What are the contraindications for Mexilitine?

Mexiletine Contraindications

Mexiletine is contraindicated in the presence of cardiogenic shock or preexisting second- or third-degree AV block (if no pacemaker is present). 1

Absolute Contraindications

• Cardiogenic shock 1
• Second- or third-degree AV block without pacemaker protection 1
• Severe sinus node dysfunction unless a pacemaker is present 2
• Marked sinus bradycardia without pacemaker protection 2

Relative Contraindications and Precautions

Cardiac Conditions

• Heart failure: Mexiletine may exacerbate heart failure in susceptible patients 3, 2
• Structural heart disease: Caution is advised as mexiletine can potentially worsen arrhythmias in patients with structural heart disease 2
• Concomitant use with QT-prolonging medications requires careful monitoring 2
• Combination with amiodarone requires vigilant monitoring due to potential additive effects on cardiac conduction 2, 4

Hepatic Impairment

• Severe liver disease: Patients require dosage adjustment due to prolonged half-life (14-16 hours vs. normal 10-14 hours) 3, 5
• Hepatic metabolism is the primary route of elimination, so impaired liver function significantly affects drug clearance 6, 5

Other Medical Conditions

• Blood dyscrasias have been associated with mexiletine use 3, 2
• History of seizures or neurological disorders (due to potential CNS side effects) 7, 8

Special Populations

Post-Myocardial Infarction

• Unlike other sodium channel blockers used after myocardial infarction that increased mortality in the CAST trial, mexiletine does not prolong QT intervals 3
• However, elimination half-life may be prolonged in patients with acute myocardial infarction 5

Long QT Syndrome

• Mexiletine is not contraindicated in patients with inherited long QT syndrome type 3 (LQT3) and may actually be beneficial 3, 9
• In long QT syndrome type 3, mexiletine, ranolazine, and flecainide shorten the QTc and have been used to reduce recurrent arrhythmias 3

Monitoring Requirements

• ECG monitoring is essential during initiation of therapy, particularly when used in combination with other antiarrhythmic agents 2, 4
• Liver function tests should be monitored in patients with hepatic impairment 5
• Monitor for neurological and cardiac adverse effects (tremor, ataxia, paresthesias, dizziness) 2, 8
• Watch for potential AV block or worsening of arrhythmias 2, 10

Common Adverse Effects

• Gastrointestinal: Nausea (most common), anorexia, gastric irritation (occur in up to 40% of patients) 8, 10
• Neurological: Tremor, dizziness, memory loss, sleep disturbance, headache, shakiness (occur in approximately 10% of patients) 7, 8
• Cardiac: Heart failure, AV block 3

Drug Interactions

• Phenytoin and rifampicin induce the metabolism of mexiletine, potentially reducing its effectiveness 7
• Mexiletine inhibits CYP2D6-mediated metabolism of metoprolol and CYP1A2-mediated metabolism of theophylline 7
• Patients with the CYP2D6 extensive metabolizer phenotype are susceptible to drug interactions between mexiletine and drugs that inhibit CYP2D6 (e.g., quinidine) 7

Remember that mexiletine is a Class IB antiarrhythmic agent with electrophysiologic properties similar to lidocaine, and while it has important contraindications, it remains a valuable option for specific arrhythmias, particularly in patients with long QT syndrome type 3 3.