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Home Articles Vol 35,2026 No.4 Detail

Signals mining and analysis of adverse drug events of three proton pump inhibitors based on JADER database

Published on Apr. 28, 2026Total Views: 70 times Total Downloads: 17 times Download Mobile

Author: WANG Ziyi 1 YU Binbin 2

Affiliation: 1. Department of Science and Education, The First People's Hospital of Zhangjiagang, Suzhou 215600, Jiangsu Province, China 2. Department of Pharmacy, The First People's Hospital of Zhangjiagang, Suzhou 215600, Jiangsu Province, China

Keywords: Proton pump inhibitors Adverse drug events Skin and subcutaneous tissue disorders JADER database

DOI: 10.12173/j.issn.1005-0698.202507052

Reference: WANG Ziyi, YU Binbin. Signals mining and analysis of adverse drug events of three proton pump inhibitors based on JADER database[J]. Yaowu Liuxingbingxue Zazhi, 2026, 35(4): 388-397. DOI: 10.12173/j.issn.1005-0698.202507052.[Article in Chinese]

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Abstract

Objective  To mine the risk signals of adverse drug events (ADEs) associated with proton pump inhibitors (PPIs), and to provide a reference for the safe clinical use of such drugs.

Methods  The ADE reports of omeprazole, lansoprazole, and esomeprazole from the first quarter of 2004 to the first quarter of 2025 were obtained from the Japan Adverse Drug Event Report (JADER) database. The report odds ratio (ROR) method, UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standards method, Bayesian confidence propagation neural network (BCPNN) method, and multi-item gamma Poisson shrinkage (MGPS) method were employed to mine ADE signals and positive signals were screened for comparative analysis.

Results  A total of 43 ADE signals were identified for omeprazole, involving 18 system organ classes (SOCs). A total of 75 ADE signals were mined by lansoprazole, involving 14 SOCs, and 42 ADE signals were mined by esomeprazole, involving 12 SOCs. All three ADEs mainly involved skin and subcutaneous tissue disorders. In the ADEs signals, omeprazole, lansoprazole and esomeprazole had 8, 7 and 6 preferred terms (PTs) that were not mentioned in the instructions, respectively.

Conclusion  The ADE signals of the three PPIs have certain commonalities. Clinicians should be alert to the risk of skin and subcutaneous tissue disorders caused by PPIs. Meanwhile, attention should be paid to new ADE signals, and close monitoring of the risks of infection and tumor potentially caused by long-term use of PPIs should be carried out to ensure the safety of medication in patients.

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References

1. 中华人民共和国国家卫生健康委员会. 质子泵抑制剂临床应用指导原则（2020年版）[J]. 中国实用乡村医生杂志, 2021, 28(1): 1-9. DOI: 10.3969/j.issn.1672-7185.2021.01.001.

2. Dharmarajan TS. The use and misuse of proton pump inhibitors: an opportunity for deprescribing[J]. J Am Med Dir Assoc, 2021, 22(1): 15-22. DOI: 10.1016/j.jamda.2020.09.046.

3. Young PJ, Bagshaw SM, Forbes AB, et al. Effect of stress ulcer prophylaxis with proton pump inhibitors vs histamine-2 receptor blockers on in-hospital mortality among ICU patients receiving invasive mechanical ventilation: the PEPTIC randomized clinical trial[J]. JAMA, 2020, 323(7): 616-626. DOI: 10.1001/jama.2019.22190.

4. Wang Y, Parpia S, Ge L, et al. Proton-pump inhibitors to prevent gastrointestinal bleeding-an updated Meta-analysis[J]. NEJM Evid, 2024, 3(7): EVIDoa2400134. DOI: 10.1056/EVIDoa2400134.

5. Palmowski L, von Busch A, Unterberg M, et al. Timely cessation of proton pump inhibitors in critically ill patients impacts morbidity and mortality: a propensity score-matched cohort study[J]. Crit Care Med, 2024, 52(2): 190-199. DOI: 10.1097/CCM.0000000000006104.

