Proton Pump Inhibitors Adverse Effects Research Articles

Overutilization of Proton Pump Inhibitors (PPIs) in a Community-Based Hospital: A QI Initiative

Introduction: Proton pump inhibitors (PPIs) are indicated for GERD, erosive esophagitis, and prophylactic use in patients at high risk for stress ulcerations. Long-term PPI therapy is associated with increased incidence of C. diff infections and community- and hospital-acquired pneumonia. Discontinuation of stress ulcer prophylaxis upon discharge and reevaluation of continued therapy will help reduce chronic, inappropriate treatment, which predisposes patients to adverse side effects. Aim: We sought to reform the process of inpatient PPI prescriptions based on clinical indications of therapy in order to reduce use and associated costs of PPIs by 30% over 6 months. Model for Improvement: We obtained an IRB exemption for a retrospective chart review study and collected pre-intervention data from 200 patients who had received PPI therapy between July-Aug 2022. Of these, 186 met inclusion criteria. We identified PPT overuse among all inpatient admissions, including those admitted under teaching services. Evaluating the timing of PPI initiation after admission, we found that a majority (83.8%) were started upon admission; 28.5% required PPIs throughout; and 25.2% of orders were placed within 1 day of discharge. The average duration of therapy was 3.9  2.59 days. On average, 50.5% of patients had a prior diagnosis of GERD, gastritis, or erosive esophagitis, justifying initiation of PPI therapy. However, almost a third (32.8%) met the criteria for stress ulcer prophylaxis. 17% of the cohort developed an adverse side effect, and almost 53% of patients were discharged with a new prescription for PPI. Measures: Root cause analysis revealed a lack of knowledge regarding adverse PPI effects leading to longer hospital stays. During the first PDSA, we conducted a session on “Use of PPI Inhibitors: Indications for Inpatient Prescriptions and Stress Ulcer Prophylaxis” in April 2023, educating Internal Medicine and Family Medicine resident teaching services about PPI therapy indications, contraindications, and adverse effects. Results: After our educational intervention, we collected and analyzed data from May 2023 to August 2023 and found 301 patients who met inclusion criteria. Their average age was 73.29 years. 169 patients (56%) had pre-existing diagnoses (GERD or erosive esophagitis), justifying initiation of Protonix. Of the remaining 132 without pre-existing conditions, 44 (35%) met criteria for starting stress ulcer prophylaxis. This was a 3% increase in appropriate utilization when compared to our pre-intervention data. 181 patients were discharged with a prescription for pantoprazole, of which 46 were PPI-naïve prior to admission. Conclusion: We found a decrease in inappropriate inpatient PPI administration by 3% after education. Although the post-intervention sample size was larger, the education resulted in a positive response in 1 month. The next PDSA cycle will alter the EMR order to provide only 3 orders for pantoprazole – one oral, one IV, and one for infusion, and orders will also require the selection of indication.

Physicians' perceptions and awareness of adverse effects of proton pump inhibitors and impact on prescribing patterns.

