Ethmozine ® (moricizine HCl) therapy for complex ventricular arrhythmias

Abstract

Moricizine HCl (Ethmozine ®), a new antiarrhythmic agent, was administered to 102 patients with refractory ventricular fibrillation (n = 31), sustained ventricular tachycardia (VT) (n = 46) or symptomatic nonsustained VT (n = 25). A noninvasive approach utilizing monitoring and exercise testing was used in 82 patients who had a high density of reproducible spontaneous arrhythmia, whereas 20 patients without such arrhythmia required invasive electrophysiologic testing. The dosage of moricizine HCl was 200 mg 3 times daily, and during 5 to 6 days was titrated up to a maximum of 400 mg 3 times daily or 15 mg/kg daily, based on arrhythmia suppression and occurrence of side effects. Criteria for efficacy were a > 90% reduction in repetitive ventricular premature beats (couplets and runs of VT) and a > 50% reduction in ventricular premature beats when noninvasive methods were used. When electrophysiologic testing was used, the drug was judged effective if it prevented the induction of > 2 repetitive responses. Of 75 patients completing noninvasive study, 30 (40%) responded to moricizine HCl therapy, whereas only 1 of 20 patients undergoing electrophysiologic testing responded. There was no difference in moricizine HCl blood levels between responders and nonresponders (0.41 μg/ml vs 0.43 μg/ml, difference not significant). Side effects occurred in 28 patients (27%). Most frequent were aggravation of arrhythmia (n = 12), nausea and vomiting (n = 5), central nervous system toxicity (n = 3) and anticholinergic side effects (n = 3). The response rate to moricizine HCl therapy was higher in patients with nonsustained VT (62%) compared with those with sustained VT (19%) or ventricular fibrillation (33%). The response rate was 35% in patients with a left ventricular ejection fraction > 40% and 18% in those with an ejection fraction < 40% (p < 0.05). There was no difference in the density of arrhythmia during baseline studies between responders and nonresponders. Of 23 patients discharged while taking moricizine HCl, 12 patients have continued the drug for a mean follow-up of 17 months. Four patients died suddenly after 24 months, and 4 patients had a nonfatal recurrence after 5 months. Moricizine HCl is a well-tolerated antiarrhythmic drug particularly effective in patients with nonsustained VT and intact left ventricular function.