Moricizine arrhythmia with

As with other antiarrhythmic drugs, moricizine has proarrhythmic activity, which may manifest as new ventricular ectopic beats or a worsening of preexisting ventricular arrhythmias. These effects are most common in patients with depressed left ventricular function and a history of congestive heart failure. Cardiovascular ef-... 

Proarrhythmic effects of antiarrhythmic drugs In the Cardiac Arrhythmia Suppression Trial (CAST) treatment with encainide and flecainide, two class IC antiarrhythmic agents, successfully prevented ventricular ectopic beats in patients who had myocardial infarction. However, continued therapy with either drug was associated with a two- to three-fold increase in death due to cardiac arrhythmias. Similar results were reported for moricizine. Increased death was probably due to drug-induced fatal arrhythmias triggered by recurrent myocardial ischemia. 

Flecainide slows conduction in all cardiac cells including the anomalous pathways responsible for the Wolff-Parkinson-White (WPW) syndrome. Together with encainide and moricizine, it underwent clinical trials to establish if suppression of asymptomatic premature beats with antiarrhythmic drugs would reduce the risk of death from arrhythmia after myocardial infarction. The study was terminated after preliminary analysis of 1727 patients revealed that mortality in the groups treated with flecainide or encainide was 7.7% compared with 3.0% in controls. The most likely explanation for the result was the induction of lethal ventricular arrhythmias possibly due to ischaemia by flecainide and encainide, i.e. a proarrhythmic effect. In the light of these findings the indications for flecainide are restricted to patients with no evidence of structural heart disease. The most common indication, indeed where it is the drug of choice, is atrioventricular re-entrant tachycardia, such as AV nodal tachycardia or in the tachycardias associated with the WPW syndrome or similar conditions with anomalous pathways. This should be as a prelude to definitive treatment with radiofrequency ablation. Flecainide may also be useful in patients with paroxysmal atrial fibrillation. 

Bigger JT Jr. The events surrounding the removal of encainide and flecainide from the Cardiac Arrhythmia Suppression Trial (CAST) and why CAST is continuing with moricizine. J Am Coll Cardiol 1990 15(l) 243-5. 

Class 1C drugs (flecainide, moricizine, propafenone) block sodium channels but do not affect potassium current. Therefore, they do not prolong the ventricular action potential or increase the QT interval. However, this class of drugs is quite proarrhythmic, and its use should be reserved for patients who have arrhythmias refractory to other treatments. Additionally, these drugs should not be used in patients with underlying heart disease. 

The CAST was initiated by the NIH in 1987 to determine if suppression of ventricular ectopy with encainide, flecainide, or moricizine could decrease the incidence of death from arrhythmia in patients who had suffered an MI. Entrance criteria included documented MI between 6 days and 2 years prior to enrollment and six or more PVCs per hour without runs of ventricular tachycardia greater than 15 beats in length. Also, patients were required to have an ejection fraction of 55% or less if recruited within 90 days of MI or 40% or less if recruited 90 days or more after MI. Patients with an ejection fraction of less than 30% were randomized only to encainide or moricizine. Patients were randomized to receive drug therapy or placebo after demonstrating PVC suppression with one of the agents. The drug and dose were determined during an open-label dose-titration phase that preceded randomization. 

Moricizine (600 to 900 mg/day given every 8 hours in three equally divided doses) is indicated in the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that are life threatening. Because of the proarrhythmic effects of moricizine, its use should be reserved for patients in whom the benefits of treatment outweigh the risks. Moricizine is a class 1C antiarrhythmic agent with potent local anesthetic activity and myocardial-membrane-stabilizing effects. It shares some of the characteristics of the class lA (disopyramide, procainamide, or quinidine), of class IB (lidocaine, mexiletene, phenytoin, or tocainide), or class 1C agents (encainide, flecainide, or propafenone) in that it reduces the fast inward current carried by sodium ions. Moricizine shortens phase 2 and 3... 

MORICIZINE Moricizine (ETHMOZINE) is a phenothiazine analog with Na channel-blocking properties used in the chronic treatment of ventricular arrhythmias. Moricizine undergoes extensive first-pass hepatic metabohsm despite its short elimination its antiarrhythmic effect can persist for many hours after a single dose, suggesting that some of its metabolites may be active. 

CAST-11 compared moricizine with placebo. The protocol for the CAST-11 was modified in an attempt to enroll patients more likely to experience serious arrhythmias and to observe for early risk of antiarrhythmic drugs. The qualifying ejection fraction was lowered to < 0.40, a higher dose of moricizine could be used, and the definition of disqualifying ventricular tachycardia was changed to allow patients with more serious arrhythmias to be entered into the trial. CAST II was subsequently terminated prematurely because patients treated with moricizine had an increased cardiac mortality rate during the first... 

Anderson, J.L., et al., Interaction of baseline characteristics with the hazard of encainide, flecainide, and moricizine therapy in patients with myocardial infarction. A possible explanation for increased mortality in the Cardiac Arrhythmia Suppression Trial (CAST). Circulation, 1994. 90(6) p. 2843-52. 

---