1. Antifungal Prophylaxis with Posaconazole Delayed-Release Tablet and Oral Suspension in a Real-Life Setting: Plasma Levels, Efficacy, and Tolerability
- Author
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Wilma Zinke-Cerwenka, Robert Krause, Hildegard Greinix, Jürgen Prattes, Timothy C Lin, Martin Hoenigl, Andreas Meinitzer, Albert Wölfler, Ines Zollner-Schwetz, Thomas Valentin, and David Lenczuk
- Subjects
0301 basic medicine ,Antifungal ,Adult ,Male ,medicine.medical_specialty ,Posaconazole ,Antifungal Agents ,medicine.drug_class ,030106 microbiology ,plasma concentration ,Clinical Therapeutics ,Gastroenterology ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Aged ,Retrospective Studies ,Pharmacology ,medicine.diagnostic_test ,business.industry ,Liter ,Breakthrough infection ,Plasma levels ,Pharmacology and Pharmaceutical Sciences ,Middle Aged ,Triazoles ,posaconazole ,Infectious Diseases ,Tolerability ,Therapeutic drug monitoring ,Medical Microbiology ,Plasma concentration ,Female ,business ,Infection ,medicine.drug - Abstract
We continuously determined posaconazole plasma concentrations (PPCs) in 61 patients with hematological malignancies receiving posaconazole (PCZ) delayed-release tablets (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 of >0.7 mg/liter, while 14 of 48 patients (29%) had at least one PPC of ≤0.7 mg/liter. In patients receiving OS, 4 of 13 patients (31%) always had PPCs of >0.7 mg/liter, 6 of 13 patients (46%) had at least one PPC of ≤0.7 mg/liter, and 3 (23%) patients never reached a PPC of 0.7 mg/liter. In patients with at least one determined PPC, the mean proportion of all PPCs of >0.7 mg/liter was 91% for PCZ DRT, whereas it was 52% for PCZ OS ( P = 0.001). In the per sample analysis, PPCs were significantly more likely to be >0.7 mg/liter in patients receiving DRT than in patients receiving OS (PPCs were >0.7 mg/liter in 91.4% [297/325] of patients receiving DRT versus 70.3% [85/121] of patients receiving OS; P < 0.001). Patients receiving PCZ DRT had higher proportions of PPCs of >0.7 mg/liter than patients receiving OS both in the per patient and in the per sample analyses. Two patients (3%) had side effects during PCZ prophylaxis, and one (2%) had fungal breakthrough infection. Therapeutic drug monitoring enables detection of extended periods of PPCs of ≤0.7 mg/liter (e.g., due to nonadherence or graft-versus-host disease), which may also be associated with the loss of protective intracellular PCZ concentrations, regardless of the PCZ formulation.
- Published
- 2017