title: Efficacy, safety and feasibility of antifungal prophylaxis with posaconazole tablet in paediatric patients after haematopoietic stem cell transplantation.
abstract: OBJECTIVE
  Paediatric recipients of haematopoietic stem cell transplantation (HSCT) have a high risk for invasive fungal infections. Posaconazole oral suspension has proven to be effective in antifungal prophylaxis in adult and paediatric patients. A new posaconazole tablet formulation with absorption independent of the gastric conditions was approved by the FDA in 2013. This is the first report on the use of posaconazole tablets in paediatric patients.
  
  
  METHODS
  This single-centre study included 63 paediatric patients with haemato-oncological malignancies who received posaconazole for antifungal prophylaxis after HSCT. They were analysed for efficacy, feasibility and the safety of posaconazole. Out of 63 patients, 31 received posaconazole oral suspension and 32 received posaconazole tablets up to 200 days after transplantation. Analyses of the posaconazole trough levels were determined.
  
  
  RESULTS
  No possible, probable or proven invasive fungal infection was observed in either group. Posaconazole trough levels were significantly higher in the tablet group than in the suspension group at all analysed time points. Drug-related adverse events were similarly low in both groups.
  
  
  CONCLUSIONS
  Posaconazole tablets are effective in preventing invasive fungal infections in paediatric patients. As early as day 3 after starting posaconazole tablets, over 50% of the posaconazole trough levels were >500 ng/mL, while this was observed on day 14 after start with posaconazole suspension. The administration of posaconazole tablets was safe, effective and feasible as antifungal prophylaxis in paediatric patients after HSCT.
authors.affiliation: Department I - General Paediatrics, Haematology/Oncology, Children's Hospital, University Hospital Tübingen, Hoppe-Seyler-Str.1, 72076, Tübingen, Germany. michaela.doering@med.uni-tuebingen.de.
authors.forename: Michaela
authors.initials: M
authors.lastname: Döring
authors.affiliation: Department I - General Paediatrics, Haematology/Oncology, Children's Hospital, University Hospital Tübingen, Hoppe-Seyler-Str.1, 72076, Tübingen, Germany.
authors.forename: Karin Melanie
authors.initials: KM
authors.lastname: Cabanillas Stanchi
authors.affiliation: Department I - General Paediatrics, Haematology/Oncology, Children's Hospital, University Hospital Tübingen, Hoppe-Seyler-Str.1, 72076, Tübingen, Germany.
authors.forename: Manon
authors.initials: M
authors.lastname: Queudeville
authors.affiliation: Department I - General Paediatrics, Haematology/Oncology, Children's Hospital, University Hospital Tübingen, Hoppe-Seyler-Str.1, 72076, Tübingen, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Feucht
authors.affiliation: Ludwig-Maximilians-University München, Dr. von Hauner'sches Kinderspital, Paediatric Haematology, Oncology and Stem Cell Transplantation, Lindwurmstrasse 4, 80337, Munich, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Blaeschke
authors.affiliation: Department I - General Paediatrics, Haematology/Oncology, Children's Hospital, University Hospital Tübingen, Hoppe-Seyler-Str.1, 72076, Tübingen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schlegel
authors.affiliation: Ludwig-Maximilians-University München, Dr. von Hauner'sches Kinderspital, Paediatric Haematology, Oncology and Stem Cell Transplantation, Lindwurmstrasse 4, 80337, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Feuchtinger
authors.affiliation: Department I - General Paediatrics, Haematology/Oncology, Children's Hospital, University Hospital Tübingen, Hoppe-Seyler-Str.1, 72076, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.affiliation: Department of Paediatrics Haematology and Oncology, University Hospital Hamburg-Eppendorf, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Müller
authors.affiliation: Department I - General Paediatrics, Haematology/Oncology, Children's Hospital, University Hospital Tübingen, Hoppe-Seyler-Str.1, 72076, Tübingen, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine II, University Medical Centre Würzburg, Oberdürrbacher Straße 6, 97080, Würzburg, Germany.
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Heinz
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D019337:Hematologic Neoplasms / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016867:Immunocompromised Host / Q000187:drug effects; D008297:Male; D009181:Mycoses / Q000276:immunology / Q000517:prevention & control*; D013607:Tablets; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000935:Antifungal Agents; D013607:Tablets; D014230:Triazoles; C101425:posaconazole
keywords: Antifungal prophylaxis; Azole antifungals; Haematopoietic stem cell transplantation; Invasive fungal infections; Paediatric patients