Clinical considerations on posaconazole administration and therapeutic drug monitoring in allogeneic hematopoietic cell transplant recipients
Authors: Kraljevic Mateja , Khanna Nina , Medinger Michael , Passweg Jakob , Masouridi-Levrat Stavroula , Chalandon Yves , Mueller Nicolas J , Schanz Urs , Vernaz Nathalie , Van Delden Christian , Neofytos Dionysios ,   for the Swiss Transplant Cohort Study, Patrizia Amico , Andres Axel , John-David Aubert , Vanessa Banz , Beckmann Sonja , Guido Beldi , Christian Benden , Christoph Berger , Isabelle Binet , Pierre-Yves Bochud , Sanda Branca , Heiner Bucher , Thierry Carrel , Emmanuelle Catana , Yves Chalandon , Sabina de Geest , Olivier de Rougemont , Michael Dickenmann , Joëlle Lynn Dreifuss , Michel Duchosal , Thomas Fehr , Sylvie Ferrari-Lacraz , Alexander Leichtle , Christian Garzoni , Paola Gasche Soccal , Christophe Gaudet , Emiliano Giostra , Déla Golshayan , Karine Hadaya , Jörg Halter , Dimitri Hauri , Dominik Heim , Christoph Hess , Sven Hillinger , Hans Hirsch , Patricia Hirt , Günther Hofbauer , Uyen Huynh-Do , Franz Immer , Michael Koller , Bettina Laesser , Brian Lang , Roger Lehmann , Christian Lovis , Oriol Manuel , Hans-Peter Marti , Pierre Yves Martin , Michele Martinelli , Katell Mellac , Pascal Meylan , Aurélia Merçay , Karin Mettler , Nicolas Mueller , Antoniaüller M , Thomasüller M , Ulrike Müller-Arndt , Beat Müllhaupt , Mirjam Nägeli , Manuel Pascual , Klara Posfay-Barbe , Juliane Rick , Anne Rosselet , Simona Rossi , Silvia Rothlin , Frank Ruschitzka , Urs Schanz , Stefan Schaub , Aurelia Schnyder , Federico Simonetta , Katharina Staufer , Jürg Steiger , Guido Stirniman , Christian Toso , Christian Van Delden , Jean-Pierre Venetz , Jean Villard , Madeleine Wick , Markus Wilhlem , Patrick Yerly 
Published: December 2020

There is a paucity of data on posaconazole (PCZ) dosing and therapeutic-drug-monitoring (TDM) in allogeneic hematopoietic cell transplant recipients (allogeneic-HCTr). This was a 3-year retrospective multicenter study (January 1, 2016 to December 31, 2018) in adult allogeneic-HCTr who received PCZ (intravenously, IV and/or as delayed-release tablet, DRT) as prophylaxis or treatment for ≥7 consecutive days (D) with at least 1-PCZ-level available using data of the Swiss Transplant Cohort Study. The primary objective was to describe the distribution of PCZ-level and identify predictors of therapeutic PCZ-level and associations between PCZ-dosing and PCZ-level. A total of 288 patients were included: 194 (67.4%) and 94 (32.6%) received PCZ as prophylaxis and treatment, respectively, for a median of 90 days (interquartile range, IQR: 42–188.5). There were 1944 PCZ-level measurements performed, with a median PCZ level of 1.3 mg/L (IQR: 0.8-1.96). PCZ-level was &lt;0.7 mg/L in 383/1944 (19.7%) and &lt;1.0 mg/L in 656/1944 (33.7%) samples. PCZ-level was &lt;0.7 mg/L in 260/1317 (19.7%) and &lt;1.0 mg/L in 197/627 (31.4%) in patients who received PCZ-prophylaxis versus treatment, respectively. There were no significant differences in liver function tests between baseline and end-of-treatment. There were nine (3.1%) breakthrough invasive fungal infections (bIFI), with no difference in PCZ levels between patients with or without bIFI. Despite a very intensive PCZ-TDM, PCZ-levels remain below target levels in up to one-third of allogeneic-HCTr. Considering the low incidence of bIFI observed among patients with PCZ levels in the targeted range, our data challenge the clinical utility of routine universal PCZ-TDM.