Voriconazole: an audit of hospital-based dosing and monitoring and evaluation of the predictive performance of a dose-prediction software package

Background: Therapeutic drug monitoring (TDM) is recommended to guide voriconazole therapy. Objectives: To determine compliance of hospital-based voriconazole dosing and TDM with the Australian national guidelines and evaluate the predictive performance of a one-compartment population pharmacokinetic voriconazole model available in a commercial dose-prediction software package. Methods: A retrospective audit of voriconazole therapy at an Australian public hospital (1 January to 31 December 2016) was undertaken. Data collected included patient demographics, dosing history and plasma concentrations. Concordance of dosing and TDM with Australian guidelines was assessed. Observed concentrations were compared with those predicted by dose-prediction software. Measures of bias (mean prediction error) and precision (mean squared prediction error) were calculated. Results: Adherence to dosing guidelines for 110 courses of therapy (41% for prophylaxis and 59% for invasive fungal infections) was poor, unless oral formulation guidelines recommended a 200mg dose, the most commonly prescribed dose (56% of prescriptions). Plasma voriconazole concentrations were obtained for 82% (90/110) of courses [median of 3 (range: 1-27) obtained per course]. A minority (27%) of plasma concentrations were trough concentrations [median concentration: 1.5mg/L (range: <0.1 to >5.0mg/L)]. Of trough concentrations, 57% (58/101) were therapeutic, 37% (37/101) were subtherapeutic and 6% (6/101) were supratherapeutic. The dose-prediction software performed well, with acceptable bias and precision of 0.09mg/L (95% CI -0.08 to 0.27) and 1.32 (mg/L) (95% CI 0.96-1.67), respectively. Conclusions: Voriconazole dosing was suboptimal based on published guidelines and TDM results. Dose-prediction software could enhance TDM-guided therapy.