CORVERT- ibutilide fumarate injection, solution
Pharmacia and Upjohn Company
For intravenous infusion only
DESCRIPTION
CORVERT Injection (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 CORVERT Injection contains 0.1 mg of ibutilide fumarate (equivalent to 0.087 mg ibutilide free base), 0.189 mg sodium acetate trihydrate, 8.90 mg sodium chloride, hydrochloric acid to adjust pH to approximately 4.6, and Water for Injection.
CORVERT 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 C22 H38 N2 O5 S, 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
(click image for full-size original)
Ibutilide Fumarate
CLINICAL PHARMACOLOGY
Mechanism of Action
CORVERT Injection prolongs action potential duration in isolated adult cardiac myocytes and increases both atrial and ventricular refractoriness in vivo , ie, class III electrophysiologic effects. Voltage clamp studies indicate that CORVERT, 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 prolongation of atrial and ventricular action potential duration and refractoriness, the predominant electrophysiologic properties of CORVERT in humans that are thought to be the basis for its antiarrhythmic effect.
Electrophysiologic Effects
CORVERT produces mild slowing of the sinus rate and atrioventricular conduction. CORVERT produces no clinically significant effect on QRS duration at intravenous doses up to 0.03 mg/kg administered over a 10-minute period. Although there is no established relationship between plasma concentration and antiarrhythmic effect, CORVERT produces dose-related prolongation of the QT interval, which is thought to be associated with its antiarrhythmic activity. (See WARNINGS for relationship between QTc prolongation and torsades de pointes-type arrhythmias.) In a study in healthy volunteers, intravenous infusions of CORVERT resulted in prolongation of the QT interval that was directly correlated with ibutilide plasma concentration during and after 10-minute and 8-hour infusions. A steep ibutilide concentration/response (QT prolongation) relationship was shown. The maximum effect was a function of both the dose of CORVERT and the infusion rate.
