Open AccessInfluence of CYP2D6 genetic variation on adverse events with propafenone in the pediatric and young adult population
Author(s) -
Sunthankar Sudeep D.,
Kannankeril Prince J.,
Gaedigk Andrea,
Radbill Andrew E.,
Fish Frank A.,
Van Driest Sara L.
Publication year - 2022
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.13296
Subject(s) - propafenone , cyp2d6 , medicine , adverse effect , population , genetic variation , variation (astronomy) , pharmacology , environmental health , cytochrome p450 , physics , astrophysics , metabolism , atrial fibrillation
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 ( β 1 = −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.