Clinical considerations on posaconazole administration and therapeutic drug monitoring in allogeneic hematopoietic cell transplant recipients
Mateja Kraljevic, Nina Khanna, Michael Medinger, Jakob Passweg, Stavroula Masouridi‐Levrat, Yves Chalandon, Nicolas J. Mueller, Urs Schanz, Nathalie Vernaz, Christian van Delden, Dionysios Neofytos, for the Swiss Transplant Cohort Study, Patrizia Amico, Axel Andrés, Aubert John-David, Banz Vanessa, Sonja Beckmann, Guido Beldi, Christian Benden, Berger Christoph, Binet Isabelle, Pierre–Yves Bochud, Sanda Branca, Bucher Heiner, Carrel Thierry, Catana Emmanuelle, Yves Chalandon, Geest Sabina de, Rougemont Olivier de, Michael Dickenmann, Lynn Dreifuss Joëlle, Michel Duchosal, Thomas Fehr, Sylvie Ferrari‐Lacraz, Leichtle Alexander, Christian Garzoni, Gasche Soccal Paola, Christophe Gaudet, Giostra Emiliano, Golshayan Déla, Karine Hadaya, Halter Jörg, Hauri Dimitri, Dominik Heim, Christoph Hess, Sven Hillinger, Hirsch Hans, Patricia Hirt, Hofbauer Günther, Uyen Huynh‐Do, Immer Franz, Michael Koller, Bettina Laesser, Lang Brian, Roger Lehmann, Lovis Christian, Manuel Oriol, Marti Hans-Peter, Martin Pierre Yves, Martinelli Michele, Katell Mellac, Meylan Pascal, Aurélia Merçay, Karin Mettler, Mueller Nicolas, M Antoniaüller, M Thomasüller, Ulrike Müller-Arndt, Müllhaupt Beat, Nägeli Mirjam, Pascual Manuel, Posfay-Barbe Klara, Juliane Rick, Anne Rosselet, Simona Rossi, Silvia Rothlin, Ruschitzka Frank, Urs Schanz, Stefan Schaub, Aurelia Schnyder, Simonetta Federico, Katharina Staufer, Jürg Steiger, Guido Stirniman, Christian Toso, Delden Christian Van, Venetz Jean-Pierre, Villard Jean, Madeleine Wick, Markus Wilhlem, Yerly Patrick
Abstract
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 <0.7 mg/L in 383/1944 (19.7%) and <1.0 mg/L in 656/1944 (33.7%) samples. PCZ-level was <0.7 mg/L in 260/1317 (19.7%) and <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.