Sotalol (DB00489): A Comprehensive Monograph on its Pharmacology, Clinical Utility, and Safety Profile

Executive Summary

Sotalol is an antiarrhythmic agent with a unique pharmacological profile, functioning as both a non-selective beta-adrenergic antagonist (Vaughan Williams Class II) and a potent potassium channel blocker (Vaughan Williams Class III). This dual mechanism of action endows it with efficacy in managing a range of cardiac arrhythmias, with primary US Food and Drug Administration (FDA) approvals for the treatment of life-threatening ventricular arrhythmias and the maintenance of normal sinus rhythm in patients with highly symptomatic atrial fibrillation or atrial flutter.[1] First synthesized in 1960, sotalol is administered as a racemic mixture, with its distinct enantiomers contributing different aspects of its overall effect: the l-isomer provides virtually all of the beta-blocking activity, while both isomers possess comparable Class III effects.[3]

The clinical utility of sotalol is fundamentally defined by a central paradox: its therapeutic efficacy in suppressing arrhythmias is inextricably linked to a significant, dose-dependent proarrhythmic risk. The primary safety concern is the prolongation of the QT interval, which can precipitate a life-threatening polymorphic ventricular tachycardia known as Torsade de Pointes (TdP).[5] This risk is magnified by the drug's pharmacokinetic and pharmacodynamic properties, including a phenomenon known as "reverse use-dependence," where its proarrhythmic potential is greatest at slower heart rates.[1] Furthermore, sotalol is eliminated almost exclusively by the kidneys, making its clearance directly dependent on renal function.[7] Consequently, renal impairment leads to drug accumulation and a markedly increased risk of toxicity.