What is the recommended use and dosage of Mexiletine (mexiletine) for treating ventricular arrhythmias?

Mexiletine Use for Ventricular Arrhythmias

Mexiletine is recommended for treating hemodynamically stable monomorphic ventricular tachycardia at a starting dose of 200 mg orally every 8 hours, with titration based on response and tolerance up to a maximum of 400 mg every 8 hours (not exceeding 1200 mg/day). 1

Indications

• Mexiletine is indicated for treatment of hemodynamically stable monomorphic ventricular tachycardia (VT) 2
• It can be used as an adjunctive therapy in patients with recurrent ventricular arrhythmias, particularly when other agents have failed or caused intolerable side effects 2, 3
• Mexiletine is effective in suppressing 60-80% of spontaneous ventricular arrhythmias when used as monotherapy 3
• It is particularly useful in patients with hypertrophic cardiomyopathy and symptomatic ventricular arrhythmias or recurrent ICD shocks despite beta-blocker use 2

Dosing Recommendations

Initial Dosing

• Start with 200 mg orally every 8 hours when rapid control is not essential 1
• For rapid control of ventricular arrhythmia, an initial loading dose of 400 mg may be administered, followed by 200 mg after 8 hours 1
• Administration with food or antacid is recommended to improve gastrointestinal tolerance 1, 4

Dose Titration

• Allow a minimum of 2-3 days between dose adjustments 1
• Adjust dose in 50-100 mg increments based on clinical response and electrocardiographic evaluation 1
• Most patients achieve satisfactory control with 200-300 mg every 8 hours 1, 4
• If satisfactory response is not achieved at 300 mg every 8 hours and the patient tolerates mexiletine well, a dose of 400 mg every 8 hours may be tried 1
• Maximum daily dose should not exceed 1200 mg due to increased risk of CNS side effects 1

Alternative Dosing Schedule

• Patients responding to mexiletine may be transferred to a 12-hour dosing schedule to improve convenience and compliance 1
• If adequate suppression is achieved on 300 mg or less every 8 hours, the same total daily dose may be given in divided doses every 12 hours 1
• Maximum dose for 12-hour schedule is 450 mg every 12 hours 1

Special Populations

• Patients with renal failure generally require usual doses of mexiletine 1
• Patients with severe liver disease may require lower doses and must be monitored closely 1, 5
• Patients with marked right-sided congestive heart failure may require lower doses due to reduced hepatic metabolism 1
• Mexiletine has minimal effects on hemodynamic variables and cardiac function, making it suitable for patients with left ventricular dysfunction 5

Monitoring and Follow-up

• Clinical and electrocardiographic evaluation (including Holter monitoring if necessary) is needed to determine efficacy and guide dose adjustments 1
• Monitor for neurological side effects (tremor, dizziness, memory loss) which occur in approximately 10% of patients 3
• Monitor for gastrointestinal side effects (nausea, anorexia, gastric irritation) which occur in up to 40% of patients 3, 6

Efficacy and Outcomes

• Mexiletine effectively suppresses premature ventricular contractions in 25-79% of patients 5
• It abolishes spontaneous or inducible ventricular tachycardia or fibrillation in 20-50% of patients with refractory arrhythmias 5
• Long-term efficacy is maintained in 57-80% of initial responders, either alone or in combination with another antiarrhythmic drug 5, 7
• As monotherapy, mexiletine is effective in preventing induction of ventricular tachycardia in approximately 20% of patients 3
• Efficacy may be enhanced when used in combination with Class IA antiarrhythmic drugs or beta-blockers 3, 4

Advantages and Limitations

Advantages

• Low proarrhythmic potential compared to other antiarrhythmic agents 5
• Minimal negative inotropic effect compared to procainamide or disopyramide 3
• Can be safely used in patients with compromised left ventricular function 5

Limitations

• Gastrointestinal side effects are common but can often be managed with dose adjustments 5, 6
• Neurological side effects may limit use in some patients 3, 6
• Less effective as monotherapy for induced ventricular arrhythmias compared to spontaneous arrhythmias 3

Transferring from Other Antiarrhythmics

• When transferring from lidocaine, stop the lidocaine infusion when the first oral dose of mexiletine is administered 1
• For patients on other Class I oral antiarrhythmics, initiate mexiletine with a 200 mg dose:
  • 6-12 hours after the last dose of quinidine sulfate 1
  • 3-6 hours after the last dose of procainamide 1
  • 6-12 hours after the last dose of disopyramide 1
  • 8-12 hours after the last dose of tocainide 1
• Hospitalization is recommended when withdrawing previous antiarrhythmic agents that may produce life-threatening arrhythmias 1