Safety, clinical effectiveness and trough plasma concentrations of intravenous posaconazole in patients with haematological malignancies and/or undergoing allogeneic haematopoietic stem cell transplantation: Off-trial experience

Objectives: This study describes the safety, clinical effectiveness and trough plasma concentration (C_min) of intravenous (iv) posaconazole, provided as part of Merck Sharp and Dohme Australia's Named Patient Programme (NPP) in non-clinical trial settings. Methods: A multicentre, retrospective study on the NPP use of iv posaconazole between July 2014 and March 2015 across seven Australian hospitals. Results: Seventy courses of iv posaconazolewere prescribed and evaluated in 61 patients receiving treatment for haematological malignancy. Sixty-one courses were prescribed for prophylaxis against invasive fungal disease (IFD), the majority of which (59) were initiated in patients with gastrointestinal disturbances and/or intolerance to previous antifungals. The median (IQR) duration for prophylaxis was 10 (6-15) days. No breakthrough IFD was observed during or at cessation of iv posaconazole. Nine courses of iv posaconazole were prescribed for treatment of IFD with a median (IQR) duration of 19 (7-30) days. Improvement in signs and symptoms of IFD was observed in five cases at cessation of, and six cases at 30 days post-iv posaconazole. C_min was measured in 39 courses of iv posaconazole, with the initial level taken [median (IQR)] 4 (3-7) days after commencing iv posaconazole. The median (IQR) of initial C_min was 1.16 (0.69-2.06) mg/L. No severe adverse events specifically attributed to iv posaconazole were documented, although six courses were curtailed due to potential toxicity. Conclusions: This non-clinical trial experience suggests that iv posaconazole appeared to be safe and clinically effective for prophylaxis or treatment of IFD in patients receiving treatment for haematological malignancies.