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.

Voriconazole-induced QT prolongation among hemato-oncologic patients: clinical characteristics and risk factors.

PURPOSE: The purpose of this study is to determine the rate of QTcP and associated risk factors in patients treated with voriconazole. METHODS: We conducted a retrospective chart review of all patients treated with voriconazole in a large tertiary center between 2009 and 2015, using paired comparison of QTc intervals on and off voriconazole treatment, adjusted for comorbidities, electrolyte abnormalities, and concurrent medications. RESULTS: Fifty-four patients were included, of whom 53 were diagnosed with oncologic/hemato-oncologic disease. Mean QTc during voriconazole therapy (448.0 ± 52.9 msec) was significantly longer compared to QTc off voriconazole (421.8 ± 42.2 msec; p = 0.002). QTcP ≥30 msec and ≥60 msec was demonstrated in 43% (23 patients) and 28% (15 patients), respectively. Multivariate analysis showed that QTcP was significantly associated with baseline QTc ≥ 450 msec (upper QTc quartile) (p < 0.01) and low serum potassium levels (p < 0.01). Contrarily, no significant association was found between mean voriconazole daily and cumulative dose and QTcP. CONCLUSION: Our findings indicate that hemato-oncologic patients treated with voriconazole are at increased risk for QTcP, especially in the presence of baseline QTc ≥ 450 msec and low serum potassium levels.