What are the indications for Maxiletine (mexiletine)?

Mexiletine Indications

Mexiletine is FDA-approved for documented life-threatening ventricular arrhythmias such as sustained ventricular tachycardia, and is recommended by the 2024 AHA/ACC guidelines as a Class I indication for symptomatic ventricular arrhythmias or recurrent ICD shocks in patients with hypertrophic cardiomyopathy who have failed beta-blocker therapy. 1, 2

FDA-Approved Indication

• Life-threatening ventricular arrhythmias: Mexiletine is indicated for documented ventricular arrhythmias, such as sustained ventricular tachycardia, that are judged by the physician to be life-threatening 1
• Not for minor arrhythmias: Due to proarrhythmic effects, mexiletine should not be used for lesser arrhythmias or asymptomatic ventricular premature contractions 1
• Hospital initiation required: Treatment should be initiated in the hospital setting 1

Guideline-Directed Indications

Hypertrophic Cardiomyopathy (HCM) - Primary Indication

Adults with HCM:

• Class I recommendation (Level B-NR): Mexiletine is recommended for adults with HCM who have symptomatic ventricular arrhythmias or recurrent ICD shocks despite beta-blocker use 2
• The choice between mexiletine, amiodarone, dofetilide, or sotalol should be guided by age, underlying comorbidities, severity of disease, patient preferences, and balance between efficacy and safety 2
• Amiodarone remains superior in efficacy (reducing ICD shocks from 38.5% to 10.3% vs 24.3% for sotalol), but mexiletine offers an alternative with fewer adverse effects 2

Pediatric patients with HCM:

• Class I recommendation (Level C-LD): Mexiletine is recommended for children with HCM and recurrent ventricular arrhythmias despite beta-blocker use 2
• Particularly important in pediatric populations where ICD shocks cause significant psychological trauma 2

Role in Treatment Algorithm

Step 1: Beta-blockers are first-line therapy for ventricular arrhythmias in HCM 2

Step 2: When beta-blockers fail, mexiletine is one of four recommended antiarrhythmic options 2

Step 3: Mexiletine is often used adjunctively with amiodarone when amiodarone alone is insufficient 2

Step 4: If mexiletine and other antiarrhythmics fail, catheter ablation should be considered 2

Step 5: Heart transplantation assessment is indicated for refractory life-threatening ventricular tachyarrhythmias unresponsive to maximal antiarrhythmic therapy and ablation 2

Clinical Evidence Supporting Use

• Refractory ventricular arrhythmias: Mexiletine effectively suppresses premature ventricular contractions in 25-79% of patients and abolishes spontaneous or inducible ventricular tachycardia/fibrillation in 20-50% of patients with refractory arrhythmias 3
• ICD shock reduction: In a retrospective cohort of 17 patients, mexiletine significantly reduced electrical storm events (14 vs 2 episodes, p=0.0010), VT/VF episodes (285 vs 74 episodes, p=0.0115), and ICD interventions (317 vs 9 interventions, p=0.0006) 4
• Tolerability: 82% of patients demonstrated sufficient tolerability in short-term treatment, with only 18% requiring discontinuation due to severe side effects 4

Important Caveats and Contraindications

Absolute contraindications:

• Severe sinus node dysfunction without pacemaker protection 5
• Marked sinus bradycardia without pacemaker 5

Use with caution in:

• Heart failure (may exacerbate in susceptible patients) 5
• Severe liver disease (requires dosage adjustment due to prolonged half-life of 14-16 hours vs normal 10-14 hours) 5
• Structural heart disease (potential for worsening arrhythmias) 5

Monitoring requirements:

• ECG monitoring is essential during initiation, particularly when combined with other antiarrhythmic agents 5
• Watch for neurological effects (tremor, ataxia, paresthesias, dizziness) and cardiac effects (AV block, arrhythmia worsening) 5

Drug interactions:

• Combination with amiodarone requires careful monitoring due to additive effects on cardiac conduction 5
• Concomitant use with QT-prolonging medications requires careful consideration 5

Key Clinical Pearls

• No survival benefit: Like other antiarrhythmic drugs, mexiletine has not been shown to enhance survival in patients with ventricular arrhythmias 1
• Minimal hemodynamic effects: Unlike many antiarrhythmics, mexiletine has minimal effects on hemodynamic variables and can be safely used in patients with left ventricular dysfunction 3
• Low proarrhythmic potential: Mexiletine has a relatively low proarrhythmic potential compared to other antiarrhythmic agents 3
• Evidence quality: The evidence for mexiletine efficacy in HCM is limited (Level C-LD for most indications), as recommendations are extrapolated from studies in non-HCM populations 2