Posaconazole in paediatric malignancy and haematopoietic stem cell transplant: dosing to achieve therapeutic concentration.

Abstract

Posaconazole is increasingly used for the treatment and prophylaxis of invasive fungal infections in immunocompromised children. We aimed to review evidence for paediatric posaconazole dosing regimens focusing on attainment of target concentrations and frequency of adverse effects. In May 2023, the Cochrane, Embase, MEDLINE and PubMed databases were searched for articles reporting posaconazole dosing in children with malignancy or post-haematopoietic stem cell transplantation. Studies reporting the attainment of target serum concentrations were included. Overall, 24 studies were included. Eighteen studies of the oral suspension consistently reported poor attainment of target concentrations for prophylaxis (≥0.7 µg/mL, 12%-78%) despite high daily doses of 14-23 mg/kg/day (max. 1200 mg/day). Target attainment was significantly affected by gastric pH and food intake. Six studies of the delayed-release tablet (DRT) reported 58%-94% achieved concentrations ≥0.7 µg/mL, with the majority using lower doses of 4-12 mg/kg/day (max. 300 mg/day). Similarly, one study of powder for oral suspension found 67%-100% achieved target concentrations with a dose of 6 mg/kg/day (max. 300 mg/day). As expected, the IV formulation had high attainment of prophylaxis targets (81%-90%) with 6-10 mg/kg/day (max. 400 mg/day). All formulations were well tolerated, and no relationship between adverse effects and posaconazole concentrations was identified. The required posaconazole dose in immunocompromised children varies depending on the formulation. The IV infusion had the highest attainment of therapeutic concentration followed by the DRT and powder for suspension. By contrast, the oral suspension had low attainment of target concentrations despite higher daily doses.