Effectiveness of combined proton pump inhibitors and posaconazole prophylaxis against invasive fungal infections in patients with hematologic malignancies: A retrospective study

Abstract

Background: Posaconazole (POS) is widely recommended for the prophylaxis and treatment of invasive fungal infections (IFIs) in immunocompromised patients, particularly those with prolonged neutropenia and a high risk of infection. The oral suspension form of POS, although commonly used, has its concentration influenced by various factors, impacting its effectiveness and safety. Aim: This retrospective study aimed to investigate the effects of PPIs on POS concentrations and C/D to explore their impact on prophylactic outcomes and examine other potential factors that influence POS concentration. Method: This retrospective study involved patients who received POS for IFI prophylaxis or treatment. The study specifically focused on the effects of PPIs on POS plasma trough concentrations (Cmin) and concentration-to-dose (C/D) ratios. Results: The analysis included 283 POS trough concentrations from 86 patients. The incidence of probable and proven IFIs was 6.4% (5/78). The use of PPI reduced POS Cmin levels but did not significantly affect the effectiveness of prophylaxis. Esomeprazole and rabeprazole were found to lower POS Cmin. The occurrence of hepatotoxicity was associated with the co-administration of drugs known to cause liver damage, indicating that POS was not the sole factor in these cases. Conclusion: Co-administration of esomeprazole or rabeprazole with posaconazole reduces its plasma concentrations but does not compromise prophylactic effectiveness against invasive fungal infections. This observation underscores the critical importance of vigilant management and comprehensive follow-up to optimize therapeutic outcomes in this high-risk patient population.