In-hospital gastric protection with proton pump inhibitors: adverse effects beyond (over)utilization?

Italian Journal of Medicine ◽

10.4081/itjm.2010.51 ◽

2013 ◽

pp. 51-56

Author(s):

Paolo Montanari

Keyword(s):

Adverse Effects ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Competitive Inhibition ◽

Treatment Strategies ◽

Vitamin B12 Deficiency ◽

Antiinflammatory Drugs ◽

Ulcer Disease ◽

Increased Risk ◽

Enteric Infections

Background: Proton pump inhibitors (PPIs) have provided important benefits in the management of gastroesophageal reflux disease (GERD), peptic ulcer disease and in the prevention of non steroidal antiinflammatory drugs and aspirin-related ulcer complications. PPIs are also the most commonly used medications for stress ulcer prophylaxis, despite little evidence to support their use in non-intensive care unit. Discussion: Considering the widespread use of PPIs, these agents’ overall safety profile is unquestionable. However, there is growing evidence that PPIs use may be associated with an increased risk of enteric infections, pneumonia, hip fractures, vitamin B12 deficiency. Overall, until now, none of these adverse effects have discouraged the PPIs treatment. Recently attention has been placed on a more important potential adverse effect of PPIs, their interaction with clopidogrel to which they are associated for the prophylaxis of gastrointestinal bleeding. Preliminary results of laboratory tests suggest that omeprazole reduces clopidogrel’s antiplatelet effect. The interaction seems to involve the competitive inhibition of the CYP2C19 isoenzyme. The effect appears to be clinically important, as some retrospective studies have shown an increase in adverse cardiovascular outcomes when PPIs and clopidogrel are used concomitantly. Some studies indicate that pantoprazole and esomeprazole are not associated with impaired response to clopidogrel. However, the available data for PPIs other than omeprazole do not allow definitive conclusions to be drawn about whether is a class effect. Conclusions: Specifically designed and randomized clinical studies are needed to define the interaction between PPIs and clopidogrel. Moreover, alternative treatment strategies with histamine- 2 receptor antagonists that are not dependent on cytochrome p450 2C19 should be tested in future studies.

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Long Term Use of Proton Pump Inhibitors: Where to Draw the Line

Integrative Gastroenterology and Hepatology ◽

10.18314/igh.v1i1.1185 ◽

2018 ◽

Vol 1 (1) ◽

pp. 20-35

Author(s):

M. Manzurul Haque

Keyword(s):

Adverse Effects ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Community Acquired Pneumonia ◽

Ulcer Disease ◽

Increased Risk ◽

Prospective Trials ◽

Evidence Based Therapy ◽

Clostridium Difficile Associated Diarrhea

Proton pump inhibitors are the leading evidence-based therapy for acid related upper gastrointestinal disorders including dyspepsia, GERD and peptic ulcer disease. These are among the most frequently prescribed drugs globally. However, PPIs have been subjected to studies and have been associated with increased risk of adverse effects like Clostridium difficile-associated diarrhea, community-acquired pneumonia, bone fracture, reduced intestinal absorption of vitamins and minerals, and more recently kidney damage and dementia etc. In this review the recent literature regarding these adverse effects and their association with long-term proton pump inhibitor treatment is discussed. The objective of this review is to analyse the potential adverse effects of long-term PPI use and summarize the clinical implications. We documented a considerable increase in the use of PPIs over the last decade. This increase is due to over-prescription and use of PPIs for inappropriate indications. On the other hand, some patients may have had PPI therapy discontinued abruptly or inappropriately due to safety concerns. However the patients with a proven indication for a PPI should continue to receive it in the lowest effective dose for a shortest possible time. Finally, in most cases and based on the available evidence, PPIs benefits seem to outweigh potential adverse effects. Large randomized prospective trials are required to more firmly establish direct cause and effect relationships between PPIs and adverse events.

