E Furfaro1, A Signori2, C Di Grazia3, A Dominietto3, A M Raiola3, S Aquino3, C Ghiggi4, A Ghiso4, R Ungaro1,5, E Angelucci3, C Viscoli1,5, M Mikulska1,5. 1. Division of Infectious Diseases, Department of Health Science DISSAL, University of Genoa, Genoa, Italy. 2. Section of Biostatistics, Department of Health Science DISSAL, University of Genoa, Genoa, Italy. 3. Division of Hematology and Bone Marrow Transplantation, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 4. Division of Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 5. Division of Infectious Diseases, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Abstract
BACKGROUND: Isavuconazole is the newest triazole antifungal approved for the treatment of invasive aspergillosis (IA) and invasive mucormycosis in adult patients. OBJECTIVES: To characterize the assessment of the blood levels of isavuconazole and their association with efficacy and toxicity. METHODS: From January 2017 to May 2018, blood samples obtained from patients receiving isavuconazole were analysed for therapeutic drug monitoring. Factors influencing the blood concentrations of isavuconazole, such as weight, length of treatment, route of administration and results of selected liver function tests, were analysed in univariate and multivariate models. The receiver operating characteristic (ROC) curve was analysed to detect the best cut-off for isavuconazole toxicity. RESULTS: A total of 264 isavuconazole blood concentrations in 19 patients were analysed. The median value of isavuconazole concentration in all patients during the first 30 days of therapy was 3.69 mg/L (range 0.64-8.13 mg/L). A linear increase of 0.032 mg/L (range 0.023-0.041 mg/L) for each day of treatment (P = 0.002) was observed. In multivariate analysis the association between the length of treatment and higher levels of isavuconazole (P < 0.001) and higher serum GGT and lower isavuconazole levels (P = 0.001) was confirmed. Adverse events, mainly gastrointestinal, were reported in six patients (31.6%). Based on time-dependent and fixed-time ROC curve analysis, 4.87 mg/L and 5.13 mg/L, respectively, were the identified thresholds for toxicity. CONCLUSIONS: Isavuconazole was efficacious and well tolerated. Side effects, mainly gastrointestinal, were associated with prolonged administration and high serum levels.
BACKGROUND:Isavuconazole is the newest triazole antifungal approved for the treatment of invasive aspergillosis (IA) and invasive mucormycosis in adult patients. OBJECTIVES: To characterize the assessment of the blood levels of isavuconazole and their association with efficacy and toxicity. METHODS: From January 2017 to May 2018, blood samples obtained from patients receiving isavuconazole were analysed for therapeutic drug monitoring. Factors influencing the blood concentrations of isavuconazole, such as weight, length of treatment, route of administration and results of selected liver function tests, were analysed in univariate and multivariate models. The receiver operating characteristic (ROC) curve was analysed to detect the best cut-off for isavuconazoletoxicity. RESULTS: A total of 264 isavuconazole blood concentrations in 19 patients were analysed. The median value of isavuconazole concentration in all patients during the first 30 days of therapy was 3.69 mg/L (range 0.64-8.13 mg/L). A linear increase of 0.032 mg/L (range 0.023-0.041 mg/L) for each day of treatment (P = 0.002) was observed. In multivariate analysis the association between the length of treatment and higher levels of isavuconazole (P < 0.001) and higher serum GGT and lower isavuconazole levels (P = 0.001) was confirmed. Adverse events, mainly gastrointestinal, were reported in six patients (31.6%). Based on time-dependent and fixed-time ROC curve analysis, 4.87 mg/L and 5.13 mg/L, respectively, were the identified thresholds for toxicity. CONCLUSIONS:Isavuconazole was efficacious and well tolerated. Side effects, mainly gastrointestinal, were associated with prolonged administration and high serum levels.
Authors: Erin K McCreary; M Hong Nguyen; Matthew R Davis; Jared Borlagdan; Ryan K Shields; Anthony D Anderson; Ryan M Rivosecchi; Rachel V Marini; Lauren M Sacha; Fernanda P Silveira; David R Andes; Alexander J Lepak Journal: J Antimicrob Chemother Date: 2020-10-01 Impact factor: 5.790
Authors: James S Lewis; Nathan P Wiederhold; Morgan Hakki; George R Thompson Journal: Antimicrob Agents Chemother Date: 2022-08-15 Impact factor: 5.938