Background: Heightened scrutiny surrounds the inappropriate use of proton pump inhibitors (PPIs) due to concerns regarding potential serious adverse effects (AEs). Understanding the impact of these AEs on real-world practice is crucial. This study aimed to assess physicians' perceptions, experiences, awareness, and beliefs regarding published data on potential AEs associated with PPIs. Additionally, it sought to determine alterations in PPI prescribing patterns resulting from these AEs, explore attitudes towards PPI use, and ascertain recommendations for PPI use in clinical scenarios with varying levels of risk for upper gastrointestinal bleeding (UGIB). Method: A quantitative, cross-sectional study utilized a self-administered questionnaire, inviting 282 physicians from 55 primary healthcare centers and 334 internal medicine physicians from seven governmental hospitals to participate. Results: With a response rate of 87.8% (541/616), 74% (95% CI: 70.2-77.7) of respondents were somewhat or very familiar with published data on PPI AEs. Among the familiar, 69.5% (CI: 65.2-73.5) had somewhat or very much changed their PPI prescribing patterns. General concerns about AEs when prescribing PPIs were reported by 62% (CI: 56.7-65.1). Respondents displayed awareness of a median (IQR) of 15 (9) different AEs associated with long-term PPI use, including osteoporosis or osteopenia (90.2%), hypomagnesemia (81.5%), vitamin B12 deficiency (80.6%), and bone fracture (80.0%). Respondents believed that PPIs elevate the risk for a median (IQR) of 7 (6) different AEs, with osteoporosis or osteopenia (81.8%) being the most common, followed by hypomagnesemia (67.1%), and vitamin B12 deficiency (62.3%). The most common strategies for PPI de-escalation were PPI discontinuation (61%) and using PPI on-demand/as-needed (57.9%). The majority (87.4%) agreed or strongly agreed that PPI overuse is prevalent in Kuwait and 78.2% emphasized the necessity for large-scale education on rational PPI use for medical staff and the public. In the UGIB prevention scenarios, 43.6% recommended appropriately the PPI discontinuation in the minimal-risk scenario, while 56% recommended appropriately the PPI continuation in the high-risk scenario. Associations and comparative analyses revealed predictors influencing physicians' practices and attitudes toward PPI usage. Conclusion: These findings lay the foundation for future research and targeted interventions aimed at optimizing PPI prescribing practices and ensuring patient safety.

Evaluating physicians' awareness and prescribing trends regarding proton pump inhibitors: a cross-sectional study.

Introduction: Proton pump inhibitors (PPIs) are commonly used to treat acid-related disorders. Their appropriate use depends on the correct indications from the clinician. Owing to the high incidence of use and misuse, PPIs have been identified as an essential pharmacological class for developing deprescribing recommendations. Therefore, assessing physicians' knowledge and practice regarding PPI usage is critical for paving the way toward targeted recommendations and efforts. Objective: This study aimed to assess Syrian physicians' perceptions of proton pump inhibitors adverse effects, their benefit in upper gastrointestinal bleeding (UGIB) prophylaxis, and how these perceptions are related to PPI prescription practice. Methods: A cross-sectional study was performed using a web-based questionnaire distributed among Syrian physicians in internal medicine between 28 November and 23 December 2022. The questionnaire assessed perceptions and experiences of PPIs, concerns about specific adverse effects, and their effectiveness for UGIB prophylaxis, in addition to the different scenarios used to determine the best practice for appropriate treatment to manage minimal, mild, moderate, and high-risk UGIB patients. Results: A total of 473 participants completed the questionnaire, with median age ±SD was (28.46 ± 4.58), and most participants (83.3%) were residents. Approximately half of the participants (45.5%) agreed that discussion assistance was provided to continue or terminate PPIs properly. Only 8.9% were very familiar with published evidence of PPI adverse effects. Bone weakening and vitamin B12 deficiency were the most frequently reported side effects (81.8% and 79.7%, respectively). However, dementia (0.4%) and mortality (1.9%) were the least reported adverse effects. More than half of the participants (64%) perceived using PPIs to prevent upper GI bleeding. Non-trainee physicians were less knowledgeable about appropriate GERD management than resident physicians (p < 0.001). Conclusion: The study showed a gap between Syrian physicians' perceptions and practices regarding PPI use, which necessitates spreading awareness of updated guidelines for PPI usage and their side effects.

Patient Awareness of Reported Adverse Effects Associated with Proton Pump Inhibitors in a Medically Underserved Community.

