Association of Torsade de Pointes and QT Prolongation With Antifungal Triazoles: Analysis Using a Pharmacovigilance Database.

BACKGROUND/AIM: Torsade de pointes (TdP)/QT prolongation (QTP) is one of the most life-threatening adverse effects of antifungal triazoles. The aim of the present study was to evaluate the association of antifungal triazoles with TdP/QTP by age group and the profile of the time of TdP/QTP onset by analyzing the spontaneous adverse event database for Japan.

PATIENTS AND METHODS

Data registered in the Japanese Adverse Drug Event Report database (JADER) from April 2004 to March 2022 were analyzed. The association between the administration of antifungal triazoles and TdP/QTP according to age was evaluated using an adjusted reporting odds ratio (aROR). In addition, the time-to-onset of TdP/QTP after antifungal triazole treatment was analyzed using the Weibull distribution according to the route of administration.

RESULTS

Antifungal triazole treatment was associated with TdP/QTP (aROR=1.77, 95% confidence interval=1.52-2.07). In the subgroup analyses by age group, antifungal triazole treatments in patients ≤29 years old and ≥50 (except ≥90) years old were associated with TdP/QTP. The medians (quartiles) of time-to-onset for intravenous and oral antifungal triazole treatment were 8 (6-12) and 23 (8-86) days, respectively. In addition, the shape parameter in the Weibull distribution analysis of oral triazole treatment revealed that the hazard exhibited an early failure profile.

CONCLUSION

TdP/QTP is associated with antifungal triazoles even in young patients, and patients should be monitored for the development of TdP/QTP, especially early after the initiation of treatment.