Abstract
BackgroundVoriconazole has been used in the treatment and prophylaxis of invasive fungal infections (IFIs) while its wide use was limited by some frequent adverse events, especially neurotoxicity, hepatotoxicity and even renal disruption. The aim of this study was to comprehensively compare voriconazole-induced toxicity, including tolerability, neurotoxicity, visual toxicity, hepatotoxicity and nephrotoxicity with the composite of other antifungals commonly used in clinic.MethodsBibliography databases were searched to select randomized controlled trials providing information about the incidence of toxicity referred above. A total of 4122 patients from 16 studies were included in the meta-analysis.ResultsAnalysis of individual types of toxicity showed that there was a significant difference between voriconazole and the composite of other antifungal agents. The primary outcome, the tolerability of voriconazole was slightly inferior (OR = 1.71, 95% CI = 1.21–2.40, P = 0.002) and it is noteworthy that the probabilities of neurotoxicity and visual toxicity were around twice higher and six-fold for voriconazole compared with the counterpart (OR = 1.99, 95% CI = 1.05–3.75, P = 0.03 and OR = 6.50, 95% CI = 2.93–14.41, P < 0.00001, respectively). Hepatotoxicity was more common in voriconazole group (OR = 1.60, 95% CI = 1.17–2.19, P = 0.003) whereas its pooled risk of nephrotoxicity was about half of the composite of other five antifungal agents (OR = 0.46, 95% CI = 0.26–0.84, P = 0.01).ConclusionOur analysis has revealed differences in multiple types of toxicity induced by VRC versus other antifungals and quantified the corresponding pooled risks, which could provide an alternative for patients with a certain antifungal intolerance and help the clinician to select the optimal intervention.
Highlights
Voriconazole has been used in the treatment and prophylaxis of invasive fungal infections (IFIs) while its wide use was limited by some frequent adverse events, especially neurotoxicity, hepatotoxicity and even renal disruption
We evaluated the cumulative incidence of laboratory tests of liver dysfunction and renal dysfunction, which represented the safety outcomes of hepatotoxicity and nephrotoxicity
A flow diagram of the study selection process is shown in Fig. 1
Summary
Voriconazole has been used in the treatment and prophylaxis of invasive fungal infections (IFIs) while its wide use was limited by some frequent adverse events, especially neurotoxicity, hepatotoxicity and even renal disruption. Prophylaxis usually recommended for those patients with unidentified diagnosis but with high risk factors. Amphotericin B (AMB), triazoles including itraconazole, voriconazole (VRC), posaconazole, isavuconazole as well as combination antifungal therapy with voriconazole and an echinocandin are preferred agents for treatment and prevention of invasive aspergillosis in most patients [2]. Fluconazole and echinocandin including caspofungin, micafungin and anidulafungin are usually recommended for invasive candidiasis while some triazole and AMB are recommended if there is intolerance limited availability, or resistance to other antifungal agents [3]
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