Safety of Dofetilide Initiation Following a Shortened Amiodarone Washout Period

Dofetilide, a class III antiarrhythmic for atrial fibrillation, frequently requires dose reduction or discontinuation for QT interval prolongation or ventricular arrhythmias. Food and Drug Administration guidelines mandate a 3-month amiodarone washout or serum amiodarone <0.3 mcg/mL before dofetilide initiation, potentially prolonging therapy interruption.

This study aimed to evaluate the safety of a shortened amiodarone to dofetilide transition by assessing dose reduction, drug discontinuation, and arrhythmic events.

Mayo Clinic patients transitioned from amiodarone to dofetilide in <90 days with ≥12 weeks of amiodarone therapy and serum concentration ≥0.3 mcg/mL if measured were identified. The primary end point was ventricular arrhythmias requiring dofetilide discontinuation.

The final cohort included 66 patients (mean age 65 ± 14 years; 74.2% of the patients were men). Atrial fibrillation classification was 33.3% paroxysmal, 54.5% persistent, and 12.1% long-standing persistent. A total of 22.7% had implantable cardioverter-defibrillators. The median transition period was 43 days; 16 patients (24%) transitioned within 30 days (5 [8%] within 14 days), 20 (30%) between 31 and 45 days, 16 (24%) between 46 and 60 days, and 14 (21%) between 61 and 90 days. Dose reduction occurred in 24.2% and discontinuation in 10.6%, with no difference between ≤30- and >30-day transitions (dose reduction: 12.5% vs 28.0%, P = 0.319; discontinuation: 6.3% vs 12.0%, P = 1). No torsades de pointes (TdP) occurred during inpatient dofetilide initiation/loading. One TdP episode (339 days after dofetilide initiation, 419 days postamiodarone) was associated with intercurrent illness and additional QT-prolonging medication exposure.

In this cohort, dofetilide initiation within 90 days of amiodarone discontinuation was not associated with TdP during inpatient loading, supporting the feasibility of monitored, expedited transitions in select patients.