Ibutilide: a new class III antiarrhythmic agent.

Abstract

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of ibutilide are reviewed. Ibutilide is the first class III antiarrhythmic agent to rely on activation of a slow inward sodium current to prolong the action potential and effective refractory period of atrial and ventricular tissue. The drug is indicated for the rapid restoration of normal sinus rhythm in patients with atrial fibrillation or atrial flutter of recent onset who are hemodynamically stable. The effects of ibutilide are concentration dependent. The drug undergoes rapid and extensive hepatic metabolism. The pharmacokinetics of ibutilide fumarate are linear well above the maximum proposed therapeutic dose of 2 mg. The elimination half-life averages six hours. Clinical trials have established ibutilide's efficacy in converting sustained atrial flutter and atrial fibrillation to normal sinus rhythm. It has been shown that patients with atrial flutter respond at a greater rate than patients with atrial fibrillation, but that atrial fibrillation is converted more rapidly than atrial flutter. In one study, atrial flutter and atrial fibrillation were successfully converted in significantly more patients receiving ibutilide than those receiving sotalol. Ventricular tachycardia is the adverse event of primary concern, occurring in 4.3% of patients in clinical trials. The recommended initial dose is 0.01 mg/kg for patients weighing less than 60 kg and 1 mg for patients weighing 60 kg or more, infused over 10 minutes. About 70% of patients will require a second dose. The list price is $119.75 per dose. Ibutilide appears to be an effective alternative to other antiarrhythmic agents for rapid conversion of arrhythmias to normal sinus rhythm in hemodynamically stable patients.