Vernakalant, sold under the brand name Brinavess, is a class III antiarrhythmic drug for the acute conversion of atrial fibrillation, in form of an intravenous infusion. It produces rapid atrial-selective electrophysiological effects by blocking atrial potassium currents including the ultra-rapid delayed rectifier current and the acetylcholine-activated inward rectifier, with additional rate-dependent inhibition of the sodium current, thereby prolonging atrial refractoriness with minimal direct ventricular action. The marketed intravenous dosing regimen uses an initial infusion of 3 mg per kg given over 10 minutes with a second infusion of 2 mg per kg over 10 minutes if atrial fibrillation persists, and administration requires ECG and hemodynamic monitoring. Pharmacokinetics are characterized by rapid onset, predominant hepatic metabolism by CYP2D6 with variable clearance in poor metabolizers, moderate plasma protein binding, and renal elimination of metabolites. It has been approved for use in the European Union and the United Kingdom since 2010.
Typical quality specifications for vernakalant drug substance and finished intravenous formulations control related substances and degradation products according to ICH Q3A and Q3B principles and compendial practice; individual specified related compounds are generally limited to not more than 0.10 percent w by weight, unspecified individual impurities are often limited to 0.05 percent w by weight, and total impurities and degradation products are controlled to a combined limit commonly at or below 0.50 percent w by weight, with residual solvents, heavy metals and microbial limits set per relevant pharmacopeial monographs. Routine impurity profiling is performed by validated reversed phase HPLC with UV detection and by LC MS for structural identification, with stability stress studies used to identify potential degradants and to set specification limits for release and shelf life.
Vernakalant is classified as a class III antiarrhythmic agent with atrial-selective potassium channel blockade and additional rate-dependent sodium channel inhibition.
No, vernakalant (Brinavess) is not approved by the United States Food and Drug Administration; it is approved for intravenous use in the European Union and the United Kingdom since 2010.
Common adverse effects include dysgeusia, sneezing, paresthesia, headache, nausea, transient hypotension and bradycardia; serious but less frequent events reported include atrial flutter with 1 to 1 conduction and rare ventricular arrhythmias, therefore monitoring of blood pressure and ECG is recommended during and after infusion.
The terminal elimination half life of vernakalant is approximately 3 to 5 hours, with a rapid distribution phase and variable clearance influenced by CYP2D6 metabolic status.
