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A prospective evaluation on the interaction of fluconazole and voriconazole on serum concentrations of budesonide in patients treated for gastrointestinal GVHD

Bone Marrow Transplantation volume 55, pages 1085–1092 (2020)Cite this article

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Abstract

The gastrointestinal (GI) tract is commonly affected by acute and chronic graft-versus-host disease (GVHD) in patients who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). For patients developing GI GVHD, nonabsorbable corticosteroids such as budesonide may be used alone to reduce the risk of systemic corticosteroid toxicities or combined with systemic steroids to enhance clinical responses and to allow more rapid tapering of systemic corticosteroid doses. This prospective crossover study was conducted to evaluate what effect two commonly used antifungal agents, fluconazole, and voriconazole, would have on the trough (Cmin) and peak (Cmax) levels of budesonide in adult patients who had undergone allo-HSCT who subsequently developed clinical GI GVHD. Fifteen subjects were enrolled and nine completed the study and were evaluable. When coadministered with budesonide, voriconazole significantly increased the geometric mean of budesonide Cmin and Cmax levels by 8.52- and 6.63-fold, respectively. The cohort to evaluate the interaction with fluconazole did not meet accrual goals to reach definitive conclusions. In conclusion, this prospective study demonstrated that when patients with GI GVHD are treated with budesonide concurrently with voriconazole, the systemic concentrations of budesonide increase substantially which could increase the risk of steroid-associated toxicities.

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Acknowledgements

The authors gratefully acknowledge the contributions of Juan Gea-Banacloche, MD for his assistance in the initial design of the protocol, Jaydira Del Rivero, MD for her assistance in the review of the final paper, and to all the research subjects who participated in the trial. This research was supported [in part] by the Intramural Research Program of the NIH, National Heart, Lung, and Blood Institute.

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Authors and Affiliations

  1. Clinical Center, Pharmacy Department, National Institutes of Health, Bethesda, MD, USA

    Thomas E. Hughes

  2. Verastem Oncology, Needham, MA, USA

    Lindsay Stansfield

  3. Otsuka Pharmaceutical Development and Commercialization, Inc, Rockville, MD, USA

    Parag Kumar

  4. Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    Tat’Yana Worthy & Richard W. Childs

  5. Office of Biostatistics Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    Xin Tian

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  1. Thomas E. Hughes
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Correspondence to Thomas E. Hughes.

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Hughes, T.E., Stansfield, L., Kumar, P. et al. A prospective evaluation on the interaction of fluconazole and voriconazole on serum concentrations of budesonide in patients treated for gastrointestinal GVHD. Bone Marrow Transplant 55, 1085–1092 (2020). https://doi.org/10.1038/s41409-020-0786-8

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