PMID- 35514162
OWN - NLM
STAT- MEDLINE
DCOM- 20220718
LR  - 20221209
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 15
IP  - 7
DP  - 2022 Jul
TI  - Influence of CYP2D6 genetic variation on adverse events with propafenone in the 
      pediatric and young adult population.
PG  - 1787-1795
LID - 10.1111/cts.13296 [doi]
AB  - 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 
      (beta(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.
CI  - (c) 2022 The Authors. Clinical and Translational Science published by Wiley 
      Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Sunthankar, Sudeep D
AU  - Sunthankar SD
AUID- ORCID: 0000-0002-2687-8204
AD  - Thomas P. Graham Jr. Division of Pediatric Cardiology, Department of Pediatrics, 
      Vanderbilt University Medical Center|, Nashville, Tennessee, USA.
AD  - Center for Pediatric Precision Medicine, Vanderbilt University Medical Center, 
      Nashville, Tennessee, USA.
FAU - Kannankeril, Prince J
AU  - Kannankeril PJ
AUID- ORCID: 0000-0002-1529-9872
AD  - Thomas P. Graham Jr. Division of Pediatric Cardiology, Department of Pediatrics, 
      Vanderbilt University Medical Center|, Nashville, Tennessee, USA.
AD  - Center for Pediatric Precision Medicine, Vanderbilt University Medical Center, 
      Nashville, Tennessee, USA.
FAU - Gaedigk, Andrea
AU  - Gaedigk A
AUID- ORCID: 0000-0001-6968-1893
AD  - Division of Clinical Pharmacology, Toxicology, & Therapeutic Innovation, 
      Children's Mercy Kansas City, Kansas City, Missouri, USA.
FAU - Radbill, Andrew E
AU  - Radbill AE
AD  - Thomas P. Graham Jr. Division of Pediatric Cardiology, Department of Pediatrics, 
      Vanderbilt University Medical Center|, Nashville, Tennessee, USA.
FAU - Fish, Frank A
AU  - Fish FA
AD  - Thomas P. Graham Jr. Division of Pediatric Cardiology, Department of Pediatrics, 
      Vanderbilt University Medical Center|, Nashville, Tennessee, USA.
FAU - Van Driest, Sara L
AU  - Van Driest SL
AD  - Center for Pediatric Precision Medicine, Vanderbilt University Medical Center, 
      Nashville, Tennessee, USA.
AD  - Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University 
      Medical Center, Nashville, Tennessee, USA.
AD  - Division of General Pediatrics, Department of Pediatrics, Vanderbilt University 
      Medical Center, Nashville, Tennessee, USA.
LA  - eng
GR  - UL1 TR000445/TR/NCATS NIH HHS/United States
GR  - P50GM115305/NH/NIH HHS/United States
GR  - T32 HL105334/HL/NHLBI NIH HHS/United States
GR  - S10RR025141/NH/NIH HHS/United States
GR  - R01 HD074711/HD/NICHD NIH HHS/United States
GR  - U01 HG004798/HG/NHGRI NIH HHS/United States
GR  - RC2GM092618/NH/NIH HHS/United States
GR  - U01HG006378/NH/NIH HHS/United States
GR  - U19HL065962/NH/NIH HHS/United States
GR  - P50 HD106446/HD/NICHD NIH HHS/United States
GR  - UL1 RR024975/RR/NCRR NIH HHS/United States
GR  - R01 NS032830/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220526
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - 0 (Anti-Arrhythmia Agents)
RN  - 68IQX3T69U (Propafenone)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Alleles
MH  - *Anti-Arrhythmia Agents/adverse effects
MH  - Child
MH  - Child, Preschool
MH  - *Cytochrome P-450 CYP2D6/genetics
MH  - Genetic Variation
MH  - Genotype
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - *Long QT Syndrome/chemically induced/genetics
MH  - *Propafenone/adverse effects
MH  - Young Adult
PMC - PMC9283732
COIS- The authors declared no competing interests for this work.
EDAT- 2022/05/07 06:00
MHDA- 2022/07/19 06:00
PMCR- 2022/07/01
CRDT- 2022/05/06 02:53
PHST- 2022/04/12 00:00 [revised]
PHST- 2022/03/09 00:00 [received]
PHST- 2022/04/17 00:00 [accepted]
PHST- 2022/05/07 06:00 [pubmed]
PHST- 2022/07/19 06:00 [medline]
PHST- 2022/05/06 02:53 [entrez]
PHST- 2022/07/01 00:00 [pmc-release]
AID - CTS13296 [pii]
AID - 10.1111/cts.13296 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2022 Jul;15(7):1787-1795. doi: 10.1111/cts.13296. Epub 2022 May 
      26.