Amiodarone × Duloxetine

Duloxetine is cleared by CYP1A2 and CYP2D6 (duloxetine label, US Food and Drug Administration, FDA). Amiodarone and its metabolite desethylamiodarone inhibit both enzymes (amiodarone SmPC), so duloxetine levels may rise. Amiodarone is not named as a potent CYP1A2 inhibitor: the duloxetine contraindication covers only fluvoxamine, ciprofloxacin and enoxacin (duloxetine SmPC). Duloxetine does not prolong the QT interval, even at 2.7–3.3 times the maximum dose (duloxetine label, FDA).

The combination may intensify the usual duloxetine adverse effects: nausea, headache, dry mouth, drowsiness and dizziness (duloxetine SmPC). Duloxetine can raise blood pressure, up to hypertensive crisis in patients with pre-existing hypertension (duloxetine SmPC). Duloxetine overdose has caused drowsiness, seizures, vomiting, tachycardia, serotonin syndrome and coma (duloxetine SmPC).

The combination is acceptable with monitoring: the duloxetine SmPC asks for caution when it is given with drugs that impair its metabolism (duloxetine SmPC). In patients with heart disease, blood pressure is monitored, especially in the first month of duloxetine treatment, and a sustained rise calls for a lower duloxetine dose or gradual withdrawal (duloxetine SmPC). Amiodarone interactions can persist for several months after it is stopped (amiodarone SmPC).