Safety of Dofetilide Initiation Following a Shortened Amiodarone Washout Period

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