6. Chen G, Ning L, Qin Y, et al. Acute kidney injury following the use of different proton pump inhibitor regimens: a real-world analysis of post-marketing surveillance data[J]. J Gastroenterol Hepatol, 2021, 36(1): 156-162. DOI: 10.1111/jgh.15151.

7. 刘丽阳, 高楚蒙, 王效影, 等. 基于FAERS数据库泮托拉唑在胃肠疾病中应用的安全性评价[J]. 中国药物应用与监测, 2024, 21(6): 846-851. [Liu LY, Gao CM, Wang XY, et al. Evaluation of safety of pantoprazole in gastroenterology based on FAERS database[J]. Chinese Journal of Drug Application and Monitoring, 2024, 21(6): 846-851.] DOI: 10.3969/j.issn.1672-8157.2024.06.037.

8. 潘伟萍, 颜少伟, 李炳煌, 等. 基于JADER数据库的恩美曲妥珠单抗和德曲妥珠单抗不良事件信号挖掘与分析[J]. 药物流行病学杂志, 2024, 33(8): 841-850. [Pan WP, Yan SW, Li BH, et al. Signal mining and analysis of adverse drug events related to trastuzumab emtansine and trastuzumab deruxtecan based on JADER database[J]. Chinese Journal of Pharmacoepidemiology, 2024, 33(8): 841-850.] DOI: 10.12173/j.issn.1005-0698.202405070.

9. 朱志朋, 吕强, 叶小飞, 等. 基于美国FAERS数据库的KRAS G12C抑制剂不良事件不相称测定分析[J]. 中国药物警戒, 2025, 22(3): 297-304. [Zhu ZP, Lyu Q, Ye XF, et al. Disproportionality of adverse events to KRAS G12C inhibitors based on the FAERS database[J]. Chinese Journal of Pharmacovigilance, 2025, 22(3): 297-304.] DOI: 10.19803/j.1672-8629.20240841.

10. 钟玲, 曾慧妍, 袁鑫, 等. 基于美国FAERS数据库的利拉鲁肽和司美格鲁肽不良事件信号挖掘与分析[J]. 中国药物警戒, 2025, 22(3): 305-312. [Zhong L, Zeng HY, Yuan X, et al. Adverse event signals of liraglutide and semaglutide based on the FAERS database[J]. Chinese Journal of Pharmacovigilance, 2025, 22(3): 305-312.] DOI: 10.19803/j.1672-8629.20240753.

11. 董家潇, 王轶雷, 李修政, 等. 基于FAERS数据库的未成年人使用重组人生长激素不良事件信号挖掘与分析[J]. 药物流行病学杂志, 2025, 34(2): 157-165. [Dong JX, Wang YL, Li XZ, et al. Signals mining and analysis of adverse drug events in minors using recombinant human growth hormone based on the FAERS database[J]. Chinese Journal of Pharmacoepidemiology, 2025, 34(2): 157-165.] DOI: 10.12173/j.issn.1005-0698.202407021.

12. 中华医学会老年医学分会, 《中华老年医学杂志》编辑委员会. 老年人质子泵抑制剂合理应用专家共识[J]. 中华老年病研究电子杂志, 2015, 2(4): 1-7. DOI: 10.3760/cma.j.issn.0254-9026.2015.10.001.

13. 王新桃, 高萍, 向道春. 兰索拉唑药动学和药物相互作用的研究进展[J]. 医药导报, 2011, 30(7): 922-925. DOI: 10.3870/yydb.2011.07.030.

14. Ishida R, Yamada N, Sato K, et al. Effectiveness of a formulary system on prophylactic oral proton pump inhibitors for drug-induced peptic ulcer in a Japanese tertiary hospital: an interrupted time series analysis[J]. J Pharm Health Care Sci, 2025, 11(1): 51. DOI: 10.1186/s40780-025 -00459-w.

15. 袁洪. 湖南省质子泵抑制剂的临床应用指导原则（试行） [J]. 中南药学, 2016, 14(7): 673-683. DOI: 10.7539/j.issn.1672- 2981.2016.07.001.

16. Grice S, Hammond S, Hampson L, et al. Omeprazole-associated atypical drug reaction with eosinophilia and systemic symptoms (DRESS) in a patient with positive in vitro diagnostic testing to multiple proton pump inhibitors[J]. Chem Res Toxicol, 2024, 37(9): 1484-1487. DOI: 10.1021/acs.chemrestox.4c00225.

17. Bavbek S, Kepil Özdemir S, Bonadonna P, et al. Hypersensitivity reactions to proton pump inhibitors. An EAACI position paper[J]. Allergy, 2024, 79(3): 552-564. DOI: 10.1111/all.15961.

18. Pirson F, Geubel A, Marot L. Late hypersensitivity to omeprazole and other proton pump inhibitors[J]. Acta Clin Belg, 2012, 67(4): 301-303. DOI: 10.2143/ACB.67.4.2062678.

19. Deng Z, Guo A, Wu C, et al. Proton pump inhibitors-related subacute cutaneous lupus erythematosus: clinical characteristics, management, and outcome[J]. J Cosmet Dermatol, 2022, 21(12): 7202-7208. DOI: 10.1111/jocd.15450.

20. Lin CY, Wang CW, Hui CR, et al. Delayed-type hypersensitivity reactions induced by proton pump inhibitors: a clinical and in vitro T-cell reactivity study[J]. Allergy, 2018, 73(1): 221-229. DOI: 10.1111/all.13235.

21. Daldoul M, Charfi O, Bouattour E, et al. Pantoprazole-induced Stevens-Johnson syndrome: a case-report[J]. Curr Drug Saf, 2024, 19(1): 148-150. DOI: 10.2174/1574886318666230224092818.

22. Fracaroli TS, Miranda LQ, Sodré

1. 中华人民共和国国家卫生健康委员会. 质子泵抑制剂临床应用指导原则（2020年版）[J]. 中国实用乡村医生杂志, 2021, 28(1): 1-9. DOI: 10.3969/j.issn.1672-7185.2021.01.001.

2. Dharmarajan TS. The use and misuse of proton pump inhibitors: an opportunity for deprescribing[J]. J Am Med Dir Assoc, 2021, 22(1): 15-22. DOI: 10.1016/j.jamda.2020.09.046.

3. Young PJ, Bagshaw SM, Forbes AB, et al. Effect of stress ulcer prophylaxis with proton pump inhibitors vs histamine-2 receptor blockers on in-hospital mortality among ICU patients receiving invasive mechanical ventilation: the PEPTIC randomized clinical trial[J]. JAMA, 2020, 323(7): 616-626. DOI: 10.1001/jama.2019.22190.

4. Wang Y, Parpia S, Ge L, et al. Proton-pump inhibitors to prevent gastrointestinal bleeding-an updated Meta-analysis[J]. NEJM Evid, 2024, 3(7): EVIDoa2400134. DOI: 10.1056/EVIDoa2400134.

5. Palmowski L, von Busch A, Unterberg M, et al. Timely cessation of proton pump inhibitors in critically ill patients impacts morbidity and mortality: a propensity score-matched cohort study[J]. Crit Care Med, 2024, 52(2): 190-199. DOI: 10.1097/CCM.0000000000006104.

6. Chen G, Ning L, Qin Y, et al. Acute kidney injury following the use of different proton pump inhibitor regimens: a real-world analysis of post-marketing surveillance data[J]. J Gastroenterol Hepatol, 2021, 36(1): 156-162. DOI: 10.1111/jgh.15151.

7. 刘丽阳, 高楚蒙, 王效影, 等. 基于FAERS数据库泮托拉唑在胃肠疾病中应用的安全性评价[J]. 中国药物应用与监测, 2024, 21(6): 846-851. [Liu LY, Gao CM, Wang XY, et al. Evaluation of safety of pantoprazole in gastroenterology based on FAERS database[J]. Chinese Journal of Drug Application and Monitoring, 2024, 21(6): 846-851.] DOI: 10.3969/j.issn.1672-8157.2024.06.037.

8. 潘伟萍, 颜少伟, 李炳煌, 等. 基于JADER数据库的恩美曲妥珠单抗和德曲妥珠单抗不良事件信号挖掘与分析[J]. 药物流行病学杂志, 2024, 33(8): 841-850. [Pan WP, Yan SW, Li BH, et al. Signal mining and analysis of adverse drug events related to trastuzumab emtansine and trastuzumab deruxtecan based on JADER database[J]. Chinese Journal of Pharmacoepidemiology, 2024, 33(8): 841-850.] DOI: 10.12173/j.issn.1005-0698.202405070.

9. 朱志朋, 吕强, 叶小飞, 等. 基于美国FAERS数据库的KRAS G12C抑制剂不良事件不相称测定分析[J]. 中国药物警戒, 2025, 22(3): 297-304. [Zhu ZP, Lyu Q, Ye XF, et al. Disproportionality of adverse events to KRAS G12C inhibitors based on the FAERS database[J]. Chinese Journal of Pharmacovigilance, 2025, 22(3): 297-304.] DOI: 10.19803/j.1672-8629.20240841.

10. 钟玲, 曾慧妍, 袁鑫, 等. 基于美国FAERS数据库的利拉鲁肽和司美格鲁肽不良事件信号挖掘与分析[J]. 中国药物警戒, 2025, 22(3): 305-312. [Zhong L, Zeng HY, Yuan X, et al. Adverse event signals of liraglutide and semaglutide based on the FAERS database[J]. Chinese Journal of Pharmacovigilance, 2025, 22(3): 305-312.] DOI: 10.19803/j.1672-8629.20240753.

11. 董家潇, 王轶雷, 李修政, 等. 基于FAERS数据库的未成年人使用重组人生长激素不良事件信号挖掘与分析[J]. 药物流行病学杂志, 2025, 34(2): 157-165. [Dong JX, Wang YL, Li XZ, et al. Signals mining and analysis of adverse drug events in minors using recombinant human growth hormone based on the FAERS database[J]. Chinese Journal of Pharmacoepidemiology, 2025, 34(2): 157-165.] DOI: 10.12173/j.issn.1005-0698.202407021.

12. 中华医学会老年医学分会, 《中华老年医学杂志》编辑委员会. 老年人质子泵抑制剂合理应用专家共识[J]. 中华老年病研究电子杂志, 2015, 2(4): 1-7. DOI: 10.3760/cma.j.issn.0254-9026.2015.10.001.

13. 王新桃, 高萍, 向道春. 兰索拉唑药动学和药物相互作用的研究进展[J]. 医药导报, 2011, 30(7): 922-925. DOI: 10.3870/yydb.2011.07.030.

14. Ishida R, Yamada N, Sato K, et al. Effectiveness of a formulary system on prophylactic oral proton pump inhibitors for drug-induced peptic ulcer in a Japanese tertiary hospital: an interrupted time series analysis[J]. J Pharm Health Care Sci, 2025, 11(1): 51. DOI: 10.1186/s40780-025 -00459-w.

15. 袁洪. 湖南省质子泵抑制剂的临床应用指导原则（试行） [J]. 中南药学, 2016, 14(7): 673-683. DOI: 10.7539/j.issn.1672- 2981.2016.07.001.

16. Grice S, Hammond S, Hampson L, et al. Omeprazole-associated atypical drug reaction with eosinophilia and systemic symptoms (DRESS) in a patient with positive in vitro diagnostic testing to multiple proton pump inhibitors[J]. Chem Res Toxicol, 2024, 37(9): 1484-1487. DOI: 10.1021/acs.chemrestox.4c00225.

