Complete Heart Block Secondary to Flecainide Toxicity: Is It Time for CYP2D6 Genotype Testing?

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.

A Retrospective Review of the Efficiency of First-Dose Therapeutic Drug Monitoring of Gentamicin, Amikacin, and Vancomycin in the Pediatric Population.

Therapeutic drug monitoring (TDM) has become standard clinical practice for gentamicin, amikacin, and vancomycin to optimize efficacy and reduce toxicity. TDM after the first dose of antibiotic was adopted in our institution. This study aims to evaluate if target therapeutic drug concentrations could be achieved more rapidly in patients with TDM performed after the first dose of gentamicin, amikacin, or vancomycin compared to TDM at steady state. A single-center retrospective cohort study was conducted at KK Women's and Children's Hospital, Singapore. Patients aged 1 month to 18 years old who received amikacin, gentamicin, or vancomycin between October 2012 to March 2016 and had at least 2 serum drug concentrations done within the same dosing interval were included. The primary objective was to compare the time taken to achieve target serum drug concentrations between first-dose and steady-state TDM. A total of 334 patients on amikacin, 211 patients on gentamicin, and 140 patients on vancomycin were included. Using Kaplan-Meier analysis, the median number of days to optimize therapy was significantly shorter after first-dose TDM was performed for amikacin (first dose, 1.51 [95% confidence interval (CI), 1.44-1.89] days vs steady state, 2.85 [95%CI, 2.50-3.25] days; P < .01] and gentamicin (first dose, 1.66 [95%CI, 1.25-2.08] days vs steady state, 3.54 [95%CI, 2.40-4.75] days; P < .01] but not vancomycin (first dose, 1.34 [95%CI, 1.06-1.52] days vs steady state, 1.42 [95%CI, 1.26-1.59] days; P = .99]. First-dose TDM for gentamicin and amikacin resulted in faster attainment of target serum concentrations but did not for vancomycin. Further validation of its impact on actual clinical outcomes may be required.