Proton pump inhibitors and cancer treatments: Emerging evidence against coadministration.

BACKGROUND: Proton pump inhibitors (PPIs) are widely used in cancer patients despite accumulating data showing that they can impact the efficacy of major anticancer drugs. This is particularly important with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (CPIs). RESULTS: Most TKIs require gastric acidity for their absorption and some retrospective series demonstrated that coprescription decreases the survival benefit of some TKI use (erlotinib, gefitinib and pazopanib). Relations between microbiota, the immune system, and the efficacy of immunotherapy are now obvious, just as modifications to gut flora after PPIs use are well-known. Many retrospective articles, including articles based on individual-participant data from randomized studies, demonstrated that patients treated with CPIs have a poorer outcome (overall survival, progression-free survival and response rate) when they received PPIs concomitantly, while there was no impact of such coprescription among patients in control arms, not treated with immunotherapies. Similar data were also observed in patients treated with palbociclib. CONCLUSION: For these interactions, it is very important to use the precautionary principle and warn patients and physicians about this. In patients who require acid suppression because of severe symptoms, using antacids or H2 blockers could be recommended.

The Impact of Proton Pump Inhibitors on the Efficacy of Immune Checkpoint Inhibitor Combinations in Patients with HBV-Associated Advanced Hepatocellular Carcinoma.

Purpose: There is limited research on whether Proton Pump Inhibitors (PPIs) will affect the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC).This study aimed to determine whether PPIs affect the survival outcomes of patients with HBV-associated advanced HCC receiving combination therapy based on ICIs. Methods: We retrospectively analyzed patients with hepatitis B virus (HBV)-associated advanced HCC who underwent ICIs combination therapy from January 1, 2020, to December 30, 2022. Patients were stratified into PPI and non-PPI groups based on whether they received PPI treatment within 30 days before or after ICIs therapy. Patients' survival and the risk of PPI-associated mortality was assessed. Adverse events were also evaluated. Results: A total of 183 patients with HBV-associated HCC treated with ICI combination therapy were included. The median survival time (12.5 months vs 13.7 months, P = 0.285) and incidence of adverse events (P = 0.729) did not significantly differ between the PPI and non-PPI groups. Even after propensity score matching, the difference in median overall survival (OS) between the two groups was not significant (10.7 months vs 11.4 months; P = 0.596) and the patient's OS is not significantly related to the dosage of PPI application (P > 0.05).However, according to our subgroup analysis, among HCC patients with a serum HBV DNA concentration ≥ 200 IU/mL, the use of PPIs significantly increased the risk of mortality in patients receiving ICI combination therapy (P = 0.024). Conclusion: PPIs do not notably influence the survival prognosis of patients receiving ICI combination therapy for HBV-associated advanced HCC. However, among patients with high levels of HBV DNA, PPIs increase the risk of mortality. Therefore, antiviral therapy should be intensified in the patients with HBVDNA > 200 IU/mL. Additionally, PPIs do not impact the incidence of adverse reactions in these patients.

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.

Impact of proton pump inhibitors on the efficacy of androgen receptor signaling inhibitors in metastatic castration-resistant prostate cancer patients.

BACKGROUND: Proton pump inhibitors (PPIs) are widely used due to their affordability and minimal severe side effects. However, their influence on the efficacy of cancer treatments, particularly androgen receptor signaling inhibitors (ARSIs), remains unclear. This study investigates the impact of PPI usage on the treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: A total of 117 mCRPC patients were retrospectively analyzed and divided into two groups based on the concomitant use of PPI at the initiation of ARSI treatment: PPI+ (n = 38) and PPI- (n = 79). Patient characteristics, including age at ARSI treatment administered, prostate-specific antigen (PSA) value at ARSI treatment administered, International Society of Urological Pathology grade group at prostate biopsy, metastatic site at ARSI treatment administered, prior docetaxel (DTX) treatment, and type of ARSI (abiraterone acetate or enzalutamide) were recorded. Progression-free survival (PFS), overall survival (OS), and PSA response rates were compared between the two groups. Patients were further stratified by clinical background to compare PFS and OS between the two groups. RESULTS: The PPI- group exhibited significantly extended PFS and a trend toward improved OS. For PSA response (reduction of 50% or more from baseline), the rates were 62.3% and 45.9% in the PPI- group and the PPI+ group, respectively. For deep PSA response (reductions of 90% or more from baseline), the rates were 36.4% and 24.3% in the PPI- group and the PPI+ group, respectively. The effects were consistent across subgroups divided by prior DTX treatment and type of ARSI administered. CONCLUSIONS: The administration of PPIs appears to diminish the therapeutic efficacy of ARSIs in mCRPC patients. Further prospective studies are needed to confirm these findings and explore the biological mechanisms involved.