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Drug-Induced Vitamin B12 Deficiency: A Focus on Proton Pump Inhibitors and Histamine-2 Antagonists

Journal of Pharmacy Practice ◽

10.1177/0897190016663092 ◽

2016 ◽

Vol 30 (6) ◽

pp. 639-642 ◽

Cited By ~ 12

Author(s):

Lauren Linder ◽

Cynthia Tamboue ◽

Jennifer N. Clements

Keyword(s):

Elderly Patients ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Vitamin B12 Deficiency ◽

Vitamin B ◽

Patient Centered ◽

Drug Induced ◽

Data Synthesis ◽

Increased Risk ◽

B12 Deficiency

Objective: To review primary literature of gastric acid suppressive agents and vitamin B12 deficiency. Data Synthesis: From the published articles, proton pump inhibitors (PPIs) are associated with a higher risk of inducing vitamin B12 deficiency than histamine-2 receptor antagonists (H2RAs). Literature suggests that there is an increased risk of developing vitamin B12 deficiency in patients who are exposed to extended durations of therapy with PPIs. There are, however, some conflicting data in elderly patients suggesting that the PPI use for more than 3 years does not increase the risk of vitamin B12 deficiency. No evidence was found to support the extended use of H2RA monotherapy causing vitamin B12 deficiency. The inconsistency of results reported could be due to the differing patient populations studied, such as Zollinger-Ellison syndrome (ZES) and elderly patients. Overall, the lack of consistent evidence shows the need for more research in this area. Conclusion: To investigate the clinical significance of vitamin B12 deficiency caused by acid suppression with PPIs and H2RAs, longer prospective studies are needed. These studies should focus on patient-centered outcomes to accurately determine the extended usage of PPI and H2RA and the true effects on vitamin B12 deficiency.

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Adverse effects of proton-pump inhibitor use in older adults: a review of the evidence

Therapeutic Advances in Drug Safety ◽

10.1177/2042098617715381 ◽

2017 ◽

Vol 8 (9) ◽

pp. 273-297 ◽

Cited By ~ 69

Author(s):

Marina L. Maes ◽

Danielle R. Fixen ◽

Sunny Anne Linnebur

Keyword(s):

Older Adults ◽

Adverse Effects ◽

Proton Pump ◽

Vitamin B12 Deficiency ◽

Community Acquired Pneumonia ◽

Increased Risk ◽

Pubmed Search ◽

Post Marketing ◽

Meta Analyses

Proton-pump inhibitors (PPIs) are a widely prescribed class of medications used to treat acid-related disorders and use has significantly increased over the last few decades. PPIs are often inappropriately prescribed and since they have been on the market, a number of post-marketing studies have been published demonstrating associations between longer duration of PPI therapy and a number of adverse effects that are a concern in older adults. The objective of this review is to discuss the existing literature of potential adverse effects with long-term PPI use in older adults and to summarize the implications in clinical practice. A PubMed search was conducted to identify studies evaluating the potential long-term adverse effects of PPI therapy in older adults, and publications were selected based on relevant criteria. PPIs have been associated with an increased risk of a number of adverse effects including osteoporotic-related fractures, Clostridium difficile infection, community-acquired pneumonia, vitamin B12 deficiency, kidney disease, and dementia, demonstrated by a number of case-control, cohort studies, and meta-analyses. Older adults should be periodically evaluated for the need for continued use of PPI therapy given the number of potential adverse effects associated with long-term use.

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Abrupt-onset, profound erectile dysfunction in a healthy young man after initiating over-the-counter omeprazole: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-021-02981-5 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Theodore W. Perry

Keyword(s):

Adverse Effect ◽

Erectile Dysfunction ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Young Patients ◽

Vitamin B12 Deficiency ◽

Abrupt Onset ◽

Over The Counter ◽

Increased Risk ◽

B12 Deficiency

Abstract Background Proton pump inhibitors are frequently used (and often overused) medications with adverse effects including vitamin B12 deficiency, Clostridium difficile colitis, and increased risk of chronic kidney disease. Erectile dysfunction is largely unrecognized as an adverse effect of proton pump inhibitors despite increasing evidence that proton pump inhibitors may contribute to impaired nitric oxide generation and endothelial dysfunction. Case presentation A 38-year-old Caucasian man with mild hypertension and no other significant medical history developed profound erectile dysfunction within 2 days of initiating over-the-counter omeprazole therapy, with erectile function rapidly normalizing following discontinuation of the drug. At the time of the episode, the patient was on a stable dose of lisinopril and was taking no other medications or supplements. In the 2 years following the episode, the patient has had no further erectile difficulties. Conclusion Further study of erectile dysfunction as an adverse effect of proton pump inhibitors is needed. In the meantime, proton pump inhibitors should be considered as a potential cause of erectile dysfunction in healthy young patients and as a cause or contributor to erectile dysfunction in older patients in whom erectile dysfunction is often attributed to age or comorbidities.

