Description of Ibutilide (Corvert)

Ibutilide, a substituted methane sulfonamide derivative, is an intravenous Class III antiarrhythmic agent indicated for rapid conversion of atrial fibrillation or atrial flutter to normal sinus rhythm. Prior to approval of ibutilide, electrical cardioversion was the recommended choice for rapid conversion of atrial fibrillation or flutter to normal sinus rhythm.

No other approved pharmacologic agent is indicated for rapid conversion of atrial arrhythmias. Ibutilide began the FDA approval process in October 1994 and was finally approved December 28, 1995. Application to market the drug in Sweden and England has also been made.

Mechanism of Action of Ibutilide (Corvert)

Unlike other commercially available class III antiarrhythmic agents that block outward potassium currents, ibutilide exerts its actions by promoting the influx of sodium through slow inward sodium channels. As a result of its actions, ibutilide prolongs the action potential duration, thereby causing a mild slowing of the sinus rate and AV conduction.

These effects are in contrast to class I antiarrhythmic agents, which inhibit the influx of sodium. Clinically, ibutilide converts atrial fibrillation or flutter to normal sinus rhythm without altering blood pressure, heart rate, QRS duration, or PR interval.

Pharmacokinetics of Corvert

Ibutilide is administered by intravenous infusion.  The pharmacokinetics of ibutilide show considerable intersubject variability. Systemic clearance is approximately equal to liver blood flow (29 mL/minute/kg), and protein binding is about 40%. Metabolism occurs in the liver by omega-oxidation with sequential beta-oxidation to eight metabolites. According to animal models, only one metabolite possesses class III antiarrhythmic effects that are similar to those of ibutilide, however, the plasma concentration of this metabolite is less than 10% of that of ibutilide.

Excretion of ibutilide and its metabolites occurs via the urine and feces. Approximately 82% of a 0.01 mg/kg dose may be excreted in the urine, with 7% as unchanged drug. About 19% may be excreted in the feces. The elimination half-life of ibutilide is about 6 hours, with a range of 2—12 hours.

Route-Specific Pharmacokinetics

Intravenous Route
Following intravenous infusion, ibutilide is rapidly cleared from the plasma.

• Ibutilide Fumarate

• Corvert

• Antiarrhythmic, Group III
• Methanesulfonanilide

• Atrial arrhythmia, recent-onset atrial fibrillation and atrial flutter: Adult

Serious Effects

• Cardiovascular: Bradyarrhythmia (1.2% ), Heart block (1.5% to 1.9% ), Prolonged QT interval (1.2% ), Torsades de pointes, Ventricular arrhythmia (0.2% to 5.1% )
• Neurologic: Cerebrovascular accident (rare )
• Renal: Renal failure (0.3%.)
• Respiratory: Pulmonary edema (rare )

• Intravenous: injection may be given undiluted or diluted in 50 mL of D5W or NS
• Intravenous: contents of one 10 mL vial may be added to 50 mL infusion bag
• Intravenous: polyolefin and polyvinyl chloride (PVC) plastic bags are compatible containers
• Intravenous: (initial infusion) infuse over a period of 10 min
• Intravenous: (second infusion) may repeat infusion over 10 min if arrhythmia does not terminate within 10 min after the end of the initial infusion

• Corvert: Intravenous Solution: 0.1 MG/1 ML
• Corvert Novaplus: Intravenous Solution: 0.1 MG/1 ML

• Intravenous Solution: 0.1 MG/1 ML

Adult Dose

• Atrial arrhythmia, recent-onset atrial fibrillation and atrial flutter: (patients 60 kg or more) 1 mg IV over 10 minutes, may repeat same dose 10 min after completion of first infusion if arrhythmia is not terminated; dose of 2 mg as a single IV infusion has been used
• Atrial arrhythmia, recent-onset atrial fibrillation and atrial flutter: (patients less than 60 kg) 0.01 mg/kg IV over 10 minutes, may repeat same dose 10 min after completion of first infusion if arrhythmia is not terminated

• General Dosage Information: safety and efficacy not established in children

Black Box Warning

• Intravenous (Solution): Ibutilide (Corvert) can cause potentially fatal arrhythmias which require cardioversion, particularly sustained polymorphic ventricular tachycardia, usually in association with QT prolongation (torsades de pointes), but sometimes without documented QT prolongation. It is essential that ibutilide be administered in a setting of continuous ECG monitoring and by personnel trained in identification and treatment of acute ventricular arrhythmias. Patients with atrial fibrillation of more than 2 to 3 days’ duration must be adequately anticoagulated, generally for at least 2 weeks. Treatments to maintain sinus rhythm after cardioversion carry risks; patients should be carefully selected such that the expected benefits of maintaining sinus rhythm outweigh the immediate risks of ibutilide fumarate, and the risks of maintenance therapy, and are likely to offer an advantage compared with alternative management .