17. Bavbek S, Kepil Özdemir S, Bonadonna P, et al. Hypersensitivity reactions to proton pump inhibitors. An EAACI position paper[J]. Allergy, 2024, 79(3): 552-564. DOI: 10.1111/all.15961.

18. Pirson F, Geubel A, Marot L. Late hypersensitivity to omeprazole and other proton pump inhibitors[J]. Acta Clin Belg, 2012, 67(4): 301-303. DOI: 10.2143/ACB.67.4.2062678.

19. Deng Z, Guo A, Wu C, et al. Proton pump inhibitors-related subacute cutaneous lupus erythematosus: clinical characteristics, management, and outcome[J]. J Cosmet Dermatol, 2022, 21(12): 7202-7208. DOI: 10.1111/jocd.15450.

20. Lin CY, Wang CW, Hui CR, et al. Delayed-type hypersensitivity reactions induced by proton pump inhibitors: a clinical and in vitro T-cell reactivity study[J]. Allergy, 2018, 73(1): 221-229. DOI: 10.1111/all.13235.

21. Daldoul M, Charfi O, Bouattour E, et al. Pantoprazole-induced Stevens-Johnson syndrome: a case-report[J]. Curr Drug Saf, 2024, 19(1): 148-150. DOI: 10.2174/1574886318666230224092818.

22. Fracaroli TS, Miranda LQ, Sodré JL, et al. Toxic epidermal necrolysis induced by lansoprazole[J]. An Bras Dermatol, 2013, 88(1): 117-120. DOI: 10.1590/s0365-05962013000100018.

23. Chularojanamontri L, Jiamton S, Manapajon A, et al. Cutaneous reactions to proton pump inhibitors: a case-control study[J]. J Drugs Dermatol, 2012, 11(10): e43-e47. https://pubmed.ncbi.nlm.nih.gov/23134998/.

24. Kepil Özdemir S, Yılmaz I, Aydin Ö, et al. Immediate-type hypersensitivity reactions to proton pump inhibitors: usefulness of skin tests in the diagnosis and assessment of cross-reactivity[J]. Allergy, 2013, 68(8): 1008-1014. DOI: 10.1111/all.12189.

25. Evrard J, Farnier E, Carcel C, et al. Proton pump inhibitor and high-dose methotrexate: two cases reports[J]. Therapie, 2015, 70(6): 527-535. DOI: 10.2515/therapie/2015047.

26. Schumacher J, Muller P, Sulzer J, et al. Proton-pump inhibitors increase C. difficile infection risk by altering pH rather than by affecting the gut microbiome based on a bioreactor model[J]. Gut Microbes, 2025, 17(1): 2519697. DOI: 10.1080/19490976. 2025.2519697.

27. Xiao X, Zhang X, Wang J, et al. Proton pump inhibitors alter gut microbiota by promoting oral microbiota translocation: a prospective interventional study[J]. Gut, 2024, 73(7): 1098-1109. DOI: 10.1136/gutjnl-2023-330883.

28. Pissas G, Tziastoudi M, Poulianiti C, et al. In human CD4+ T-Cells, omeprazole suppresses proliferation, downregulates V-ATPase, and promotes differentiation toward an autoimmunity-favoring phenotype[J]. Int Immunopharmacol, 2025, 144: 113728. DOI: 10.1016/j.intimp.2024.113728.

29. Choden T, Zhang H, Sakuraba A. Influence of proton pump inhibitor use on clinical outcomes of patients with inflammatory bowel disease[J]. Ann Med, 2023, 55(1): 2198775. DOI: 10.1080/07853890.2023.2198775.

30. Piovani D, Tsantes AG, Schünemann HJ, et al. Meta-analysis: use of proton pump inhibitors and risk of gastric cancer in patients requiring gastric acid suppression[J]. Aliment Pharmacol Ther, 2023, 57(6): 653-665. DOI: 10.1111/apt.17360.

31. Gong EJ, Jung H, Lee B, et al. Proton pump inhibitor use and the risk of metachronous gastric cancer after H. pylori eradication in patients who underwent endoscopic resection for gastric neoplasms: a population-based cohort study[J]. Aliment Pharmacol Ther, 2023, 58(7): 668-677. DOI: 10.1111/apt.17676.

32. Seo SI, Park CH, You SC, et al. Association between proton pump inhibitor use and gastric cancer: a population-based cohort study using two different types of nationwide databases in Korea[J]. Gut, 2021, 70(11): 2066-2075. DOI: 10.1136/gutjnl-2020-323845.

JL, et al. Toxic epidermal necrolysis induced by lansoprazole[J]. An Bras Dermatol, 2013, 88(1): 117-120. DOI: 10.1590/s0365-05962013000100018.

23. Chularojanamontri L, Jiamton S, Manapajon A, et al. Cutaneous reactions to proton pump inhibitors: a case-control study[J]. J Drugs Dermatol, 2012, 11(10): e43-e47. https://pubmed.ncbi.nlm.nih.gov/23134998/.

24. Kepil Özdemir S, Yılmaz I, Aydin Ö, et al. Immediate-type hypersensitivity reactions to proton pump inhibitors: usefulness of skin tests in the diagnosis and assessment of cross-reactivity[J]. Allergy, 2013, 68(8): 1008-1014. DOI: 10.1111/all.12189.

25. Evrard J, Farnier E, Carcel C, et al. Proton pump inhibitor and high-dose methotrexate: two cases reports[J]. Therapie, 2015, 70(6): 527-535. DOI: 10.2515/therapie/2015047.

26. Schumacher J, Muller P, Sulzer J, et al. Proton-pump inhibitors increase C. difficile infection risk by altering pH rather than by affecting the gut microbiome based on a bioreactor model[J]. Gut Microbes, 2025, 17(1): 2519697. DOI: 10.1080/19490976. 2025.2519697.

27. Xiao X, Zhang X, Wang J, et al. Proton pump inhibitors alter gut microbiota by promoting oral microbiota translocation: a prospective interventional study[J]. Gut, 2024, 73(7): 1098-1109. DOI: 10.1136/gutjnl-2023-330883.

28. Pissas G, Tziastoudi M, Poulianiti C, et al. In human CD4+ T-Cells, omeprazole suppresses proliferation, downregulates V-ATPase, and promotes differentiation toward an autoimmunity-favoring phenotype[J]. Int Immunopharmacol, 2025, 144: 113728. DOI: 10.1016/j.intimp.2024.113728.

29. Choden T, Zhang H, Sakuraba A. Influence of proton pump inhibitor use on clinical outcomes of patients with inflammatory bowel disease[J]. Ann Med, 2023, 55(1): 2198775. DOI: 10.1080/07853890.2023.2198775.

30. Piovani D, Tsantes AG, Schünemann HJ, et al. Meta-analysis: use of proton pump inhibitors and risk of gastric cancer in patients requiring gastric acid suppression[J]. Aliment Pharmacol Ther, 2023, 57(6): 653-665. DOI: 10.1111/apt.17360.

31. Gong EJ, Jung H, Lee B, et al. Proton pump inhibitor use and the risk of metachronous gastric cancer after H. pylori eradication in patients who underwent endoscopic resection for gastric neoplasms: a population-based cohort study[J]. Aliment Pharmacol Ther, 2023, 58(7): 668-677. DOI: 10.1111/apt.17676.

32. Seo SI, Park CH, You SC, et al. Association between proton pump inhibitor use and gastric cancer: a population-based cohort study using two different types of nationwide databases in Korea[J]. Gut, 2021, 70(11): 2066-2075. DOI: 10.1136/gutjnl-2020-323845.

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