Multicenter Study of Posaconazole Therapeutic Drug Monitoring: Exposure-Response Relationship and Factors Affecting Concentration

A Single Center Experience for Antifungal Prophylaxis in Patients with Acute Myelogenous Leukemia

“…Seven of the patients receiving posaconazole had severe diarrhea or vomiting in our cohort. Posaconazole has a highly variable bioavailability and the association between prophylaxis failure and posaconazole serum levels was reported [16]. A recent multicenter study from Italy showed that posaconazole was switched to empirical systemic antifungal therapy in 102 (20 %) out of 510 AML patients with persistent neutropenia and fever [17].…”

Coadministration of posaconazole and sirolimus in allogeneic hematopoietic stem cell transplant recipients

“…However, the factor most significantly and strongly associated with the risk of IFI development was insufficient posaconazole serum levels ( o0.5 mL/L), 5 especially in patients with intestinal GvHD and/or diarrhea, given the drug's reported limitation of the oral solution formulation (P-value o0.0001; OR = 35.14, CI: 6.43-192).…”

“…Posaconazole dose was adjusted as required to maintain trough serum levels within the therapeutic range (40.5 mL/L, according to the majority of literature and center guidelines). 5 However, some recent studies identified a number of breakthrough fungal infections in patients with posaconazole concentrations between 0.5 and 0.7 mL/L, suggesting a different concentration target of 0.7 mL/L for antifungal prophylaxis. 5 Median follow-up was 357 days (range 43-1884) after HSCT.…”

“…5 However, some recent studies identified a number of breakthrough fungal infections in patients with posaconazole concentrations between 0.5 and 0.7 mL/L, suggesting a different concentration target of 0.7 mL/L for antifungal prophylaxis. 5 Median follow-up was 357 days (range 43-1884) after HSCT. Neutrophil engraftment occurred within a median of 18 days (range 10-30).…”

“…4 The oral solution formulation has the potential limitation of erratic oral absorption (in patients with intestinal GvHD and/or diarrhea), supporting the utility of therapeutic drug monitoring (TDM) in such conditions. 5 Moreover, posaconazole prophylaxis in allo-HSCT recipients is normally administered in combination with drugs for GvHD prophylaxis and/or treatment, most commonly cyclosporine (CsA) or tacrolimus. On the basis of its cytochrome P450 3A4 (CYP3A4) inhibitory activity, posaconazole may increase the exposure to CsA, warranting a recommendation for close monitoring of blood CsA levels and subsequent CsA dose adjustment, as required.…”