Voriconazole-induced QTc prolongation in a paediatric population

Area of Science:

• Pediatric Cardiology
• Clinical Pharmacology
• Antifungal Therapy

Background:

• Voriconazole (VRC) is a crucial antifungal medication used in pediatric patients.
• QTc interval prolongation (QTcP) is a known adverse effect of some medications, potentially leading to serious cardiac events.
• Limited data exists on QTcP specifically in pediatric populations treated with VRC.

Purpose of the Study:

• To evaluate the incidence of corrected QT (QTc) interval prolongation (QTcP) in pediatric patients receiving voriconazole (VRC).
• To identify risk factors associated with QTcP in this patient group.

Main Methods:

• Retrospective analysis of electronic medical records from a tertiary medical center (2011-2016).
• Inclusion of pediatric patients who underwent electrocardiography before and during VRC therapy.
• Paired QTc interval comparison, adjusted for concurrent medications, electrolyte disturbances, and comorbidities.

Main Results:

• Fifty-five pediatric patients (mean age 10.1 years) were analyzed.
• A significant increase in mean QTc interval was observed during VRC treatment (402.8 to 440.0 msec, p < 0.001).
• Clinically significant QTcP (≥30 msec) occurred in 61.8% of patients, and ≥60 msec in 30.9%. Older age, lower potassium, and longer baseline QTc were associated with QTcP ≥60 msec.

Conclusions:

• Voriconazole treatment is associated with a high rate of clinically significant QTc prolongation in children.
• Monitoring QTc intervals, laboratory values, and correcting electrolyte imbalances are crucial for preventing cardiac arrhythmias in pediatric patients on VRC.
• Risk factors for significant QTcP include older age, hypokalemia, and prolonged baseline QTc.