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

Abstract

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.

Intravenous and tablet formulation of posaconazole in antifungal therapy and prophylaxis: A retrospective, non-interventional, multicenter analysis of hematological patients treated in tertiary-care hospitals

“…Our data demonstrates stable median posaconazole serum levels at steady-state of 1,067 mg/L (IQR 574-1,498 mg/L) for antifungal prophylaxis and 904 mg/L (IQR 728-1,550 mg/L) for antifungal therapy. These results are in line with several studies in patients with hematological/oncological underlying diseases reaching these targeted exposure ranges (Cornely et al, 2016;Cumpston et al, 2015;Jeong et al, 2016;Pham et al, 2016). Nevertheless, the rate of patients who achieved the targeted posaconazole serum levels at steady state is comparable to a study by Miceli et al (2015), but lower compared to other published data (Durani et al, 2015;Liebenstein et al, 2018).…”

“…Furthermore, our study demonstrates only a small number of adverse drug reactions rated as at least possibly associated with novel posaconazole formulations, which is comparable to other published data (Belling et al, 2017;Jeong et al, 2016;Kim et al, 2016). However, a study by Pham et al reported a relatively high rate of hepatotoxity of >10% of the observed patient population who received posaconazole tablet for prophylaxis and therapy of IFDs (Pham et al, 2016).…”

“…Out of 151 patients who received antifungal prophylaxis, a moderate number of nine (6%) breakthrough IFDs were reported by the participating investigators. This result is also within the range of breakthrough IFDs in other studies, reporting rates during posaconazole prophylaxis with novel formulations between 0-15% (Belling et al, 2017;Chin et al, 2017;Cumpston et al, 2015;Jeong et al, 2016;Tverdek et al, 2017), probably reflecting different exposure of patients to mold in various hospital settings and heterogeneity in patient-based risk factors.…”

“…Additionally, nine cases (31%) of rare proven mucormycosis, fusariosis, and trichosporosis were included in the therapy group, well known for high morbidity, mortality, and treatment costs (Heimann et al, 2019;Menzin et al, 2009;Seidel et al, 2017). Nevertheless, the failure rate as reported by the participating investigators is higher than those in previously reported studies (Jeong et al, 2016;Kim et al, 2016;Yi et al, 2017). The high mortality rate in this patient population underlines the urgent need of appropriate empiric and targeted antifungal therapy with respect to both, clinical outcome and associated costs (Zilberberg et al, 2010).…”

“…Several recent studies suggest superior pharmacokinetics and a similar safety profile of novel posaconazole formulations (tablet and intravenous solution) (Duarte et al, 2014;Krishna et al, 2012a;Krishna et al, 2012b;Maertens et al, 2014). A first multicenter observational study analyzing 61 hematological patients receiving posaconazole intravenous solution for antifungal prophylaxis and therapy demonstrated clinical efficacy with stable posaconazole serum levels of 1,000 mg/L, without any breakthrough IFDs (Jeong et al, 2016). Other studies, including one phase III interventional trial, analyzed the use of posaconazole tablet for antifungal prophylaxis with comparable results attaining target posaconazole serum levels while maintaining a favorable safety and tolerability profile (Cornely et al, 2016;Pham et al, 2016).…”