Journal Article

Clinical Considerations of Isavuconazole Administration in High-Risk Hematological Patients: A Single-Center 5-Year Experience

Kronig Ilona, Vernaz Nathalie, Masouridi-Levrat Stavroula, Neofytos Dionysios, Glampedakis Emmanouil, Christian, Van Delden, Chalandon Yves

2021

Overview

BackgroundThere are limited real-life data on isavuconazole prophylaxis and treatment of invasive mold infections (IMI) in hematological patients and allogeneic hematopoietic cell transplant (HCT) recipients.ObjectivesPrimary objective was to describe the indications of real-life isavuconazole administration at a university hospital. Secondary objectives included the description of liver function tests and QTc interval between baseline and end of treatment (EOT), clinical outcomes and breakthrough IMI by the EOT.Patients/MethodsThis was a 5-year single-center retrospective study of all adult patients with acute myeloid leukemia and/or allogeneic HCT recipients who received isavuconazole as prophylaxis and/or treatment between June 1, 2016, and July 31, 2020.ResultsAmong 30 identified patients, the indications for isavuconazole administration were adverse events associated with prior antifungal treatment (N: 18, 60%: hepatotoxicity, renal insufficiency, long QTc interval, neurotoxicity, and potential drug–drug interactions in 6, 4, 3, 1 and 4 patients, respectively), clinical efficacy (N: 5, 16.6%), and other reasons (N: 10, 33.3%; 5/10 patients treated with isavuconazole to facilitate hospital discharge with orally administered appropriate treatment). Alanine aminotransferase significantly decreased from baseline (mean: 129 IU/L, range: 73, 202) to a mean of 48 IU/L (range: 20, 80) by day 14 (P-value: 0.02), 23.5 IU/L (range: 20, 27) by day 28 (P-value: 0.03) and 16.5 IU/L (range: 16, 17) by day 42 (P-value: 0.009). The QTc interval decreased from baseline (mean: 456.8 ms, range: 390, 533) to EOT (mean: 433.8 ms, range: 400, 472; P-value: 0.03). The mean isavuconazole plasma concentration was 2.9 mg/L (range: 0.9, 6.7). There was no breakthrough IMI observed.ConclusionIsavuconazole is a safe and reliable antifungal agent in complex hematological patients, with relatively low hepatotoxicity and QTc interval shortening properties.

• Publisher: Springer Nature B.V
• Subject: Acute myeloid leukemia / Adverse events / Alanine / Alanine transaminase / Antifungal agents / Disease prevention / Hematology / Hepatotoxicity / Invasiveness / Myeloid leukemia / Neurotoxicity / Oral administration / Patients / Prophylaxis / Renal insufficiency / Stem cell transplantation