A Prospective Evaluation on the Interaction of Fluconazole and Voriconazole on Serum Concentrations of Budesonide in Patients Treated for Gastrointestinal GVHD.

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.