Voriconazole-induced QTc prolongation in a paediatric population

Aim: To evaluate Corrected QT (QTc) interval prolongation (QTcP) in paediatric patients treated with voriconazole (VRC) and identify its associated risk factors in this setting. Methods: Clinical, VRC-related and QTc interval data were collected retrospectively from the electronic medical records of VRC-treated paediatric patients attending a large tertiary medical centre in 2011–2016 who underwent electrocardiography before and during therapy. Paired comparison of QTc intervals before and during VRC treatment was performed, adjusted for concurrent medications, electrolyte disturbances and co-morbidities. Results: Fifty-five patients (mean age 10.1 ± 5.4 years) met the inclusion criteria; 34 had an oncologic or hemato-oncologic diagnosis. Mean QTc interval was 402.8 ± 27.9 msec before VRC treatment and 440.0 ± 45.3 msec on treatment (p < 0.001). During treatment, 38 patients (61.8%) had QTcP ≥30 msec and 17 (30.9%), QTcP ≥60 msec; 10 patients (18.2%) had QTc ≥500 msec of whom one acquired torsades de pointes. On multivariate analysis, older age (p = 0.025), lower potassium level (p = 0.025) and longer baseline QTc (0.032) were associated QTcP ≥60 msec, but not daily or cumulative dose of VRC. Conclusion: This study demonstrated a high rate of clinically significant QTcP in VRC-treated children. Proper QTc monitoring, together with laboratory monitoring and electrolyte imbalance correction, is important to prevent cardiac arrhythmias in this patient population.