Why the study?
Flecainide has a narrow therapeutic index and proarrhythmic effects metabolized by polymorphic CYP2D6, but flecainide toxicity contributed by genetic polymorphism in an infant had not been previously reported.
Does CYP2D6 polymorphism contribute to flecainide toxicity in infants?
Does CYP2D6 polymorphism contribute to flecainide toxicity in infants?
This case highlights the potential importance of evaluating the CYP2D6 genotype before initiating flecainide in the neonatal population to prevent severe toxicity.
Suggests CYP2D6 genotyping in flecainide-treated infants with toxicity; leaves open whether testing should guide therapy.
Flecainide acetate is a Vaughan-Williams class IC antiarrhythmic drug prescribed for the treatment of supraventricular arrhythmias. It has a narrow therapeutic index and proarrhythmic effects even at therapeutic doses. Flecainide is metabolized by a CYP2D6 enzyme that exhibits polymorphism. In this case report, we present, to our best knowledge, the first case of toxicity contributed by genetic polymorphism in an infant. Our patient with recurrent supraventricular tachycardia was treated with a therapeutic dose of flecainide but developed heart block requiring extracorporeal membrane oxygenation support and subsequent treatment with lipid emulsion therapy. He was found to have supratherapeutic serum flecainide concentration, and gene testing revealed the patient to be an intermediate metabolizer. With this case report, we reinforce the importance of evaluating the CYP2D6 genotype before drug initiation in the neonatal population and recommend regular monitoring of serum flecainide levels and electrocardiograms in these patients.
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Poh et al. (2020) studied this question.
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