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SMERNICE ZA PREPREČEVANJE IN ZDRAVLJENJE NEŽELENIH UČINKOV NESTEROIDNIH PROTIVNETNIH IN ANTIAGREGACIJSKIH UČINKOVIN NA PREBAVILA

Slovenian Medical Journal ◽

10.6016/zdravvestn.1171 ◽

2015 ◽

Vol 84 (1) ◽

Author(s):

Borut Štabuc ◽

Bojan Tepeš ◽

Pavel Skok ◽

Miroslav Vujasinović ◽

Aleš Blinc ◽

...

Keyword(s):

Risk Factors ◽

Helicobacter Pylori ◽

High Risk ◽

Adverse Effects ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Nonsteroidal Antiinflammatory Drugs ◽

Antiinflammatory Drugs ◽

Risk Patients ◽

Upper Gastrointestinal

Adverse effects of nonsteroidal antiinflammatory drugs and antiaggregants on gastrointestinal tract can be prevented or reduced by rational prescribing, use of proton pump inhibitors and Helicobacter pylori eradication.Nonsteroidal antiinflammatory drugs should not be used to treat patients with high risk for serious adverse effects on either upper gastrointestinal or cardiovascular system. Proton pump inhibitors in standard oral dosages are used for treatment of dyspepsia or gastric and duodenal erosions and ulcers, caused by nonsteroidal antiinflammatory drug or antiaggregant use. Peptic ulcer hemorrhage is treated with endoscopic hemostasis and proton pump inhibitors (72-hour continuous infusion followed by 4 – 8 week standard dose oral treatment).Patients can be stratified into three groups based on risk for upper gastrointestinal system adverse effects associated with nonsteroidal antiinflammatory drugs or antiaggregants use. Absence of risk factors denotes low-risk patient population, one or two risk factors are associated with medium risk; high-risk patients harbor either three or more risk factors or history of complicated peptic ulcer disease. Helicobacter pylori should be eradicated (if present) in all medium and high-risk patients prior to introduction of nonsteroidal antiinflammatory drugs or antiaggregants and proton pump inhibitors in standard daily dose should be prescribed for the duration of the treatment.Risk of gastrointestinal hemorrhage should be considered when planning invasive cardiovascular procedures or introduction of antiaggregant or anticoagulant treatment. In the context of acute gastrointestinal hemorrhage, antiaggregants should not be discontinued for longer than 7 days and oral anticoagulant therapy should be stopped and converted to low-molecular-weight heparin after complete hemostasis.

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Intermittent concurrent use of clopidogrel and proton pump inhibitors did not increase risk of adverse clinical outcomes in Chinese patients with coronary artery disease

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-01884-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wanbing He ◽

Xiaorong Shu ◽

Enyi Zhu ◽

Bingqing Deng ◽

Yongqing Lin ◽

...

Keyword(s):

Clinical Outcomes ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Cox Regression ◽

