Effects of antifungal drugs on the plasma concentrations and dosage of tacrolimus in kidney transplant patients

Objectives Tacrolimus is one of the three basic immunosuppressants used following kidney transplantation, and its plasma concentration is susceptible to antifungal drugs. Abnormal tacrolimus concentrations may lead to adverse outcomes for patients. Adjustment of the tacrolimus dose after administering antifungal drugs to patients with fungal infection after transplantations therefore has important clinical significance. Our objective is to measure the impact of antifungal drugs on the plasma concentration of tacrolimus in kidney transplant patients. Methods A retrospective study was carried out in 109 kidney transplant recipients treated with a tacrolimus-based regimen and antifungal drugs simultaneously. Tacrolimus levels and dosage requirements were compared before and during antifungal therapy. Results The plasma levels of tacrolimus were significantly increased after the combination with voriconazole and fluconazole (p<0.05). Consequently, the daily dose of tacrolimus was significantly reduced after the combination (p<0.05). However, although the tacrolimus concentration was significantly decreased after the administration of caspofungin (p<0.05), no apparent change in the daily dose of tacrolimus was found. Moreover, there were no significant changes in the tacrolimus levels and the daily dose after the combination with micafungin (p>0.05). Conclusions Our results suggest that there is considerable variability in the interaction between tacrolimus and different antifungal drugs. The dose of tacrolimus should be reduced by two-thirds and one-third before the combination with voriconazole and fluconazole, respectively. It is not recommended that the dose should be adjusted before combination with other antifungal drugs, and the dose should be adjusted under the guidance of therapeutic drug monitoring.