Drug interaction between voriconazole and calcineurin inhibitors in allogeneic hematopoietic stem cell transplant recipients

Abstract

Although voriconazole has been shown to interact with calcineurin inhibitors, this interaction has not been thoroughly examined. The purpose of this study was to evaluate the drug interaction between voriconazole and calcineurin inhibitors among recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Twenty-one recipients of allogeneic HSCT were evaluated. Those recipients had been on CsA (n=10) or tacrolimus (n=11) when voriconazole (400 mg per day orally, or 8 mg/kg per day, i.v.) was initiated. Trough concentrations of calcineurin inhibitors were measured before and periodically after initiating voriconazole to determine the concentration/dose (C/D) ratio of calcineurin inhibitors. Median C/D ratio significantly increased by initiating voriconazole: from 86.0 (range, 43.5–178.8) to 120.2 (range, 86.1–379.4) in CsA (P<0.05), and from 595.9 (range, 51.3–1643.3) to 890.7 (range, 94.1–4658.3) (ng/ml)/(mg/kg) in tacrolimus (P<0.01). Median increases in the C/D ratio did not differ significantly between CsA and tacrolimus (82.1%, ranging from −9.4 to 266.9% vs 115.6%, ranging from 25.4 to 307.6%). These results indicate that voriconazole alters the blood concentration of calcineurin inhibitors with a wide range of interindividual variability after allogeneic HSCT. Dose adjustment of calcineurin inhibitors on initiating voriconazole should not be decided uniformly, but determined on an individual basis by close monitoring of their blood concentrations.