Side Effects of Proton Pump Inhibitors: What are Patients’ Concerns?

Published:February 21, 2020DOI:



      Proton pump inhibitors (PPIs) are the fourth most widely sold drugs in the United States. Mounting evidence suggests PPIs may not be as safe as originally thought. We hypothesize that increased awareness of PPI side effects and patient education may influence patient interest in PPI use and compliance. We aimed to investigate patient concerns and education regarding PPI use and side effects.

      Study design

      Prospective questionnaire.


      Tertiary care center.

      Subjects and methods

      Consecutive patients with a diagnosis of gastroesophageal or laryngopharyngeal reflux currently on PPI, or having discontinued PPIs within 6 months, completed a questionnaire regarding level of concern regarding PPI side effects and level of education.


      Fifty consecutive patients completed the questionnaire. The mean age was 64 (±12.2) years and 47.8% was male. The majority of surveyed patients (52.2%) were concerned about the side effects of PPIs. Among these patients, the most common concerns were increased bone fracture (23.9%) and cardiovascular risk (21.7%). The most common source of PPI side-effect information was healthcare professionals (45.7%). Age, specific type of concern, side-effect experience, and reflux symptom index scores, but not level of education, proved to be statistically significant predictor variables for patients’ overall concern with taking PPI, based on logistic regression.


      There was a high prevalence of concern regarding PPI side effects in patients with reflux. The most common concern was bone fracture. Level of education was not associated with greater concern for PPI side effects.

      Key Words

      To read this article in full you will need to make a payment
      Subscribe to Journal of Voice
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Katz MH
        Failing the acid test: benefits of proton pump inhibitors may not justify the risks for many users.
        Arch Intern Med. 2010; 170: 747-748
      1. Gatyas G. IMS Health reports U.S. prescription sales grew 5.1 percent in 2009, to $300.3 Billion. IMS Health. Available at: Accessed 7 October 2010.