Identification of novel signal of proton pump inhibitor-associated drug reaction with eosinophilia and systemic symptoms: a disproportionality analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for treating upper gastrointestinal hemorrhage, eradicating Helicobacter pylori, and stress ulcer prophylaxis, among other digestive system diseases. Recent case reports provided limited evidence of a correlation between PPIs and drug reactions with eosinophilia and systemic symptoms (DRESS). However, there is currently no established association between PPIs and DRESS. AIM: This research aimed to identify the associations between PPIs and DRESS using the US Food and Drug Administration Adverse Events Reporting System (FAERS) database. METHOD: A retrospective investigation of DRESS associated with six PPIs used FAERS data from Q1 2004 to Q3 2023. Data mining algorithms were used to identify adverse events in the FAERS database that met the following criteria: (1) proportional reporting ratio (PRR) ≥ 2; (2) reporting odds ratio (ROR) > 1; (3) 95% confidence interval (CI) of ROR > 1; (4) Chi-square (χ2) ≥ 4 and case count ≥ 3. RESULTS: There were 495 reports of PPI-related DRESS, including pantoprazole (174, 35.2%), omeprazole (103, 20.8%), lansoprazole (103, 20.8%), esomeprazole (101, 20.4%), rabeprazole (8, 1.6%), and dexlansoprazole (6, 1.2%). The results indicated a significant association of three PPIs (pantoprazole, omeprazole, and lansoprazole) with DRESS. The sensitivity analysis demonstrated that only pantoprazole remained significantly associated with DRESS after 10 concomitant drugs had been removed (ROR: 3.00, PRR: 2.99, and information component [IC]: 1.57). CONCLUSION: This study identified the signals suggesting a potential association between DRESS and six PPIs. However, more investigation of epidemiological data is required to validate of these conclusions.

Pantoprazole and riluzole target H+/K+-ATPases and pH-sensitive K+ channels in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) remains the most lethal cancer type. PDAC is characterized by fibrotic, hypoxic, and presumably acidic tumor microenvironment (TME). Acidic TME is an important player in tumor development, progression, aggressiveness, and chemoresistance. The dysregulation of ductal ion transporters/channels might contribute to extracellular pH (pHe) acidification and PDAC progression. Our aim was to test whether H+/K+-ATPases and pH-sensitive K+ channels contribute to these processes and could be targeted by clinically approved drugs. We used human pancreatic cancer cells adapted to various pHe conditions and grown in monolayers and spheroids. First, we created cells expressing pHoran4 at the outer plasma membrane and showed that pantoprazole, the H+/K+-ATPase inhibitor, alkalinized pHe. Second, we used FluoVolt to monitor the membrane voltage (Vm) and showed that riluzole hyperpolarized Vm, most likely by opening of pH-sensitive K+ channels such as TREK-1. Third, we show that pantoprazole and riluzole inhibited cell proliferation and viability of monolayers and spheroids of cancer cells adapted to various pHe conditions. Most importantly, combination of the two drugs had significantly larger inhibitory effects on PDAC cell survival. We propose that co-targeting H+/K+-ATPases and pH-sensitive K+ channels by re-purposing of pantoprazole and riluzole could provide novel acidosis-targeted therapies of PDAC.

