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. 2025 Mar 14;13(3):210.
doi: 10.3390/toxics13030210.

Safety Profile and Hepatotoxicity of Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors: A Disproportionality Analysis Based on FDA Adverse Event Reporting System Database

Yun Yang  1 , Shiyi Tan  1 , Yuepu Pu  1 , Juan Zhang  1   2
Affiliations

Safety Profile and Hepatotoxicity of Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors: A Disproportionality Analysis Based on FDA Adverse Event Reporting System Database

Yun Yang et al. Toxics. .

Abstract

Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have become first-line therapies for advanced non-small cell lung cancer (NSCLC) with ALK rearrangements. This study investigates ALK-TKI-associated adverse events (AEs), focusing on identifying hepatotoxicity signals and previously undocumented safety concerns. Using disproportionality analysis of 56,864 reports from the FDA Adverse Event Reporting System (FAERS) database, we systematically classified AEs via the Medical Dictionary for Regulatory Activities (MedDRA). At the System Organ Class (SOC) level, crizotinib exhibited a significantly stronger signal for eye disorders, ceritinib was uniquely linked to gastrointestinal disorders, and loratinib was predominantly associated with metabolism and nutrition disorders. Several AEs previously undocumented in drug labels were identified, including pericardial effusion, elevated C-reactive protein, hemolytic anemia, hemoptysis, and decreased hemoglobin. Furthermore, crizotinib, ceritinib, and alectinib were significantly associated with hepatotoxicity, marked by elevated alanine aminotransferase, aspartate aminotransferase, and hepatic enzyme levels. These findings highlight the need for vigilant monitoring of unlabeled AEs and potential label updates, particularly for hepatotoxicity risks associated with crizotinib, ceritinib, and alectinib.

Keywords: ALK-TKIs; U.S. FDA adverse event reporting system; adverse events; hepatotoxicity; pharmacovigilance.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The flow diagram showing the analysis process of the study. “×” indicates the removal of duplicate reports.
See this image and copyright information in PMC

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