Prevention Of Nonsteroidal Anti-inflammatory Drug Research Articles

Zastaprazan: First Approval.

Zastaprazan (JAQBO®) is a next-generation potassium-competitive acid blocker being developed by Onconic Therapeutics, a subsidiary of Jeil Pharmaceutical, for the treatment of acid-related diseases. Zastaprazan binds directly to proton pumps in a competitive manner to reduce gastric acid secretion, allowing for a quick onset of action. On 24 April 2024, zastaprazan received approval in South Korea for the treatment of erosive gastroesophageal reflux disease (GERD). Zastaprazan is also undergoing phaseIII development for the treatment of gastric ulcer and for the prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer. This article summarizes the milestones in the development of zastaprazan leading to this first approval for erosive GERD.

A Contemporary Review on the Critical Role of Nonsteroidal Anti-inflammatory Agents in Colorectal Cancer Therapy.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are widely recognized as effective pain relievers and function by inhibiting the cyclooxygenase enzyme (COXs). Moreover, they have been found to participate in various cellular processes through different signaling pathways, such as WNT, MAPK, NF-κB, and PI3K/AKT/mTOR. This makes them potential candidates for chemoprevention of several malignancies, particularly colorectal cancer (CRC). However, the use of NSAIDs in cancer prevention and treatment is a complex issue due to their adverse effects and gastrointestinal toxicity. Therefore, it is crucial to explore combination therapies that can minimize side effects while maximizing synergistic effects with other agents and to evaluate the success rate of such approaches in both pre-clinical and clinical studies. In this review, we aim to provide an overview of the effects of NSAIDs in the prevention and treatment of CRC. We will focus on elucidating the possible mechanisms of action of these drugs, the signaling pathways involved in CRC, and the potential synergistic effects when combined with other therapeutic agents.

Pharmacokinetic interactions between fexuprazan, a potassium-competitive acid blocker, and nonsteroidal anti-inflammatory drugs in healthy males.

Fexuprazan, a novel potassium-competitive acid blocker, is expected to be used for the prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) induced ulcer. This study aimed to evaluate pharmacokinetic (PK) interactions between fexuprazan and NSAIDs in healthy subjects. A randomized, open-label, multicenter, six-sequence, one-way crossover study was conducted in healthy male subjects. Subjects randomly received one of the study drugs (fexuprazan 40 mg BID, celecoxib 200 mg BID, naproxen 500 mg BID, or meloxicam 15 mg QD) for 5 or 7 days in the first period followed by the combination of fexuprazan and one of NSAIDs for the same days and the perpetrator additionally administered for 1-2 days in the second period. Serial blood samples for PK analysis were collected until 48- or 72-h post-dose at steady state. PK parameters including maximum plasma concentration at steady state (Cmax,ss) and area under plasma concentration-time curve over dosing interval at steady state (AUCτ,ss) were compared between monotherapy and combination therapy. The PKs of NSAIDs were not significantly altered by fexuprazan. For fexuprazan, differences in PK parameters (22% in Cmax, 19% in AUCτ,ss) were observed when co-administered with naproxen, but not clinically significant. The geometric mean ratio (90% confidence interval) of combination therapy to monotherapy for Cmax,ss and AUCτ,ss was 1.22 (1.02-1.46) and 1.19 (1.00-1.43), respectively. There were no significant changes in the systemic exposure of fexuprazan by celecoxib and meloxicam. Fexuprazan and NSAIDs did not show clinically meaningful PK interactions.

Application of non-steroidal anti-inflammatory drugs in prevention of pancreatitis after endoscopic retrograde cholangiopancreatography

Application of non-steroidal anti-inflammatory drugs in prevention of pancreatitis after endoscopic retrograde cholangiopancreatography

Preoperative atropine and non-steroidal anti-inflammatory drugs for the prevention of intraoperative floppy iris syndrome.

