Superior Serum Concentrations with Posaconazole Delayed-Release Tablets Compared to Suspension Formulation in Hematological Malignancies

ABSTRACT Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in high-risk patients, is commercially available orally as a suspension formulation (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum steady-state concentrations ( C ss ) of PCZ stratified by the administered formulation for antifungal prophylaxis in patients with myeloid malignancies ( n = 150). The primary outcome was the attainment rate of the target C ss of ≥700 ng/ml. Secondary outcomes included toxicity assessment (hepatotoxicity and corrected QT QTc interval prolongation) and breakthrough fungal infections. Patients who received the PCZ-susp ( n = 118) or PCZ-tab ( n = 32) and had PCZ C ss assessment after at least 7 days of therapy were eligible. The median C ss in the PCZ-susp group was 390 ng/ml (range, 51 to 1,870 ng/ml; mean, 436 ng/ml) compared to 1,740 ng/ml (range, 662 to 3,350 ng/ml; mean, 1,781 ng/ml) in the PCZ-tab group ( P < 0.0001). The percentages of patients achieving the target goal of ≥700 ng/ml were 17% versus 97%, respectively ( P < 0.0001). Hepatotoxicity (grade 2 or higher) occurred in 1 patient in each group. QTc interval measurements were available for 32 patients in the PCZ-susp group and for 12 patients in the PCZ-tab group, and prolonged intervals of grade 2 or higher were noted in 9% ( n = 3) and 17% ( n = 2), respectively ( P = 0.6). Breakthrough fungal infections in the PCZ-susp and PCZ-tab groups were 7% ( n = 8) and 3% ( n = 1), respectively ( P = 0.68). We conclude that the use of PCZ-tab was associated with higher C ss and with the probability of achieving therapeutic goals without worsening of adverse effects.