Major
Amiodarone × Tramadol
Class III antiarrhythmics (Vaughan Williams)×Other opioids
Mechanism
Dual mechanism: tramadol weakly prolongs QT (additive with amiodarone) and lowers the seizure threshold. Amiodarone also blocks CYP2D6 – the main tramadol activation route – so analgesia weakens while serotonergic activity persists.
Symptoms
QT prolongation on ECG, palpitations, syncope. Seizures may occur, especially in patients with prior epilepsy. Weakened tramadol analgesic effect.
Management
Avoid the combination. For analgesia in patients on amiodarone, use paracetamol, NSAIDs (with caution in heart failure), or morphine/oxycodone (pure opioids without QT effect).