Inappropriate Use of Proton Pump Inhibitors (PPIs) in Elderly and Drug-Drug Interaction: A Narrative Review
DOI:
https://doi.org/10.36733/medicamento.v12i1.11519Keywords:
drug interaction, elderly, inappropriate, PPIAbstract
Background: PPIs are highly effective for treating gastrointestinal disorders, including dyspepsia, peptic ulcer disease, gastritis, and gastroesophageal reflux disease (GERD). Furthermore, for the prophylaxis of NSAIDs and to mitigate gastrointestinal bleeding in patients receiving glucocorticoids, antiplatelet agents, or anticoagulants, particularly in the elderly population. The prescribing of PPIs among elderly patients remains a widespread issue that can lead to inappropriate use, hospital admission, or discharge. Additionally, the inappropriate use of PPIs can lead to possible drug-drug interactions.
Objective: This narrative review aims to comprehensively assess inappropriateness associated with PPIs use in the elderly population and drug-drug interactions.
Methods: Studies published from 2014 to 2024 were identified through a comprehensive search of multiple databases, including PubMed, Google Scholar, and ScienceDirect.
Results: Long-term dangers such as infections and nutritional deficits are increased by inappropriate usage, which is defined by unwarranted commencement and lengthy duration. Simultaneously, PPIs present significant DDI hazards through modulating the absorption of pH-dependent medications and blocking cytochrome P450 enzymes, particularly CYP2C19. These risks are made worse by the prevalence of polypharmacy and aging-related deterioration of renal and hepatic function.
Conclusion: In clinical practice, these findings call for systematic drug reviews and organized deprescribing programs to detect and manage high-risk combos. Implementing PPI stewardship programs in hospital and community settings is highly advised at the policy and systems level to enhance pharmaceutical safety in this susceptible population and to encourage evidence-based, guideline-concordant prescription.
References
1. Dipasquale V, Cicala G, Spina E, Romano C. A Narrative Review on Efficacy and Safety of Proton Pump Inhibitors in Children. Front Pharmacol. Frontiers Media S.A. 2022;13. doi:10.3389/fphar.2022.839972
2. Zhang Y, Liu M, Zhu Z, Chen H. Proton pump inhibitors use is associated with a higher prevalence of kidney stones: NHANES 2007–2018. BMC Public Health. 2024;24(1). doi:10.1186/s12889-024-18710-8
3. Yadlapati R, DeLay K. Proton Pump Inhibitor–Refractory Gastroesophageal Reflux Disease. Medical Clinics of North America. W.B. Saunders. 2019;103(1):15-27. doi:10.1016/j.mcna.2018.08.002
4. Steinsdóttir HR, Sigurðsson MI, Björnsson ES, Jónsdóttir F. The incidence and prevalence of proton pump inhibitor usage among internal medicine patients after hospital admission: A retrospective cohort study. Eur J Clin Pharmacol. 2024;80(2):273-281. doi:10.1007/s00228-023-03607-z
5. Liu Y, Zhu X, Li R, Zhang J, Zhang F. Proton pump inhibitor utilisation and potentially inappropriate prescribing analysis: Insights from a single-centred retrospective study. BMJ Open. 2020;10(11). doi:10.1136/bmjopen-2020-040473
6. Condur LM, Chirila SI, Alexandrescu L, Iancu MA, Neculau AE, Berariu FV, Toma L, Nicoara AD. Proton Pump Inhibitor Use in Older Adult Patients with Multiple Chronic Conditions: Clinical Risks and Best Practices. J Clin Med. Multidisciplinary Digital Publishing Institute (MDPI). 2025;14(15). doi:10.3390/jcm14155318
7. Andrawes M, Andrawes W, Das A, Siau K. Proton Pump Inhibitors (PPIs)—An Evidence-Based Review of Indications, Efficacy, Harms, and Deprescribing. Medicina (Lithuania). Multidisciplinary Digital Publishing Institute (MDPI). 2025;61(9). doi:10.3390/medicina61091569
8. Ben-Eltriki M, Chhabra M, Cassels A, Wright JM. Inappropriate Use of Proton Pump Inhibitor Among Elderly Patiens in British Columbia: What are the Long-term Adverse Events? J Neurogastroenterol Motil. 2024;19:244-247. doi:10.5056/jnm18001
9. Mohamed MR, Itani M, Abohelwa M, Ahmed MA, Abdouni L, Doumat G, Azzo M, Dabdoub F, Al-Tfaili H, Elziny M, Assaf G. The silent epidemic: Inappropriate use of proton pump inhibitors among hospitalized patients. Arab Journal of Gastroenterology. 2024;2024(December 2023). doi:10.1016/j.ajg.2024.07.001
10. Ben-Eltriki M, Chhabra M, Cassels A, Wright JM. Inappropriate Use of Proton Pump Inhibitor Among Elderly Patients in British Columbia: What are the Long-term Adverse Events? Curr Drug Saf. 2024;19(2):244-247. doi:10.2174/1574886318666230726124540
11. Raoul JL, Edeline J, Simmet V, Moreau-Bachelard C, Gilabert M, Frénel JS. Long-Term Use of Proton Pump Inhibitors in Cancer Patients: An Opinion Paper. Cancers (Basel). MDPI. 2022;14(5). doi:10.3390/cancers14051156
12. Raoul JL, Moreau-Bachelard C, Gilabert M, Edeline J, Frénel JS. Drug–drug interactions with proton pump inhibitors in cancer patients: an underrecognized cause of treatment failure. ESMO Open. Elsevier B.V. 2023;8(1). doi:10.1016/j.esmoop.2023.100880
13. Veettil SK, Sadoyu S, Bald EM, Chandran VP, Khuu SAT, Pitak P, Lee YY, Nair AB, Antony PT, Ford AC, Chaiyakunapruk N. Association of proton-pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta-analyses of cohort studies and randomised controlled trials. Br J Clin Pharmacol. 2022;88(4):1551-1566. doi:10.1111/bcp.15103
14. Cena C, Traina S, Parola B, Bo M, Fagiano R, Siviero C. Prescription of proton pump inhibitors in older adults with complex polytherapy. European Journal of Hospital Pharmacy. 2020;27(6):341-345. doi:10.1136/ejhpharm-2018-001697
15. Edinoff AN, Wu NW, Parker K, Dudossat E, Linquest L, Flanagan CJ, Dharani A, Patel H, Willett O, Cornett EM, Kaye AM, Kaye AD. Proton Pump Inhibitors, Kidney Damage, and Mortality: An Updated Narrative Review. Adv Ther. Adis. 2023;40(6):2693-2709. doi:10.1007/s12325-023-02476-3
16. Franchi C, Mannucci PM, Nobili A, Ardoino I. Use and prescription appropriateness of drugs for peptic ulcer and gastrooesophageal reflux disease in hospitalized older people. Published online 2020:459-465.
17. Schepisi R, Fusco S, Sganga F, Falcone B, Vetrano DL, Abbatecola A, Corica F, Maggio M, Ruggiero C, Fabbietti P, Corsonello A, Onder G, Lattanzio F. Inappropriate Use of Proton Pump Inhibitors in Elderly Patients Discharged from Acute Care Hospitals. 2015;(18).
18. Ladjouzi N, Romdhani A, Zouloumis G, Schlatter J. Inappropriate proton pump inhibitor lansoprazole prescription in older adults hospitalized in long term care unit. Irish Journal of Medical Science (1971 -). Published online 2023:1661-1664. doi:10.1007/s11845-022-03207-3
19. Bužančić I, Držaić M, Kummer I, Ortner Hadžiabdić M, Brkić J, Fialová D. Deprescribing potential of commonly used medications among community-dwelling older adults: insights from a pharmacist’s geriatric assessment. Sci Rep. 2024;14(1):1-10. doi:10.1038/s41598-024-56780-1
20. Rababa M, Rababa’h A. Community-dwelling older adults’ awareness of the inappropriate use of proton pump inhibitors. BMC Geriatr. 2020;20(1):431. doi:10.1186/s12877-020-01844-w
21. Lee C, Lo A, Ubhi K, Milewski M. Outcome after Discontinuation of Proton Pump Inhibitors at a Residential Care Site : Quality Improvement Project. 2017;70(3):215-223.
22. Wang Y, Spence L, Tung A, Bubbar CD, Thompson W, Tejani AM. Prescribing Portraits to Optimize Prescribing of Proton Pump Inhibitors in Long-Term Care: PPI-T STOP Study. Canadian Journal of Hospital Pharmacy. 2024;77(1):1-10. doi:10.4212/cjhp.3461
23. Aubert CE, Blum MR, Gastens V, Dalleur O, Vaillant F, Jennings E, Aujesky D, Thompson W, Kool T, Kramers C, Knol W, O’Mahony D, Rodondi N. Prescribing, deprescribing and potential adverse effects of proton pump inhibitors in older patients with multimorbidity: an observational study. CMAJ Open. 2023;11(1):E170-E178. doi:10.9778/cmajo.20210240
24. Mehta N, Martinez Guasch F, Kamen C, Shah S, Burry LD, Soong C, Mehta S. Proton Pump Inhibitors in the Elderly Hospitalized Patient: Evaluating Appropriate Use and Deprescribing. Journal of Pharmacy Technology. 2020;36(2):54-60. doi:10.1177/8755122519894953
25. Wang ZY, Chen M, Zhu LL, Yu LS, Zeng S, Xiang MX, Zhou Q. Pharmacokinetic drug interactions with clopidogrel: Updated review and risk management in combination therapy. Ther Clin Risk Manag. Dove Medical Press Ltd. 2015;11:449-467. doi:10.2147/TCRM.S80437
26. Stemkens R, de Jager V, Dawson R, Diacon AH, Narunsky K, Padayachee SD, Boeree MJ, van Beek SW, Colbers A, Coenen MJH, Svensson EM, Fuhr U, Phillips PPJ, te Brake LHM, Aarnoutse RE. Drug interaction potential of high-dose rifampicin in patients with pulmonary tuberculosis. Antimicrob Agents Chemother. 2023;67(10). doi:10.1128/aac.00683-23
27. Czyrski A, Resztak M, Świderski P, Brylak J, Główka FK. The overview on the pharmacokinetic and pharmacodynamic interactions of triazoles. Pharmaceutics. MDPI. 2021;13(11). doi:10.3390/pharmaceutics13111961
28. Tan CM, Juurlink DN. Navigating Drug Interactions with Proton Pump Inhibitors. JAMA Netw Open. American Medical Association. Preprint posted online 2024:e2419818. doi:10.1001/jamanetworkopen.2024.19818
29. Rodriguez-Vera L, Yin X, Almoslem M, Romahn K, Cicali B, Lukacova V, Cristofoletti R, Schmidt S. Comprehensive Physiologically Based Pharmacokinetic Model to Assess Drug–Drug Interactions of Phenytoin. Pharmaceutics. 2023;15(10). doi:10.3390/pharmaceutics15102486
30. Ngcobo NN. Influence of Ageing on the Pharmacodynamics and Pharmacokinetics of Chronically Administered Medicines in Geriatric Patients: A Review. Clin Pharmacokinet. Adis. 2025;64(3):335-367. doi:10.1007/s40262-024-01466-0
31. Lima JJ, Thomas CD, Barbarino J, Desta Z, Driest SL Van, Rouby N El, Johnson JA, Cavallari LH, Shakhnovich V, Thacker DL, Scott SA, Schwab M, Uppugunduri CRS, Formea CM. Clinical Pharmacogenetics Implementation Consortium ( CPIC ) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. 2020;0(0):1-7. doi:10.1002/cpt.2015
32. El Rouby N, Lima JJ, Johnson JA. Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine. Expert Opin Drug Metab Toxicol. 2018;14(4):447-460. doi:10.1080/17425255.2018.1461835
33. Botton MR, Lu X, Zhao G, Repnikova E, Seki Y, Gaedigk A, Schadt EE, Edelmann L, Scott SA. Structural variation at the CYP2C locus: Characterization of deletion and duplication alleles. Hum Mutat. 2019;40(11):e37-e51. doi:10.1002/humu.23855
34. Łój P, Olender A, Ślęzak W, Krzych ŁJ. Pharmacokinetic drug-drug interactions in the intensive care unit-single-centre experience and literature review. Anaesthesiol Intensive Ther. 2017;49:259-267. doi:10.5603/aAIT.2017.0053
