Concomitant Use of Mexiletine and Amiodarone

Pharmacological Considerations

Amiodarone is a class III antiarrhythmic with multiple mechanisms of action, including potassium channel blockade leading to QT prolongation, as stated by the European Society of Cardiology 1
Amiodarone is metabolized by CYP3A4 and CYP2C8 and acts as an inhibitor of multiple cytochrome P450 enzymes including CYP3A4, CYP1A2, CYP2C9, and CYP2D6 2
Amiodarone has an extremely long half-life, allowing for potential interactions months after discontinuation 2

The European Society of Cardiology guidelines specifically list mexiletine as a potential treatment option for ventricular arrhythmias, but caution about its use with other QT-prolonging drugs 1
Amiodarone may cause hypotension, bradycardia, heart block, prolonged QT interval, and torsades de pointes VT, according to the American Academy of Pediatrics 3
Amiodarone should not be used in combination with procainamide or other drugs that cause QT prolongation without expert consultation, as recommended by the American Academy of Pediatrics 3

Consultation with a cardiologist is strongly recommended when considering the use of amiodarone outside of the cardiac arrest setting, as advised by the American Academy of Pediatrics 3

Continuous electrocardiographic monitoring should be employed during initiation of therapy, as recommended by the American Academy of Pediatrics 3
A defibrillator must be immediately available when administering these medications, according to the American Academy of Pediatrics 3
The combination is contraindicated in severe sinus node dysfunction, marked sinus bradycardia, and second- and third-degree AV block unless a pacemaker is present, as stated by the American Academy of Pediatrics 3