Mexiletine (DB00379): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

[Mexiletine is a Class Ib antiarrhythmic agent, structurally analogous to the local anesthetic lidocaine, that functions as a non-selective, voltage-gated sodium channel blocker. Its primary, approved indication is for the management of documented, life-threatening ventricular arrhythmias, where it acts to stabilize cardiac myocyte membranes and suppress ectopic electrical activity. Over several decades of clinical use, Mexiletine has undergone a significant evolution, emerging as a cornerstone therapy for certain neurological channelopathies, most notably myotonic disorders. This repositioning is underscored by its Orphan Drug Designation in the United States and the approval of a distinct brand, Namuscla, in Europe for this neurological indication. The therapeutic utility of Mexiletine is defined by a critical balance between its efficacy and a prominent profile of gastrointestinal and central nervous system side effects, which frequently limit tolerability. Its complex pharmacokinetic profile, governed by the polymorphic cytochrome P450 enzymes CYP2D6 and CYP1A2, necessitates careful dose individualization and vigilance for numerous drug-drug interactions. The drug's unique regulatory history, including the discontinuation of its original brand (Mexitil) followed by an FDA determination of non-safety-related withdrawal, further shapes its current clinical landscape. This report provides a comprehensive analysis of Mexiletine, integrating its chemical properties, pharmacological mechanisms, diverse clinical applications, safety profile, and regulatory context.]

Identity, Chemical Structure, and Physicochemical Properties