Treatment Response With Potassium-competitive Acid Blockers Based on Clinical Phenotypes of Gastroesophageal Reflux Disease: A Systematic Literature Review and Meta-analysis.

Background/Aims: Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes. Methods: Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated. Results: In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs. Conclusions: Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.

An update on oral antiplatelet drug interactions with proton pump inhibitors: what are the risks?

INTRODUCTION: Aspirin and anti-P2Y12 are widely prescribed in cardiovascular patients, often in combination with proton pump inhibitors (PPIs) to limit the risk of upper gastrointestinal bleedings. The potential interaction between PPIs and antiplatelet agents has been widely discussed, but doubts remain as to whether PPIs may reduce the cardiovascular protection provided by aspirin, prasugrel, ticagrelor, and clopidogrel. AREAS COVERED: Many pharmacokinetic (PK) and pharmacodynamic (PD) studies have confirmed the interaction, especially between PPIs and clopidogrel, but with uncertain consequences on clinical outcomes. Therefore, we aimed to summarize the evidence for the widespread combined use of oral antiplatelet drugs and PPIs, to outline the current evidence supporting or opposing drug-drug interaction, and to discuss the clinical implications of such interactions. EXPERT OPINION: A large body of evidence describes the PK/PD interaction of antiplatelet drugs with PPIs and its potential role in increasing clinical cardiovascular adverse events, but no solid clinical data have confirmed these effects. In the light of the published studies, there seems to be no restriction on the choice of PPI with aspirin, prasugrel, and/or ticagrelor. The choice of a PPI with no (or minimal) interference with the hepatic cytochrome P450 2C19 is preferred in patients receiving clopidogrel.

Gastric Polyps in Long-Term Proton Pump Inhibitor Use: Identification of Risks and Characteristics.

Aim Estimate the prevalence of gastric polyps linked to long-term use of proton pump inhibitor (PPI), determine the various risk factors that promote this association, and identify the characteristics associated with these polyps. Methods This prospective cross-sectional study was conducted on approximately 1000 patients presenting to the Gastroenterology Endoscopic Department for upper GI endoscopy at two hospital centers in Beirut, Lebanon, over a period of 12 months from September 2021 to September 2022. The demographic and clinical data of patients who had been taking PPIs for at least one month were collected via a questionnaire. All patients with a previous Helicobacter pylori (H. pylori) infection, presence of hypergastrinemia, or a personal/family history of gastric polyps were excluded from this study. Statistical analyses were performed using SPSS 20 software. Categorical variables were compared by Fisher's exact test; p-values of less than 0.05 were considered statistically significant. Results The prevalence of gastric polyps linked to long-term PPI use was 30%. The minimum duration of daily PPI use required for the formation of polyps is around 24 months. The dosage did not play a significant role in increasing this prevalence. A significant correlation was found between chronic PPI use and factors such as sex, age range, duration, and type of PPI used. These polyps were predominantly found in females (with an OR of 2.9), increased with age, were mostly of the fundic gland type, and their size was proportionally linked to both the dosage and duration of daily PPI use. No cases of dysplasia within the fundic gland polyps (FGPs) were demonstrated in our study. Conclusion To date, there is no current data that prove an association between gastric cancer and PPI-induced FGPs. Additionally, the incidence of FGPs has increased with the widespread chronic use of PPIs. Therefore, attention should be drawn to the potential risk of dysplasia. Thus, the present study highlights the importance of limiting the prescription of PPIs to globally well-defined indications and determining the various risk factors that promote the association between gastric polyps and PPI use. This abstract was recently presented as an E-poster at the ESGE Days 2024 Congress on April 25-27, 2024, in Berlin, Germany.

High Dose Pantoprazole for Gastroesophageal Reflux Disease: Need, Evidence, Guidelines and Our Experience.

