin, and gemfibrozil developed rhabdomyolysis after initiation of the antifungal agent itraconazole.


CONCLUSIONS
Drug-drug interactions due to shared metabolism via the CYP3A4 pathway can result in significant adverse outcomes. This article discusses concurrent use of an HMG-CoA reductase inhibitor with other drugs that inhibit the CYP3A4 isoenzyme, leading to a case of possible fatal rhabdomyolysis.


CONCLUSIONS
Clinicians must be aware of drugs metabolized via cytochrome P450 isoenzymes and identify those requiring risk-versus-benefit analysis before prescribing. Patients need to be educated as to signs and symptoms requiring immediate physician intervention.
Maxa
Jan L
JL
Baylor University Medical Center, 3500 Gaston Avenue, Dallas, TX 75246-2088, USA. janma@bhcs.com
Melton
Larry B
LB
Ogu
Chris C
CC
Sills
Michael N
MN
Limanni
Alex
A
D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D017809:Fatal Outcome; D015248:Gemfibrozil / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D017964:Itraconazole / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016377:Organ Transplantation; D012206:Rhabdomyolysis / Q000139:chemically induced*; D018570:Risk Assessment; D019821:Simvastatin / Q000009:adverse effects* / Q000627:therapeutic use
D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D000960:Hypolipidemic Agents; D007166:Immunosuppressive Agents; D017964:Itraconazole; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; D019821:Simvastatin; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D015248:Gemfibrozil