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Δευτέρα 26 Μαρτίου 2018

Antifungal prophylaxis with Posaconazole delayed-release tablet and oral suspension in a Real-life setting: plasma levels, efficacy and tolerability [PublishAheadOfPrint]

We continuously determined Posaconazole plasma concentrations (PPCs) in 61 patients with hematological malignancies receiving Posaconazole (PCZ) delayed-release tablet (DRT) (48 patients, median duration of intake 92 days) and PCZ oral solution (OS) (13 patients, median duration of intake 124 days). PCZ DRT and OS antifungal prophylaxis was efficient and well tolerated. Thirty-four of 48 patients (71%) receiving DRT always had PPCs >0.7 mg/L, while 14 of 48 patients (29%) had at least one PPC ≤0.7 mg/L. In patients receiving OS 4 of 13 patients (31%) always had PPCs >0.7 mg/L, 6 of 13 patients (46%) had at least one PPC ≤0.7 mg/L, and 3 (23%) patients never reached a PPC of 0.7 mg/L. In patients with at least one determined PPCs the mean proportion of all PPCs >0.7 mg/L was 91% for PCZ DRT versus 52% for PCZ OS (p=0.001). In per sample analysis PPCs in patients receiving DRT were significantly more likely to be >0.7 mg/L when compared to PPCs in patients receiving OS [lsqb]91.4% (297/325) of PPCs >0.7 mg/L in DRT versus 70.3% (85/121) in OS; p<0.001[rsqb]. PCZ DRT has higher proportions of PPCs >0.7 mg/L compared to OS, both in per patient and in per sample analysis. Two patients (3%) had side effects during PCZ prophylaxis and one (2%) had fungal breakthrough infection. TDM enables to detect extended periods of PPCs ≤0.7 mg/L (e.g., due to non-adherence or GHVD), which may be associated also with loss of protective intracellular PCZ concentrations regardless of PCZ formulation.



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