Gastroesophageal reflux disease (GERD) has a pooled prevalence of 15.2% in India with varying presentation in different subset of patients. The approach towards the management of GERD includes use of monotherapy or a combination of OTCs like antacids and/or prescription drugs like H2 receptor antagonists and proton pump inhibitors (PPI). Better efficacy and safety profile of PPIs have contributed to its wide spread use as compared with other drugs for the same indication. Among PPIs, most of the healthcare professionals prefer to prescribe pantoprazole in India. Standard dose of Pantoprazole (40 mg) is unable to meet the needs in case of extraesophageal symptoms, partial responders, patients with concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs), or severe presentation in cases of overweight/obese patients. Multiple guidelines recommend doubling the dose of PPI in such cases. Twice daily dosing of PPI may reduce compliance. Thus, there is a need for a higher dose of Pantoprazole (80 mg) to be prescribed once daily in these cases so that improved compliance leads to better outcomes. The use of dual release Pantoprazole 80 mg may help to improve compliance and also enhance the time for which acid suppression takes place. In this review, we discuss the use of higher dose PPI based on scientific evidence and experience of clinicians for the same. How to cite this article: Upadhyay R, Soni NK, Kotamkar AA, et al. High Dose Pantoprazole for Gastroesophageal Reflux Disease: Need, Evidence, Guidelines and Our Experience. Euroasian J Hepato-Gastroenterol 2024;14(1):86-91.

Multidisciplinary Consensus for Rationalizing the Use of Acid Suppressants in Children and Adults: CONFOR.

The use of acid suppression therapy (AST) is a common approach for managing a wide spectrum of acid peptic disorders. Histamine type 2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are the most widely prescribed AST in routine clinical practice. However, an exponential surge in the prescriptions of PPIs, such as Omeprazole, Esomeprazole, Pantoprazole, Lansoprazole in recent years and their associated adverse effects have raised concern about their inappropriate and overuse, both in children and adults. To address these issues, a three-step modified Delphi polling process was employed to establish best practice consensus statements for rationalizing the use of acid suppressants. A multidisciplinary expert panel of 13 health professionals across medical specialties, including gastroenterologists, hepatologists, pediatric gastroenterologists, pediatricians, otolaryngologists, cardiologists, nephrologists, gynecologist and orthopedists actively contributed to this collaborative process of consensus development. The expert panel proposed 21 consensus statements providing best practice points on the general use and safety of acid suppressants based on a comprehensive review of scientific literature and clinical expertise. The panel also collaboratively developed a PPI deprescribing algorithm. Altogether, this consensus paper offers evidence-based recommendations and guidance for the rational use of acid suppressants with a blueprint for deprescribing PPIs. This consensus paper contributes to aiding primary care practitioners in improving patient outcomes and minimizing healthcare costs. Additionally, it enhances patient safety and curtail inappropriate usage. How to cite this article: Prabhoo RY, Pai UA, Wadhwa A, et al. Multidisciplinary Consensus for Rationalizing the Use of Acid Suppressants in Children and Adults: CONFOR. Euroasian J Hepato-Gastroenterol 2024;14(1):99-119.

Concomitant Administration of VEGFR Tyrosine Kinase and Proton Pump Inhibitors May Impair Clinical Outcome of Patients With Metastatic Renal Cancer.

INTRODUCTION: The administration of proton pump inhibitors (PPIs) is a common practice to reduce gastro-esophageal adverse events associated with drug treatments but may impair absorption and exposure to oncology drugs. This study investigated the effect of concomitant administration of PPIs and pazopanib, sunitinib and cabozantinib on survival of patients with metastatic clear cell renal carcinoma (mRCC). PATIENTS AND METHODS: Total 451 patients receiving pazopanib, sunitinib and cabozantinib as first line treatment were enrolled in this retrospective study. Patients were defined as "no concomitant PPIs (PPI-)" if no PPIs were administered during TKIs, and as "concomitant PPIs (PPI+)" if the administration of PPIs was at least 75% of the time during which TKIs were given. RESULTS: Eighty patients administered pazopanib were PPI- and 86 PPI+; no difference in PFS was observed (10.7 vs. 11.9 months, P = .79). If patients were stratified as short (n = 89) and long (n = 77) responders, there was a significant difference in terms of PFS in PPI+ (n = 47) versus PPI- (n = 30) in long responders, being 24.7 versus 38 months (P = .04), respectively. In the sunitinib cohort, no significant difference of PFS in PPI+ (n = 102) versus PPI- (n = 131) was found, being 11.3 versus 18.1 months, respectively (P=0.15). In the cabozantinib cohort, there was a statistically significant difference in PFS of PPI+ versus PPI- (6 months vs. not reached, P = .04). No correlation with adverse events was found. CONCLUSIONS: This study demonstrates an association between PPIs and impaired PFS in mRCC patients given pazopanib and cabozantinib and recommends caution on their concomitant use.