To examine the efficacy of preoperative administration of topical atropine 1% and non-steroidal anti-inflammatory drugs (NSAIDs) for prevention of intraoperative floppy iris syndrome (IFIS). In this retrospective cohort study, patients who underwent cataract surgery by phacoemulsification between July 2019 and February 2020 in two hospitals were included. Both hospitals are located in central Israel, have similar patient demographics and employ similar surgical techniques. They, however, differ in policy of IFIS prevention. In Meir Medical Center no preventive medications are given pre-operatively, while in Shamir Medical Center patients at-risk for IFIS receive topical atropine 1% once daily and non-steroidal anti-inflammatory drugs (NSAIDs) thrice daily for 3days preoperatively. Overall, 207 eyes of 207 patients with history of alpha-antagonist use were included. Mean age was 74.9 ± 7.8years and 82.1% (n = 170) were male. Among patients from the pretreating center 86.8% (n = 92/106) were pre-treated with either NSAIDs or atropine preoperatively, while in the non-pretreating center no treatment was prescribed (n = 0/101). IFIS rate among the non-pretreating center was 29.7% (n = 30/101) compared to 15.1% (n = 16/106) in the pretreating center (p = 0.012). When strictly comparing treated to untreated patients, the treated group had an IFIS rate of 12.0% compared to 30.4% among untreated (p = 0.001). Adjusted for age and gender results remain consistent (odds ratio 0.329 for treated patients, 95% confidence interval: 0.150-0.720; p = 0.005). IFIS rates were significantly lower in the pretreating center compared to the non-pretreating center. When comparing strictly treated to untreated patients, differences were even more pronounced.

Development of a module for the prevention of nonsteroidal anti-inflammatory drugs-associated gastrointestinal adverse reactions in the elderly at a primary health center.

The prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) adverse reactions should start from the primary health center (PHC), as the first gatekeeper in community health services. However, there is no specific module available for health care professionals (HCPs) in Indonesia for the prevention of adverse drug reactions (ADR) at PHCs. NSAID is commonly used for the elderly treated at PHC in Indonesia, even though the ADR risk is well-known. We aimed to develop a module to be used in PHC for preventing NSAID-associated upper gastrointestinal (GI) ADRs in elderly patients treated for musculoskeletal diseases. The module was developed based on inputs from focus group discussions (FGD) among government health officers, PHC representatives, clinical pharmacologists, internal medicine and community medicine clinicians, pharmacovigilance experts, and professional organizations. A pilot implementation was conducted to test its feasibility and its effect on the HCPs' knowledge. Capacity building of HCPs, development of intra-HCP cooperation, as well as standard operating procedure (SOP) for the prescription of NSAID constituted important components of the module. A pilot study of the module in two PHCs showed that it was applicable with some recommendations for improvement in duration, number of participants, room space, presentation, and use of credit points as compliments. The HCPs' knowledge was improved after following the module. Our study showed that the module is feasible in PHC in Indonesia and useful in improving knowledge of HPC.

Role of Nonsteroidal Anti-Inflammatory Drugs in Prevention of Macular Edema after Uneventful Phacoemulsification in Diabetic and Non-Diabetic Patients

Role of Nonsteroidal Anti-Inflammatory Drugs in Prevention of Macular Edema after Uneventful Phacoemulsification in Diabetic and Non-Diabetic Patients

Role of Nonsteroidal Anti-Inflammatory Drugs in Prevention of Macular Edema after Uneventful Phacoemulsification in Diabetic and Non-Diabetic Patients

