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Pharmacoepidemiology and Risk Management 2024; 16(1): 49-56

Published online March 31, 2024 https://doi.org/10.56142/perm.24.0005

Copyright © Korean Society for Pharmacoepidemiology and Risk Management.

Hepatotoxicity and Related Factors Induced by Sulfamethoxazole/Trimethoprim in Pediatric Patients with Acute Lymphoblastic Leukemia

소아 급성림프구성백혈병 환자에서 Sulfamethoxazole/Trimethoprim에 의한 간독성 및 관련인자

Yu Been Park1*, Sukmin Hong1*, Hye Jin Jang1, Sung Hwan Kim1, Eun Jung Cho1, Yoon Sook Cho1, Hyoung Jin Kang2,3,4, Ju-Yeun Lee5

박유빈1*, 홍석민1*, 장혜진1, 김성환1, 조은정1, 조윤숙1, 강형진2,3,4, 이주연5

1Department of Pharmacy, Seoul National University Hospital, Seoul, Korea
2Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
3Seoul National University Cancer Institute, Seoul, Korea
4Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
5College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea

1서울대학교병원 약제부, 2서울대학교 의과대학 소아과, 3서울대학교 암연구소, 4서울대학교병원 소아청소년과, 5서울대학교 약학대학

Correspondence to:Ju-Yeun Lee
College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea
Tel: +82-2-3668-7472
E-mail: jypharm@snu.ac.kr

Hyoung Jin Kang
Department of Pediatrics, Seoul National University Children’s Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
Tel: +82-2-2072-3304
E-mail: kanghj@snu.ac.kr

* The first two authors contributed equally for this work.

Received: March 1, 2024; Revised: March 18, 2024; Accepted: March 18, 2024

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective: This study aimed to examine the causality of hepatotoxicity related to sulfamethoxazole/trimethoprim (SMX/TMP) in pediatric patients with acute lymphoblastic leukemia (ALL). Methods: We retrospectively analyzed medical records of pediatric ALL patients, who were transitioned from SMX/TMP to aerosolized pentamidine (AP) for Pneumocystis jirovecii pneumonia prevention due to suspected hepatotoxicity between 2010 and 2023. The Roussel Uclaf causality assessment method (RUCAM) was used to assess hepatotoxicity due to SMX/ TMP, emphasizing cases considered “high probability” (RUCAM ≥ 6). Results: Of the 176 pediatric ALL patients who switched from SMX/TMP to AP, 112 did so due to elevated liver enzyme levels, and 38 of these (33.9%) were classified as “high probability” for hepatotoxicity according to RUCAM. Hepatotoxicity induced by SMX/TMP is characterised by an average ALT level of 430.6 IU/L, a total bilirubin level of 1.2 mg/dL at onset, typically manifesting after 223.1 days and resolving within 110.7 days. Multivariable analysis identified significant factors such as age (1–5 years), obesity, onset time (≤ 20 days), recovery time (≤ 20 days), and treatments with L-asparaginase and 6-mercaptopurine as associated with an increased risk of hepatotoxicity. Conclusion: This study found that 21.6% of pediatric ALL patients who discontinued SMX/TMP for prophylaxis had hepatotoxicity with a ‘probable or higher’ causality due to SMX/TMP. Identifying factors associated with ‘probable or higher’ causality for SMX/TMP-induced hepatotoxicity in these patients may be valuable for future research in this domain.

KeywordsAcute lymphoblastic leukemia, Trimethoprim-sulfamethoxazole, Pentamidine, Hepatotoxicity, Pediatrics

Korean Society for Pharmacoepidemiology and Risk Management

Vol.16 No.2
September, 2024

eISSN 2982-5954

Frequency: Bimonthly

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