Meta-analysis of the safety of voriconazole in definitive, empirical, and prophylactic therapies for invasive fungal infections

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.Electronic supplementary materialThe online version of this article (10.1186/s12879-017-2913-8) contains supplementary material, which is available to authorized users.

Assessment of the proposed EBMT pediatric criteria for diagnosis and severity grading of sinusoidal obstruction syndrome

“…The comparatively large number of patients fulfilling the pediatric EBMT criteria indicates a risk of over-diagnosis. There is, for instance, a risk that slight increases in bilirubin may be caused by hepatotoxic side effects of medication frequently used in the clinic, such as antibiotics, antiviral drugs and antifungals (in particular voriconazole [33] and carbapenems [34]). As we are the first to assess these proposed criteria, we have only our own numbers to consider regarding the risk of over-diagnosis.…”

Evolution in the Management of Invasive Fungal Infections in Liver Transplant Recipients

“…A recent meta-analysis of studies has found that the tolerability of voriconazole was slightly inferior, and the risk of neurotoxicity and visual toxicity were higher than those of alternative drugs. Only the risk of nephrotoxicity proved to be lower than that of alternatives [117]. Hence, voriconazole should be used as prophylaxis for LTR at high risk for IA.…”

Effects of antifungal stewardship using therapeutic drug monitoring in voriconazole therapy on the prevention and control of hepatotoxicity and visual symptoms: A multicentre study conducted in Japan

“…1,2 It is associated with adverse side effects including visual symptoms, neurological disorders and hepatotoxicity. [3][4][5][6][7][8] Xing et al 9 comprehensively compared voriconazole-induced toxicity with other antifungals, and there were significant differences in hepatotoxicity (odds ratio [OR] 1.60), visual symptoms (OR 6.50) and neurotoxicity (OR 1.99). Therapeutic drug monitoring (TDM) is used to guide voriconazole therapy to prevent drug-related adverse events and to improve clinical responses by individualising dose regimens.…”