Dofetilide: A new antiarrhythmic agent approved for conversion and/or maintenance of atrial fibrillation/atrial flutter

Dofetilide is a new antiarrhythmic agent recently approved for the conversi on of and maintenance of sinus rhythm in patients with atrial fibrillation (AF) and atrial flutter (AFI). Dofetilide is a selective class iii antiarrh ythmic drug which works by selectively blocking the rapid component of the delayed rectifier outward potassium current (I-Kr). Dofetilide has been sho wn to prolong the effective refractory period which is accompanied by a dos e-dependent prolongation of the QT and QTc intervals, with par-allel increa ses in ventricular refractoriness. Approximately 80% of dofetilide is excre ted in the urine which requires dose adjustments in renal insufficiency. Th e elimination half-life is approximately 10 h in patients with normal renal function. The therapeutic blood level range of dofetilide is presently unk nown and monitoring of dofetilide blood levels is not available at this tim e. Clinical trials have shown dofetilide to be superior to flecainide in co nverting AFI patients to normal sinus rhythm (NSR) (70% vs. 9%; p <0.01). I t also was more effective than sotalol in converting AF and AF[ patients to NSR (29% vs. 6%; p <0.05) and maintaining these patients in NSR for up to 1 year (p <0.05). Most patients convert to NSR within 24-36 h. Torsade de p ointes is the most serious side effect occurring in 0.3-10.5% of patients a nd is dose related. Other common side effects include headache, chest pain and dizziness. To minimize the risk of induced arrhythmia, patients initiat ed or reinitiated on dofetilide should be hospitalized for a minimum of 3 d ays where continuous electrocardiographic monitoring, evaluation of renal f unction and serum electrolytes and cardiac resuscitation can be provided. ( C) 2000 Prous Science. All rights reserved.