Document Type

Article

Publication Date

7-2022

Identifier

DOI: 10.1111/cts.13296; PMCID: PMC9283732

Abstract

Propafenone is an antiarrhythmic drug metabolized primarily by cytochrome P450 2D6 (CYP2D6). In adults, propafenone adverse events (AEs) are associated with CYP2D6 poor metabolizer status; however, pediatric data are lacking. Subjects were tested for 10 CYP2D6 allelic variants and copy number status, and activity scores assigned to each genotype. Seventy-six individuals (median 0.3 [range 0-26] years old) were included. Propafenone AEs occurred in 29 (38%); 14 (18%) required drug discontinuation due to AE. The most common AEs were QRS (n = 10) and QTc (n = 6) prolongation. Those with AEs were older at the time of propafenone initiation (1.58 [0.13-9.92] vs. 0.20 [0.08-2.01] years old; p = 0.042). CYP2D6 activity scores were not associated with presence of an AE (odds ratio [OR] 0.48 [0.22-1.03]; p = 0.055) but with the total number of AE (β1 = -0.31 [-0.60, -0.03]; p = 0.029), systemic AEs (OR 0.33 [0.13-0.88]; p = 0.022), and drug discontinuation for systemic AEs (OR 0.28 [0.09-0.83]; p = 0.017). Awareness of CYP2D6 activity score and patient age may aid in determining an individual's risk for an AE with propafenone administration.

Journal Title

Clin Transl Sci

Volume

15

Issue

7

First Page

1787

Last Page

1795

MeSH Keywords

Adolescent; Adult; Alleles; Anti-Arrhythmia Agents; Child; Child, Preschool; Cytochrome P-450 CYP2D6; Genetic Variation; Genotype; Humans; Infant; Infant, Newborn; Long QT Syndrome; Propafenone; Young Adult

Keywords

Alleles; Anti-Arrhythmia Agents; Cytochrome P-450 CYP2D6; Genetic Variation; Genotype; Long QT Syndrome; Propafenone

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