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

Posaconazole is widely recommended for preventing and treating invasive fungal infections (IFIs) in immunocompromised patients, especially those with prolonged neutropenia. However, the concentration of the oral suspension formulation can be affected by factors such as co-administration with acid-suppressing medications, influencing its efficacy and safety.

This study examined the impact of proton pump inhibitors (PPIs) and other factors on posaconazole concentrations and the concentration-to-dose ratio (C/D) while also evaluating adverse drug reactions in patients with hematologic malignancies.

We conducted a retrospective analysis of patients who received posaconazole for IFI prophylaxis or treatment, assessing demographic and clinical data, adverse reactions, treatment outcomes, and drug concentration assays. The study focused on the effects of PPIs on Cmin and C/D.

Data from 283 posaconazole Cmin measurements in 86 patients were analyzed. The incidence of probable or proven IFIs was 6.4% (5/78). PPI use reduced posaconazole Cmin levels but did not significantly impact prophylactic efficacy. Esomeprazole and rabeprazole were explicitly associated with decreased Cmin. Hepatotoxicity was linked to the co-administration of hepatotoxic drugs, indicating that posaconazole was not the sole contributor.

Co-administration of esomeprazole or rabeprazole lowers posaconazole plasma concentrations without compromising prophylactic efficacy against IFIs. Nonetheless, caution is advised when combining these drugs in high-risk immunocompromised patients.