Abstract
Background:
There are limited researches about posaconazole enteric-coated tablets on the efficacy and tolerability of secondary antifungal prophylaxis(SAP)for invasive fungal disease (IFD) in haploidentical allogeneic hematopoietic stem cell transplantation༈allo-HSCT༉.
Objective:
To investigate the plasma concentration of posaconazole enteric-coated tablets on the efficacy and tolerability of SAP and drug-drug interactions between posaconazole, cyclosporine A (CsA) and mycophenolate mofetil (MMF) in haploidentical allo-HSCT.
Methods:
We conducted a single-arm, open-label, prospective trial (ChiCTR2200059472, Date of Registration 30th April, 2022) to assess efficacy and tolerability of posaconazole enteric-coated tablets as SAP in haploidentical allo-HSCT patients. Plasma concentrations of posaconazole and mycophenolic acid (MPA,active metabolites of MMF) as well as CsA were monitored within 30 days post-transplantation. Additionally, the incidence of IFD was observed.
Results
Fourty-six patients previously with IFD were enrolled in the trial. The incidence of IFD was 4.35% at 100 days and 10.86% at 6 months. The primary cause of prophylaxis failure was gastrointestinal intolerance. The mean plasma concentrations of posaconazole were 0.48 ± 0.06ug/ml at week 1, 0.54 ± 0.07ug/ml at week 2, 0.75 ± 0.08ug/ml at week 3 and 0.90 ± 0.08ug/ml at week 4. The mean plasma concentrations of CsA were 133.04 ± 0.13ng/ml at week 1, 179.53 ± 11.19ng/ml at week 2, 225.02 ± 13.80ng/ml at week 3 and 278.61 ± 13.61ng/ml at week 4. The mean plasma concentrations of MPA during week 2, 3 and 4 were 0.41 ± 0.06mg/L, 0.84 ± 0.08mg/L and 1.08 ± 0.13mg/L, respectively. Posaconazole reached steady state concentrations by week 2 and MPA reached target concentrations at week 3.
Conclusion
Posaconazole enteric-coated tablets appears to be effective and tolerability for SAP of IFD after haploidentical allo-HSCT. When cyclosporine, MMF, and posaconazole are used in combination, the dosage of MMF does not need to be adjusted. The dosage of CsA needs to be personalized and adjusted based on therapeutic drug monitoring.