Adverse cardiovascular outcomes associated with proton pump inhibitor use after percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for gastroprotection in patients undergoing percutaneous coronary intervention (PCI), who are at increased risk of gastrointestinal bleeding due to antiplatelet therapy. However, emerging evidence suggests that PPIs may adversely impact cardiovascular outcomes. This systematic review and meta-analysis sought to assess the relationship between using PPIs and cardiovascular outcomes in patients following PCI. METHODS: We searched various databases up to March 15, 2024, for observational studies and randomized controlled trials (RCTs) assessing the cardiovascular effects of PPIs in PCI patients. Data were extracted on study characteristics, patient demographics, PPI use, and cardiovascular outcomes. The Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool 2 assessed study quality. Meta-analyses were conducted using a random-effects model using R software version 4.3. RESULTS: A total of 21 studies involving diverse populations and study designs were included. Observational studies suggested a moderate increase in risk for composite cardiovascular diseases (CVD), myocardial infarction (MI), and major adverse cardiac events (MACE) associated with PPI use, with pooled hazard ratios (HRs) of 1.20 (95% CI: 1.093-1.308) for CVD, 1.186 (95% CI: 1.069-1.303) for MI, and 1.155 (95% CI: 1.001-1.309) for MACE. However, RCTs showed no significant link between PPI therapy and negative cardiovascular events (Relative Risk: 1.016, 95% CI: 0.878-1.175). Substantial heterogeneity was observed among observational studies but not RCTs. CONCLUSION: The findings indicate that while observational studies suggest a potential risk of adverse cardiovascular events with post-PCI use of PPI, RCTs do not support this association. Further large-scale, high-quality studies are required to understand the cardiovascular implications of individual PPIs better and optimize patient management post-PCI. This analysis shows the complexity of PPI use in patients with coronary artery diseases and the necessity to balance gastroprotective benefits against potential cardiovascular risks.

Long-term proton pump inhibitors therapy and prevalence of hyperprolactinaemia: A cross-sectional study in outpatient gastroenterology clinics.

Objectives: To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy. METHODS: The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. The study included patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for ≥3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25. RESULTS: Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinaemia and 70(42%) with hypreprolactinaemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Patients having treatment duration 11-20 months (p=0.006) and >40 months (p=0.001) were at high risk of developing hyperprolactinaemia. CONCLUSIONS: Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management.

Estimation of CDK inhibitors by RP-HPLC: application for pharmacokinetic interactions studies with PPIs.

Background: The study investigated pharmacokinetic interactions between palbociclib and ribociclib with proton pump inhibitors (PPIs) using the reverse-phase high-performance liquid chromatography (RP-HPLC) method. Methods: Developed RP-HPLC method quantified palbociclib and ribociclib in biological matrices. In vitro metabolic stability assays and in vivo studies in rats evaluated effect of omeprazole and esomeprazole on pharmacokinetics of palbociclib and ribociclib. Results: The RP-HPLC method was sensitive, accurate and linear. Esomeprazole and omeprazole decreased metabolic clearance of palbociclib and ribociclib by several folds. In vivo, esomeprazole elevated Cmax of palbociclib and ribociclib by 90.1% and 86.4%, whereas omeprazole reduced it by 32.0% and 16.8%, respectively. Conclusion: The RP-HPLC method was used to analyze in vitro and in vivo samples. Long-term treatment with PPIs affects pharmacokinetics of palbociclib and ribociclib, necessitating optimal chemotherapy regimen.

