What does Mexiletine do?

Mexiletine's Role in Cardiac Arrhythmia Management

Mexiletine is a Class IB antiarrhythmic drug that primarily blocks fast sodium channels to treat ventricular tachycardia (VT), ventricular fibrillation (VF), and has specific utility in Long QT Syndrome type 3 (LQT3). It works by reducing the rate of rise of the action potential (phase 0) and has minimal effects on QRS and QT intervals 1.

Mechanism of Action

• Acts as a sodium channel blocker (Class IB antiarrhythmic)
• Structurally similar to lidocaine but orally active 1
• Inhibits inward sodium current, reducing action potential upstroke velocity
• Increases the ratio of effective refractory period to action potential duration 1
• Unlike Class IA drugs, does not significantly prolong QRS or QT intervals 2

Primary Clinical Indications

Mexiletine is indicated for:

• Ventricular tachycardia (VT) management 3
• Treatment of premature ventricular contractions (PVCs) 3
• Specific utility in Long QT Syndrome type 3 (LQT3) 3
• Management of torsades de pointes in LQT3 patients 3
• Adjunctive therapy for refractory ventricular arrhythmias 3

Dosing and Administration

• Typical dosage range: 450-900 mg daily 3
• Usually administered in divided doses (150-300 mg every 8-12 hours) 4
• Oral bioavailability is approximately 90% 1
• Plasma half-life of 10-12 hours in normal subjects 1
• Primarily metabolized in the liver via CYP2D6 and CYP1A2 pathways 1

Efficacy Profile

• Effectively suppresses premature ventricular contractions in 25-79% of patients 2
• Abolishes spontaneous or inducible VT/VF in 20-50% of patients with refractory arrhythmias 2
• Maintains arrhythmia suppression in 57-80% of initial responders long-term 2
• Particularly effective when combined with other antiarrhythmics in refractory cases 4
• Recent systematic review showed >50% reduction in ventricular arrhythmias in most studies 5

Safety Profile and Side Effects

Common adverse effects include:

• Tremor and neurological symptoms (dizziness, dysarthria) 3
• Gastrointestinal disturbances (nausea, anorexia) 3, 6
• Hypotension and sinus bradycardia 3

Mexiletine has several important advantages:

• Minimal negative inotropic effect compared to other antiarrhythmics 2
• Low proarrhythmic potential 2
• Does not significantly depress myocardial function 4
• Can be used in patients with left ventricular dysfunction 2

Contraindications and Precautions

Mexiletine should be avoided in:

• Sinus node dysfunction (unless a pacemaker is present) 3
• Severe AV conduction disturbances (unless a pacemaker is present) 3
• Severe heart failure 3
• Reduced left ventricular ejection fraction 3
• Inherited LQTS (other than LQTS3) 3
• Concomitant treatments associated with QT-interval prolongation 3

Clinical Applications in Specific Conditions

Hypertrophic Cardiomyopathy (HCM)

In HCM patients with ventricular arrhythmias:

• Mexiletine is recommended as part of antiarrhythmic therapy for symptomatic ventricular arrhythmias or recurrent ICD shocks despite beta-blocker use 3
• Often used as adjunctive therapy to amiodarone, though evidence for efficacy is limited 3

Long QT Syndrome Type 3 (LQT3)

• Specifically beneficial in LQT3 patients with torsades de pointes 3
• Shortens QT interval in LQT3 patients 3
• May be considered in patients who present with LQT3 and torsades de pointes 3

Refractory Ventricular Arrhythmias

• Effective in 30-50% of patients with ventricular arrhythmias refractory to other antiarrhythmic drugs 4
• Often used in combination therapy with amiodarone, beta-blockers, or Class IA antiarrhythmics for enhanced efficacy 4, 6

Important Clinical Considerations

• Mexiletine has minimal effect on cardiac impulse generation and propagation in patients with normal conduction systems 1
• Does not typically cause development of second-degree or third-degree AV block 1
• Hemodynamic effects are generally minimal, with small decreases in cardiac output and increases in systemic vascular resistance 1
• Gastrointestinal side effects occur in up to 40% of patients and may limit long-term use 6, 7
• Neurological side effects (tremor, dizziness, memory loss) occur in approximately 10% of patients 6

Mexiletine represents an important option in the antiarrhythmic armamentarium, particularly for patients with ventricular arrhythmias who cannot tolerate or have failed other therapies, and specifically for those with LQT3.