Asian Population ◽

Chinese Patients ◽

Clinical Event ◽

Cardiac Events ◽

Concurrent Use ◽

Increased Risk

Abstract Background Proton pump inhibitors (PPIs) are frequently prescribed to patients with coronary heart disease (CHD) under antiplatelet therapy to prevent gastrointestinal (GI) bleeding. However, its clinical impact is still under debate, especially in Asian population. This study was undertaken to explore the effects of concurrent use of clopidogrel and PPIs on the clinical outcomes in Chinese patients with CHD in secondary prevention. Methods A single-center retrospective study was conducted in 638 patients with CHD on consecutive clopidogrel therapy for at least 1 year. After 18-month follow-up, adverse clinical events were collected. Cox regression was used to calculate hazard ratios (HR) and 95% confidence interval (CI) for the effect of PPI use on the outcomes. A total of 638 patients were recruited from 2014 to 2015 in this study, among whom 201 were sustained PPI users, 188 were intermittent PPI users and the remaining 249 were non-PPI users. Results Compared with sustained PPI users, intermittent use of PPIs was associated with a lower risk of stroke, major adverse cardiac events (MACE) and net adverse clinical event (NACE) (stroke: adjusted HR: 0.109, 95% CI 0.014–0.878, p = 0.037; MACE: adjusted HR: 0.293, 95% CI 0.119–0.722; p = 0.008; NACE: adjusted HR: 0.357, 95% CI 0.162–0.786, p = 0.011). Subgroup analysis further revealed the benefit of intermittent PPI use was significant in male CHD patients over 60 years old, with hypertension or chronic kidney disease, and undergoing percutaneous coronary intervention during hospitalization. Conclusion The current findings suggest that the intermittent concurrent use of PPIs and clopidogrel is not associated with an increased risk of 18-month adverse clinical outcomes, and intermittent use of PPIs is associated with a lower rate of MACE and NACE.

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Proton-pump inhibitors are associated with increased risk of prosthetic joint infection in patients with total hip arthroplasty: a case-cohort study

Acta Orthopaedica ◽

10.1080/17453674.2021.1920687 ◽

2021 ◽

pp. 1-5

Author(s):

Maarten M Bruin ◽

Ruud L M Deijkers ◽

Roos Bazuin ◽

Erika P M Elzakker ◽

Bart G Pijls

Keyword(s):

Cohort Study ◽

Total Hip Arthroplasty ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Hip Arthroplasty ◽

Prosthetic Joint Infection ◽

Joint Infection ◽

Total Hip ◽

Prosthetic Joint ◽

Increased Risk

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Association of proton pump inhibitors and concomitant drugs with risk of acute kidney injury: a nested case–control study

BMJ Open ◽

10.1136/bmjopen-2020-041543 ◽

2021 ◽

Vol 11 (2) ◽

pp. e041543

Author(s):

Keiko Ikuta ◽

Shunsaku Nakagawa ◽

Kenji Momo ◽

Atsushi Yonezawa ◽

Kotaro Itohara ◽

...

Keyword(s):

Acute Kidney Injury ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Case Control Study ◽

Kidney Injury ◽

Case Control ◽

Renal Diseases ◽

Increased Risk ◽

Nested Case Control ◽

Control Study

ObjectivesThis study aimed to assess whether the combined use of proton pump inhibitors (PPIs) with non-steroidal anti-inflammatory drugs (NSAIDs) or antibiotics (penicillins, macrolides, cephalosporins or fluoroquinolones) was associated with an increased risk of acute kidney injury (AKI).DesignA nested case–control study.SettingA health insurance claims database constructed by the Japan Medical Data Center.ParticipantsPatients were eligible if they were prescribed a PPI, NSAID and antibiotic at least once between January 2005 and June 2017. The patients who were new PPI users and did not have any history of renal diseases before cohort entry were included (n=219 082). The mean age was 45 and 44% were women.InterventionsCurrent use of PPIs, NSAIDs, or antibiotics.Primary outcome measuresAcute kidney injury.ResultsDuring a mean follow-up of 2.4 (SD, 1.7) years, 317 cases of AKI were identified (incidence rate of 6.1/10 000 person-years). The current use of PPIs was associated with a higher risk of AKI compared with past PPI use (unadjusted OR, 4.09; 95% CI, 3.09 to 5.44). The unadjusted ORs of AKI for the current use of PPIs with NSAIDs, cephalosporins and fluoroquinolones, compared with the current use of PPIs alone, were 3.92 (95% CI, 2.40 to 6.52), 2.57 (1.43 to 4.62) and 3.08 (1.50 to 6.38), respectively. The effects of concurrent use of PPIs with NSAIDs, cephalosporins or fluoroquinolones remain significant in the adjusted model. The analyses on absolute risk of AKI confirmed the results from the nested case–control study.ConclusionsConcomitant use of NSAIDs with PPIs significantly increased the risk for AKI. Moreover, the results suggested that concomitant use of cephalosporins or fluoroquinolones with PPIs was associated with increased risk of incident AKI.

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