Reports of adverse effects associated with proton pump inhibitors (PPIs) are concerning because of high usage and over-the-counter availability. We sought to determine the awareness of PPI adverse effects among our patient population, which is medically underserved, low-income, and racially diverse. A 21-item survey was administered to gastroenterology-clinic outpatients. It collected information about age, gender, education, race, specialty of the prescriber, specific PPI, indication, knowledge of dose, adherence, duration of use and awareness of any risks. Medical records were reviewed to verify survey responses pertaining to indication, dosing, and adherence. A vast majority (96%) of 101 participants were not aware of PPI adverse effects. In total, 63% of the patients completed a high school education or less, which was associated with a higher risk of long-term PPI use than completion of at least an undergraduate degree (p = 0.05). In contrast to other studies, the shockingly low patient awareness about PPI adverse effects in our patient population is particularly concerning, especially as it is tied to their demographic attributes. This may lead to long-term and high-dose PPI use. Our study highlights the need for effective provider-driven education regarding medication risks, especially in the communities with significant health disparities.

S3292 Increased Admissions From Side Effects Reported With Therapeutic Use of Acid Suppression Medications: A Nationwide Inpatient Database Analysis of the Last Two Decades

INTRODUCTION: Increased awareness has been placed on potential side effects of Proton pump inhibitors (PPIs) and its safety profile due to publication bias towards retrospective studies showing potential associations. The International Classification of Diseases (ICD) coding of drug adverse effects yields valuable evidence. We aimed to quantify and analyze the trends in documentation of the admissions related to acid suppression medication adverse effects. METHODS: We utilized the National Inpatient Sample Database to analyze longitudinal trends related to all hospitalizations due to acid suppression medication causing adverse effects in therapeutic use (ICD-9 E943.0) between 1993 and 2014 in the US. Similar query was also made for antidiarrheal agents (ICD-9 E943.5) and laxatives (ICD-9 E943.2, E943.3). Trends in admission, discharge rates and payor were analyzed. RESULTS: The total number of reported admissions related to adverse effects of acid suppression medications nationwide were 1,009 with a discharge rate of 0.4 per 100,000 in 1993, which declined to 696 annual admissions and a discharge rate of 0.2 per 100,000 by 2003. An increase was observed until 2014, with 2,640 admissions and 0.8 discharge rate in 2014 (Figure 1). The number of admissions/years increased by 279% from 1993 to 2014. For admitted patients, average age was 65-84 years old, and 57.39% were females (Figure 2). Most of the discharges were covered under Medicare (52.3%), followed by private insurance (30.1%). In the year 2014, secondary diagnosis coded along with PPI adverse effects were chronic kidney disease, urinary tract infection, and fracture of unspecified bone. CONCLUSION: Our findings show that the number of admissions reported due to acid suppression medication adverse effects in the US has increased over the past two decades. This increase became prominent starting in the early 2000s, which coincides with the wider implementation of electronic medical records in the US. However similar trend was not observed in documentation of side-effects of anti-diarrheal agents and laxatives suggesting that the coding of adverse effects related to acid suppression medications might have been driven by publication bias of multiple studies showing associations of potential side effects related to these medications. Given recent updates with prospective studies showing well tolerance of these medications, outside of slightly increased risk of enteric infection, the accuracy of these codes should be evaluated.Figure 1.: Rate of Admission for Adverse Effects in Therapeutic Use.Figure 2.: Age Group Distribution of Admissions due to Adverse Effects of Acid Suppression Medication in Therapeutic Use in 2014.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing.

Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacterpylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long-term PPI use, particularly at higher plasma concentrations.

Physicians' Perceptions of Proton Pump Inhibitor Risks and Recommendations to Discontinue: A National Survey.

