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 conversion of and maintenance of sinus rhythm in patients with atrial fibrillation (AF) and atrial flutter (AFl). Dofetilide is a selective class III antiarrhythmic drug which works by selectively blocking the rapid component of the delayed rectifier outward potassium current (I(kr)). Dofetilide has been shown to prolong the effective refractory period which is accompanied by a dose-dependent prolongation of the QT and QTc intervals, with parallel increases in ventricular refractoriness. Approximately 80% of dofetilide is excreted in the urine which requires dose adjustments in renal insufficiency. The elimination half-life is approximately 10 h in patients with normal renal function. The therapeutic blood level range of dofetilide is presently unknown and monitoring of dofetilide blood levels is not available at this time. Clinical trials have shown dofetilide to be superior to flecainide in converting AFl patients to normal sinus rhythm (NSR) (70% vs. 9%; p<0.01). It also was more effective than sotalol in converting AF and AFl 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 pointes is the most serious side effect occurring in 0.3-10.5% of patients and is dose related. Other common side effects include headache, chest pain and dizziness. To minimize the risk of induced arrhythmia, patients initiated or reinitiated on dofetilide should be hospitalized for a minimum of 3 days where continuous electrocardiographic monitoring, evaluation of renal function and serum electrolytes and cardiac resuscitation can be provided.
Lenz
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Cardiology, Creighton University, Omaha, Nebraska 68131, USA.
Hilleman
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