Neurological adverse events to voriconazole: evidence for therapeutic drug monitoring

BACKGROUND: Voriconazole shows a considerable interpatient variation of serum concentrations. METHODS AND RESULT: In an analysis of 28 treatment courses, 6 patients presented with neurological adverse events (hallucination, encephalopathy, and visual disturbance). The hazard ratio per 0.1 mg/mL voriconazole serum level (sVL) increase was 2.27 (95% CI: 1.45-3.56, p <0.001). There was no correlation between sVL and creatinine (r = 0.12, p = 0.114), ALT (r = -0.14, p = 0.072), AST (r = 0.003, p = 0.964), alkaline phosphatase (r = 0.03, p = 0.723). CONCLUSIONS: Our findings demonstrate that elevated sVL is associated with neurological adverse events, and measurement of its serum concentration could improve voriconazole treatment and safety.