Critical
Amitriptyline × Dronedarone
Tricyclic antidepressants (TCA)×Class III antiarrhythmic
Mechanism
Amitriptyline (tricyclic antidepressant) prolongs QT. Dronedarone also prolongs QT. Additive effect raises ventricular arrhythmia risk. FDA Multaq Section 4.3 specifically lists QT-prolonging antidepressants as contraindications.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk rises with hypokalaemia and hypomagnesaemia.
Management
The combination is not prescribed. Replace the TCA with sertraline (minimal QT effect, up to 100 mg/day) or agomelatine. If a TCA is required, choose a non-QT antiarrhythmic (beta-blocker).