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Meta-Analysis
. 2016 Jul;71(7):1772-85.
doi: 10.1093/jac/dkw045. Epub 2016 Mar 10.

Trough concentration of voriconazole and its relationship with efficacy and safety: a systematic review and meta-analysis

Haiying Jin  1 , Tiansheng Wang  2 , Bonnie A Falcione  3 , Keith M Olsen  4 , Ken Chen  5 , Huilin Tang  6 , John Hui  7 , Suodi Zhai  6
Affiliations
Meta-Analysis

Trough concentration of voriconazole and its relationship with efficacy and safety: a systematic review and meta-analysis

Haiying Jin et al. J Antimicrob Chemother. 2016 Jul.

Abstract

Objectives: The optimum trough concentration of voriconazole for clinical response and safety is controversial. The objective of this review was to determine the optimum trough concentration of voriconazole and evaluate its relationship with efficacy and safety.

Methods: MEDLINE, EMBASE, ClinicalTrials.gov, the Cochrane Library and three Chinese literature databases were searched. Observational studies that compared clinical outcomes below and above the trough concentration cut-off value were included. We set the trough concentration cut-off value for efficacy as 0.5, 1.0, 1.5, 2.0 and 3.0 mg/L and for safety as 3.0, 4.0, 5.0, 5.5 and 6.0 mg/L. The efficacy outcomes were invasive fungal infection-related mortality, all-cause mortality, rate of successful treatment and rate of prophylaxis failure. The safety outcomes included incidents of hepatotoxicity, neurotoxicity and visual disorders.

Results: A total of 21 studies involving 1158 patients were included. Compared with voriconazole trough concentrations of >0.5 mg/L, levels of <0.5 mg/L significantly decreased the rate of treatment success (risk ratio = 0.46, 95% CI 0.29-0.74). The incidence of hepatotoxicity was significantly increased with trough concentrations >3.0, >4.0, >5.5 and >6.0 mg/L. The incidence of neurotoxicity was significantly increased with trough concentrations >4.0 and >5.5 mg/L.

Conclusions: A voriconazole level of 0.5 mg/L should be considered the lower threshold associated with efficacy. A trough concentration >3.0 mg/L is associated with increased hepatotoxicity, particularly for the Asian population, and >4.0 mg/L is associated with increased neurotoxicity.

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Figures

Figure 1.
Figure 1.
Flow chart of study selection.
Figure 2.
Figure 2.
Meta-analysis for successful treatment rate (trough concentration of <0.5 mg/L comparison with >0.5 mg/L, RR <1 favours Ctrough >0.5 mg/L).
Figure 3.
Figure 3.
Sensitivity analysis that included only patients on monotherapy for treatment success rate (trough concentration of <0.5 mg/L comparison with >0.5 mg/L, RR <1 favours Ctrough >0.5 mg/L).
Figure 4.
Figure 4.
Meta-analysis for all-cause mortality (trough concentration of <3.0 mg/L comparison with >3.0 mg/L, RR <1 favours Ctrough <3.0 mg/L).
Figure 5.
Figure 5.
Meta-analysis for incidence of hepatotoxicity (trough concentration of <3.0 mg/L comparison with >3.0 mg/L, RR <1 favours Ctrough <3.0 mg/L).
Figure 6.
Figure 6.
Meta-analysis for incidence of neurotoxicity (trough concentration of <4.0 mg/L comparison with >4.0 mg/L, RR <1 favours Ctrough <4.0 mg/L).
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