35. Marano M, Nicoletti F, Pro S, Goffredo BM, Cecchetti C, Piervincenzi E, Agolini E, Cocciadiferro D. Phenytoin intoxication associated with omeprazole administration in a child with defective CYP2C9. Eur J Clin Pharmacol. Springer. 2020;76(5):731-732. doi:10.1007/s00228-019-02821-y
36. Cena C, Traina S, Parola B, Bo M, Fagiano R, Siviero C. Prescription of proton pump inhibitors in older adults with complex polytherapy. European Journal of Hospital Pharmacy. 2020;27(6):341-345. doi:10.1136/ejhpharm-2018-001697
37. Gilard M, Arnaud B, Cornily JC, Le Gal G, Lacut K, Le Calvez G, Mansourati J, Mottier D, Abgrall JF, Boschat J. Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin. The Randomized, Double-Blind OCLA (Omeprazole CLopidogrel Aspirin) Study. J Am Coll Cardiol. 2008;51(3):256-260. doi:10.1016/j.jacc.2007.06.064
38. Tao D, Wang H, Xia F, Ma W. Pancytopenia Due to Possible Drug–Drug Interactions Between Low-Dose Methotrexate and Proton Pump Inhibitors. Drug Healthc Patient Saf. 2022;14:75-78. doi:10.2147/DHPS.S350194
39. Troger U, Stotzel B, Martens-Lobenhoffer J, Gollnick H, Meyer FP. Severe myalgia from an interaction between treatments with pantoprazole and methotrexate. BMJ. 2002;324.
40. Raoul JL, Moreau-Bachelard C, Gilabert M, Edeline J, Frénel JS. Drug–drug interactions with proton pump inhibitors in cancer patients: an underrecognized cause of treatment failure. ESMO Open. Elsevier B.V. 2023;8(1). doi:10.1016/j.esmoop.2023.100880
41. Sharma M, Holmes HM, Mehta HB, Chen H, Aparasu RR, Shih YCT, Giordano SH, Johnson ML. The concomitant use of tyrosine kinase inhibitors and proton pump inhibitors: Prevalence, predictors, and impact on survival and discontinuation of therapy in older adults with cancer. Cancer. 2019;125(7):1155-1162. doi:10.1002/cncr.31917
42. Budha NR, Frymoyer A, Smelick GS, Jin JY, Yago MR, Dresser MJ, Holden SN, Benet LZ, Ware JA. Drug absorption interactions between oral targeted anticancer agents and PPIs: Is pH-dependent solubility the achilles heel of targeted therapy. Clin Pharmacol Ther. 2012;92(2):203-213. doi:10.1038/clpt.2012.73
43. Silva DA, Duque MD, Davies NM, Löbenberg R, Gomes Ferraz H. Application of in Silico Tools in Clinical Practice Using Ketoconazole as a Model Drug. Vol 21. 2018. www.cspsCanada.org
44. Bottiger Y, Tybring G, Gotharson E, Bertilsson L. Inhibition of the Sulfoxidation of Omeprazole by Ketoconazole in Poor and Extensive Metabolizers of S-Mephenytoin. 1997.
45. Blume H, Donath F, Warnke A, Schug BS. Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors. Vol 29. 2006.
46. Brett S. Science review: The use of proton pump inhibitors for gastric acid suppression in critical illness. Crit Care. 2005;9(1):45-50. doi:10.1186/cc2980
47. Syafhan NF, Augustine M, Ramadhani U, Hersunaryati Y. Proton-pump inhibitor use and potential drug interactions in outpatients. International Journal of Applied Pharmaceutics. 2018;10(Special Issue 1):358-363. doi:10.22159/ijap.2018.v10s1.79
Downloads
Submitted
Accepted
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Thendi Abdul Arief, Nabila Risti Rachmadi, Hanum Hasifah Fahriah, Agung Endro Nugroho

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.











