title: Posaconazole prophylaxis in neutropenic patients with hematological malignancies: limits in clinical practice.
abstract: Posaconazole (PSZ) is being used for prophylaxis in hematological patients who are at high risk for invasive fungal disease (IFD), but absorption limitations have been reported. Our objective was to assess both the feasibility and the efficacy of PSZ prophylaxis in clinical practice. From March 2010 to September 2010, all patients admitted to our unit for chemotherapy for acute leukemia or hematopoietic stem cell transplantation received optimized PSZ prophylaxis 200 mg four times daily with cola soda. PSZ trough concentrations (Cmin) were monitored at days 5, 7, 14, and 21. The incidence of IFDs was determined and compared to that of a historical control group. Thirty-five consecutive patients were prospectively included. PSZ prophylaxis was interrupted for 29% of them at day 14 and 51% of them at day 21. The main limitations were impracticality of oral feeding (29%) and occurrence of suspected IFDs (23%). PSZ median Cmin were 0.47, 0.40, 0.24, 0.36 μg/mL at days 5, 7, 14, and 21, respectively. Eighty percent of patient results were lower than the target Cmin of 0.5 μg/ml on day 14, the higher-risk period associated with neutropenia. Four probable breakthrough IFDs (11%) were diagnosed in 2010; no clear association between PSZ Cmin and occurrence of infection was observed. The incidence of IFDs was unchanged (historical control group: 9.7%; P = 0.72). Implementation of systematic PSZ prophylaxis did not significantly decrease the incidence of IFDs at our center. PSZ interruptions related to mucositis and too low Cmin were the main limitations to its use.
authors.affiliation: Centre Hospitalier Régional Universitaire, Pole Pharmaceutique, Besançon, France Centre Hospitalier Régional Universitaire, Service d'Hématologie, Besançon, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Bourdelin
authors.affiliation: Centre Hospitalier Régional Universitaire, Service de Mycologie et Parasitologie, Besançon, France Université de Franche Comté, Unité Mixte de Recherche CNRS 6249, 25000 Besançon, France fgrenouillet@chu-besancon.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Grenouillet
authors.affiliation: Centre Hospitalier Régional Universitaire, Service d'Hématologie, Besançon, France Université de Franche-Comté, Unité Mixte de Recherche UMR Inserm 1098, Structure fédérative de recherche SFR-FED 4234, Besançon, France Centre Hospitalier Régional Universitaire, Centre d'Investigation Clinique en Biothérapies 506, Besançon, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Daguindau
authors.affiliation: Centre Hospitalier Régional Universitaire, Laboratoire de Pharmacologie, Besançon, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Muret
authors.affiliation: Centre Hospitalier Régional Universitaire, Service d'Hématologie, Besançon, France.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Desbrosses
authors.affiliation: Centre Hospitalier Régional Universitaire, Pole de radiologie, Besançon, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dubut
authors.affiliation: Centre Hospitalier Régional Universitaire, Service d'Hématologie, Besançon, France Université de Franche-Comté, Unité Mixte de Recherche UMR Inserm 1098, Structure fédérative de recherche SFR-FED 4234, Besançon, France Centre Hospitalier Régional Universitaire, Centre d'Investigation Clinique en Biothérapies 506, Besançon, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Deconinck
authors.affiliation: Centre Hospitalier Régional Universitaire, Pole Pharmaceutique, Besançon, France Université de Franche-Comté, Unité Mixte de Recherche UMR Inserm 1098, Structure fédérative de recherche SFR-FED 4234, Besançon, France Centre Hospitalier Régional Universitaire, Centre d'Investigation Clinique en Biothérapies 506, Besançon, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Limat
authors.affiliation: Centre Hospitalier Régional Universitaire, Service d'Hématologie, Besançon, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Larosa
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D018890:Chemoprevention / Q000009:adverse effects / Q000379:methods*; D002648:Child; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole
keywords: acute leukemia; hematopoietic stem cell transplantation; invasive fungal infection; posaconazole prophylaxis