Therapeutic Drug Monitoring of Posaconazole in Hematology Patients: Experience with a New High-Performance Liquid Chromatography-Based Method

Abstract

Parallel administration of the proton pump inhibitor (PPI) esomeprazole has been shown to decrease oral bioavailability of posaconazole in healthy volunteers. We prospectively analyzed serum samples (n ‫؍‬ 59) obtained from hematology patients (n ‫؍‬ 27) under posaconazole prophylaxis. Patients treated concomitantly with pantoprazole had significantly lower posaconazole levels than patients without PPI treatment (median levels of 630 g/liter versus 1,125 g/liter, respectively). These results suggest that drug monitoring is relevant when posaconazole and pantoprazole are administered concomitantly.

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

“…3A). In a cohort of 17 cardiothoracic transplant recipients, Shields and colleagues found significantly lower posaconazole concentrations in patients receiving proton pump inhibitors (37); a similar result was identified by Neubauer et al (31). Controlled studies in healthy volunteers have identified reductions in the area under the posaconazole concentration-time curve (AUC) of 32% (20) and 37% (41) with esomeprazole, with the later study also confirming the pH-dependent solubility (and absorption) of posaconazole through monitoring of intraluminal posaconazole concentrations (41).…”

“…Coadministration with food has been shown to increase posaconazole bioavailability by up to 4-fold (20); conversely, medications such as proton pump inhibitors have been shown to significantly decrease posaconazole exposure due to increased gastric pH (41). Low posaconazole concentrations have been commonly reported in clinical practice (3,10,23,31,37,39), with the current lack of an intravenous formulation of the drug complicating efforts to increase posaconazole exposure, particularly in critically ill patients (34).…”

“…Previous studies of posaconazole TDM have typically included small patient cohorts from a single institution (3,10,23,31,37). Using a multicenter retrospective design, this study aimed to investigate relationships between posaconazole concentration and clinical outcomes and adverse events, while also examining potential drug-drug interactions and clinical factors that may affect posaconazole concentrations.…”

Antifungal Prophylaxis with Posaconazole in Patients with Acute Myeloid Leukemia: Dose Intensification Coupled with Avoidance of Proton Pump Inhibitors Is Beneficial in Shortening Time to Effective Concentrations

“…Although conflicting data on this topic still exist in the literature (14,27), it should be noticed that in a study assessing posaconazole exposure after standard dosages in relation to the use or nonuse of pantoprazole in hematological patients, significantly lower median C min values were reported for patients taking this PPI than for those who did not (630 and 1,125 ng/ml, respectively) (20).…”

“…C ss values of Ͻ500 ng/ml were reported in several cases with this regimen by various authors (in 79.6% of cases [16], in 76.2% of cases [17], and in 44% of cases [18]). Likewise, when considering the threshold of 700 ng/ml, even higher percentages of cases with subtherapeutic C ss values were reported (in 85.2% of cases [16], in 90.5% of cases [17], in 70.3% of cases [19], in 48% of cases [20], and in 20% of cases [21]). Of note, it should not be overlooked that most of those studies considered either patients taking posaconazole alone or those taking it concomitantly with PPIs or with H 2 antagonists (22), which are known to impair the posaconazole absorption rate.…”