Ibutilide: A New Class III Antiarrhythmic Agent

Abstract

Ibutilide fumarate is a new antiarrhythmic agent recently approved for the conversion of atrial flutter (AFl) and atrial fibrillation (AF) to normal sinus rhythm. A class III agent in the Vaughan Williams classification system, ibutilide prolongs cardiac repolarization by activating a slow inward, predominantly sodium current. An alternative or additive mechanism to prolong repolarization may be blockade of the outward delayed rectifier potassium rapid current. Ibutilide is administered intravenously, and approximately 40% of the drug in serum is protein bound. It is eliminated through hepatic metabolism by undefined enzyme systems, and it appears that none of the metabolites contributes significantly to antiarrhythmic activity. The elimination half‐life of ibutilide ranges from 2–12 hours. When administered by 10‐minute infusion, ibutilide 1 mg (approximately 0.015 mg/kg) resulted in conversion to sinus rhythm in 24–58% of patients with AFl and 20–32% with AF, compared with about 5% for placebo. Administering a second dose of 0.5–1 mg improved the overall response rates to approximately 75% and 45%, respectively. In randomized comparative trials, ibutilide was more effective than sotalol in converting AFl (70% vs 19%) and AF (44% vs 11%) and more effective than procainamide (76% vs 12% and 51% vs 20%, respectively). The time to conversion in most trials was usually 20–30 minutes. Nausea is the most common noncardiac adverse effect (< 2%). Nonsustained and sustained polymorphic ventricular tachycardia occurred in 2.7–6.7% and 1.7% of patients, respectively.