FLECAINIDE ACETATE - flecainide acetate tablet
Roxane Laboratories, Inc
FLECAINIDE ACETATE Tablets, USP
Rx only
DESCRIPTION
Flecainide Acetate Tablets, USP are an antiarrhythmic drug available in tablets of 50, 100 or 150 mg for oral administration.
Flecainide acetate is benzamide, N-(2-piperidinylmethyl)-2,5-bis (2,2,2-trifluoroethoxy)- monoacetate. The structural formula is given below.
Flecainide acetate is a white crystalline substance with a pKa of 9.3. It has an aqueous solubility of 48.4 mg/mL at 37°C.
Flecainide Acetate Tablets, USP also contain: hydrogenated cottonseed oil, magnesium stearate, microcrystalline cellulose, modified cellulose gum, and pregelatinized starch.
CLINICAL PHARMACOLOGY
Flecainide has local anesthetic activity and belongs to the membrane stabilizing (Class 1) group of antiarrhythmic agents; it has electrophysiologic effects characteristic of the IC class of antiarrhythmics.
Electrophysiology
In man, flecainide produces a dose-related decrease in intracardiac conduction in all parts of the heart with the greatest effect on the His-Purkinje system (H-V conduction). Effects upon atrioventricular (AV) nodal conduction time and intra-atrial conduction times, although present, are less pronounced than those on ventricular conduction velocity. Significant effects on refractory periods were observed only in the ventricle. Sinus node recovery times (corrected) following pacing and spontaneous cycle lengths are somewhat increased. This latter effect may become significant in patients with sinus node dysfunction. (See WARNINGS.)
Flecainide causes a dose-related and plasma-level related decrease in single and multiple PVCs and can suppress recurrence of ventricular tachycardia. In limited studies of patients with a history of ventricular tachycardia, flecainide has been successful 30 to 40% of the time in fully suppressing the inducibility of arrhythmias by programmed electrical stimulation. Based on PVC suppression, it appears that plasma levels of 0.2 to 1 mcg/mL may be needed to obtain the maximal therapeutic effect. It is more difficult to assess the dose needed to suppress serious arrhythmias, but trough plasma levels in patients successfully treated for recurrent ventricular tachycardia were between 0.2 and 1 mcg/mL. Plasma levels above 0.7 to 1 mcg/mL are associated with a higher rate of cardiac adverse experiences such as conduction defects or bradycardia. The relation of plasma levels to proarrhythmic events is not established, but dose reduction in clinical trials of patients with ventricular tachycardia appears to have led to a reduced frequency and severity of such events.
Hemodynamics
Flecainide does not usually alter heart rate, although bradycardia and tachycardia have been reported occasionally.
In animals and isolated myocardium, a negative inotropic effect of flecainide has been demonstrated. Decreases in ejection fraction, consistent with a negative inotropic effect, have been observed after single administration of 200 to 250 mg of the drug in man; both increases and decreases in ejection fraction have been encountered during multidose therapy in patients at usual therapeutic doses. (See WARNINGS.)
Metabolism in Humans
Following oral administration, the absorption of flecainide is nearly complete. Peak plasma levels are attained at about three hours in most individuals
