Therapeutic use of dofetilide
- Raymond L Woosley, MD, PhD
Raymond L Woosley, MD, PhD
- Professor of Medicine and Pharmacology
- University of Arizona
- President and CEO
- The Critical Path Institute
Dofetilide is a class III antiarrhythmic agent (table 1) available for use in the United States and other countries for the acute termination of atrial fibrillation or flutter as well as prevention of atrial fibrillation or flutter recurrence. Dofetilide has also been used in an off-label manner to treat paroxysmal supraventricular tachycardias. Some investigators have studied the efficacy of dofetilide in the treatment of life-threatening ventricular arrhythmias, although the drug is not approved for this indication. In contrast to some other antiarrhythmic medications, dofetilide appears to be hemodynamically safe for use in patients with heart failure or a prior myocardial infarction . Because of a relatively high risk of torsades de pointes as an adverse effect of dofetilide, it has a formal risk evaluation and mitigation program that requires training and certification of treatment sites. (See 'Drug interactions' below.)
The basic pharmacologic properties of dofetilide, its clinical uses, and its safety profile are discussed in detail here. Alternative treatment approaches for supraventricular and ventricular arrhythmias are discussed separately. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials" and "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations" and "Atrioventricular nodal reentrant tachycardia", section on 'Initial management' and "Sustained monomorphic ventricular tachycardia in patients with a prior myocardial infarction: Treatment and prognosis".)
Dofetilide is a class III antiarrhythmic agent that blocks the delayed rectifier cardiac potassium channel and prolongs repolarization (table 1). Dofetilide has relative selectivity for blocking the rapidly-activating component of the delayed rectifier potassium current (IKr) at concentrations of 10 to 30 nanomole/L [2,3]. At these concentrations, it does not block the slow component of the delayed rectifier potassium current (IKs) or the inward rectifier (IKi) and does not affect calcium currents. Evidence from one study shows that dofetilide and several other drugs known to cause torsades de pointes (d-sotalol, thioridazine, and erythromycin) increase the late sodium current (INaL) in cardiac cells, an action (IC50 = 0.1 micromole/L) that could contribute to their arrhythmogenic potential .
As a result of its electrophysiologic actions on IKr and possibly INaL, dofetilide has a selective effect on the QT interval of the surface ECG. In clinical electrophysiologic studies, it prolongs the QT interval with little, if any, effect on QT dispersion . Purkinje fibers from female dogs are more sensitive to dofetilide than fibers from male dogs, which is consistent with the threefold greater incidence of torsades de pointes in women . (See "Acquired long QT syndrome".)
Like other class III agents, dofetilide exhibits reverse use dependency (greater prolongation of repolarization and the refractory period during slower heart rates). The drug prolongs the effective refractory period of atrial and ventricular myocardium and accessory pathways, but it has no effect on conduction parameters, sinus cycle length, or sinus node recovery [7,8]. (See "Myocardial action potential and action of antiarrhythmic drugs".)
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- ELECTROPHYSIOLOGIC ACTION
- PHARMACOLOGIC DATA
- DRUG APPROVAL AND RESTRICTIONS
- CLINICAL USE
- Oral dofetilide for atrial fibrillation/atrial flutter terminatinon and prevention
- Dofetilide for preventing recurrence of paroxysmal supraventricular tachycardia
- Ventricular tachyarrhythmias
- Heart failure
- Postmyocardial infarction
- Drug interactions