Publication details

Utility of voriconazole therapeutic drug monitoring: a meta-analysis

Authors

LUONG Me-Linh AL-DABBAGH Mona GROLL Andreas H. RÁČIL Zdeněk NANNYA Yasuhito MITSANI Dimitra HUSAIN Shahid

Year of publication 2016
Type Article in Periodical
Magazine / Source Journal of Antimicrobial Chemotherapy
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1093/jac/dkw099
Field Pharmacology and pharmaceutical chemistry
Keywords INVASIVE FUNGAL-INFECTIONS; ADVERSE EVENTS; PLASMA-CONCENTRATIONS; BLOOD-CONCENTRATION; CLINICAL-OUTCOMES; EFFICACY; ASPERGILLOSIS; MULTICENTER; GUIDELINES; DISEASES
Description Background: Voriconazole therapeutic drug monitoring (TDM) is increasingly used in clinical practice. However, the utility of voriconazole TDM to guide therapy remains uncertain and controversial. We conducted a metaanalysis of studies assessing the relationship between voriconazole serum concentration and clinical outcomes of success and toxicity. Methods: We searched bibliographic databases for studies on voriconazole serum concentrations and clinical outcomes. We compared success outcomes between patients with therapeutic and subtherapeutic voriconazole serum concentrations, and toxicity outcomes between patients with and without supratherapeutic serum concentrations. Results: Twenty-four studies were analysed. Pooled analysis for efficacy endpoint demonstrated that patients with therapeutic voriconazole serum concentrations (1.0–2.2 mg/L) were more likely to have successful outcomes compared with those with subtherapeutic voriconazole serum concentrations (OR 2.30; 95% CI 1.39–3.81). A therapeutic threshold of 1.0 mg/L was most predictive of successful outcome (OR 1.94; 95% CI 1.04–3.62). Patients with therapeutic concentrations did not have better survival rates. Pooled analysis for toxicity endpoint demonstrated that patients with supratherapeutic voriconazole serum concentrations (4.0–6.0 mg/L) were at increased risk of toxicity (OR 4.17; 95% CI 2.08–8.36). A supratherapeutic threshold of 6.0 mg/L was most predictive of toxicity (OR 4.60; 95% CI 1.49–14.16). Conclusions: Patients with therapeutic voriconazole serum concentrations were twice as likely to achieve successful outcomes. The likelihood of toxicity associated with supratherapeutic voriconazole serum concentrations was 4-fold that of therapeutic concentrations. Our findings suggest that the use of voriconazole TDM to aim for serum concentrations between 1.0 and 6.0 mg/L during therapy may be warranted to optimize clinical success and minimize toxicity.

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