Table of Contents
ISRN Transplantation
Volume 2013 (2013), Article ID 281285, 5 pages
http://dx.doi.org/10.5402/2013/281285
Clinical Study

Tacrolimus Dose Modification in Hematopoietic Cell Transplant Recipients Following a Change in Therapy from Fluconazole to Voriconazole

1College of Pharmacy, The University of Tennessee, Knoxville Campus, 1924 Alcoa Highway, P.O. Box 117, Knoxville, TN 37920, USA
2Department of Clinical Pharmacy, School of Pharmacy and Section of Infectious Diseases, School of Medicine, West Virginia University, Morgantown, WV 26506, USA
3Department of Pharmacy and Mary Babb Randolph Cancer Center, West Virginia University Healthcare, Morgantown, WV 26506, USA

Received 13 August 2012; Accepted 30 August 2012

Academic Editors: R. De la Camara, H.-J. Kim, and R. Rezzani

Copyright © 2013 Anthony J. Guarascio et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Antifungal therapy with voriconazole or fluconazole in combination with the calcineurin inhibitor tacrolimus exhibits significant CYP3A4 drug interaction potential in allogeneic hematopoietic cell transplant (HCT) recipients. The package insert for voriconazole has dosing recommendations for tacrolimus when voriconazole is started, but these do not apply to patients already receiving fluconazole therapy. The purpose of this retrospective study is to estimate appropriate dose modification of tacrolimus following a change in therapy from fluconazole to voriconazole. We performed a retrospective case-series analysis of five patients. The mean steady-state concentration/dose (C/D) ratio of tacrolimus increased from 413 (range, 255–642) to 850 (range, 670–953) following a switch from fluconazole to voriconazole ( ). This data represents a mean 2-fold increase in C/D ratios following the switch, indicating that the dose of tacrolimus may be most accurately reduced by approximately 50% following this switch in therapy. This provides some guidance for practitioners to estimate dose adjustments but will require close pharmacokinetic monitoring and adjustments on an individual patient basis.