title: Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections.
abstract: BACKGROUND
  Invasive fungal infections are found most frequently in immunosuppressed and critically ill hospitalized patients. Antifungal therapy is often required for long periods. Safety data from the clinical development program of the triazole antifungal agent, posaconazole, were analyzed.
  
  
  METHODS
  A total of 428 patients with refractory invasive fungal infections (n = 362) or febrile neutropenia (n = 66) received posaconazole in 2 phase II/III open-label clinical trials. Also, 109 of these patients received posaconazole therapy for > or = 6 months. Incidences of treatment-emergent, treatment-related, and serious adverse events and abnormal laboratory parameters were recorded during these studies.
  
  
  RESULTS
  Treatment-emergent, treatment-related adverse events were reported in 38% of the overall patient population. The most common treatment-related adverse events were nausea (8%) and vomiting (6%). Treatment-related serious adverse events occurred in 8% of patients. Low rates of treatment-related corrected QT interval and/or QT interval prolongation (1%) and elevation of hepatic enzymes (2%) were reported as adverse events. Treatment-emergent, treatment-related adverse events occurred at similar rates in patients who received posaconazole therapy for < 6 months and > or = 6 months.
  
  
  CONCLUSIONS
  Prolonged posaconazole treatment was associated with a generally favorable safety profile in seriously ill patients with refractory invasive fungal infections. Long-term therapy did not increase the risk of any individual adverse event, and no unique adverse event was observed with longer exposure to posaconazole.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. iraad@mdanderson.org
authors.forename: Issam I
authors.initials: II
authors.lastname: Raad
authors.forename: John R
authors.initials: JR
authors.lastname: Graybill
authors.forename: Ana Beatriz
authors.initials: AB
authors.lastname: Bustamante
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Cornely
authors.forename: Veronica
authors.initials: V
authors.lastname: Gaona-Flores
authors.forename: Claude
authors.initials: C
authors.lastname: Afif
authors.forename: Donald R
authors.initials: DR
authors.lastname: Graham
authors.forename: Richard N
authors.initials: RN
authors.lastname: Greenberg
authors.forename: Susan
authors.initials: S
authors.lastname: Hadley
authors.forename: Amelia
authors.initials: A
authors.lastname: Langston
authors.forename: Ricardo
authors.initials: R
authors.lastname: Negroni
authors.forename: John R
authors.initials: JR
authors.lastname: Perfect
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.forename: Angela
authors.initials: A
authors.lastname: Restrepo
authors.forename: Gary
authors.initials: G
authors.lastname: Schiller
authors.forename: Lisa
authors.initials: L
authors.lastname: Pedicone
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ullmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000473:pathology*; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole