Pharmacoepidemiol Risk Manage.  2024 Mar;16(1):49-56. 10.56142/perm.24.0005.

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

• Park YB
• Hong S
• Jang HJ
• Kim SH
• Cho EJ
• Cho YS
• Kang HJ
• Lee JY

• KMID: 2556392
• DOI: http://doi.org/10.56142/perm.24.0005

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.

Keyword

Acute lymphoblastic leukemia; Trimethoprim-sulfamethoxazole; Pentamidine; Hepatotoxicity; Pediatrics