Background: Pseudophakic cystoid macular edema (PCME) is one of the most important complications after cataract surgery. This can result in decreased visual acuity. Purpose: The study aimed to assess the efficacy of using Non-steroidal anti inflammatory drugs (NSAIDs) as a prophylaxis, to prevent macular edema. Patients and methods: The study included 100 eyes with cataract and accepted phacoemulsification, classified into: Group 1: Non-diabetic patients were subdivided into: (1A didn’t receive NSAIDs, 1B received NSAIDs). Group 2: Type 2 diabetic patients were subdivided into: (2A didn’t receive NSAIDs, 2B received NSAIDs). One drop of nepafenac 0.1% was administrated four times daily for 2 days before surgery, 30-120 minutes prior to surgery. Postoperatively nepafenac was given four times daily for four weeks. SD-OCT was performed to measure central macular thickness(CMT) before phacoemulsification, repeated 1 week and 1 month postoperatively. Results: In subgroup 1A; CMT increased through one month, while subgroup 1B, CMT decreased through the same time. There was significant difference in CMT between preoperative and 1week postoperative as well as between preoperative and 1 month postoperative (p=0.025, 0.037 respectively). For subgroup 2A; CMT increased through one month. There was significant difference in CMT (p<0.001) between preoperative and 1week postoperative as well as between preoperative and 1 month postoperative (p<0.008) between subgroup 2B and subgroup2A Conclusion: The prophylactic use of topical NSAIDs appears to be effective for preventing CMT change after phacoemulsification. It reduces the incidence of PCME in normal and diabetic patients and ensures a favorable outcome.

The efficacy and safety of irsogladine maleate in nonsteroidal anti-inflammatory drug or aspirin-induced peptic ulcer and gastritis.

Background/AimsIrsogladine maleate, an enhancer of gastric mucosal protective factors, has demonstrated its efficacy for various gastric mucosal injuries. The aim of this study was to evaluate the efficacy and safety of irsogladine for prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin-induced peptic ulcer and gastritis.MethodsIn this multicenter, randomized, double-blind, exploratory clinical trial, 100 patients over 50 years of age who needed continuous NSAIDs or aspirin for more than 8 weeks were randomly assigned to either test group (irsogladine maleate 2 mg, twice daily, 39 patients for full analysis) or placebo group (37 patients for full analysis). Primary outcomes were incidence of peptic ulcer and ratio of modified Lanza score (MLS) 2 to 4. Secondary outcome was the number of acute erosions confirmed by endoscopy at 8 weeks. Adverse effects were also compared.ResultsThere were no significant differences in gastric protective effects between test and placebo groups. However, two cases of peptic ulcer in the placebo group but none in the test group were observed. These two cases of peptic ulcer were Helicobacter pylori-negative. In addition, H. pylori-negative group showed significant changes in MLS score (p = 0.0247) and edema score (p = 0.0154) after the treatment compared to those before treatment in the test group. There was no significant difference in adverse events between the two groups.ConclusionsThe efficacy of irsogladine maleate was found in H. pylori-negative group, suggesting its potential as a protective agent against NSAIDs or aspirin-induced peptic ulcer and gastritis.

Impact of topical nonsteroidal anti-inflammatory drugs in prevention of macular edema following cataract surgery in diabetic patients.

To evaluate the efficacy of prophylactic administration of topical non-steroidal anti-inflammatory drugs (NSAIDs) on macular edema following cataract surgery in diabetic patients, and to compare between types of NSAIDs (ketorolac tromethamine 0.4% and nepafenac 0.1%). Group 1 (control) received artificial tears substitute as a placebo group, group 2 (nepafenac) received topical nepafenac 0.1%, and group 3 (ketorolac) received topical ketorolac tromethamine 0.4%. Patients were examined postoperatively after completing one week, one month, two months and three months' intervals for evaluating cystoid macular edema (CME) development. The main study outcomes were achieving the best corrected visual acuity (BCVA) and change in the central macular thickness (CMT) measured with optical coherence topography (OCT). Eighty eyes of 76 patients were included in this study. BCVA showed a statistically significant difference at the third month postoperative follow up between the control group and the NSAIDs groups (P=0.04). There was an increase in the CMT in all cases starting from postoperative first week until third month. CMT showed a statistically significant difference between control group and NSAIDs groups from postoperative first month until third month (P=0.008, 0.027, 0.004). There was no statistically significant difference between nepafenac and ketorolac groups in BCVA and OCT CMT. Prophylactic preoperative and postoperative NSAIDs may have a role in reducing the frequency and severity of CME in diabetic eyes following cataract surgery.

Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study

ObjectiveTo assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use.DesignA phase 3, 24-week,...

Nonsteroidal Anti-inflammatory Drugs for Prevention of Post-ERCP Pancreatitis: Sooner Rather Than Later during ERCP?

Nonsteroidal Anti-inflammatory Drugs for Prevention of Post-ERCP Pancreatitis: Sooner Rather Than Later during ERCP?

An update on nonsteroidal anti-inflammatory drugs and gastrointestinal risk

Recommendations for the prevention of nonsteroidal anti-inflammatory drug (NSAID)-related gastrointestinal ulceration and cardiovascular (CV) complications were recently made available through an initiative designed in collaboration with leading specialists in South Africa. The prevention of CV complications and NSAID-related ulceration are discussed in two articles for the purposes of this publication. The first article in this two-part series presented an update on NSAID-related CV risk. This is the second article, and provides an update on NSAIDs and gastrointestinal risk.

Effectiveness of nonsteroidal anti-inflammatory drugs in prevention of post-ERCP pancreatitis: a meta-analysis.

To investigate the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Two independent reviewers searched PubMed (1966 to October 2013), Embase (1984 to October 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 4, 2013) for relevant randomized controlled trials (RCTs) studying the effectiveness of prophylactic NSAID administration in the prevention of PEP. Using the Cochrane Collaboration Handbook, meta-analyses were conducted to evaluate the overall effect of NSAIDs in preventing the incidences of PEP and moderate to severe pancreatitis. Eight RCTs were identified from the literature search and included 1883 patients that underwent ERCP, with 971 patients in the NSAID group and 912 patients in the placebo group. Sixty-nine out of 971 (7.11%) patients developed PEP in the NSAID group in comparison to 143 out of 912 (15.68%) patients in the placebo group. The pooled RR of PEP incidence with prophylactic NSAID administration was 0.43 (95%CI: 0.33-0.56), which demonstrates that NSAID administration after ERCP significantly reduced the incidence of PEP when compared to the placebo group (P < 0.0001). Subgroup analysis was performed and revealed that the presence (NSAID group) or absence (placebo group) of NSAIDs had no significant effect on the development of moderate to severe pancreatitis (RR = 0.79, 95%CI: 0.52-1.18). Moreover, the administration of NSAIDs as a rectal suppository (RR = 0.35, 95%CI: 0.26-0.48; P < 0.0001) was more effective than oral administration (RR = 0.97, 95%CI: 0.53-1.80) or through infusion (RR = 0.43, 95%CI: 0.12-1.54). NSAIDs effectively reduce the incidence of PEP but not of moderate to severe pancreatitis.

Continuing Medical Education Exam: December 2012

Instructions: The GIE: Gastroinintestinal Endoscopy CME Activity can now be completed entirely on-line. To complete do the following: 1. Read the CME article in this issue carefully and complete the activity: Ding X, Chen M, Huang S, et al. Nonsteroidal anti-inflammatory drugs for prevention of post-ERCP pancreatitis: a meta-analysis. Gastrointest Endosc 2012;76:1152-9. Conio M, De Ceglie A, Filiberti R, et al. Cap-assisted EMR of large, sporadic, nonampullary duodenal polyps. Gastrointest Endosc 2012;76:1160-9. Gardner TB. Endoscopic management of necrotizing pancreatitis. [Review] Gastrointest Endosc 2012;76:1214-23. Ali MA, Lam-Himlin D, Voltaggio L, et al. Eosinophilic esophagitis: a clinical, endoscopic, and histopathologic review. Gastrointest Endosc 2012;76:1224-37. 2. Log in on-line to complete a single examination with multiple choice questions followed by a brief post-test evaluation. Visit the Journal’s Web site at www.asge.org (members) or www.giejournal.org (nonmembers). 3. Persons scoring greater than or equal to 75% pass the examination and can print a CME certificate. Persons scoring less than 75% cannot print a CME certificate; however, they can retake the exam. Exams can be saved to be accessed at a later date. ou may create a free personal account to save and return to your work in progress, as well as save and track your completed activities o that you may print a certificate at any time. The complete articles, detailed instructions for completion, as well as past Journal CME ctivities can also be found at this site.

