Impact of posaconazole tablets for secondary prophylaxis on drug interactions in haploidentical allogeneic stem cell transplantation: A single-arm, open-label, prospective study

Posaconazole (POS) tablets were approved for prophylaxis of invasive fungal disease (IFD) in patients with hematological disorders undergoing haploidentical allogeneic stem cell transplantation (haplo-HSCT). There is limited research on drug-drug interactions (DDIs) between POS, cyclosporine A (CsA), and mycophenolate mofetil (MMF), as well as the impact of POS on acute graft versus host disease (aGVHD) in haplo-HSCT patients receiving POS for secondary antifungal prophylaxis (SAP). This study aims to investigate the DDI between POS, CsA, and MMF, as well as the incidence of aGVHD in haplo-HSCT patients with prior-IFD. This is a single-arm, open-label, prospective trial. Plasma concentrations of POS, mycophenolic acid (MPA), and CsA were monitored within 30 days post-transplantation. In addition, the incidences of aGVHD and IFD were observed. Forty-six patients with prior-IFD were enrolled. POS reached a steady state by week 2, with the mean through blood concentration (TBC) of 0.54 ± 0.07 μg/mL. MPA achieved target levels by week 3 without dose adjustment, with a mean TBC of 0.84 ± 0.08 mg/L. The CsA TBC levels required individualized dose modifications. The incidences of grade II-IV and grade III-IV aGVHD were 47.83% and 21.74%, respectively. The breakthrough rate of SAP was 4.35% at 100 days and 10.86% at 6 months. The conclusions indicate that POS tablets do not require dose adjustments for MMF; however, CsA dosing must be individualized. POS tablets appear to be effective and well-tolerated for SAP in haplo-HSCT (the Chinese Clinical Trial Registry: www.chictr.org.cn (ChiCTR2200059472)).