Major
Dronedarone × Fluoxetine
Class III antiarrhythmic×Selective serotonin reuptake inhibitors
Mechanism
Fluoxetine blocks CYP2D6 (strongly) and CYP3A4 (moderately). Dronedarone plasma levels may rise. Additive QT risk.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination. Alternative antidepressants without CYP3A4/CYP2D6 inhibition: sertraline or escitalopram. Alternative antiarrhythmic: a beta-blocker for rate control.