Effects of voriconazole on tacrolimus metabolism in a kidney transplant recipient

Abstract

Infection occurs frequently in the organ transplant recipients during the post-transplant period because of immunosuppression. Therefore, prophylactic antimicrobial agents are often used. The azole antifungals, widely prescribed prophylactically, are known to have many drug-drug interactions. This report presents a case of drug-drug interaction between voriconazole and tacrolimus in a kidney transplant recipient. Voriconazole treatment led to a dramatic increase in tacrolimus concentration that required its discontinuation in spite of the manufacturer's guidelines that recommend a reduction of tacrolimus dosage by one-third. The present drug-drug interaction can be attributed to a strong inhibitory effect on cytochrome P450-3A4 activity by voriconazole. When voriconazole and tacrolimus are coadministered, close monitoring of tacrolimus blood levels is recommended as the rule-of-thumb reduction of tacrolimus dose by one-third may not be satisfactory.

Cytochrome P450 genetic polymorphisms influence the serum concentration of calcineurin inhibitors in allogeneic hematopoietic SCT recipients

“…There are some studies describing a clinically significant drug interaction with calcineurin inhibitors in renal transplants and HSCT recipients. [18][19][20] In order to reduce the impact of other drug interactions, our study compared the initial concentration of calcineurin inhibitor, because at that time the patients were uniformly administered omeprazole, itraconazole, ciprofloxacin and acyclovir. In our study, the conditioning regimen also did not affect the initial concentration of the calcineurin inhibitor.…”

Dosing equation for tacrolimus using genetic variants and clinical factors

“…Haematocrit and aspartate aminotransferase (AST) have been previously shown to be important clinical factors [10] and neither was collected in our study. Future studies should also consider concomitant administration of anti-fungals given the potential for drug interactions [51,52].…”

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“…14 Voriconazole is characterized by a strong inhibitory effect on cytochrome P450-3A4 activity, leading to clinically relevant interactions with calcineurin inhibitors such as tacrolimus and cyclosporine. 15 In our case, vori conazole caused reversible increase in cyclosporine levels along with a decrease in renal function. Antifungal therapy also was associated with a significant increase in cholestatic liver enzymes.…”