Isavuconazole–tacrolimus drug–drug interactions in HSCT patients

Abstract

Abstract Objectives Because tacrolimus has a narrow therapeutic window and exhibits both intraindividual and interindividual variability, we attempted to establish the percentage of calcineurin inhibitor (CNI) dose reduction to prevent toxicity and ensure stem cell engraftment when using this immunosuppressant with the antifungal isavuconazole (ISA). By calculating the tacrolimus concentration/dose (C/D) ratio, we expected to demonstrate the magnitude of change in the C/D ratio from baseline after ISA administration. Methods We evaluated the interaction between ISA, a new triazole antifungal used in prophylaxis for invasive fungal infections, and the CNI class of immunosuppressive drugs, specifically tacrolimus, in 11 blood samples from HSCT recipients. Results The mean tacrolimus C/D ratio increased 1.44-fold from baseline 48 h after ISA administration (P = 0.001). Conclusions Although further investigation is needed, the results of this study suggest that a reduction of 18% in tacrolimus may be recommended.