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Title: Assessing the safety profile of voriconazole use in suspected COVID-19-associated pulmonary aspergillosis-a two-centre observational study.
Austin Authors: Costa-Pinto, Rahul;Klink, Sarah;Rotherham, Hannah;Perera, Padeepa;Finlay, Liam;Urbancic, Karen F ;Vaz, Karl;Trubiano, Jason ;Bellomo, Rinaldo 
Affiliation: Department of Critical Care, Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia.
Intensive Care
Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Infectious Diseases
Gastroenterology and Hepatology
Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Data Analytics Research and Evaluation (DARE) Centre
Issue Date: 5-Jun-2023
Publication information: Medical Mycology 2023-06-05; 61(6)
Abstract: The decision to use voriconazole for suspected COVID-19-associated pulmonary aspergillosis (CAPA) is based on clinical judgement weighed against concerns about its potential toxicity. We assessed the safety profile of voriconazole for patients with suspected CAPA by conducting a retrospective study of patients across two intensive care units. We compared changes in any liver enzymes or bilirubin and any new or increasing corrected QT interval (QTc) prolongation following voriconazole use to patient baseline to indicate possible drug effect. In total, 48 patients with presumed CAPA treated with voriconazole were identified. Voriconazole therapy was administered for a median of 8 days (interquartile range [IQR] 5-22) and the median level was 1.86 mg/L (IQR 1.22-2.94). At baseline, 2% of patients had a hepatocellular injury profile, 54% had a cholestatic injury profile, and 21% had a mixed injury profile. There were no statistically significant changes in liver function tests over the first 7 days after voriconazole initiation. At day 28, there was a significant increase in alkaline phospahte only (81-122 U/L, P = 0.006), driven by changes in patients with baseline cholestatic injury. In contrast, patients with baseline hepatocellular or mixed injury had a significant decrease in alanine transaminase and aspartate transaminase. Baseline QTc was 437 ms and remained unchanged after 7 days of voriconazole therapy even after sensitivity analysis for concomitantly administered QT prolonging agents. Therefore, at the doses used in this study, we did not detect evidence of significant liver or cardiac toxicity related to voriconazole use. Such information can be used to assist clinicians in the decision to initiate such treatment.
DOI: 10.1093/mmy/myad054
ORCID: 0000-0003-4007-7849
Journal: Medical Mycology
PubMed URL: 37286877
ISSN: 1460-2709
Type: Journal Article
Subjects: COVID-19
adverse drug reactions
drug interactions
invasive pulmonary aspergillosis
Voriconazole/adverse effects
Antifungal Agents/adverse effects
Triazoles/adverse effects
Pulmonary Aspergillosis/drug therapy
Pulmonary Aspergillosis/veterinary
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