Vernakalant (DB06217): A Comprehensive Pharmacological and Clinical Monograph

Drug Profile and Executive Summary

Vernakalant is a novel, small-molecule antiarrhythmic agent developed for the rapid pharmacological cardioversion of recent-onset atrial fibrillation (AF).[1] Classified as an atypical Class III antiarrhythmic, its mechanism of action is distinguished by a relatively atrial-selective blockade of multiple cardiac ion channels, which underlies both its therapeutic efficacy and its specific safety profile.[1] The primary indication for its intravenous formulation, marketed as Brinavess, is the conversion of recent-onset AF to normal sinus rhythm in specific adult populations: non-surgery patients with AF of seven days or less duration, and post-cardiac surgery patients with AF of three days or less duration.[1]

The pharmacodynamic profile of vernakalant is characterized by a multi-channel blockade that preferentially targets atrial tissue. It potently inhibits atrial-specific potassium currents, such as the ultra-rapid delayed rectifier current (IKur​) and the acetylcholine-activated potassium current (IKACh​), which prolongs the atrial action potential and refractory period.[1] Crucially, this is combined with a frequency-dependent blockade of sodium channels, an effect that is enhanced at the rapid heart rates characteristic of AF, thereby slowing conduction in a pathology-selective manner.[2] This unique combination of actions allows for rapid termination of the reentrant circuits that sustain AF, with minimal effects on ventricular repolarization, theoretically reducing the risk of Torsade de Pointes associated with other Class III agents.[1]