Clinical considerations on posaconazole administration and therapeutic drug monitoring in allogeneic hematopoietic cell transplant recipients. (31st December 2020)

• Record Type: Journal Article
• 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
• Is Part Of: Medical mycology. Volume 59:Number 7(2021)
• Page Start: 701
• Page End: 711
• Publication Date: 2020-12-31
• Subjects: posaconazole -- therapeutic drug monitoring -- allogeneic hematopoietic cell transplant recipients -- antifungal prophylaxis -- antifungal treatment; Medical mycology -- Periodicals; Veterinary mycology -- Periodicals; Mycology -- Periodicals; Mycoses -- Periodicals; Pathogenic fungi -- Periodicals; 616.969005
• DOI: 10.1093/mmy/myaa106
• Languages: English
• ISSNs: 1369-3786

Abstract

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.