Moderate
Amiodarone × duloxetine
Class III antiarrhythmics (Vaughan Williams)×SNRI
Mechanism
Duloxetine is a CYP1A2 and CYP2D6 substrate. Amiodarone weakly inhibits CYP1A2 — duloxetine levels can rise. There is also an additive QT effect at high duloxetine doses (over 60 mg/day).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease. On high-dose duloxetine: nausea, insomnia, dry mouth, elevated blood pressure.
Management
On starting the combination, begin duloxetine at 30 mg/day. Check ECG at 1 and 2 weeks. In hypertension and tachycardia, do not exceed 60 mg/day. Antidepressant alternative without CYP1A2 or QT effect: sertraline.