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Use of Proton Pump Inhibitors Is Not Associated with Post-Dialysis Fatigue and Time of Recovery after Dialysis in Patients on Maintenance Hemodialysis.

Objectives: To define if the use of proton pump inhibitors (PPI) is associated with PDF prevalence and characteristics and with time of recovery after dialysis in patients on maintenance hemodialysis. Methods: Patients were defined as experiencing PDF if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis?". Time of recovery after dialysis (TIRD) was also assessed for each patient. Each patient was invited to rate the intensity, duration and frequency of PDF from 1 to 5. We defined if patients used PPI (no PPI use or PPI use), the type of used PPI, the dose of used PPI, and the duration of the use of PPI (<1 year or ≥1 year). Results: A total of 346 patients were studied: 259 used PPI (55 used omeprazole, 63 esomeprazole, 54 pantoprazole, 87 lansoprazole, and 7 rabeprazole) and 87 did not. Two hundred and thirty-two patients declared PDF and 114 did not. The median [min-max] TIRD was 210 min [0-1440]. The prevalence of PDF in PPI users and PPI non-users was 67% and 68%, respectively (p = 0.878). The median [min-max] TIRD did not differ significantly between PPI users and PPI non-users (180 [0-1440] and 240 [0-1440], respectively; p = 0.871). Median PDF intensity, duration, frequency, and severity did not differ significantly between PPI use and no use. The prevalence of PDF was similar among the different types of PPI use and did not differ with respect to PPI non-users. Duration of PPI exposure was <1 year in 40 patients and ≥1 year in 219 patients. The prevalence of PDF did not differ between the two exposures. The correlation matrix between PPI equivalent dose, PPI treatment duration and PDF frequency, PDF characteristics, and TIRD showed whether there was statistical significance. Conclusions: The use of PPI is not associated with PDF and time of recovery after dialysis in patients on maintenance hemodialysis.

A Phase III Head-to-Head Study to Compare the Efficacy and Safety of Fexuprazan and Esomeprazole in Treating Patients with Erosive Esophagitis.

Background: Fexuprazan (Fexuclue®; Daewoong Pharmaceutical Co., Ltd., Seoul, Korea) is a novel potassium-competitive acid blocker (P-CAB). This multi-center, randomized, double-blind, active-controlled, parallel-group, therapeutic confirmatory, phase III study was conducted to assess its efficacy and safety compared with esomeprazole (Nexium®; AstraZeneca, Gothenburg, Mölndal, Sweden) in Korean patients with erosive esophagitis (EE). Methods: This study evaluated patients diagnosed with EE at a total of 25 institutions in Korea between 13 December 2018 and 7 August 2019. After voluntarily submitting a written informed consent form, the patients were evaluated using a screening test and then randomized to either of the two treatment arms. The proportion of the patients who achieved the complete recovery of mucosal breaks at 4 and 8 weeks, the proportion of those who achieved the complete recovery of heartburn at 3 and 7 days and 8 weeks, and changes in the GERD-Health-Related Quality of Life Questionnaire (GERD-HRQL) scores at 4 and 8 weeks from baseline served as efficacy outcome measures. The incidence of treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) and the serum gastrin levels served as safety outcome measures. Results: The study population comprised a total of 231 patients (n = 231) with EE, including 152 men (65.80%) and 79 women (34.20%); their mean age was 54.37 ± 12.66 years old. There were no significant differences in the efficacy and safety outcome measures between the two treatment arms (p > 0.05). Conclusions: It can be concluded that the efficacy and safety of Fexuclue® are not inferior to those of esomeprazole in Korean patients with EE.

Proton pump inhibitor use is associated with increased liver steatosis.

