Nephrotoxicity of Concomitant Administration of Tacrolimus and Nephrotoxic Antimicrobial Agents (Aminoglycosides and Glycopeptides) After Allogeneic Hematopoietic Stem Cell Transplantation

Tacrolimus has been widely used for the prophylaxis or treatment of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nephrotoxicity is one of its most important toxicities. Recipients of all-HSCT are highly susceptible to infectious complications and are often treated with nephrotoxic antimicrobial agents such as aminoglycosides (AGs) and glycopeptides (GPs). Since nephrotoxicity of concomitant use of tacrolimus and these nephrotoxic agents has yet to be fully and systematically evaluated, we retrospectively evaluated it in the recipients of allo-HSCT. Recipients of allo-HSCT who received intravenous AGs or GPs during the continuous intravenous infusion of tacrolimus within 30 days after transplantation were selected from the data base and 50 patients were included. Patients who received liposomal amphotericin-B or foscarnet were excluded. The data including patient characteristics, whole blood concentration of tacrolimus, dose and duration of AG/GP treatment, and serum creatinine (sCr) were evaluated. Therapeutic drug monitoring of AGs, GPs, and tacrolimus was performed in all the patients. Median age of the patients was 47.5 years (range: 18-60) and diagnoses were all hematological diseases. In the 50 patients, there were 40 episodes of tacrolimus concomitant with AGs (amikacin, gentamicin, arbekacin) and 38 with GPs (teicoplanin, vancomycin). Median duration of the concomitant administration with tacrolimus was 8 days (range: 2-22) for AGs and 11.5 days (range: 4-40) for GPs. Mean blood concentrations of tacrolimus during AG and GP administration were 17.1±2.1 and 16.2±1.6 μg/ml, respectively. Twice or greater increases of sCr compared with that before initiating AGs or GPs were observed only in 2 of 40 (5.0%) episodes with AGs and 1 of 38 (2.8%) with GPs. Nephrotoxicity was reversible and manageable in all cases and no patient required hemodialysis. Concomitant administration of tacrolimus and AGs or GPs is feasible even in the early post-transplant period. However, appropriate management with therapeutic drug monitoring for each agent is essential.