title: Safety, clinical effectiveness and trough plasma concentrations of intravenous posaconazole in patients with haematological malignancies and/or undergoing allogeneic haematopoietic stem cell transplantation: off-trial experience.
abstract: This study describes the safety, clinical effectiveness and trough plasma concentration (Cmin) of intravenous (iv) posaconazole, provided as part of Merck Sharp and Dohme Australia's Named Patient Programme (NPP) in non-clinical trial settings.
  
  
  
  A multicentre, retrospective study on the NPP use of iv posaconazole between July 2014 and March 2015 across seven Australian hospitals.
  
  
  
  Seventy courses of iv posaconazole were prescribed and evaluated in 61 patients receiving treatment for haematological malignancy. Sixty-one courses were prescribed for prophylaxis against invasive fungal disease (IFD), the majority of which (59) were initiated in patients with gastrointestinal disturbances and/or intolerance to previous antifungals. The median (IQR) duration for prophylaxis was 10 (6-15) days. No breakthrough IFD was observed during or at cessation of iv posaconazole. Nine courses of iv posaconazole were prescribed for treatment of IFD with a median (IQR) duration of 19 (7-30) days. Improvement in signs and symptoms of IFD was observed in five cases at cessation of, and six cases at 30 days post-iv posaconazole. Cminwas measured in 39 courses of iv posaconazole, with the initial level taken [median (IQR)] 4 (3-7) days after commencing iv posaconazole. The median (IQR) of initial Cminwas 1.16 (0.69-2.06) mg/L. No severe adverse events specifically attributed to iv posaconazole were documented, although six courses were curtailed due to potential toxicity.
  
  
  
  This non-clinical trial experience suggests that iv posaconazole appeared to be safe and clinically effective for prophylaxis or treatment of IFD in patients receiving treatment for haematological malignancies.
authors: Centre for Medicine Use and Safety, Monash University, VIC, Australia.
authors: Wirawan
authors: W
authors: Jeong
authors: Department of Clinical Haematology and Bone Marrow Transplant Service, Royal Melbourne Hospital, VIC, Australia.
authors: Peter
authors: P
authors: Haywood
authors: Department of Haematology, Royal Adelaide Hospital, SA, Australia.
authors: Naranie
authors: N
authors: Shanmuganathan
authors: Pharmacy Department, Royal North Shore Hospital, NSW, Australia.
authors: Julian
authors: J
authors: Lindsay
authors: Pharmacy Department, Austin Health, VIC, Australia.
authors: Karen
authors: K
authors: Urbancic
authors: General Medical Unit, Alfred Health and Central & Eastern Clinical School, Monash University, VIC, Australia.
authors: Michelle R
authors: MR
authors: Ananda-Rajah
authors: Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead Hospital, The University of Sydney, NSW, Australia.
authors: Sharon C A
authors: SC
authors: Chen
authors: Department of Clinical Haematology and Bone Marrow Transplant Service, Royal Melbourne Hospital, VIC, Australia.
authors: Ashish
authors: A
authors: Bajel
authors: Department of Clinical Haematology and Bone Marrow Transplant Service, Royal Melbourne Hospital and The University of Melbourne, VIC, Australia.
authors: David
authors: D
authors: Ritchie
authors: Department of Clinical Haematology, Austin Health and The University of Melbourne, VIC, Australia.
authors: Andrew
authors: A
authors: Grigg
authors: Department of Haematology, Peter MacCallum Cancer Centre and The University of Melbourne, VIC, Australia.
authors: John F
authors: JF
authors: Seymour
authors: Department of Infectious Diseases, Alfred Health and Central Clinical School, Monash University, VIC, Australia.
authors: Anton Y
authors: AY
authors: Peleg
authors: Centre for Medicine Use and Safety, Monash University, VIC, Australia.|Pharmacy Department, Ballarat Health Services, VIC, Australia.
authors: David C M
authors: DC
authors: Kong
authors: Department of Infectious Diseases, Peter MacCallum Cancer Centre, VIC, Australia monica.slavin@petermac.org.|Victorian Infectious Diseases Service, Royal Melbourne Hospital, VIC, Australia.
authors: Monica A
authors: MA
authors: Slavin
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D001315:Australia; D018890:Chemoprevention / Q000009:adverse effects / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000517:prevention & control*; D010949:Plasma / Q000737:chemistry; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole