Background

Flecainide is a class IC antiarrhythmic drug indicated for patients with supraventricular arrhythmias. It has proarrhythmic effects and although toxicity is rare, mortality rate can be as high as 10%.

Objectives

Flecainide is primarily metabolized by CYP2D6. We present a case of flecainide toxicity contributed by CYP2D6 polymorphism.

Methods

Patient was born at 29+5 weeks and was initially treated with propranolol for supraventricular tachycardia (SVT). However, he developed a recurrence of SVT and was switched to oral flecainide.

7 days after flecainide initiation, he became bradycardic. Electrocardiogram (ECG) showed sinus node dysfunction and atrioventricular block. The bradycardia was refractory to drugs, transcutaneous and transvenous pacing. In view of poor perfusion and severely reduced biventricular function on 2D-echocardiogram, extracorporeal membrane oxygenation (ECMO) was initiated. He was treated with IV calcium chloride and lipid emulsion and subsequently reverted to sinus rhythm with return of arterial pulsatility. Patient was supported on ECMO for 12 days and started on sotalol for SVT control.

Results

While other causes of flecainide toxicity were ruled out, investigations revealed supratherapeutic serum flecainide concentrations. Since flecainide is metabolised by CYP2D6 which exhibits polymorphism, a gene test was sent out to determine patient’s genotype. Patient has CYP2D6*10X2/*36 genotype that is predicted to have intermediate CYP2D6 enzyme activity which is associated with lower flecainide clearance.

Conclusion

Based on patient’s genotype, 25% dose reduction of flecainide is recommended by some national guidelines. This case report highlights the importance of ECG and flecainide levels monitoring when treating neonates. CYP genotype testing can further identify at-risk patients of toxicity.