What are the contraindications for Mexilitine?

Mexiletine Contraindications

Mexiletine is absolutely contraindicated in patients with cardiogenic shock or preexisting second- or third-degree AV block without a pacemaker, and should not be used in patients with severe sinus node dysfunction or marked sinus bradycardia unless pacemaker protection is in place. 1, 2

Absolute Contraindications

• Cardiogenic shock is an absolute contraindication to mexiletine use 1
• Preexisting second- or third-degree AV block without a pacemaker is an absolute contraindication 1
• Severe sinus node dysfunction without pacemaker protection is contraindicated, as mexiletine can worsen conduction abnormalities 2
• Marked sinus bradycardia without pacemaker should preclude mexiletine use 2

Relative Contraindications and High-Risk Situations

Cardiac Conditions Requiring Caution

• Structural heart disease warrants careful consideration, as mexiletine can potentially worsen arrhythmias in susceptible patients 2
• Heart failure may be exacerbated by mexiletine, particularly in patients with reduced left ventricular ejection fraction 2, 3
• Severe AV conduction disturbances (even if not complete block) require extreme caution due to risk of progression 3

Hepatic Impairment

• Severe liver disease requires dosage adjustment because mexiletine's elimination half-life increases from the normal 10-14 hours to 14-16 hours in hepatic dysfunction 2
• Mexiletine is predominantly metabolized by the liver, making hepatic impairment clinically significant 4, 5

Critical Drug Interactions

• Concomitant use with QT-prolonging medications (particularly amiodarone) requires careful monitoring due to additive effects on cardiac conduction 2, 6
• Combination with amiodarone specifically demands expert consultation and continuous ECG monitoring, with a defibrillator immediately available 6
• The combination is contraindicated in severe sinus node dysfunction, marked bradycardia, and second- or third-degree AV block unless a pacemaker is present 6

Important Clinical Distinctions

• Mexiletine does NOT prolong the QT interval, unlike other sodium channel blockers, making it potentially safer in certain contexts and even beneficial in long QT syndrome type 3 (LQT3) 2, 3
• This distinguishes mexiletine from the sodium channel blockers used in the CAST trial that increased mortality after myocardial infarction 3

Monitoring Requirements

• ECG monitoring is essential during therapy initiation, particularly when combined with other antiarrhythmic agents 2
• Watch for blood dyscrasias, which have been associated with mexiletine use 2
• Monitor for neurological adverse effects (tremor, ataxia, paresthesias, dizziness) and cardiac complications (AV block, arrhythmia worsening) 2, 7

Common Pitfalls to Avoid

• Do not overlook preexisting conduction abnormalities—mexiletine may aggravate impaired impulse generation and conduction 5
• Gastrointestinal side effects occur in up to 40% of patients but can often be managed by dose reduction and administering with food rather than discontinuing the drug 8
• Renal disease has minimal effect on mexiletine clearance, so dosage adjustment is generally not needed for renal impairment (unlike hepatic disease) 5