Departments of Pharmacy,
Children's Intensive Care Unit, KK Women's and Children's Hospital, Singapore; and.
Pediatrics. 2020 Jul;146(1). doi: 10.1542/peds.2019-2608. Epub 2020 Jun 19.
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.
醋氟酰胺是一种 Vaughan-Williams 类 IC 抗心律失常药物，用于治疗室上性心律失常。即使在治疗剂量下，它也具有狭窄的治疗指数和致心律失常作用。醋氟酰胺由 CYP2D6 酶代谢，该酶表现出多态性。在本病例报告中，我们根据现有知识，报告了首例由婴儿遗传多态性引起的毒性病例。我们的复发性室上性心动过速患者接受了治疗剂量的醋氟酰胺治疗，但出现了需要体外膜氧合支持的心脏阻滞，随后接受了脂肪乳剂治疗。发现他的血清醋氟酰胺浓度高于治疗范围，基因检测显示该患者为中间代谢者。通过本病例报告，我们强调了在新生儿人群中开始药物治疗前评估 CYP2D6 基因型的重要性，并建议这些患者定期监测血清醋氟酰胺水平和心电图。
