What are the contraindications for Mexilitine?

Contraindications for Mexiletine

Mexiletine is absolutely contraindicated in patients with cardiogenic shock or preexisting second- or third-degree AV block without a pacemaker. 1

Absolute Contraindications

• Cardiogenic shock - Mexiletine should not be administered to patients experiencing cardiogenic shock due to potential worsening of hemodynamic status 1
• Second- or third-degree AV block without a functioning pacemaker - Mexiletine can further depress conduction in these patients 1
• Severe sinus node dysfunction unless a pacemaker is present 2
• Marked sinus bradycardia without pacemaker protection 2

Relative Contraindications and Cautions

Cardiac Conditions

• Heart failure - Mexiletine may exacerbate heart failure in susceptible patients 3
• Structural heart disease - Caution is advised as mexiletine can potentially worsen arrhythmias in patients with myocardial scarring 3
• Concomitant use with QT-prolonging medications - Requires careful consideration and monitoring 2

Hepatic Impairment

• Severe liver disease - Mexiletine is primarily metabolized by the liver, and its clearance is impaired in patients with hepatic dysfunction 4, 5
• Prolonged half-life in hepatic impairment (14-16 hours vs normal 10-14 hours) requiring dosage adjustment 3, 5

Drug Interactions

• CYP2D6 inhibitors (such as quinidine) - May increase mexiletine levels in extensive metabolizers 4
• Phenytoin and rifampicin - May decrease mexiletine effectiveness by inducing its metabolism 4
• Combination with amiodarone - Requires careful monitoring due to potential additive effects on cardiac conduction 2
• Theophylline - Mexiletine inhibits theophylline metabolism, potentially leading to toxicity 4
• Metoprolol - Mexiletine inhibits CYP2D6-mediated metabolism of metoprolol 4

Other Considerations

• Blood dyscrasias - Mexiletine has been associated with blood disorders in some patients 3
• Seizure disorders - Mexiletine can lower seizure threshold 6

Monitoring Requirements

• ECG monitoring is essential during initiation of therapy, particularly when used in combination with other antiarrhythmic agents 2
• Liver function tests should be performed periodically due to hepatic metabolism 5
• Therapeutic drug monitoring may be considered, with target plasma concentrations of 0.75-2.0 mg/L 5

Common Adverse Effects to Monitor

• Neurological: Tremor, ataxia, paresthesias, dizziness, memory disturbances 3, 7
• Gastrointestinal: Nausea, anorexia, gastric irritation (occurring in up to 40% of patients) 7
• Cardiac: Potential for AV block, worsening of arrhythmias 3

Special Populations

• Elderly patients - May require lower doses due to age-related changes in pharmacokinetics 5
• Patients with acute myocardial infarction - Elimination half-life may be prolonged 5
• Patients on hemodialysis - Increased clearance during dialysis may require dosage adjustments 5

Mexiletine should be used with caution in patients with a history of adverse reactions to other sodium channel blockers such as lidocaine, given their structural and pharmacological similarities 8, 5.