To provide contemporary estimates of internists' perceptions of adverse effects associated with proton pump inhibitors (PPIs) and self-reported clinical use. We invited 799 internists, including specialists and postgraduate trainees, to complete an online survey. Topics included perceptions of PPI adverse effects (AEs) and effectiveness for upper gastrointestinal bleeding (UGIB) prevention, changes in prescribing, and management recommendations for patients using PPIs for gastroesophageal reflux disease or UGIB prevention. We used logistic regression to identify factors associated with appropriate PPI continuation in the scenario of a patient at high risk for UGIB. Among 437 respondents (55% response rate), 10% were trainees and 72% specialized in general medicine, 70% were somewhat/very concerned about PPI AEs, and 76% had somewhat/very much changed their prescribing. A majority believed PPIs increase the risk for 6 of 12 AEs queried. Fifty-two percent perceived PPIs to be somewhat/very effective for UGIB prevention. In a gastroesophageal reflux disease scenario in which PPI can be safely discontinued, 86% appropriately recommended PPI discontinuation. However, in a high-risk UGIB prevention scenario in which long-term PPI use is recommended, 79% inappropriately recommended discontinuation. In this latter scenario, perceived effectiveness for bleeding prevention was strongly associated with continuing PPI (odds ratio 7.68, P < 0.001 for moderately; odds ratio 17.3, P < 0.001 for very effective). Other covariates, including concern about PPI AEs, had no significant association. Most internists believe PPIs cause multiple AEs and recommend discontinuation even in patients at high risk for UGIB. Future interventions should focus on ensuring that PPIs are prescribed appropriately according to individual risks and benefits.

Monitoring the growing use of esomeprazole

Like all proton‐pump inhibitors (PPIs), esomeprazole has a generally good safety record. However, there is no true lowpotency formulation of esomeprazole available and therefore the growing use of this drug may increase the risk of dosedependent PPI adverse effects, argues Angus Thompson.

Patients' Perceptions of Proton Pump Inhibitor Risks and Attempts at Discontinuation: A National Survey.

Little is known about how reports on the adverse effects of proton pump inhibitors (PPIs) impact patients' perceptions of these drugs and medication use. We sought to determine patients' level of concern about PPI adverse effects and its association with attempts to discontinue these drugs. This study is an online survey of US adults who use PPIs for gastroesophageal reflux disease. Topics included awareness of and concern about PPI adverse effects, prior discussion with providers, and attempts to stop PPI because of concern about adverse effects. For the primary analysis, we used logistic regression to identify associations between having attempted to stop PPI and concern about PPI-related adverse effects, a provider's recommendation to stop, risk of upper gastrointestinal bleeding (UGIB), age, and gender. Among 755 patient participants, mean age was 49 years (s.d. 16), 71% were women, and 24% were at high risk of UGIB. Twenty percent of patients were able to write in ≥1 reported adverse effect, and 46% endorsed awareness of ≥1 adverse effect when presented with a list, most commonly chronic kidney disease (17%). Thirty-three percent of patients were slightly concerned, 32% somewhat concerned, and 14% extremely concerned about adverse effects. Twenty-four percent of patients had discussed PPI risks and benefits with a provider, and 9% had been recommended to stop. Thirty-nine percent had attempted to stop their PPI, most (83%) without a provider recommendation. Factors associated with an attempt at stopping PPI included: (i) provider recommendation to stop (odds ratio [OR] 3.26 [1.82-5.83]); (ii) concern about adverse effects (OR 5.13 [2.77-9.51] for slightly, 12.0 [6.51-22.2] for somewhat, and 19.4 [9.75-38.7] for extremely concerned); and (iii) female gender (OR 1.64 [1.12-2.39]). Patients at high risk of UGIB were as likely to have attempted to stop as others (OR 0.98 [0.66-1.44]). Concern about PPIs is common and strongly associated with attempts at discontinuation, even without a provider's recommendation. Notably, individuals at high risk of UGIB, who benefit from PPIs, were equally likely to have tried stopping PPIs as others. Providers should proactively discuss the risks and benefits of PPIs with their patients, who may otherwise make unwise decisions about PPI management on their own.

