Case report: Use of therapeutic drug monitoring and pharmacogenetic testing as opportunities to individualize care in a case of flecainide toxicity after fetal supraventricular tachycardia

Abstract

Flecainide is a class IC antiarrhythmic utilized in prophylaxis of refractory paroxysmal supraventricular tachycardias in pediatric populations. Despite being a highly effective agent, its narrow therapeutic index increases the risk of toxicity and proarrhythmic events, including wide-complex tachycardia. In the absence of direct plasma sampling in the fetus to quantitate flecainide systemic concentrations, clinicians typically make drug dosing decisions from maternal plasma concentrations and QRS duration on maternal ECGs. There remains a paucity of standard guidelines and data to inform the timing and frequency of the aforementioned test in pregnancy and timing of flecainide discontinuation prior to childbirth. Flecainide primarily undergoes metabolism via cytochrome P450 (CYP). Given the variance of CYP-mediated metabolism at the level of the individual patient, pharmacogenomics can be considered in patients who present with flecainide toxicity to determine the maternal vs. fetal factors as an etiology for the event. Finally, pharmacogenetic testing can be utilized as an adjunct to guide flecainide dosing decisions, but must be done with caution in neonates <2 weeks of age. This case report highlights utilization of pharmacogenomic testing and therapeutic drug monitoring as adjuncts to guide therapy for a newborn with refractory supraventricular tachycardia, who experienced flecainide toxicity immediately post-partum and was trialed unsuccessfully on multiple alternative antiarrhythmics without rhythm control.

Keywords: drug monitoring; flecainide; pharmacogenetic; pharmacogenomics; toxicity.

Figure 1

(A) Electrocardiogram during flecainide toxicity demonstrating 1:1 AV conduction with a prolonged PR interval, left axis deviation, nonspecific intra-ventricular conduction block and prolonged QTC. Rate 125 bpm, PR interval 190 ms, QRS duration 100 ms, QTc 494 ms. (B) Electrocardiogram following sodium bicarbonate treatment demonstrating sinus bradycardia with normalization of the QRS duration, diffusely flat T wave changes and prolonged QTc. Rate 88 bpm, PR interval 146 ms, QRS duration 70 ms, QTc 529 ms.

Figure 2

Bedside telemetry demonstrating a regular, narrow complex tachycardia with long RP morphology and deeply negative P waves in the inferior leads with PJRT.