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Title: Pharmacokinetics and safety results from the Phase 3 randomized, open-label, study of intravenous posaconazole in patients at risk of invasive fungal disease.
Austin Authors: Cornely, Oliver A;Robertson, Michael N;Haider, Shariq;Grigg, Andrew P ;Geddes, Michelle;Aoun, Mickael;Heinz, Werner J;Raad, Issam;Schanz, Urs;Meyer, Ralf G;Hammond, Sarah P;Mullane, Kathleen M;Ostermann, Helmut;Ullmann, Andrew J;Zimmerli, Stefan;Van Iersel, M L P S;Hepler, Deborah A;Waskin, Hetty;Kartsonis, Nicholas A;Maertens, Johan
Affiliation: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, ZKS Köln, University of Cologne, Germany, Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany
Merck & Co., Inc., Kenilworth, NJ, USA
Juravinski Hospital & Cancer Centre, Hamilton, Ontario, Canada
Austin Health, Heidelberg, Victoria, Australia
Tom Baker Cancer Centre, Calgary, Alberta, Canada
Institut Jules Bordet, Brussels, Belgium
The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Universitatsspital Zürich, Division of Hematology, University Hospital, Zürich, Switzerland
St Johannes Hospital Dortmund, Dortmund, Germany
Brigham & Women's Hospital, Boston, MA, USA
Department of Medicine, University of Chicago, Chicago, IL, USA
Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany
Universitätsklinikum Würzburg, Würzburg, Germany
Department of Infectious Diseases, University Hospital and Institute for Infectious Diseases, University of Bern, Bern, Switzerland
NVWA, Wageningen, The Netherlands
UZ Leuven Gasthuisberg Hematology, Leuven, Belgium
Issue Date: 1-Dec-2017
Publication information: The Journal of antimicrobial chemotherapy 2017; 72(12): 3406-3413
Abstract: A two-part (Phase 1B/3), sequential, open-label, multicentre study evaluated the pharmacokinetics (PK) and safety of intravenous (iv) posaconazole given as antifungal prophylaxis to neutropenic patients with AML or myelodysplastic syndrome (MDS) or to recipients at risk of invasive fungal disease (IFD) after allogeneic HSCT. Patients (N = 237) received 300 mg of posaconazole iv twice daily on day 1, followed by 300 mg of posaconazole iv once daily for 4-28 days. After at least 5 days, patients were randomly assigned to receive posaconazole oral suspension, 400 mg twice daily or 200 mg three times daily, to complete a 28 day treatment course. Primary PK parameters were steady-state average concentration over the dosing interval (Cavg) and posaconazole trough levels (Cmin). Mean posaconazole Cmin was 1320 ng/mL (day 6) and 1297 ng/mL (day 8); steady-state Cmin was 1090 ng/mL (day 10). Mean steady-state posaconazole Cavg was 1500 ng/mL (day 10 or 14) and was similar in HSCT recipients (1560 ng/mL) and AML/MDS patients (1470 ng/mL). The most commonly reported treatment-related adverse events were diarrhoea (8%), nausea (5%) and rash (5%). IFD was reported in 3/237 patients (1%; 2 proven, 1 probable). Intravenous posaconazole at 300 mg was well tolerated, resulted in adequate steady-state systemic exposure and was associated with a low incidence of IFD in this population at high risk., NCT01075984.
DOI: 10.1093/jac/dkx263
PubMed URL: 28961714
Type: Journal Article
Appears in Collections:Journal articles

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