Randomised clinical trial: esomeprazole for the prevention of nonsteroidal anti‐inflammatory drug‐related peptic ulcers in Japanese patients

The use of proton pump inhibitors for prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal adverse events is well documented. However, data regarding the efficacy and safety of this approach in Japan are scarce. To evaluate the efficacy and tolerability of esomeprazole in preventing NSAID-induced peptic ulcers in Japanese at-risk patients. Male and female Japanese adult patients (aged ≥ 20 years) with endoscopically confirmed history of peptic ulcers who required long-term oral NSAID therapy for a chronic inflammatory condition were randomised to 24 weeks' treatment with esomeprazole 20 mg once daily or matching placebo. The primary end point was the Kaplan-Meier estimated proportion of ulcer-free patients. Overall, 343 patients were randomised to treatment (esomeprazole, n = 175; placebo, n = 168). The Kaplan-Meier estimated ulcer-free rate over the 24-week treatment period was significantly higher (log-rank P < 0.001) in esomeprazole-treated patients (96.0%; 95% CI 92.8, 99.1) than in placebo recipients (64.4%; 95% CI 56.8, 71.9). Esomeprazole was effective at preventing peptic ulcers in both Helicobacter pylori-positive and -negative patients (96.3% vs. 95.5% of patients ulcer-free, respectively); however, in the placebo group, the proportion of ulcer-free patients at 24 weeks was markedly lower among H. pylori-positive than -negative patients (59.7% vs. 69.9%). The NSAID type did not seem to affect the estimated ulcer-free rate with esomeprazole. Treatment with esomeprazole was well tolerated. Esomeprazole 20 mg once daily is effective and safe in preventing ulcer recurrence in Japanese patients with a definite history of peptic ulcers who were taking an NSAID (ClinicalTrials.gov identifier: NCT00542789).

Nonsteroidal Anti-inflammatory Drug Use Reduces Risk of Adenocarcinomas of the Esophagus and Esophagogastric Junction in a Pooled Analysis

Regular use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been reported to reduce risks of esophageal adenocarcinoma (EAC) and esophagogastric junctional adenocarcinoma (EGJA). However, individual studies have been too small to accurately assess the effects of medication type, frequency, or duration of use. We performed a pooled analysis to investigate these associations. We performed a pooled analysis of 6 population-based studies within the Barrett's and Esophageal Adenocarcinoma Consortium to evaluate the association between NSAID use and the risk of EAC and EGJA, using uniform exposure definitions. We collected information from 6 studies (5 case-control and 1 cohort), with a total of 1226 EAC and 1140 EGJA cases, on aspirin and/or NSAID use. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate adjusted logistic regression models and then pooled using a random effects meta-analysis model. Compared with nonusers, individuals who have used NSAIDs had a statistically significant reduced risk of EAC (OR, 0.68; 95% CI, 0.56-0.83); they also appeared to have a reduced risk of EGJA (OR, 0.83; 95% CI, 0.66-1.03). Similar reductions in risk were observed among individuals who took aspirin or nonaspirin NSAIDs. The highest levels of frequency (daily or more frequently) and duration (≥10 years) of NSAID use were associated with an approximately 40% reduction in risk of EAC, with ORs of 0.56 (95% CI, 0.43-0.73; P(trend) < .001) and 0.63 (95% CI, 0.45-0.90; P(trend) = .04), respectively. Although reverse causation could, in part, explain the inverse association observed between NSAID use and EAC risk, our pooled analysis suggests a possible role for NSAIDs in prevention of adenocarcinomas of the esophagus and esophagogastric junction.

