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Open Access Highly Accessed Research article

Voriconazole therapeutic drug monitoring: retrospective cohort study of the relationship to clinical outcomes and adverse events

Helen Y Chu1*, Rupali Jain2, Hu Xie3, Paul Pottinger1 and David N Fredricks13

Author affiliations

1 Division of Allergy & Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA

2 Department of Pharmacy, University of Washington Medical Center, Seattle, WA, USA

3 Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

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Citation and License

BMC Infectious Diseases 2013, 13:105  doi:10.1186/1471-2334-13-105

Published: 26 February 2013

Abstract

Background

Voriconazole is approved for treatment of invasive aspergillosis and other invasive fungal infections, but the role for therapeutic drug monitoring (TDM) is not clear.

Methods

We performed a retrospective cohort study of patients at the University of Washington Medical Center and Fred Hutchinson Cancer Research Center from 2007–2009. We compared the effect of therapeutic levels on clinical outcomes and evaluated the relationship between drug levels and adverse events.

Results

A total of 108 patients had voriconazole TDM performed, of whom 84 (77.8%) had a hematologic malignancy and 47 (43.5%) had undergone hematopoietic stem cell transplantation. The primary reasons for treatment were presumed pulmonary aspergillosis (n = 83, 76.8%), other invasive mould infections (n = 13, 12.0%) and candidiasis (n = 9, 8.3%). There was a high degree of variability in voriconazole drug levels among patients (r2 = 0.01; range, <0.10 - 20 mg/L). Of the 46 patients with proven or probable invasive fungal disease, 25 (54.3%) achieved partial or complete response to therapy. There was no significant relationship between therapeutic drug levels and achievement of complete or partial response at 12 weeks (OR 0.29, 95% CI: 0.05-1.34) or radiologic response (OR 1.46, 95% CI: 0.32-7.83). Overall, 45 (41.7%) patients experienced adverse events. Voriconazole levels > 5.5 mg/L were not associated with increased incidence of encephalopathy (OR 3.08, 95% CI 0.79-11.0) or hepatotoxicity (OR 2.45, 95% CI 0.49-10.1).

Conclusions

Voriconazole therapeutic drug levels were not associated with improvement in clinical outcomes among patients with proven or probable invasive fungal disease. We also did not find an association between supratherapeutic drug levels and hepatoxicity or encephalopathy. It is possible that the utility of voriconazole therapeutic drug monitoring to improve clinical efficacy or decrease adverse events may be limited to a subset of high-risk patients.

Keywords:
Voriconazole; Therapeutic drug monitoring; Antifungals; Clinical efficacy