Real-world implications of QT prolongation in patients receiving voriconazole and amiodarone

Voriconazole, a triazole antifungal, is frequently prescribed in a complex patient population with comorbidities that require concomitant administration of QT interval-prolonging medications. We sought to evaluate QT interval prolongation in patients receiving concomitant therapy with voriconazole and amiodarone and to assess the development of any potentially fatal cardiac arrhythmias as a result.

We conducted a retrospective observational study of patients who had received amiodarone and voriconazole concomitantly between 2005 and 2015, with a prior period of monotherapy, who had ECG data during monotherapy (baseline) and concomitant therapy (follow-up).

We included 46 patients in our final analysis. Overall, the mean change in QT corrected (QTc) from baseline to follow-up was 49.0 ms (P < 0.001). Eighteen (39.1%) patients had a follow-up QTc interval ≥500 ms, with 17 (37.0%) having a change in QTc interval ≥60 ms from baseline to follow-up. Men were more likely to have a follow-up QTc interval of ≥500 ms. In multivariate analysis, only low serum potassium concentration and concomitant 'possible' QT-prolonging drugs were associated with a follow-up QTc interval ≥500 ms and a lower baseline QTc interval was associated with a change in QTc interval of ≥60 ms. Discharge diagnoses of cardiac arrhythmias and events were assessed and none was found to be related to concomitant therapy.

Concomitant therapy with amiodarone and voriconazole significantly prolonged the QTc interval to a degree greater than that on monotherapy. However, no clinically significant cardiac events were observed.