moricizine hydrochloride
Ethmozine

Available forms
Available by prescription only
Tablets: 200 mg, 250 mg, 300 mg

Indications and dosages
 Treatment of documented, life-threatening ventricular arrhythmias when benefit of treatment outweighs risks. Adults: Individualize dosage. Usual range is 600 to 900 mg P.O. daily, given q 8 hours in equally divided doses. Dosage may be adjusted within this range in increments of 150 mg daily at 3-day intervals until desired effect is obtained. Hospitalization is recommended for start of therapy because patient will be at high risk. Patients whose arrhythmias are well controlled during q-8-hour dosing may receive the same dose daily, divided q 12 hours to increase compliance.
≡ Dosage adjustment. For patients with hepatic impairment and significant renal dysfunction, give 600 mg or less daily. Monitor ECG before increasing dose.

Pharmacodynamics
Antiarrhythmic action: Although moricizine is chemically related to the neuroleptic phenothiazines, it has no demonstrated dopaminergic activities. It does have potent local anesthetic activity and myocardial membrane-stabilizing effects. A Class I antiarrhythmic, it reduces the fast inward current carried by sodium ions. In patients with ventricular tachycardia, moricizine prolongs AV conduction but has no significant effect on ventricular repolarization. Intra-atrial conduction or atrial effective refractory periods aren’t consistently affected and moricizine has minimal effect on sinus cycle length and sinus node recovery time. This may be significant in patients with sinus node dysfunction.
 In patients with impaired left ventricular function, moricizine has minimal effects on measurements of cardiac performance: cardiac index, stroke volume, pulmonary artery wedge pressure, systemic or pulmonary vascular resistance, and ejection fraction either at rest or during exercise. A small but consistent increase in resting blood pressure and heart rate is seen. Moricizine has no effect on exercise tolerance in patients with ventricular arrhythmias, heart failure, or angina pectoris.
 Moricizine has antiarrhythmic activity similar to that of disopyramide, propranolol, and quinidine. Arrhythmia rebound isn’t noted after discontinuation of therapy.

Pharmacokinetics
Absorption: Administration within 30 minutes of mealtime delays absorption and lowers peak plasma levels but has no effect on extent of absorption.
Distribution: 95% plasma protein-bound.
Metabolism: Undergoes significant first-pass metabolism resulting in an absolute bioavailability of about 38%. At least 26 metabolites have been identified with no single one representing at least 1% of the administered dose. It has been shown to induce its own metabolism.
Excretion: About 56% is excreted in feces, 39% in urine; some is also recycled through enterohepatic circulation.

Contraindications and precautions
Contraindicated in patients with cardiogenic shock, those hypersensitive to drug, and those with second- or third-degree AV block or right bundle branch block when associated with left hemiblock (bifascicular block), unless an artificial pacemaker is present.
  Use cautiously in patients with renal or hepatic impairment, sick sinus syndrome, coronary artery disease, or left ventricular function.

Interactions
Drug-drug. Cimetidine: Decreases moricizine clearance by 49% when used together; no significant changes in efficacy or tolerance have been observed. Patients should receive decreased doses of cimetidine (not more than 600 mg daily).
Digoxin: Prolongs PR interval. Monitor patient carefully.
Propranolol: May produce a small additive increase in PR interval. Monitor patient carefully.
Theophylline: Increases theophylline clearance and decreases plasma half-life. Monitor theophylline levels.

Adverse reactions
CNS: dizziness, headache, fatigue, hyperesthesia, anxiety, asthenia, nervousness, paresthesia, sleep disorders.
CV: proarrhythmic events (ventricular tachycardia, premature ventricular contractions, supraventricular arrhythmias), ECG abnormalities (including conduction defects, sinus pause, junctional rhythm, or AV block), heart failure, palpitations, chest pain, cardiac death, hypotension, hypertension, vasodilation, cerebrovascular events.
EENT: blurred vision.
GI: nausea, vomiting, abdominal pain, dyspepsia, diarrhea, dry mouth.
GU: urine retention, urinary frequency, dysuria.
Musculoskeletal: musculoskeletal pain.
Respiratory: dyspnea.
Skin: diaphoresis, rash.
Other: drug-induced fever, thrombophlebitis.

Effects on lab test results
• May increase AST, ALT, and bilirubin levels.

Overdose and treatment
Signs and symptoms of overdose include emesis, lethargy, coma, syncope, hypotension, conduction disturbances, exacerbation of heart failure, MI, sinus arrest, arrhythmias, and respiratory failure. No specific antidote has been identified.
 Treatment should be supportive and include careful monitoring of cardiac, respiratory, and CNS changes. Gastric evacuation with care to avoid aspiration may be used as well.

Special considerations
• When switching from another antiarrhythmic to moricizine, withdraw previous therapy one to two half-lives before starting moricizine. Start moricizine 6 to 12 hours after last dose of quinidine and disopyramide; 3 to 6 hours after last dose of procainamide; 8 to 12 after encainide, propaferone, tocainide, or mexiletine; and 12 to 24 hours after flecainide.
• Correct electrolyte imbalances before starting therapy; hypokalemia, hyperkalemia, or hypomagnesemia may alter effects of drug.
• Monitor patient for increased dizziness and nausea with 12-hour dosing.
Breast-feeding patients
• Drug appears in breast milk. Because of the potential for adverse reactions in the breast-fed infant, a decision to discontinue breast-feeding or drug must be made.
Pediatric patients
• Safety and efficacy haven’t been established.

Patient education
• Instruct patient to take drug as prescribed to maintain adequate arrhythmia control.
• Tell patient to report fever or adverse reactions, especially chest pain, palpitations, or irregular heartbeat.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use