Dofetilide

DOFETILIDE

Dofetilide has class 3 action potential prolonging action. This action is effected by a dose-dependent blockade of the rapid com-ponent of the delayed rectifier potassium current (I_Kr) and the blockade of I_Kr increases in hypokalemia. Dofetilide produces no relevant blockade of the other potassium channels or the sodium channel. Because of the slow rate of recovery from blockade, the extent of blockade shows little dependence on stimulation fre-quency. However, dofetilide does show less action potential pro-longation at rapid rates because of the increased importance of other potassium channels such as I_Ks at higher frequencies.

Dofetilide is 100% bioavailable. Verapamil increases peak plasma dofetilide concentration by increasing intestinal blood flow. Eighty percent of an oral dose is eliminated unchanged by the kidneys; the remainder is eliminated in the urine as inactive metabolites. Inhibitors of the renal cation secretion mechanism, eg, cimetidine, prolong the half-life of dofetilide. Since the QT-prolonging effects and risks of ventricular proarrhythmia are directly related to plasma concentration, dofetilide dosage must be based on the estimated creatinine clearance. Treatment with dofetilide should be initiated in hospital after baseline measure-ment of the rate-corrected QT interval (QT_c) and serum electro-lytes. A baseline QT_c of > 450 ms (500 ms in the presence of an intraventricular conduction delay), bradycardia of < 50 bpm, and hypokalemia are relative contraindications to its use.

Dofetilide is approved for the maintenance of normal sinus rhythm in patients with atrial fibrillation. It is also effective in restoring normal sinus rhythm in patients with atrial fibrillation.