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Anaplastic lymphoma kinase tyrosine kinase inhibitors associated gastrointestinal obstruction, perforation, and ulceration: an analysis of the FDA adverse event reporting system database (FAERS)

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Abstract

Background 

There have been cases reporting anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) and associated serious gastrointestinal (GI) adverse drug reactions (gastrointestinal obstruction, perforation, and ulceration). These adverse drug reactions are not in the drug package inserts, and the drug relationships are not proven in the literature. 

Aim

We aimed to examine the potential association between GI obstruction, perforation, and ulceration, and ALK-TKIs by data mining of the US FDA Adverse Event Reporting System (FAERS).

Method  

We conducted a disproportionality analysis of GI obstruction, perforation, and ulceration by estimating the reporting odds ratios (ROR) and the information component (IC) with 95% confidence intervals.

Results 

A total of 279 cases of ALK-TKI-associated GI obstruction, perforation, and ulceration from January 1, 2011, to December 31, 2020, were identified. GI obstruction, perforation, and ulceration cause 16% of cases of death. A significantly increased reporting rate for GI obstruction [ROR 1.77 (1.45–2.15); IC 0.82 (0.53–2.03)] and perforation [ROR 1.61 (1.28–2.02); IC 0.68 (0.35–1.92)] was observed for ALK-TKIs as a drug class. The signal of GI ulceration was detected only in crizotinib [ROR 1.23 (1.01–1.50); IC 0.29 (0.01–1.51)]. A statistically significant ROR and IC emerged for the site of the esophagus. 

Conclusion 

Overall, the pharmacovigilance study of the FAERS indicates slightly increased reporting of GI obstruction and perforation, which may cause severe or even fatal outcomes among ALK-TKIs users.

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Acknowledgements

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Funding

This research was funded by Chongqing Health Commission (2020FYYX058).

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Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, 400016, Chongqing, China

    Jing Huang

  2. Department of Pharmacology, The Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, 400016, Chongqing, China

    Yibei Zhao & Dongzhi Ran

  3. Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuanjiagang, Yuzhong District, 400016, Chongqing, China

    Yanni Cao, Feng Qiu & Long Meng

  4. Department of Pharmacy, National Clinical Research Center for Geriatric Disease, Xuanwu Hospital Capital Medical University, 100053, Beijing, China

    Qingxia Zhang

  5. Information Center, The First Affiliated Hospital of Chongqing Medical University, 400016, Chongqing, China

    Jinyan Li

  6. Department of Pharmacy, Nanshan Community Health Service Center, 400060, Chongqing, China

    Ling Luo

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  1. Jing Huang
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  9. Long Meng
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Correspondence to Long Meng.

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Huang, J., Zhao, Y., Cao, Y. et al. Anaplastic lymphoma kinase tyrosine kinase inhibitors associated gastrointestinal obstruction, perforation, and ulceration: an analysis of the FDA adverse event reporting system database (FAERS). Int J Clin Pharm 44, 993–1003 (2022). https://doi.org/10.1007/s11096-022-01425-4

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