Korean Journal of Clinical Pharmacy (한국임상약학회지)

Korean College Of Clinical Pharmacy (한국임상약학회)
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Association of Arrhythmia in the Elderly Patients on Combination Therapy of CYP3A4 Substrates and Inhibitors with the Korean Claims Data

CYP3A4 기질과 억제제 약물의 병용 고령환자에서 부정맥 부작용 연관성

  • Tae Woo Kim (Department of Clinical Pharmacy, College of Pharmacy, Ajou University) ;
  • Junhyuk Chang (Department of Clinical Pharmacy, College of Pharmacy, Ajou University) ;
  • Eunjung Choo (Department of Biohealth Regulatory Science, College of Pharmacy, Ajou University Graduate School) ;
  • Rae Woong Park (Department of Biomedical Sciences, Ajou University Graduate School of Medicine) ;
  • Sukhyang Lee (Department of Clinical Pharmacy, College of Pharmacy, Ajou University)
  • 김태우 (아주대학교 약학대학) ;
  • 장준혁 (아주대학교 약학대학) ;
  • 추은정 (아주대학교 대학원 바이오헬스규제과학과) ;
  • 박래웅 (아주대학교 대학원 의생명과학과) ;
  • 이숙향 (아주대학교 약학대학)
  • Received : 2023.07.31
  • Accepted : 2023.10.05
  • Published : 2023.12.31
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Abstract

Background: Arrhythmia due to QT prolongation is one of the most serious adverse events with drug interactions in the elderly. This study aimed to examine the incidence of arrhythmia in Korean elderly patients who administered both cytochrome P450 3A4 (CYP3A4) substrates and inhibitors. Methods: Patients using CYP3A4 substrate and inhibitor were selected from the 2017 elderly patient dataset (the Korean Health Insurance Review and Assessment Service - Aged Population Sample). Selection criteria were patients with a medication possession ratio over 80%, medication duration of at least 7 days, and a follow-up period of 3 months or more. The patient's basic information is age, gender, health insurance type, and comorbidities. The top 50 drug pairs and comorbidity with high-incidence arrhythmia were presented. Results: In patients with drug combinations for over 7 days, there were 981 incidences of arrhythmia, and 351 incidences in those with combinations for over 30 days. The comorbidities of congestive heart failure and myocardial infarction had a significant association with incidence of arrhythmia. Among patients with 7 days or longer, the drug pairs [substrates-inhibitors] with significant adjusted odds ratio (aOR) were [propranolol-cimetidine] (aOR, 2.25; 95% confidence interval [CI], 1.66-3.04). Among patients with 30 days or longer, the drug pairs with significant aOR were [tramadol-amiodarone] (aOR, 2.87; 95% CI, 1.97-4.19). Conclusions: In elderly patients, the incidence of arrhythmia was high with drug interactions of CYP3A4 substrates and inhibitors. The comorbidity of congestive heart failure was the risk factor.

Keywords

Acknowledgement

본 연구는 2021년 식품의약품안전처의 연구과제(21153 MFDS602)로 수행하였습니다.

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