IBUTILIDE FUMARATE injection, solution
BOXED WARNING(WHAT IS THIS?)
LIFE-THREATENING ARRHYTHMIAS-APPROPRIATE TREATMENT ENVIRONMENT
Ibutilide fumarate injection can cause potentially fatal arrhythmias, particularly sustained polymorphic ventricular tachycardia, usually in association with QT prolongation (torsades de pointes), but sometimes without documented QT prolongation. In registration studies, these arrhythmias, which require cardioversion, occurred in 1.7% of treated patients during, or within a number of hours of, use of ibutilide fumarate injection. These arrhythmias can be reversed if treated promptly (see WARNINGS, PROARRHYTHMIA). It is essential that ibutilide fumarate injection be administered in a setting of continuous ECG monitoring and by personnel trained in identification and treatment of acute ventricular arrhythmias, particularly polymorphic ventricular tachycardia. Patients with atrial fibrillation of more than 2 to 3 days' duration must be adequately anticoagulated, generally for at least 2 weeks.
CHOICE OF PATIENTS
Patients with chronic atrial fibrillation have a strong tendency to revert after conversion to sinus rhythm (see CLINICAL PHARMACOLOGY: CLINICAL STUDIES) and treatments to maintain sinus rhythm carry risks. Patients to be treated with ibutilide fumarate injection, therefore, should be carefully selected such that the expected benefits of maintaining sinus rhythm outweigh the immediate risks of ibutilide fumarate injection, and the risks of maintenance therapy, and are likely to offer an advantage compared with alternative management.
SPL UNCLASSIFIED SECTION
Rx only
FOR INTRAVENOUS INFUSION ONLY
DESCRIPTION
Ibutilide fumarate injection is an antiarrhythmic drug with predominantly class III (cardiac action potential prolongation) properties according to the Vaughan Williams Classification. Each milliliter of ibutilide fumarate injection contains 0.1 mg of ibutilide fumarate (equivalent to 0.087 mg ibutilide free base), 0.189 mg sodium acetate trihydrate, 8.9 mg sodium chloride, hydrochloric acid and/or sodium hydroxide to adjust pH to approximately 4.6, and water for injection.
Ibutilide fumarate injection is an isotonic, clear, colorless, sterile aqueous solution.
Ibutilide fumarate has one chiral center, and exists as a racemate of the (+) and (−) enantiomers.
The chemical name for ibutilide fumarate is Methanesulfonamide, N-{4-{4-(ethylheptylamino)-1 -hydroxybutyl}phenyl}, (+)(−), (E)-2-butenedioate (1:0.5) (hemifumarate salt). Its molecular formula is C22H38N2O5S, and its molecular weight is 442.62.
Ibutilide fumarate is a white to off-white powder with an aqueous solubility of over 100 mg/mL at pH 7 or lower.
The structural formula is represented below:
 Chemical Structure
Ibutilide Fumerate
CLINICAL PHARMACOLOGY
Mechanism of Action
Ibutilide fumarate injection prolongs action potential duration in isolated adult cardiac myocytes and increases both atrial and ventricular refractoriness in vivo, i.e., class III electrophysiologic effects. Voltage clamp studies indicate that ibutilide fumarate injection, at nanomolar concentrations, delays repolarization by activation of a slow, inward current (predominantly sodium), rather than by blocking outward potassium currents, which is the mechanism by which most other class III antiarrhythmics act. These effects lead to prol