Active ingredient: Disopyramide - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Antiarrhythmic Agents

Dosage Forms

• Capsule
• Tablet (extended-release)

Brands / Synonyms

Dicorantil; Disopiramida [Inn-Spanish]; Disopyramide Free Base; Disopyramide Phosphate; Disopyramide [Usan:Ban:Inn:Jan]; Disopyramidum [Inn-Latin]; Isorythm; Lispine; Norpace; Norpace Cr; Ritmodan; Rythmodan; Rythmodan P; Rythmodan-La; Searle 703; Xi-Disopyramide

Indications

For the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, ventricular pre-excitation and cardiac dysrhythmias.

Pharmacology

Disopyramide is an antiarrhythmic drug indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia that are life-threatening. In man, Disopyramide at therapeutic plasma levels shortens the sinus node recovery time, lengthens the effective refractory period of the atrium, and has a minimal effect on the effective refractory period of the AV node. Little effect has been shown on AV-nodal and His-Purkinje conduction times or QRS duration. However, prolongation of conduction in accessory pathways occurs.

Mechanism of Action

Disopyramide is a Type 1 antiarrhythmic drug (ie, similar to procainamide and quinidine). It inhibits the fast sodium channels. In animal studies Disopyramide decreases the rate of diastolic depolarization (phase 4) in cells with augmented automaticity, decreases the upstroke velocity (phase 0) and increases the action potential duration of normal cardiac cells, decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium, and has no effect on alpha- or beta-adrenergic receptors.

Absorption

Nearly complete

Toxicity

LD₅₀=580 mg/kg in rats

Biotrnasformation / Drug Metabolism

Hepatic

Contraindications

Norpace and Norpace CR are contraindicated in the presence of cardiogenic shock, preexisting second- or third-degree AV block (if no pacemaker is present), congenital Q-T prolongation, or known hypersensitivity to the drug.

Drug Interactions

If phenytoin or other hepatic enzyme inducers are taken concurrently with Norpace or Norpace CR, lower plasma levels of disopyramide may occur. Monitoring of disopyramide plasma levels is recommended in such concurrent use to avoid ineffective therapy. Other antiarrhythmic drugs (eg, quinidine, procainamide, lidocaine, propranolol) have occasionally been used concurrently with Norpace. Excessive widening of the QRS complex and/or prolongation of the Q-T interval may occur in these situations. In healthy subjects, no significant drug-drug interaction was observed when Norpace was coadministered with either propranolol or diazepam. Concomitant administration of Norpace and quinidine resulted in slight increases in plasma disopyramide levels and slight decreases in plasma quinidine levels. Norpace does not increase serum digoxin levels.

Patients taking disopyramide phosphate and erythromycin concomitantly may develop increased serum concentrations of disopyramide resulting in excessive widening of the QRS complex and/or prolongation of the Q-T interval. Patients taking disopyramide phosphate and hepatic enzyme inhibitors concomitantly should be closely monitored.

Until data on possible interactions between verapamil and disopyramide phosphate are obtained, disopyramide should not be administered within 48 hours before or 24 hours after verapamil administration.