Safe and Efficacious Dosage of Flecainide Acetate for Treating Equine Atrial Fibrillation.

Abstract

ABSTRACT. To determine a safe and efficacious dose of flecainide acetate for treating equine atrial fibrillation (Af), the safe dosage level was determined by injecting 1, 2, or 3 mg/kg i.v. of 1% flecainide acetate solution at a rate of 0.2 mg/kg/min to five clinically healthy horses. Clinical signs and the ECG were monitored (HR, PR, QRS, and QT intervals) and blood was taken to measure the plasma flecainide concentration pre-and post-administration. No abnormal signs were observed in the 1-or 2-mg/kg groups, while agitation was observed in three of five horses in the 3-mg/kg group. The QRS, and QT intervals for the 3-mg/kg group increased significantly. The peak plasma flecainide concentrations were 1,316 ± 358 (SD) ng/ml, 1,904 ± 314 ng/ml, and 2,251 ± 387 ng/ml for the 1-, 2-, and 3-mg/kg groups, respectively. To evaluate the efficacy of flecainide, Af was induced by right atrial pacing in six clinically healthy horses, and 1% flecainide acetate solution was then administered until they converted to sinus rhythm. All horses with induced Af converted. For the conversion, a total dose of 1.40 ± 0.63 mg/kg flecainide was required, the duration of administration was 7.00 ± 3.15 min and plasma flecainide concentration at conversion was 1,303 ± 566 ng/ml. In conclusion, flecainide acetate is a safe and effective antiarrhythmic agent for equine Af, and the clinically effective dosage is 1 to 2 mg/kg. Atrial fibrillation (Af) is one of the most common arrhythmias encountered in horses. It is thought that treatment is necessary for Af that does not recover spontaneously [1,4]. There have been a number of reports on Af in horses. Most of these studies used quinidine for treatment [1,11,14]. However, quinidine is known to have a number of side effects, including nasal mucosal edema, dyspnea, diarrhea, colic, tachycardia and laminitis [6,9]. Successful treatment has not been reported using any drug other than quinidine [10]. It would be highly desirable to convert equine Af, using an antiarrhythmic agent with less severe side effects than quinidine.In humans, a wide variety of antiarrhythmic agents have been developed and clinically applied to Af. Flecainide is an antiarrhythmic agent of Vaughan-Williams class Ic, a different class than quinidine [7]. In humans, flecainide has been shown to be effective in treating both supraventricular and ventricular arrhythmias. The rate of cardioversion of paroxysmal Af exceeds 90%, which is higher than that for other antiarrhythmic agents [2,8]. With side effects seldom involving organs other than the heart, flecainide is a relatively safe drug [5]. Nonetheless, flecainide has not been tried in horses, nor has its ability to convert equine Af been evaluated.In this study, we examined the safety and effectiveness of flecainide acetate in treating induced Af in horses. The efficacious dosage and rate of administration of flecainide was determined using clinical observations, ECG, and measurement plasma flecainide concentrations as indicators of side effects. MATERIALS AND METHODSStu...

Antiarrhythmic and Electrophysiologic Effects of Flecainide on Acutely Induced Atrial Fibrillation in Healthy Horses

“…To obtain a more specific ventricular repolarization time, JTc intervals were calculated, and in contrast to what has been documented in humans,20 flecainide temporarily prolonged JTc in horses. The present study however did not identify any potentially dangerous ventricular arrhythmias, which is in agreement with other studies 1, 3. However, 3 cases of flecainide‐induced wide QRS‐tachycardia have been reported in horses2, 4 of which 1 episode led to ventricular fibrillation and sudden cardiac death.…”

“…To investigate whether flecainide affected ventricular repolarization, we evaluated changes in QTc and JTc intervals. In a previous study of horses, no flecainide‐induced changes in QT intervals were reported 1. In our study, QTc was significantly prolonged between 6 and 25 minutes after flecainide infusion was started.…”

“…If only a few or short‐lasting AF episodes were induced, the stimulation frequency was stepwise increased and at the final step (burst pacing at 3,000 bpm; ie, 50 Hz), the current was subsequently increased (Fig 3). Whenever an AF episode exceeded 15 minutes in duration, AF termination was attempted by IV infusion of flecainide7 (2 mg/kg) over 10 minutes according to previous recommendations 1. If no AF episodes ≥15 minutes occurred and spontaneous termination occurred repeatedly, horses were treated with flecainide while in SR.…”

Determination of Oral Dosage and Pharmacokinetic Analysis of Flecainide in Horses.

“…We have shown in a previous study that flecainide given intravenously is a safe and effective agent for treating equine atrial fibrillation [8]. For the conversion of atrial fibrillation to sinus rhythm, a total dose of 1.4 ± 0.63 mg/kg flecainide was required intravenously, the time to conversion was 7.0 ± 3.15 min and the effective plasma concentration was 1,303 ± 566 ng/ml [8]. However, that is the only report on the use of flecainide for treating atrial fibrillation in horses, thus, nothing is known about its behavior following oral administration or its pharmacokinetics in horses.…”

“…It is particularly effective as a drug for converting paroxysmal atrial fibrillation to sinus rhythm [5,7,10,11]. We have shown in a previous study that flecainide given intravenously is a safe and effective agent for treating equine atrial fibrillation [8]. For the conversion of atrial fibrillation to sinus rhythm, a total dose of 1.4 ± 0.63 mg/kg flecainide was required intravenously, the time to conversion was 7.0 ± 3.15 min and the effective plasma concentration was 1,303 ± 566 ng/ml [8].…”