Trough concentration of voriconazole and its relationship with efficacy and safety: a systematic review and meta-analysis
Journal of Antimicrobial Chemotherapy July 2016 V.71 N.7 P. 1772-1785
Haiying Jin, Tiansheng Wang, Bonnie A. Falcione, Keith M. Olsen, Ken Chen, Huilin Tang, John Hui, and Suodi Zhai
1Department of Pharmacy, Peking University Third Hospital, Beijing, China
2Department of Pharmacy, The Affiliated Hospital of Medical College, Ningbo University, Ningbo, Zhejiang, China
3Department of Pharmacy Administration and Clinical Pharmacy, Peking University School of Pharmaceutical Sciences, Beijing, China
4Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA
5Department of Pharmacy Practice, University of Arkansas for Medical Sciences, Little Rock, AR, USA
6Department of Pharmacy, Stanford University Hospital and Clinics, Palo Alto, CA, USA
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.
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.
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.
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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