Physicians’ Practice Toward and Knowledge about Proton Pump Inhibitor Prescription in Jeddah, Saudi Arabia

Proton pump inhibitors (PPI) are acid-suppressive agents widely prescribed to patients with common gastrointestinal symptoms. The common belief that PPI have a safe profile and high efficacy level leads to PPI over-prescription. However, the physicians’ knowledge about PPI could also contribute in this over-prescription. Thus, this study aimed to evaluate physicians’ practice towards and knowledge about PPI prescription in Jeddah, Saudi Arabia. A cross-sectional, questionnaire-based survey was conducted. The participants were randomly recruited from our hospital, Jeddah, Saudi Arabia between August and December 2013. The questionnaire comprised 15 items in three sections: questions regarding general background, practice of PPI prescription, and knowledge on PPI safety. The data were coded, entered, and analysed using the Statistical Package for the Social Sciences software (SPSS), version 23.0.0. The results were presented as frequencies and percentages. In total, 112 physicians responded, and 58% reported prescribing PPIs to patients. Omeprazole was the preferred PPI prescribed. Only 20% of physicians consistently warned patients about the possible adverse effects. One-third reported that they discontinued PPIs after reassessment. Gastroesophageal reflux disease and peptic ulcer disease were the most common indications for PPI use. Approximately 60% of physicians prescribed PPIs for <6 months. Physician’s knowledge about PPI adverse effects and drug–drug interactions were low. As a conclusion, physicians in our hospital showed low knowledge and poor adherence to guidelines regarding PPI prescription. Therefore, staff awareness programs and prescribing guidelines are required to ensure good clinical practice.

Internists' Perceptions of Proton Pump Inhibitor Adverse Effects and Impact on Prescribing Practices: Results of a Nationwide Survey.

BackgroundObservational studies have linked proton pump inhibitors (PPIs) with serious adverse effects. The study aimed to evaluate internists’ perceptions of PPI harms and effects on prescribing.MethodsThis was an online survey of a representative sample of the American College of Physicians in 2013. We queried familiarity with and concern about PPI adverse effects (1 - 7 Likert-type scales, anchored by “not at all” and “extremely”). We also asked how frequently (often, sometimes, rarely, or never) participants used any of three “de-escalation” strategies to stop or reduce PPIs because of concern about adverse effects: reducing patients’ PPI dose, switching to H2 blocker, or discontinuing PPI. We used multivariable logistic regression to evaluate associations between sometimes/often using any PPI de-escalation strategy and gender, time in practice, familiarity, and concern.ResultsThe response rate was 53% (487/914). Seventy percent were male, median time in practice was 11 - 15 years, and most practiced general medicine (58%). Ninety-nine percent reported at least some familiarity with reported adverse effects (mean 4.9, standard deviation (SD) 1.0), and 98% reported at least some concern (mean 4.6, SD 1.3). Sixty-three percent reported sometimes/often reducing the PPI dose, 52% switching to H2 blocker, and 44% discontinuing PPI. In multivariable analysis, familiarity with adverse effects (OR 1.66 (1.31 - 2.10) for 1-point increase, P < 0.001) and concern (OR 2.14 (1.76 - 2.61) for 1-point increase, P < 0.001) were independently associated with de-escalation. Gender and time in practice had no effects.ConclusionAlmost all internists report awareness and concern about PPI adverse effects, and most are de-escalating PPIs as a result. Research on which approach is most effective for which patients is critically important.

Characterizing Potentially Inappropriate Prescribing of Proton Pump Inhibitors in Older People in Primary Care in Ireland from 1997 to 2012.

To characterize prescribing of proton pump inhibitors (PPIs) and medicines that increase gastrointestinal bleeding risk (ulcerogenic) in older people from 1997 to 2012 and assess factors associated with maximal-dose prescribing in long-term PPI users. Repeated cross-sectional study of pharmacy claims data. Eastern Health Board region of Ireland. Individuals aged 65 and older from a means-tested health plan in 1997, 2002, 2007, and 2012 (range 78,489-133,884 individuals). PPI prescribing prevalence was determined per study year, categorized according to duration (≤8 or >8 weeks), dosage (maximal or maintenance), and co-prescribed drugs. Logistic regression in long-term PPI users was used to determine whether age, sex, polypharmacy, and ulcerogenic medicine use were associated with being prescribed a maximal dose rather than a maintenance dose. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) are presented. Half of this older population received a PPI in 2007 and 2012. Long-term use (>8 weeks) of maximal doses rose from 0.8% of individuals in 1997 to 23.6% in 2012. Although some ulcerogenic medicines and polypharmacy were significantly associated with maximal PPI doses, any nonsteroidal anti-inflammatory drug use was significantly associated with lower odds of maximal PPI dose (adjusted OR = 0.87, 95% CI = 0.85-0.89), as were aspirin use and older age. Adjusting for medication and demographic factors, odds of being prescribed a maximal PPI dose were significantly higher in 2012 than in 1997 (adjusted OR = 6.30, 95% CI = 5.76-6.88). Long-term maximal-dose PPI prescribing is highly prevalent in older adults and is not consistently associated with gastrointestinal bleeding risk factors. Interventions involving prescribers and patients may promote appropriate PPI use, reducing costs and adverse effects of PPI overprescribing.

