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

Abstract

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.

Chronic Pulmonary Aspergillosis During Convalescence From Severe COVID-19 Treated With Oral Itraconazole: A Report of Two Cases

“…It is also preferred for treating SIPA [ 8 , 9 ]. We treated our patients with oral ITCZ, but not VRCZ, for the following reasons: (1) both patients had to be transferred to chronic hospitals, and oral ITCZ is more widely available in Japan than VRCZ; (2) oral ITCZ is less expensive than oral VRCZ; and (3) less adverse effects have been reported with ITCZ compared to VRCZ [ 10 ]. The most frequent adverse effect of ITCZ is cardiotoxicity, and neither patient had any cardiovascular problems.…”

Pharmacokinetics, safety of a single dose and multiple doses of voriconazole injection of two formulations, in Chinese healthy volunteers

“…among individual studies. 20 The most common site of AEs mainly occurred in the skin, ocular, and gastrointestinal. 21 In our study, all AEs were slight.…”

“…Voriconazole of Vfend and its imitation (Hainan, Hailing Pharmaceutical) were generally well tolerated. In relevant literature reports, the range of AEs to voriconazole was 12.5%–85.7% among individual studies 20 . The most common site of AEs mainly occurred in the skin, ocular, and gastrointestinal 21 .…”

Anti‐fungal agents in the treatment of chronic pulmonary aspergillosis: Systematic review and a network meta‐analysis

“…Theoretically, voriconazole may be a better choice for CPA. Voriconazole and other newer agents are expensive and may also be associated with adverse events 24 . Due to a lack of comparative studies, the guidelines suggest using either itraconazole or voriconazole as the initial therapy and posaconazole as salvage therapy 3 .…”