Tolerability of oral itraconazole and voriconazole for the treatment of chronic pulmonary aspergillosis: A systematic review and meta-analysis

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