Voriconazole-induced QTc prolongation in a paediatric population

To evaluate Corrected QT (QTc) interval prolongation (QTcP) in paediatric patients treated with voriconazole (VRC) and identify its associated risk factors in this setting.

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.

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.

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.