Proton-pump inhibitors adverse effects: a review of the evidence and position statement by the Sociedad Española de Patología Digestiva.

In the last few years a significant number of papers have related the use of proton-pump inhibitors (PPIs) to potential serious adverse effects that have resulted in social unrest. The goal of this paper was to provide a literature review for the development of an institutional position statement by Sociedad Española de Patología Digestiva (SEPD) regarding the safety of long-term PPI use. A comprehensive review of the literature was performed to draw conclusions based on a critical assessment of the following: a) current PPI indications; b) vitamin B12 deficiency and neurological disorders; c) magnesium deficiency; d) bone fractures; e) enteric infection and pneumonia; f) interactions with thienopyridine derivatives; e) complications in cirrhotic patients. Current PPI indications have remained unchanged for years now, and are well established. A general screening of vitamin B12 levels is not recommended for all patients on a PPI; however, it does seem necessary that magnesium levels be measured at therapy onset, and then monitored in subjects on other drugs that may induce hypomagnesemia. A higher risk for bone fractures is present, even though causality cannot be concluded for this association. The association between PPIs and infection with Clostridium difficile is mild to moderate, and the risk for pneumonia is low. In patients with cardiovascular risk receiving thienopyridines derivatives it is prudent to adequately consider gastrointestinal and cardiovascular risks, given the absence of definitive evidence regardin potential drug-drug interactions; if gastrointestinal risk is found to be moderate or high, effective prevention should be in place with a PPI. PPIs should be cautiously indicated in patients with decompensated cirrhosis. PPIs are safe drugs whose benefits outweigh their potential side effects both short-term and long-term, provided their indication, dosage, and duration are appropriate.

Inhibition of lysosomal enzyme activities by proton pump inhibitors

Proton pump inhibitors (PPIs) are pro-drugs requiring an acidic pH for activation. The specificity of PPI toward the proton pump is mainly due to the extremely low pH at the parietal cell canalicular membrane where the pump is located. Reactivity of PPIs was also observed in moderately acidic environments like the renal collecting duct. But no PPI effect on lysosomal enzymes has been observed possibly because the previous studies were performed with liver tissue, where PPIs are metabolized. The reactivity of PPIs (omeprazole, lansoprazole and pantoprazole) with a cysteine-containing peptide was analyzed by mass spectrometry, and the impact of PPIs on lysosomal enzymes was evaluated in cultured cells and mice. The effect of PPIs on the immune system was examined with a mouse tumor immunotherapy model. Incubation of a cysteine-containing peptide with PPIs at pH5 led to the conversion of most of the peptide into PPI-peptide adducts. Dose dependent inhibition of lysosomal enzyme activities by PPIs was observed in cultured cells and mouse spleen. Further, PPI counteracted the tumor immunotherapy in a mouse model. Our data support the hypothesis that many of the PPI adverse effects are caused by systematically compromised immunity, a result of PPI inhibition of the lysosomal enzymes. This novel mechanism complements the existing mechanisms in explaining the increased incidence of tumorigenesis and infectious diseases among PPI users and underlie the ongoing concern about the overuse of PPIs in adult and pediatric populations.