Major
Amiodarone × Carbamazepine
Class III antiarrhythmics (Vaughan Williams)×Antiepileptics. Carboxamide derivatives
Mechanism
Dual mechanism. Carbamazepine induces CYP3A4 and lowers amiodarone levels. Amiodarone blocks CYP3A4 and partially suppresses carbamazepine metabolism, so carbamazepine plasma levels may rise.
Symptoms
From amiodarone fall: atrial fibrillation symptoms return. From carbamazepine rise: ataxia, diplopia, nausea, hyponatraemia, drowsiness.
Management
Avoid the combination. Alternative anticonvulsants without induction: levetiracetam, lamotrigine. Alternative antiarrhythmic: beta-blocker for rate control or catheter ablation. If unavoidable, check carbamazepine plasma levels at 1–2 weeks.