Analysis of the Side Effects of Long-Term Proton Pump Inhibitor (PPI) Use in Patients with Gastroesophageal Reflux Disease (GERD)
DOI:
https://doi.org/10.22487/htj.v11i2.1628Keywords:
Adverse effects, Long-term, Proton Pump Inhibitor (PPI), Gastroesophageal Reflux Disease (GERD)Abstract
Background: Proton Pump Inhibitors (PPIs) are widely prescribed to manage gastrointestinal disorders, especially gastroesophageal reflux disease (GERD). However, long-term PPI use has been linked to serious side effects and potential complications. Objective: This study aims to analyze the side effects associated with prolonged PPI use in patients with GERD. Methods: A systematic review was conducted using Google Scholar and PubMed databases with relevant keywords. Article selection was carried out carefully based on inclusion and exclusion criteria to ensure the quality and relevance of the data. Additionally, a bibliometric analysis was performed to explore research trends related to the long-term use of PPIs. Results: The review found that prolonged PPI use is associated with various adverse effects, including an increased risk of dementia, progression of chronic kidney disease (CKD), gastric cancer, bone fractures, Frailty Syndrome, hypomagnesemia, iron deficiency, vitamin B12 deficiency, myocardial infarction, and esophageal cancer. The bibliometric analysis also indicated a growing trend of research focusing on the safety and complications of long-term PPI use. Conclusion: Long-term PPI therapy carries significant risks. Therefore, regular monitoring and appropriate discontinuation strategies are essential when using PPIs over extended periods to minimize potential harm.
References
Clarrett DM, Hachem C. Gastroesophageal Reflux Disease (GERD). Sci Med Featur Ser. 2018;115(3):214-218.
Suherman LP, Ramdani R, Septiani V, Indrayani W, Islamiyah AN, Hasyim PK. Pola Penggunaan Obat Pada Pasien Gastroesophageal Reflux Disease (GERD) di Salah Satu Rumah Sakit di Bandung. Pharmacoscript. 2021;4(2):208-219.
Sandhu DS, Fass R. Current trends in the management of gastroesophageal reflux disease. Gut Liver. 2018;12(1):7-16. doi:10.5009/gnl16615
Syam AF, Sobur CS, Hapsari FP, Abdullah M, Makmun D. Prevalence and Risk Factors of GERD in Indonesian Population—An Internet-Based Study. Am Sci Publ. 2017;23(7):6734-6738(5). https://www.ingentaconnect.com/contentone/asp/asl/2017/00000023/00000007/art00173
Nurhamidah S, Sopiah P, Astuti APK. Pengaruh Merokok Elektrik Terhadap Penyakit Lambung (GERD dan Gastritis): Literature Review. Healthy Tadulako Journal (Jurnal Kesehatan Tadulako). 2024;10(3):483-492.
Dean E, B A, MRCP, Medicine SL in, Gastroenterologist HC. Drug Therapy for Gastrointestinal and Liver Diseases.; 2001. doi:10.4324/9780203213858
Abrahami D, McDonald EG, Schnitzer ME, Barkun AN, Suissa S, Azoulay L. Proton pump inhibitors and risk of gastric cancer: Population-based cohort study. Gut. 2022;71(1):16-24. doi:10.1136/gutjnl-2021-325097
Tai SY, Chien CY, Wu DC, et al. Risk of dementia from proton pump inhibitor use in Asian population: A nationwide cohort study in Taiwan. PLoS One. 2017;12(2):1-14. doi:10.1371/journal.pone.0171006
Xie Y, Bowe B, Li T, Xin H, Balasubramanian S, Al-Aly Z. Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD. J Am Soc Nephrol. 2016;27(10):3153–3163.
Peng YC, Huang LR, Lin CL, et al. Association between proton pump inhibitors use and risk of gastric cancer in patients with GERD. Gut. 2019;68(2):374-376. doi:10.1136/gutjnl-2018-316057
Jo Y, Park E, Ahn SB, et al. A proton pump inhibitor’s effect on bone metabolism mediated by osteoclast action in old age: A prospective randomized study. Gut Liver. 2015;9(5):607-614. doi:10.5009/gnl14135
Dewi S, Laksmi PW, Syam AF, Dewiasty E, Seto E. Pengaruh Penggunaan Proton Pump Inhibitor Jangka Panjang terhadap Sindrom Frailty pada Pasien Usia Lanjut. J Penyakit Dalam Indones. 2016;3(3):143. doi:10.7454/jpdi.v3i3.115
Shah DU, Sachdeva P. Association of Proton Pump Inhibitor with Hypomagnesaemia: A Cross-Sectional Study at a Tertiary Care Hospital of Anand District. Indian J Pharm Pract. 2014;7(2):10-15. doi:10.5530/ijopp.7.2.3
Lam JR, Schneider JL, Quesenberry CP, Corley DA. Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency. Gastroenterology. 2017;152(4):821-829. doi:10.1053/j.gastro.2016.11.023
Mumtaz H, Ghafoor B, Saghir H, et al. Association of Vitamin B12 deficiency with long-term PPIs use: A cohort study. Ann Med Surg. 2022;82(104762):1-4. doi:10.1016/j.amsu.2022.104762
Shah NH, LePendu P, Bauer-Mehren A, et al. Proton pump inhibitor usage and the risk of myocardial infarction in the general population. PLoS One. 2015;10(6):1-16. doi:10.1371/journal.pone.0124653
Brusselaers N, Engstrand L, Lagergren J. Maintenance proton pump inhibition therapy and risk of oesophageal cancer. Cancer Epidemiol. 2018;53:172-177. https://www.sciencedirect.com/science/article/abs/pii/S1877782118300687?via%3Dihub
Afriliana M, Yuniarti E. Analisis Bibliometrik Respon Imun Pada Penyakit Leukemia Melalui Aplikasi Vosviewer. J Pendidik Tambusai. 2024;8(02):17248-177256.
Sudarjat H. Computing Bibliometric Analysis with Mapping Visualization using VOSviewer on “Pharmacy” and “Special Needs” Research Data in 2017-2021. ASEAN J Community Spec Needs Educ. 2023;2(1):1-8. doi:p- ISSN 2828-3236
Sakti PT, Mustika S. Analisis Faktor Risiko Gastro-Esophageal Reflux Disease di Era Pandemi COVID-19 pada Mahasiswa Program Pendidikan Dokter Spesialis Fakultas Kedokteran Universitas Brawijaya. J Penyakit Dalam Indones. 2022;9(3):164. doi:10.7454/jpdi.v9i3.793
Saputera MD, Budianto W. Diagnosis dan Tatalaksana Gastroesophageal Reflux Disease (GERD) di Pusat Pelayanan Kesehatan Primer. J Contin Med Educ. 2017;44(5):329-332.
Ahmed A, Clarke JO. Proton Pump Inhibitors (PPI).; 2023. https://www.ncbi.nlm.nih.gov/books/NBK557385/#:~:text=Mechanism of Action. Ultimately, PPIs function to decrease
Syari DM, Sari H. Evaluasi Penggunaan Obat Proton-Pump Inhibitor (ppi) pada Pasien Rawat Jalan di Rumah Sakit Imelda Medan. JIFI (Jurnal Ilm Farm Imelda). 2021;5(1):1-4.
Agustin TN, Junianti R, Hafitah PI, Azzahra K, Noerwanti S, Nurhikmah A. Pengaruh Penggunaan Jangka Panjang Proton Pump Inhibitor (PPI) Terhadap Imunitas Saluran Gastrointestinal. Medimuh J Kesehat Muhammadiyah. 2023;4(2):101-112. doi:10.37874/mh.v4i2.647
Yosela KAI, Elyani H, Airlangga HH. Systematic Literature Riview: Pengaruh Penggunaan Proton Pump Inhibitor ( PPI ) Jangka Panjang terhadap Imunitas Traktus Gastrointestinal. J Kedokt Komunitas. 2021;9(1):1-10.
Gomm W, Holt K von, Thomé F, et al. Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis. JAMA Neurol. 2016;73(4):410-416. https://jamanetwork.com/journals/jamaneurology/fullarticle/2487379
Goldstein FC, Steenland K, Zhao L, Wharton W, Levey AI, Hajjar I. Proton Pump Inhibitors and Risk for Mild Cognitive Imparment and Dementia. J Am Geriatr Soc. 2017;65(9):1969-1974. doi:10.1111/jgs.14956.Proton
Mehta R, Kochar B, Zhou Z, et al. Association of proton pump inhibitor use with incident dementia and cognitive decline in older adults: a prospective cohort study. Gastroenterology. 2023;165(3):564-572.
Lazarus B, Chen Y, Wilson FP, et al. Proton Pump Inhibitor Use and Risk of Chronic Kidney Disease. JAMA Intern Med. 2016;176(2):238-246. doi:10.1001/jamainternmed.2015.7193.Proton
Xie Y, Bowe B, Li T, Xian H, Yan Y, Al-Aly Z. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int. 2017;91(6):1482-1494. doi:10.1016/j.kint.2016.12.021
Syamsi N, Tanra AAM, HS MR. Hubungan Antara Merokok dengan Gambaran Fungsi Ginjal pada Karyawan PT. X. Healthy Tadulako Journal (Jurnal Kesehatan Tadulako). 2021;7(3):147-152. doi:10.22487/htj.v7i3.181
Brusselaers N, Lagergren J, Engstrand L. Duration of use of proton pump inhibitors and the risk of gastric and oesophageal cancer. Cancer Epidemiol. 2018;53:172-177. https://pubmed.ncbi.nlm.nih.gov/31445426/
Atepela JH. Farmakoterapi GERD pada Lansia. Contin Pharm Educ. 2023;50(7):379-381.
Biyik M, Solak Y, Ucar R, et al. Hypomagnesemia Among Outpatient Long-Term Proton Pump Inhibitor Users. Am J Ther. 2017;24(1):e52-e55.
Arj A, Takizadeh ZG, Gilassi H, Razavizadeh M. Relationship between long-term use of proton pump inhibitor (PPI) and hypomagnesemia in patients with gastroesophageal reflux disease. Casp J Intern Med. 2022;13(1):107-112. doi:10.22088/cjim.13.1.107
Qorraj-Bytyqi H, Hoxha R, Sadiku S, et al. Proton pump inhibitors intake and iron and vitamin B12 status: A prospective comparative study with a follow up of 12 months. Open Access Maced J Med Sci. 2018;6(3):442-446. doi:10.3889/oamjms.2018.142
Lerman TT, Cohen E, Sochat T, Goldberg E, Goldberg I, Krause I. Proton pump inhibitor use and its effect on vitamin B12 and homocysteine levels among men and women: A large cross-sectional study. Clin Investig (Lond). 2022;364(6):746-751. https://www.amjmedsci.com/article/S0002-9629(22)00313-5/abstract
Semme MY, Salam MRR, Budiamin FA. The Role of Folate, Vitamin B12 and B6 in Hyperhomocysteinemia as the Risk Factor of Cardiovascular Disease: Narrative Review. Healthy Tadulako Journal (Jurnal Kesehatan Tadulako). 2024;10(3):387-398.
Choi HG, Lee HK, Kang HS, et al. Possible Association between the Use of Proton Pump Inhibitors and H2 Receptor Antagonists, and Esophageal Cancer: A Nested Case–Control Study Using a Korean National Health Screening Cohort. Pharmaceuticals. 2022;15(517):1-19. doi:10.3390/ph15050517
Hojo M, Asaoka D, Shimada Y, Nojiri S, Nagahara A. Strategies for discontinuation of proton pump inhibitors (PPIs) in patients with long-term PPI administration: a randomized controlled trial. BMC Gastroenterol. 2022;22(21):1-6. doi:10.1186/s12876-021-02086-9
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Healthy Tadulako Journal (Jurnal Kesehatan Tadulako)
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
