Cyclosporine a and itraconazole interaction in a renal transplant patient

Cyclosporine A (CsA) inhibits the activation of T cells theraby inhibiting production of soluble proliferative factors, interleukin-2 and other cytokines. Despite the development of newer agents, CsA is still the main immunosuppressive agent in solid organ transplantation. CsA is extensively metabolized in the liver via the cytochrome P450 enzyme system, principally by the CYP3A4 isoenzyme, and less extensively in the gastrointestinal tract and kidney. Drugs inhibiting CYP3A4 can decrease the metabolism of CsA, increase its blood concentration and damage renal function. This situation was well reported when itraconazole and CsA were concurrently administered in hearth, lung and renal transplantation. The value of monitoring plasma drug levels and individualizing dosage have been shown in several situations such as drugs interactions. We describe a case of drug interaction between CsA and itraconazole in a renal transplant patient. In this case, therapeutic drug monitoring and dose individualization avoided potential nephrotoxicity. We review the different mechanisms reported to explain this interaction.