Despite proton pump inhibitors (PPIs) being generally safe, there are questions about their potential long-term complications. The present study aimed to investigate the association between PPI therapy and the incidence of hepatic steatosis and liver fibrosis in the outpatient population of the United States. The present study included 7,395 individuals aged ≥20 years who underwent hepatic vibration-controlled transient elastography (VCTE) examination. The data were obtained from the January 2017 to March 2020 pre-pandemic National Health and Nutrition Examination Survey. Among the 7,395 adults who were included (mean age, 50.59 years; 3,656 male), 9.8% were prescribed PPIs. Following multivariable adjustment, the use of PPIs was significantly associated with hepatic steatosis [odds ratio (OR), 1.25; 95% confidence interval (CI), 1.02-1.53]. Prolonged use of PPIs was found to increase the risk of developing hepatic steatosis over time (P=0.006). Sensitivity analyses using different definitions of hepatic steatosis, such as a controlled attenuation parameter ≥285 dB/m (OR, 1.19; CI, 1.01-1.40), non-alcoholic fatty liver disease (OR, 1.50; 95% CI, 1.16-1.93) and metabolic dysfunction-associated steatotic liver disease (OR, 1.26; 95% CI, 1.05-1.52), consistently demonstrated an association between PPI prescription and hepatic steatosis. The administration of PPI therapy was linked with hepatic steatosis in US adults, although no significant association was observed with liver stiffness, as determined by VCTE.

Consumption of proton pump inhibitors in outpatients of Gastroenterology Clinics in Khyber Pakhtunkhwa: evidence of inexpedient use.

Introduction: Proton pump inhibitors (PPIs) are effective drugs used for multiple gastrointestinal complications. They are commonly used in both hospitalised and outpatients. However, little is known about its utilisation pattern in ambulatory patients. Aim: To evaluate the inexpedient continuous use of PPIs in patients with respect to treatment duration. Material and methods: A cross-sectional observational study was conducted from January 2018 to November 2019 in Khyber Pakhtunkhwa, Pakistan. Regular proton pump inhibitor users were identified through patient histories. Results: During the study period, 171 patients were included using a non-probability consecutive sampling technique, who were using regular proton pump inhibitors for a longer duration, i.e. from 3 months to 15 years. The highest proportion (42.8%) were using PPI regularly from 3 months to 1 year followed by 22.9% for 1-2 years, 12.0% for 2-3 years, 7.8% for 3-4 years, 4.2% for 4-5 years, and 10.24% for > 5 years. Omeprazole and esomeprazole were the most commonly used drugs, with 71.1% and 23.5% prevalence, respectively. A total of 33.73% of patients had continued PPI use on their own after initially being prescribed by the physician. Conclusions: It can be deduced that PPIs are used in outpatients beyond standard treatment guidelines. The inexpedient continuous use of proton pump inhibitors is of concern due to the risk of developing adverse effects. Therefore, patient counselling and periodic monitoring must be carried out to prevent the irrational use of PPIs.

Vonoprazan a novel potassium competitive acid blocker; another leap forward.

Introduction: The eradication rate of Helicobacter pylori (H. pylori) has decreased due to antibiotics resistance and inadequate acid suppression. Vonoprazan is a novel potassium-competitive acid blocker (P-CAB), which has a rapid and sustained acid inhibitory effect and may be more effective than conventional proton pump inhibitors (PPIs) in H. pylori eradication. Aim: to study the efficacy and safety of vonoprazan as a component of first-line H. pylori eradication treatment compared with conventional PPI-based therapy. Material and methods: This randomised (one to one) non-blinded study was conducted on 400 consecutive proven H. pylori infected patients, of whom 200 received vonoprazan-based triple therapy, while 200 patients received PPI-based triple therapy for 14 days. The study outcomes were evaluated as eradication rate and adverse events in both patient groups. Results: The eradication rate was 86% in the vonoprazan group and 74.5% in the PPI group. The vonoprazan eradication rate was significantly higher than that of PPIs (p = 0.004). There was no significant difference regarding adverse events between both patient groups. Conclusions: Vonoprazan-based therapy was more effective than PPI-based therapy as a first-line H. pylori eradication treatment. Vonoprazan was generally safe and well tolerated.