Clinical evidence,mechanism, importance and management
A 71-year-old woman who had undergone kidney transplantation 7 years earlier and who was taking amlodipine,losartan, furosemide, chlortalidone, calcitriol, aspirin, prednisone, ciclosporin, cyclophosphamide and insulin was also treated with flecainide, which controlled her paroxysmal atrial fibrillation. Atorvastatin was then restarted for hypercholesterolaemia and benziodarone 100mg daily (because of intolerance to allopurinol) was added to treat hyperuricaemia. Three days later she presented with asthenia and poor overall condition and later an ECG showed QRS prolongation of 169 milliseconds (21% increase) caused by complete right bundle branch block with a previous anterior hemiblock,QTc interval prolongation of 482 milliseconds (22% increase) and PR interval prolongation of 203 milliseconds (18% increase). Creatinine levels were about 127 micromol/L,creatine phosphokinase 354 units/L and urea 155 mg/dL. Atorvastatin was stopped because of mild rhabdomyolysis. Flecainide and benziodarone were discontinued because an interaction was also suspected and symptoms resolved within 48 hours, with ECG then showing values close to baseline. Flecainide was restarted and dose gradually increased to 100mg daily (See reference number 1).
It was suggested that benziodarone may inhibit cytochrome P450 isoenzyme CYP2D6 which is concerned with metabolism of flecainide (See reference number 1). Note that benziodarone is chemically related to amiodarone,which has a similar effect, see Flecainide + Amiodarone interaction. Mild renal
insufficiency in patient may also have contributed to reduced flecainide elimination
1. Gormaz CL,Page JCG, Fuentes FL. Pharmacological interaction between flecainide and benziodarone. Rev Esp Cardiol (2003) 56, 631–2.