Major
Amiodarone × Fluoxetine
Class III antiarrhythmics (Vaughan Williams)×Selective serotonin reuptake inhibitors
Mechanism
Fluoxetine blocks CYP2D6 (a minor amiodarone clearance route) and modestly prolongs QT. Amiodarone plasma levels rise and QT effects add up. The long half-life of fluoxetine and norfluoxetine (up to 5 weeks) is relevant.
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 is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antidepressants with minimal QT effect and no CYP2D6 inhibition: mirtazapine or agomelatine. Interaction potential persists up to 5 weeks after fluoxetine discontinuation.