      2. GoodRx website. Available at: Accessed October 13, 2017.

        • 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; 10e0124653
        • Gomm W
        • von Holt K
        • Thomé F
        • et al.
        Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis.
        JAMA Neurol. 2016; 73: 410-416
        • Lazarus B
        • Chen Y
        • Wilson FP
        • et al.
        Proton pump inhibitor use and the risk of chronic kidney disease.
        JAMA Intern Med. 2016; 176: 238-246
        • Yu EW
        • Bauer SR
        • Bain PA
        • et al.
        Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies.
        Am J Med. 2011; 124: 519-526
        • Leonard J
        • Marshall JK
        • Moayyedi P
        Systematic review of the risk of enteric infection in patients taking acid suppression.
        Am J Gastroenterol. 2007; 102: 2047-2056
        • Lambert AA
        • Lam JO
        • Paik JJ
        • Ugarte-Gil C
        • Drummond MB
        • Crowell TA
        Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis.
        PLoS One. 2015; 10: e0128004
        • Trikudanathan G
        • Israel J
        • Cappa J
        • et al.
        Association between proton pump inhibitors and spontaneous bacterial peritonitis in cirrhotic patients - a systematic review and meta-analysis.
        Int J Clin Pract. 2011; 65: 674-678
        • Lam JR
        • Schneider JL
        • Zhao W
        • et al.
        Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B-12 deficiency.
        JAMA. 2013; 310: 2435-2442
        • Danziger J
        • William JH
        • Scott DJ
        • et al.
        Proton-pump inhibitor use is associated with low serum magnesium concentrations.
        Kidney Int. 2013; 83: 692-699
        • Xie Y
        • Bowe B
        • Li T
        • Xian H
        • Yan Y
        • Al-Aly Z
        Risk of death among users of proton pump inhibitors: a longitudinal observational cohort study of United States veterans.
        BMJ Open. 2017; 7: e015735
        • Chan JL
        • El-Serag HB
        Is proton pump inhibitor use associated with risk of myocardial infarction?.
        Gastroenterology. 2016; 150: 526-527
        • Belafsky PC
        • Postma GN
        • Koufman JA
        Validity and reliability of the reflux symptom index (RSI).
        J Voice. 2002; 16: 274-277
        • Antoniou T
        • Macdonald EM
        • Hollands S
        • et al.
        Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study.
        CMAJ Open. 2015; 3: E166-E171
        • Perazella MA
        • Markowitz GS
        Drug-induced acute interstitial nephritis.
        Nat Rev Nephrol. 2010; 6: 461-470
        • Sierra F
        • Suarez M
        • Rey M
        • et al.
        Systematic review: proton pump inhibitor-associated acute interstitial nephritis.
        Aliment Pharmacol Ther. 2007; 26: 545-553
        • Blank ML
        • Parkin L
        • Paul C
        • et al.
        A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use.
        Kidney Int. 2014; 86: 837-844
        • Martin FC
        • Chenevix-Trench G
        • Yeomans ND
        Systematic review with meta-analysis: fundic gland polyps and proton pump inhibitors.
        Aliment Pharmacol Ther. 2016; 44: 915-925
        • Khalili H
        • Huang ES
        • Jacobson BC
        • et al.
        Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study.
        BMJ. 2012; 344: e372
        • Kieboom BC
        • Kiefte-de Jong JC
        • Eijgelsheim M
        • et al.
        Proton pump inhibitors and hypomagnesemia in the general population: a population-based cohort study.
        Am J Kidney Dis. 2015; 66: 775-782
        • Chen Y
        • Liu B
        • Glass K
        • et al.
        Use of proton pump inhibitors and the risk of hospitalization for infectious gastroenteritis.
        PLoS One. 2016; 11e0168618
        • Freedberg DE
        • Salmasian H
        • Friedman C
        • et al.
        Proton pump inhibitors and risk for recurrent Clostridium difficile infection among in patients.
        Am J Gastroenterol. 2013; 108: 1794-1801
        • Gilard M
        • Arnaud B
        • Cornily JC
        • et al.
        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: 256-260
        • O'Donoghue ML
        • Braunwald E
        • Antman EM
        • et al.
        Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials.
        Lancet. 2009; 374: 989-997
        • Bhatt DL
        • Cryer BL
        • Contant CF
        • et al.
        Clopidogrel with or without omeprazole in coronary artery disease.
        N Engl J Med. 2010; 363: 1909-1917
        • Choi YJ
        • Kim N
        • Jang IJ
        • et al.
        Pantoprazole does not reduce the antiplatelet effect of clopidogrel: a randomized controlled trial in Korea.
        Gut Liver. 2017; 11: 504-511
        • Johnstone J
        • Nerenberg K
        • Loeb M
        Meta-analysis: proton pump inhibitor use and the risk of community-acquired pneumonia.
        Aliment Pharmacol Ther. 2010; 31: 1165-1177
        • Giuliano C
        • Wilhelm SM
        • Kale-Pradhan PB
        Are proton pump inhibitors associated with the development of community-acquired pneumonia? A meta-analysis.
        Expert Rev Clin Pharmacol. 2012; 5: 337-344
        • Freedberg DE
        • Toussaint NC
        • Chen SP
        • et al.
        Proton pump inhibitors alter specific taxa in the human gastrointestinal microbiome: a cross-over trial.
        Gastroenterology. 2015; 149: 883-885
        • Othman F
        • Crooks CJ
        • Card TR
        Community acquired pneumonia incidence before and after proton pump inhibitor prescription: population based study.
        BMJ. 2016; 355: i5813
        • Kia L
        • Kahrilas PJ
        Therapy: risks associated with chronic PPI use - signal or noise?.
        Nat Rev Gastroenterol Hepatol. 2016; 13: 253-254
        • Yadlapati R
        • Kahrilas PJ
        When is proton pump inhibitor use appropriate?.
        BMC Med. 2017; 15: 36
        • Mössner J
        The indications, applications, and risks of proton pump inhibitors.
        Dtsch Arztebl Int. 2016; 113: 477-483
        • Lin HF
        • Liao KF
        • Chang CM
        • et al.
        Correlation between proton pump inhibitors and risk of pyogenic liver abscess.
        Eur J Clin Pharmacol. 2017; 73: 1019-1025
        • Cheng KC
        • Liao KF
        • Lin CL
        • et al.
        Correlation of proton pump inhibitors with pulmonary tuberculosis: a case-control study in Taiwan.
        Front Pharmacol. 2017; 8: 481
        • Shah R
        • Richardson P
        • Yu H
        • et al.
        Gastric acid suppression is associated with an increased risk of adverse outcomes in inflammatory bowel disease.
        Digestion. 2017; 95: 188-193
        • Inadomi JM
        • McIntyre L
        • Bernard L
        • et al.
        Step-down from multiple-to single-dose proton pump inhibitors (PPIs): a prospective study of patients with heartburn or acid regurgitation completely relieved with PPIs.
        Am J Gastroenterol. 2003; 98: 1940-1944
        • Dean BB
        • Gano Jr., AD
        • Knight K
        • et al.
        Effectiveness of proton pump inhibitors in non erosive reflux disease.
        Clin Gastroenterol Hepatol. 2004; 2: 656-664
        • Vaezi MF
        • Richter JE
        • Stasney CR
        • et al.
        Treatment of chronic posterior laryngitis with esomeprazole.
        Laryngoscope. 2006; 116: 254-260
        • Kahrilas PJ
        • Howden CW
        • Hughes N
        • et al.
        Response of chronic cough to acid-suppressive therapy in patients with gastroesophageal reflux disease.
        Chest. 2013; 143: 605-612
        • Gibson P
        • Wang G
        • McGarvey L
        • et al.
        • CHEST Expert Cough Panel
        Treatment of unexplained chronic cough: CHEST Guideline and Expert Panel Report.
        Chest. 2016; 149: 27-44
        • Reynolds JL
        • Zehetner J
        • Bildzukewicz N
        • et al.
        Magnetic sphincter augmentation with the LINX device for gastroesophageal reflux disease after U.S. Food and Drug Administration approval.
        Am Surg. 2014; 80: 1034-1038
        • Bell RC
        • Barnes WE
        • Carter BJ
        • et al.
        Transoral incisionless fundoplication: 2-year results from the prospective multicenter U.S. study.
        Am Surg. 2014; 80: 1093-1105