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

Mexiletine Treatment for Ventricular Arrhythmias

For ventricular arrhythmias, mexiletine is recommended at an initial dose of 200 mg every 8 hours with food or antacid, titrated up to 300-400 mg every 8 hours based on response and tolerability, with a maximum daily dose of 1200 mg. 1

Dosing Protocol for Mexiletine

Initial Dosing

• Start with 200 mg every 8 hours when rapid control is not essential 1
• For rapid control of ventricular arrhythmia, consider loading dose of 400 mg followed by 200 mg after 8 hours 1
• Always administer with food or antacid to improve tolerability 1

Dose Titration

• Allow minimum 2-3 days between dose adjustments 1
• Adjust in 50-100 mg increments based on clinical response and ECG monitoring 1
• Most patients achieve satisfactory control with 200-300 mg every 8 hours 1
• May increase to 400 mg every 8 hours if needed and tolerated 1
• Maximum daily dose should not exceed 1200 mg due to increasing CNS side effects 1

Alternative Dosing Schedule

• For improved compliance, patients responding to mexiletine may be transferred to a 12-hour schedule 1
• If adequate suppression is achieved on ≤300 mg every 8 hours, the same total daily dose can be given in divided doses every 12 hours 1
• Maximum dose on 12-hour schedule: 450 mg every 12 hours 1

Clinical Context and Evidence

Role in Treatment Algorithm

1. First-line therapy: Beta-blockers are generally first-line for ventricular arrhythmias 2
2. Second-line therapy: Mexiletine is recommended when:
   • Beta-blockers are ineffective or not tolerated
   • Patient has symptomatic ventricular arrhythmias
   • Patient experiences recurrent ICD shocks despite beta-blocker use 2

Efficacy and Monitoring

• Mexiletine effectively suppresses premature ventricular contractions in 25-79% of patients 3
• Abolishes spontaneous or inducible ventricular tachycardia/fibrillation in 20-50% of patients with refractory arrhythmias 3
• Clinical and electrocardiographic evaluation (including Holter monitoring) is essential to determine efficacy and guide titration 1
• Unlike some other antiarrhythmics, mexiletine does not prolong QRS and QT intervals 3

Special Populations

• Hypertrophic Cardiomyopathy: Mexiletine is specifically recommended for both adults and children with HCM and recurrent ventricular arrhythmias despite beta-blocker use 2
• Renal Failure: Patients generally require usual doses 1
• Severe Liver Disease: Lower doses may be required with close monitoring 1
• Right-sided Heart Failure: May reduce hepatic metabolism, requiring dose reduction 1
• Children: Recommended for pediatric patients with HCM and recurrent ventricular arrhythmias when beta-blockers are ineffective 2

Comparative Efficacy and Safety

• Mexiletine has comparable efficacy to quinidine for PVC suppression (31% vs 32% response rate) 4
• Lower proarrhythmic potential compared to quinidine (5% vs 9%) 4
• Less effective than amiodarone for life-threatening ventricular arrhythmias (16% vs 95% response rate) 5
• Often used adjunctively with amiodarone for enhanced efficacy 2

Adverse Effects and Management

Common Side Effects

• Gastrointestinal: Nausea, vomiting, dyspepsia (most common) 3, 4
• Neurological: Tremor, dizziness, coordination difficulties 3, 4
• Side effects appear to be dose-related 6

Management of Side Effects

• Administer with food or antacids to reduce GI side effects 1
• Dose adjustment if side effects occur 1
• Consider alternative dosing schedule (q12h instead of q8h) if compliance is an issue 1

Important Clinical Pearls

• Mexiletine has minimal effects on hemodynamic variables and cardiac function, making it suitable for patients with left ventricular dysfunction 3
• When transferring from other antiarrhythmics to mexiletine, specific timing intervals should be observed:
  • 6-12 hours after last dose of quinidine
  • 3-6 hours after last dose of procainamide
  • 6-12 hours after last dose of disopyramide
  • 8-12 hours after last dose of tocainide 1
• For patients on lidocaine infusion, stop the infusion when first oral dose of mexiletine is administered 1
• In patients with refractory ventricular arrhythmias despite maximal therapy, heart transplantation assessment should be considered 2