Invasive fungal infection following venetoclax and posaconazole co‐administration

Summary The co‐administration of venetoclax, a BCL‐2 inhibitor, with a mould‐active azole, such a posaconazole, has potential to both prevent invasive fungal infection (IFI) and reduce the required treatment dose, and cost, of venetoclax. Posaconazole drug‐level monitoring is critical to ensuring adequate mould prophylaxis. A retrospective audit of 99 patients at a tertiary cancer centre, with myeloid malignancies co‐prescribed venetoclax and posaconazole between January 2018 and April 2022, was undertaken to evaluate the adequacy of posaconazole prescribing and the rate of breakthrough IFI. Seventy‐six patients (77%) had at least one posaconazole level measured in the study period, with 37% requiring a dose adjustment based on steady‐state trough levels. Breakthrough IFI occurred in 4% of patients, typically within 1 month of commencing anti‐mould prophylaxis. Close monitoring of posaconazole levels in venetoclax‐treated patients, particularly in the early, outpatient setting, is critical.