Aspirin therapy in aspirin-exacerbated respiratory disease: A risk‐benefit analysis for the practicing allergist

This study was designed to investigate the risks associated with aspirin (ASA) therapy that is used in high doses for the treatment of ASA-exacerbated respiratory disease (AERD) and to review therapeutic strategies for the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced side effects. A PubMed search was performed using the key words "aspirin" and "adverse effects." Additional citations were generated by surveying the reference lists of the pulled articles. More than 120 articles were reviewed and references were selected based on their relevance to the subject matter. Prevalence rates of ASA hypersensitivity in the general population have been reported to be 0.6-2.5%. Asthmatic patients have higher rates of ASA hypersensitivity. The allergy/immunology specialty is unique in the use of prolonged high-dose ASA therapy for the treatment of AERD. ASA use is associated with an increased risk for the development of serious gastrointestinal (GI) events including GI bleeding, ulcers, and perforation. Established risk factors for GI ulcer development include advanced age, history of ulcer or GI bleed, concomitant use of corticosteroids or anticoagulants, high-dose ASA/NSAID therapy, and possibly concomitant Helicobacter pylori infection. Effective strategies to prevent GI complications include initiation of a proton pump inhibitor (PPI), misoprostol, or double dose H(2)-receptor antagonists (H(2)RAs) at the start of ASA therapy. Allergist/immunologists are involved in treatment decisions regarding high-dose ASA use in AERD. The primary risk of using ASA therapy is the development of GI complications. Cotherapy with a PPI, misoprostol, or double dose H(2)RAs can reduce GI complications associated with high-dose ASA therapy.

Education-based approach to addressing non-evidence-basedpractice in preventing NSAID-associated gastrointestinalcomplications

To evaluate an evidence-based educational program for improving strategies for prevention of nonsteroidal anti-inflammatory drug (NSAID)-associated gastrointestinal (GI) complications. Four hundred and fifty-six specialists replied to a questionnaire that covered issues related to NSAID-induced adverse effects. They also collected data from their last five consecutive patients before and after they had attended an evidence-based seminar on GI prevention strategies. Four hundred and forty-one of 456 specialists (96.7%) participated in the survey, and 382 (83.7%) in the education-based study that recorded data from 3728 patients. The specialists overestimated the risk of GI complications with NSAIDs, underestimated the GI safety profile of coxibs, but were aware of the risk factors and of the current prevention strategies. Proton pump inhibitors were co-prescribed with NSAIDs in > 80% of patients with and without risk factors. The educational program had little impact on prescribing habits. Specialists are informed of advances in NSAID-associated adverse effects and have high rates of GI-prevention therapy. Our educational program did not alter these rates.

Prevention of Indomethacin-Induced Gastric Mucosal Injury in Helicobacter pylori-Negative Healthy Volunteers: A Comparison Study Rebamipide vs Famotidine

The clinical efficacy of gastroprotective drugs or low-dose H2 receptor antagonists in the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy is limited. The aim of the present study was to investigate efficacy of rebamipide and famotidine in Helicobacter pylori (H. pylori)-negative healthy volunteers taking NSAID. This study was a randomized, two way crossover study comparing the preventive effect rebamipide 100 mg, t.i.d. and famotidine 10 mg, b.i.d against indomethacin (25 mg, t.i.d.)-induced gastric mucosal injury in H. pylori-negative healthy volunteers. 12 subjects satisfied criteria and were randomized. Endoscopy was performed at baseline and again after the treatment for 7 days, and symptoms were recorded during the treatment. Tissue levels of lipid peroxides and myeloperoxidase and serum indomethacin concentrations were also measured. Subjective symptoms were developed in 58% (7/12) of the rebamipide group, and in 75% (9/12) of the famotidine group (no significant differences). The incidence of gastric lesions (modified Lanza score 2 or higher) was 17% (2/12) in the rebamipide group and 25% (3/12) in the famotidine group. Peptic ulcers did not occur in both groups. There were no significant differences in tissue levels of lipid peroxide and myeloperoxidase and serum level of indomethacin between two groups after the treatment. In conclusion, these data recommend rebamipide (100 mg, t.i.d.) or famotidine (10 mg, b.i.d.) for the prevention of acute gastric injury induced by NSAID in patients without a particular risk factor.