PMID- 33052954
OWN - NLM
STAT- MEDLINE
DCOM- 20201204
LR  - 20240319
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 15
IP  - 10
DP  - 2020
TI  - Tolerability of oral itraconazole and voriconazole for the treatment of chronic 
      pulmonary aspergillosis: A systematic review and meta-analysis.
PG  - e0240374
LID - 10.1371/journal.pone.0240374 [doi]
LID - e0240374
AB  - BACKGROUND: Chronic pulmonary aspergillosis (CPA) requires prolonged treatment 
      with itraconazole or voriconazole. However, adverse events (AEs) are common with 
      the use of these agents, with the need to discontinue the offending drug in a 
      significant proportion of the patients. The aim of this study was to evaluate the 
      frequency of adverse events of itraconazole and voriconazole for the treatment of 
      CPA. METHODS: We searched Embase and Medline to select clinical studies providing 
      information on AEs to itraconazole or voriconazole for the treatment of CPA from 
      inception to May 2020. Reviews, single case reports, and case series reporting 
      less than 10 patients were excluded. Random effect meta-analysis was performed 
      using STATA 16.0. RESULTS: We included 9 eligible studies with an overall total 
      of 534 CPA patients enrolled. Of these, 69% (n = 366) were treated with 
      voriconazole and 31% (n = 168) with itraconazole. The median daily dose of both 
      itraconazole and voriconazole used was 400mg. In a pooled analysis, AEs were 
      observed in 36% (95% CI: 20-52%, N = 366) of patients on voriconazole and 25% 
      (95% CI: 18 to 31%, N = 168) in those treated with itraconazole. Discontinuation 
      rate due to AEs was the same for both drugs; 35% (47/366) and 35% (15/168) for 
      voriconazole and itraconazole, respectively. There were 70 AEs reported with 
      itraconazole use, the commonest being cardiotoxicity (29%). Skin AEs (28%) were 
      the most frequent among the 204 AEs reported with voriconazole use. None of the 
      studies compared the tolerability of itraconazole head-to-head with voriconazole. 
      CONCLUSIONS: AEs due itraconazole and voriconazole are common and may lead to 
      discontinuation of treatment in a significant proportion of patients. This 
      information can be used to educate patients prior to commencement of these 
      antifungal therapies. PROSPERO REGISTRATION NUMBER: CRD42020191627.
FAU - Olum, Ronald
AU  - Olum R
AUID- ORCID: 0000-0003-1289-0111
AD  - School of Medicine, College of Health Sciences, Makerere University, Kampala, 
      Uganda.
FAU - Baluku, Joseph Baruch
AU  - Baluku JB
AUID- ORCID: 0000-0002-5852-9674
AD  - Department of Programs, MildMay Uganda, Wakiso, Uganda.
AD  - Division of Pulmonology, Mulago National Referral Hospital, Kampala, Uganda.
FAU - Kazibwe, Andrew
AU  - Kazibwe A
AUID- ORCID: 0000-0002-0738-8234
AD  - The AIDS Support Organisation, Kampala, Uganda.
AD  - Department of Medicine, School of Medicine, College of Health Sciences, Makerere 
      University, Kampala, Uganda.
FAU - Russell, Laura
AU  - Russell L
AD  - Medical Library, Manchester University NHS Foundation Trust, Manchester, United 
      Kingdom.
FAU - Bongomin, Felix
AU  - Bongomin F
AUID- ORCID: 0000-0003-4515-8517
AD  - Department of Medicine, School of Medicine, College of Health Sciences, Makerere 
      University, Kampala, Uganda.
AD  - Department of Medical Microbiology and Immunology, Faculty of Medicine, Gulu 
      University, Gulu, Uganda.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20201014
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antifungal Agents)
RN  - 304NUG5GF4 (Itraconazole)
RN  - JFU09I87TR (Voriconazole)
SB  - IM
MH  - Humans
MH  - Administration, Oral
MH  - *Antifungal Agents/administration & dosage/adverse effects
MH  - Cardiotoxicity/epidemiology
MH  - *Itraconazole/administration & dosage/adverse effects
MH  - *Pulmonary Aspergillosis/drug therapy
MH  - Treatment Outcome
MH  - *Voriconazole/administration & dosage/adverse effects
PMC - PMC7556473
COIS- The authors have declared that no competing interests exist.
EDAT- 2020/10/15 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/10/14
CRDT- 2020/10/14 17:59
PHST- 2020/06/13 00:00 [received]
PHST- 2020/09/24 00:00 [accepted]
PHST- 2020/10/14 17:59 [entrez]
PHST- 2020/10/15 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/10/14 00:00 [pmc-release]
AID - PONE-D-20-17016 [pii]
AID - 10.1371/journal.pone.0240374 [doi]
PST - epublish
SO  - PLoS One. 2020 Oct 14;15(10):e0240374. doi: 10.1371/journal.pone.0240374. 
      eCollection 2020.