What is the recommended dosage of Mexiletine for treating life-threatening ventricular arrhythmias?

Mexiletine Dosage for Life-Threatening Ventricular Arrhythmias

For treating life-threatening ventricular arrhythmias, mexiletine should be initiated at 200-300 mg every 8 hours with food or antacid, with a maximum daily dose of 1200 mg. 1

Initial Dosing Strategy

When treating ventricular arrhythmias, the dosing approach depends on the urgency of the clinical situation:

Standard Initiation (Non-Emergency)

• Start with 200 mg every 8 hours when rapid control is not essential 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

Loading Dose (Emergency Situations)

• For rapid control of ventricular arrhythmia: 400 mg initial loading dose, followed by 200 mg after 8 hours 1
• Therapeutic effect usually observed within 30 minutes to 2 hours
• Continue with maintenance dosing after loading

Dose Titration and Monitoring

• Titrate based on clinical and electrocardiographic evaluation
• Holter monitoring may be necessary to guide titration
• Maximum recommended daily dose: 1200 mg (400 mg every 8 hours) 1
• Higher doses increase risk of CNS side effects

Special Populations

• Renal failure: Usually require standard doses 1
• Severe liver disease: Require lower doses with close monitoring 1
• Right-sided heart failure: May need dose reduction due to reduced hepatic metabolism 1

Alternative Dosing Schedule

For improved compliance, patients responding to mexiletine may be transferred to a 12-hour schedule:

• If adequate suppression achieved on ≤300 mg every 8 hours, same total daily dose may be given in divided doses every 12 hours 1
• Maximum dose on 12-hour schedule: 450 mg every 12 hours

Efficacy and Monitoring

Mexiletine suppresses ventricular ectopy in approximately two-thirds of stable outpatients 2. It is effective in 30-50% of patients with ventricular arrhythmias refractory to other antiarrhythmic drugs 2.

Regular monitoring should include:

• ECG evaluation to assess QRS duration and arrhythmia control
• Assessment for adverse effects, particularly gastrointestinal and CNS symptoms
• Plasma level monitoring in patients with hepatic dysfunction or heart failure

Adverse Effects

• Gastrointestinal and central nervous system side effects are most common (occurring in approximately 20% of patients) 2
• Unlike some other antiarrhythmics, mexiletine does not:
  • Depress myocardial function
  • Prolong QT interval
  • Have significant hemodynamic effects

Important Considerations

• Mexiletine has structural and electrophysiologic properties similar to lidocaine 2
• For patients transferring from lidocaine, stop the lidocaine infusion when the first oral dose of mexiletine is administered 1
• When transferring from other Class I antiarrhythmics, follow specific timing guidelines to avoid drug interactions 1
• Administration with food or antacid is recommended to improve tolerability 1