Torsade de pointes induced by systemic antifungal agents: lessons from a retrospective analysis of published case reports

Torsade de pointes (TdP) is a potentially fatal arrhythmia that might be associated with systemic antifungal agent (SAFAs) administration. The objective of this study was to investigate all published reports on TdP induced by SAFAs in order to characterise this association. Each original report was analysed for the presence of risk factors for TdP: female gender, structural heart disease, electrolyte imbalance, concomitant use of a QT interval prolonging agent which SAFA inhibits its liver metabolism, liver cirrhosis, renal failure and more. Naranjo probability scale for adverse drug reactions was applied for every full report. Twenty-one reports on 28 patients were analysed. All patients survived. Most patients (25/28; 89.2%) used one or more agents that might have prolonged the QT interval and their liver metabolism might have been inhibited by SAFA. Female gender was the second most common risk factor for TdP (20/28; 71.4%). All patients, including female patients, had one or more risk factors for TdP prior to SAFA administration. According to Narajno probability scale, there was no definite association between TdP and SAFA in any report. SAFA alone might seldom trigger TdP. We wish to raise the level of awareness of risk factors for TdP prior to SAFA administration and for concomitant use of other dysrhythmogenic agents in particular.