title: Posaconazole oral suspension primary prophylaxis in acute leukemia and allogeneic stem cell transplant patients: can it be used without measurement of plasma concentration?
abstract: Posaconazole oral suspension (PCZ-susp) can display a variable degree of inter and intra-individual absorption. However, there is no agreement on the need of plasma-posaconazole-concentration (PPC) monitoring as a routine practice in patients receiving PCZ-susp. In this prospective, multicenter study we evaluated the variability of PPCs in hematologic patients receiving PCZ-susp prophylaxis with the aim to define conditions at different risk of subtherapeutic PPCs. Overall, 103 acute leukemia (AL) patients submitted to intensive chemotherapy (115 courses) and 46 allogeneic stem cell transplant (allo-SCT) recipients (47 courses) receiving PCZ-susp prophylaxis were considered. The adequacy of PPC pattern after the steady state (≥day 7 of treatment) in courses with two or more PPC measurements was defined as follows: inadequate pattern: PPC < 0.5 mcg/ml at least once; borderline pattern: PPC always ≥0.5mcg/ml but < 0.7 mcg/ml at least once; adequate pattern: PPC always ≥0.7 mcg/ml. The PPC pattern was evaluable in 83 and 37 AL and allo-SCT patients, respectively. It was adequate, borderline and inadequate in 63.9%, 14.5%, and 21.7% of courses, respectively, in AL, and in 62.2%, 10.8%, and 27.0% of courses, respectively, in allo-SCT. In both groups, an inadequate PPC pattern was associated with the development of diarrhea. In absence of diarrhea, the probability of an inadequate PPC pattern was 11.9% in AL and 17.2% in allo-SCT patients. PCZ-susp might be used without stringent need of PPC monitoring in patients without diarrhea.
authors: Dipartimento di Ematologia, Oncologia, Anatomia Patologica e Medicina Rigenerativa, Azienda Policlinico Umberto I, Sapienza University, Rome, Italy girmenia@bce.uniroma1.it.
authors: Corrado
authors: C
authors: Girmenia
authors: Unità Operativa di Ematologia, Azienda Ospedaliera San Giovanni Addolorata, Rome, Italy.
authors: Luciana
authors: L
authors: Annino
authors: Fondazione Policlinico Tor Vergata, Unità di Trapianto Cellule Staminali, University Tor Vergata, Rome, Italy.
authors: Benedetta
authors: B
authors: Mariotti
authors: Unità Funzionale di Ematologia, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy.
authors: Rosa
authors: R
authors: Fanci
authors: Dipartimento di Ematologia, Oncologia, Anatomia Patologica e Medicina Rigenerativa, Azienda Policlinico Umberto I, Sapienza University, Rome, Italy.
authors: Clara
authors: C
authors: Minotti
authors: UOSD di Ematologia, Istituto Nazionale Tumori Regina Elena, IFO, Rome.
authors: Antonio
authors: A
authors: Spadea
authors: Ematologia con Trapianto di Midollo Osseo, Azienda Ospedaliera e Universita' degli Studi di Perugia, Perugia, Italy.
authors: Alessandra
authors: A
authors: Carotti
authors: Ematologia, Ospedale S. Andrea, Sapienza University, Rome Italy.
authors: Monica
authors: M
authors: Piedimonte
authors: Unità Operativa di Ematologia, Azienda Ospedaliera San Giovanni Addolorata, Rome, Italy.
authors: Anna
authors: A
authors: Chierichini
authors: UOC Ematologia Trapianto Cellule Staminali, Medicina Trasfusionale e Terapia Cellulare, Università Campus Biomedico, Rome.
authors: Elisabetta
authors: E
authors: Cerchiara
authors: Ospedale Pediatrico Meyer, Florence.
authors: Desiree
authors: D
authors: Caselli
authors: Divisione di Ematologia, Ospedale S.Eugenio, Rome.
authors: Luca
authors: L
authors: Cupelli
authors: Onco Ematologia Pediatrica con Trapianto di Midollo Osseo, Azienda Ospedalera Santa Maria della Misericordia, Perugia.
authors: Francesco
authors: F
authors: Arcioni
authors: Dipartimento di Oncoematologia, Ospedale pediatrico Bambino Gesù, Rome, Italy.
authors: Alice
authors: A
authors: Bertaina
authors: Istituto Mediterraneo di Ematologia, Policlinico Tor Vergata, Rome.
authors: Michela
authors: M
authors: Ribersani
authors: UOC di Ematologia e Trapianti di Cellule Staminali, Azienda Ospedaliera S. Camillo-Forlanini, Rome, Italy.
authors: Anna
authors: A
authors: Proia
authors: UOSD di Ematologia, Istituto Nazionale Tumori Regina Elena, IFO, Rome.
authors: Andrea
authors: A
authors: Mengarelli
authors: Ematologia con Trapianto di Midollo Osseo, Azienda Ospedaliera e Universita' degli Studi di Perugia, Perugia, Italy.
authors: Vincenzo
authors: V
authors: Perriello
authors: Dipartimento di Ematologia, Oncologia, Anatomia Patologica e Medicina Rigenerativa, Azienda Policlinico Umberto I, Sapienza University, Rome, Italy.
authors: Giovanni Fernando
authors: GF
authors: Torelli
authors: Unità Funzionale di Ematologia, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy.
authors: Massimo
authors: M
authors: Di Gioia
authors: Fondazione Policlinico Tor Vergata, Ematologia, University Tor Vergata, Rome, Italy.
authors: Maria Ilaria
authors: MI
authors: Del Principe
authors: Dipartimento di Farmacologia Preclinica e Clinica Mario Aiazzi Mancini, University of Florence, Florence, Italy.
authors: Maria Iris
authors: MI
authors: Cassetta
authors: Dipartimento di Farmacologia Preclinica e Clinica Mario Aiazzi Mancini, University of Florence, Florence, Italy.
authors: Stefania
authors: S
authors: Fallani
authors: Dipartimento di Farmacologia Preclinica e Clinica Mario Aiazzi Mancini, University of Florence, Florence, Italy.
authors: Andrea
authors: A
authors: Novelli
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007938:Leukemia / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*; D010949:Plasma / Q000737:chemistry*; D011446:Prospective Studies; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D014184:Transplantation, Homologous / Q000009:adverse effects*; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole
keywords: acute leukemia; allogeneic stem cell transplant; diarrhea; plasma level; posaconazole