The antiarrhythmic efficacy and safety of oral flecainide acetate were assessed during a controlled, short-term dosage-maintenance study. Thirteen patients with chronic ventricular ectopy entered a placebo control period, and 11 with persistent, frequent (greater than 600 per 12 hours) premature ventricular complexes (PVCs) advanced to drug therapy. Of 10 patients completing a trial of different doses, nine responded completely, with a mean PVC suppression of 98,3 per cent. Repetitive PVCs were eliminated. The mean effective dose was 189 mg per 12 hours, and the effective plasma concentration before administration of a dose averaged 635 ng per milliliter. One patient responded partially (68 per cent of PVCs suppressed). Flecainide continued to be effective and well tolerated at the end of a two-week outpatient trial in the nine complete responders, maintaining an average PVC suppression of 94.6 per cent. The PR and QRS intervals were mildly prolonged. The echocardiographic ejection fraction was unchanged during treatment. The elimination half-life was long - 18.8 +/- 3.8 hours. Flecainide thus appears to be a highly effective and well-tolerated antiarrhythmic agent with favorable pharmacokinetics.

In order to determine the antiarrhythmic efficacy and safety of oral flecainide acetate (FA) in man, a placebo controlled dose-ranging and short-term oral maintenance study was undertaken in 13 patients (pts) with chronic, ventricular ectopy (VE) of frequency >600 VEll2 hrs. During a 2 day placebo control period, 11113 maintained stable VE frequency (mean 11,254/12 hr,range 653-35.551) and entered dose-ranging. Dosage was increased in increments at 3 day intervals from 100-300 mg/12 hr until 95% VE suppression, limiting side effects, or dosage maximum was attained. Ten pts completed dose-ranging, and pt 11 experienced a transient ischemic attack and was exeluded. Of the 10 pts, 9(90%) were complete responders (CR) (mean suppression 98.7%. range 96.1-100%). and one responded partially (68% suppression). Repetitive VE was totally eliminated in all 10 pts. Pt 11 showed 77% VE suppression on 100 mg/12 hr before exclusion. Of CR, 2 pts ended dose-ranging successfully at 100 mg, 5 at 200 mg, and 2 at 250mg/12 hr. Average dose calculated to achieve 95% suppression was 169 mgll2 hrs. A 3 day placebocontrolled drug washout period was accompanied by a significant return in VE in each of the 9 CR. VE first recurred at 21.9 hrs (range 7-40), and by 3 days VE aver-aged149.6% of control frequency. During the subsequent outpt trial, FA remained highly effective with total and average VE suppression of 98.0% and 94.6%. respectively. ECG response included prolongation (pCO.01) of PR(16.5%) and QRS (10.6%). Echocardiographic Cl was unchanged. FA was well tolerated except for headache in 2 pts. Thus FA appears to be a highly effective antiarrhythmic in man.