Amiodarone × Amitriptyline

Both drugs prolong the QT interval on the electrocardiogram: amiodarone through its main action (amiodarone SmPC), and amitriptyline commonly prolongs QT and widens the QRS complex (amitriptyline SmPC). Together they raise the risk of torsades de pointes. There is a second mechanism: amiodarone inhibits CYP2D6 (amiodarone SmPC), amitriptyline is cleared mainly by CYP2D6 and CYP2C19, and CYP2D6 inhibitors can markedly raise its levels (amitriptyline SmPC). Amiodarone is eliminated very slowly, so the interaction is possible for several months after it is stopped (amiodarone SmPC).

QT prolongation on the electrocardiogram (ECG) causes no symptoms by itself. Palpitations, dizziness or fainting may occur. The dangerous complication is torsades de pointes or other ventricular arrhythmias, sometimes fatal (amiodarone SmPC). Amiodarone can markedly slow the heart rate, especially in older people, and cause atrioventricular block (amiodarone SmPC). The risk of arrhythmia is higher with low potassium or magnesium, marked bradycardia, decompensated heart failure or heart disease (amitriptyline and amiodarone SmPCs).

The combination is contraindicated: one of the Spanish amiodarone SmPCs contraindicates amiodarone with drugs that prolong the QT interval and names amitriptyline (amiodarone SmPC). The SmPC of the original amiodarone (Trangorex) says to avoid it with tricyclic antidepressants (amiodarone SmPC, Trangorex), and the label approved by the US Food and Drug Administration (FDA) says to avoid QT-prolonging drugs and names tricyclic antidepressants among them (amiodarone FDA label). The amitriptyline SmPC contraindicates amitriptyline in any heart block or rhythm disorder and does not recommend it with QT-prolonging drugs (amitriptyline SmPC). Before amiodarone is started, an electrocardiogram (ECG) is recorded and potassium is measured, and the ECG is monitored throughout treatment (amiodarone SmPC); low potassium, magnesium and calcium are corrected before the start (amiodarone FDA label). Amiodarone is eliminated over months, so the interaction is still possible after it is stopped (amiodarone SmPC).