A Comprehensive Monograph on Procainamide (DB01035)

Section 1: Executive Summary

Procainamide is a legacy antiarrhythmic agent, classified as a Class Ia drug within the Vaughan Williams system, that has played a significant role in the management of cardiac arrhythmias for over half a century. Its primary mechanism of action involves the blockade of voltage-gated sodium channels and, to a lesser extent, potassium channels within cardiomyocytes. This dual action slows cardiac conduction velocity and prolongs the action potential duration, thereby terminating re-entrant arrhythmias. The principal approved clinical indication for procainamide is the treatment of documented, life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia.

Despite its established efficacy, the clinical utility of procainamide is profoundly limited by a significant and predictable toxicity profile. This report provides an exhaustive analysis of the dichotomy between its therapeutic effects and its substantial risks. Three cardinal toxicities define its clinical use and have led to the discontinuation of its oral formulations in many regions, relegating it primarily to acute, in-hospital settings. These include a high incidence of drug-induced lupus erythematosus (DILE), a significant proarrhythmic potential that can lead to life-threatening arrhythmias like Torsades de Pointes, and the risk of potentially fatal hematologic dyscrasias, including agranulocytosis.