What are the guidelines for using Mexiletine in a patient with a history of cardiac arrhythmia?

Mexiletine for Cardiac Arrhythmias

Mexiletine is a Class IB antiarrhythmic agent indicated for documented life-threatening ventricular arrhythmias (such as sustained ventricular tachycardia), and should be initiated in-hospital due to proarrhythmic risk. 1

Primary Indications

For adults with hypertrophic cardiomyopathy (HCM) and symptomatic ventricular arrhythmias or recurrent ICD shocks despite beta-blocker therapy, mexiletine is a Class I recommended option alongside amiodarone, dofetilide, and sotalol. 2 The choice between these agents should be guided by:

• Age and comorbidities 2
• Severity of underlying disease 2
• Patient preferences 2
• Balance between efficacy and safety profile 2

In pediatric patients with HCM and recurrent ventricular arrhythmias despite beta-blocker use, mexiletine is specifically recommended as one of three first-line options (along with amiodarone and sotalol). 2

Evidence Hierarchy

While amiodarone demonstrates superior efficacy (reducing ICD shocks from 38.5% to 10.3% versus 24.3% for sotalol), it carries significantly more adverse effects and shows no survival benefit. 2 Mexiletine's proof of efficacy is admittedly scant but it is commonly used adjunctively with amiodarone. 2

Dosing and Administration

The typical oral dosage is 200-300 mg three to four times daily (total 600-900 mg/day). 2, 3 Intravenous loading is 150-250 mg over at least 10 minutes when rapid effect is needed. 3

Initiation must occur in-hospital with continuous ECG monitoring due to proarrhythmic potential. 1

Absolute Contraindications

Mexiletine is absolutely contraindicated in: 2, 4, 1

• Severe sinus node dysfunction without pacemaker protection 2, 4
• Marked sinus bradycardia without pacemaker 4, 1
• Severe AV conduction disturbances without pacemaker 2, 1
• Severe heart failure or reduced LVEF 2
• Inherited long QT syndromes (except LQT3, where it may be beneficial) 2, 4

Important Exception for LQT3

In long QT syndrome type 3 specifically, mexiletine may actually shorten the QTc interval and reduce recurrent arrhythmias, making it a therapeutic option rather than contraindication. 4

Relative Contraindications and Cautions

Use with extreme caution in: 1

• Hepatic impairment - elimination half-life extends from 10-14 hours to 14-16 hours, requiring dose adjustment 4, 1, 3
• Congestive heart failure - may aggravate the condition 1
• Hypotension - potential for worsening 1
• First-degree AV block - though progression to higher-degree block is uncommon 1

Critical Drug Interactions

Concomitant use with amiodarone requires careful monitoring due to additive effects on cardiac conduction. 4 Avoid concurrent QT-prolonging medications. 4

Avoid dietary regimens or concurrent drugs that markedly alter urinary pH, as this affects mexiletine excretion. 1

Monitoring Requirements

Essential monitoring includes: 4, 1

• Continuous ECG during initiation 4
• Liver function tests - SGOT elevations >3x upper limit of normal occur in ~1% of patients 1
• Complete blood count - leukopenia/agranulocytosis occurs in 0.06%, thrombocytopenia in 0.16% 1
• Neurological assessment - tremor, dysarthria, dizziness are common 2

If persistent or worsening hepatic enzyme elevation occurs, strongly consider discontinuing therapy. 1 If significant hematologic changes develop, discontinue mexiletine; blood counts typically normalize within one month. 1

Common Adverse Effects

Gastrointestinal and neurological side effects limit use in approximately 20% of patients: 3, 5

• Nausea and gastrointestinal disturbance (33% of patients) 2, 6
• Tremor, dysarthria, dizziness 2, 5
• Generalized malaise 5

Importantly, mexiletine does not depress myocardial function and has minimal hemodynamic effects, making it safer than many alternatives in patients with compromised cardiac function. 3, 7

Proarrhythmic Risk

Worsening of arrhythmias occurs in 10-15% of patients with life-threatening arrhythmias (sustained VT), though this rate is not greater than other agents. 1 This risk is uncommon in patients with less serious arrhythmias (frequent PVCs or nonsustained VT). 1

Convulsions occur in approximately 2 per 1000 patients in clinical experience. 1

Historical Context and Mortality Data

Similar to other Class I sodium channel blockers, mexiletine showed trends toward increased mortality in early trials among post-MI patients, though less pronounced than with flecainide or encainide in the CAST trial. 2 However, mexiletine does not prolong QT intervals like the agents that increased mortality in post-MI populations. 4

No antiarrhythmic drug has been shown to enhance survival in patients with ventricular arrhythmias. 1

Efficacy Data

In patients with refractory ventricular arrhythmias, mexiletine abolishes spontaneous or inducible VT/VF in 20-50% of cases short-term, with arrhythmia suppression maintained in 57-80% of responders long-term. 7, 8 A recent systematic review of 8970 patients showed >50% reduction in ventricular arrhythmias in 72% for PVCs, 64% for VT, and 33% for VF. 6

Refractory Cases

For patients with recurrent life-threatening ventricular tachyarrhythmias refractory to maximal antiarrhythmic drug therapy (including mexiletine) and catheter ablation, heart transplantation assessment is indicated. 2

Catheter ablation should be considered for recurrent symptomatic sustained monomorphic VT or recurrent ICD shocks despite optimal device programming when antiarrhythmic therapy is ineffective, not tolerated, or not preferred. 2