Tl. Lenz et De. Hilleman, Dofetilide: A new antiarrhythmic agent approved for conversion and/or maintenance of atrial fibrillation/atrial flutter, DRUGS TODAY, 36(11), 2000, pp. 759-771
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.