What is the recommended treatment and dosage for ventricular arrhythmias using mexiletine?

Mexiletine for Ventricular Arrhythmias: Treatment and Dosage

For ventricular arrhythmias, mexiletine should be initiated at 200 mg orally every 8 hours with food or antacid, with dose adjustments in 50-100 mg increments every 2-3 days based on response and tolerance, typically requiring 200-300 mg every 8 hours for effective treatment, not exceeding 1200 mg daily. 1

Mechanism and Positioning in Treatment Algorithm

Mexiletine is a class IB antiarrhythmic drug that works primarily by blocking fast sodium channels, reducing the phase 0 maximal upstroke velocity of the action potential. Unlike class IA agents, it does not prolong QRS and QT intervals 2.

In the treatment hierarchy for ventricular arrhythmias:

1. First-line agents:

   • Amiodarone (150 mg IV over 10 minutes, followed by 1 mg/min for 6 hours, then 0.5 mg/min) 3, 4
   • Lidocaine (1-1.5 mg/kg IV bolus, followed by 1-4 mg/min infusion) 3
   • Procainamide (20-50 mg/min until arrhythmia suppressed or maximum 17 mg/kg) 3

2. Second-line agent:

   • Mexiletine (oral therapy for chronic management)

Dosing Protocol for Mexiletine

Standard Initiation:

• Start with 200 mg orally every 8 hours with food or antacid 1
• Allow minimum 2-3 days between dose adjustments
• Adjust in 50-100 mg increments based on response and tolerance
• Most patients achieve satisfactory control with 200-300 mg every 8 hours 1
• Maximum dose: 1200 mg/day (due to increasing CNS side effects with higher doses) 1

Rapid Control Protocol:

• Loading dose: 400 mg orally, followed by 200 mg after 8 hours 1
• Therapeutic effect usually observed within 30 minutes to 2 hours
• Then continue with standard dosing protocol

Alternative 12-Hour Dosing:

• For improved compliance, patients responding to ≤300 mg every 8 hours may be transferred to the same total daily dose given every 12 hours
• Maximum of 450 mg every 12 hours 1

Monitoring and Dose Adjustments

• Clinical and electrocardiographic evaluation (including Holter monitoring if necessary) is essential to determine effectiveness and guide titration 1
• Monitor for CNS side effects, which increase with total daily dose
• Patients with severe liver disease require lower doses and closer monitoring 1
• Patients with marked right-sided heart failure may need dose reduction due to reduced hepatic metabolism 1
• Regular plasma level monitoring may be helpful, especially with concomitant medications that affect metabolism

Efficacy and Patient Selection

Mexiletine effectively suppresses:

• Premature ventricular contractions (PVCs) in 25-79% of patients 2
• Ventricular tachycardia or fibrillation in 20-50% of patients with refractory arrhythmias 2

A systematic review of 221 studies with 8,970 patients showed:

• 50% reduction in PVCs in 72% of studies

• 50% reduction in ventricular tachycardia in 64% of studies

• 50% reduction in ventricular fibrillation in 33% of studies 5

Special Considerations

Cautions:

• Avoid in post-MI patients with structural heart disease: Based on the CAST trial findings with similar class I antiarrhythmics, mexiletine should be avoided in patients with ischemia, prior MI, or structural heart disease 3
• Increased defibrillation energy requirement: May require reprogramming of ICDs 3
• Drug interactions: Monitor for interactions that may affect plasma levels 1

Side Effects:

• Most common: gastrointestinal (33% of patients) and CNS effects 5
• Most side effects can be managed with dose adjustments 2
• Minimal effects on hemodynamics and cardiac function, even in patients with left ventricular dysfunction 2
• Low proarrhythmic potential compared to other antiarrhythmics 2

Combination Therapy

For refractory ventricular arrhythmias, mexiletine may be combined with:

• Propranolol
• Quinidine
• Amiodarone 6

These combinations have shown enhanced efficacy in patients with refractory arrhythmias.

Transitioning from Other Antiarrhythmics

When switching from other antiarrhythmics to mexiletine:

• From quinidine: Start mexiletine 6-12 hours after last dose
• From procainamide: Start mexiletine 3-6 hours after last dose
• From disopyramide: Start mexiletine 6-12 hours after last dose
• From tocainide: Start mexiletine 8-12 hours after last dose
• From lidocaine: Stop infusion when first oral mexiletine dose is administered 1

For patients at high risk of life-threatening arrhythmias during transition, hospitalization is recommended 1.