PMID- 37286877
OWN - NLM
STAT- MEDLINE
DCOM- 20230626
LR  - 20230626
IS  - 1460-2709 (Electronic)
IS  - 1369-3786 (Linking)
VI  - 61
IP  - 6
DP  - 2023 Jun 5
TI  - Assessing the safety profile of voriconazole use in suspected COVID-19-associated 
      pulmonary aspergillosis-a two-centre observational study.
LID - myad054 [pii]
LID - 10.1093/mmy/myad054 [doi]
AB  - 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.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of The 
      International Society for Human and Animal Mycology.
FAU - Costa-Pinto, Rahul
AU  - Costa-Pinto R
AUID- ORCID: 0000-0003-4007-7849
AD  - Department of Intensive Care, Austin Hospital, Heidelberg, Victoria,, Australia.
AD  - Department of Critical Care, Department of Medicine, The University of Melbourne, 
      Parkville, Victoria, Australia.
FAU - Klink, Sarah
AU  - Klink S
AD  - Department of Intensive Care, Austin Hospital, Heidelberg, Victoria,, Australia.
FAU - Rotherham, Hannah
AU  - Rotherham H
AD  - Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, 
      Australia.
FAU - Perera, Padeepa
AU  - Perera P
AD  - Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, 
      Australia.
FAU - Finlay, Liam
AU  - Finlay L
AD  - Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, 
      Australia.
FAU - Urbancic, Karen
AU  - Urbancic K
AUID- ORCID: 0000-0002-9275-578X
AD  - Department of Infectious Diseases, Austin Hospital, Heidelberg, Victoria, 
      Australia.
FAU - Vaz, Karl
AU  - Vaz K
AD  - Department of Gastroenterology, Austin Hospital, Heidelberg, Victoria, Australia.
FAU - Trubiano, Jason
AU  - Trubiano J
AD  - Department of Infectious Diseases, Austin Hospital, Heidelberg, Victoria, 
      Australia.
FAU - Bellomo, Rinaldo
AU  - Bellomo R
AUID- ORCID: 0000-0002-1650-8939
AD  - Department of Intensive Care, Austin Hospital, Heidelberg, Victoria,, Australia.
AD  - Department of Critical Care, Department of Medicine, The University of Melbourne, 
      Parkville, Victoria, Australia.
AD  - Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, 
      Australia.
AD  - Australian and New Zealand Intensive Care Research Centre, Department of 
      Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, 
      Australia.
AD  - Data Analytics Research and Evaluation Centre, The University of Melbourne and 
      Austin Hospital, Melbourne, Victoria, Australia.
LA  - eng
PT  - Journal Article
PT  - Observational Study, Veterinary
PL  - England
TA  - Med Mycol
JT  - Medical mycology
JID - 9815835
RN  - JFU09I87TR (Voriconazole)
RN  - 0 (Antifungal Agents)
RN  - 0 (Triazoles)
SB  - IM
MH  - Animals
MH  - Voriconazole/adverse effects
MH  - Antifungal Agents/adverse effects
MH  - Retrospective Studies
MH  - Triazoles/adverse effects
MH  - *COVID-19/veterinary
MH  - *Pulmonary Aspergillosis/drug therapy/veterinary
OAB - Our study did not show significant voriconazole-related liver or cardiac side 
      effects in a critically ill cohort of patients with suspected COVID-19-associated 
      pulmonary aspergillosis. These findings may allay specific clinician concerns 
      when commencing therapy for such patients.
OABL- eng
OTO - NOTNLM
OT  - COVID-19
OT  - adverse drug reactions
OT  - drug interactions
OT  - invasive pulmonary aspergillosis
OT  - voriconazole
EDAT- 2023/06/08 01:08
MHDA- 2023/06/26 06:41
CRDT- 2023/06/07 23:33
PHST- 2023/04/19 00:00 [received]
PHST- 2023/06/01 00:00 [revised]
PHST- 2023/06/03 00:00 [accepted]
PHST- 2023/06/26 06:41 [medline]
PHST- 2023/06/08 01:08 [pubmed]
PHST- 2023/06/07 23:33 [entrez]
AID - 7191845 [pii]
AID - 10.1093/mmy/myad054 [doi]
PST - ppublish
SO  - Med Mycol. 2023 Jun 5;61(6):myad054. doi: 10.1093/mmy/myad054.