Efficacy of fexuprazan compared with rebamipide in Korean patients with gastritis: A matching-adjusted indirect comparison.

BACKGROUND: Gastritis is one of the most frequently diagnosed diseases requiring medical treatment in South Korea. Fexuprazan, a novel potassium-competitive acid blocker, has been approved for treating gastritis and erosive esophagitis. Meanwhile, rebamipide is the most commonly used mucoprotective agent for acute and chronic gastritis in real-world settings in South Korea. However, there have been no studies comparing the efficacy of these two drugs yet. AIM: To compare the efficacy of fexuprazan with that of rebamipide for acute and chronic gastritis. METHODS: This was a matching-adjusted indirect comparison. Individual patient data from a phase III study of fexuprazan (10 mg BID) were compared with cumulative data from two matching studies of rebamipide (100 mg TID). Erosion improvement and healing rates were compared between two weeks of fexurapan, two weeks of rebamipide, and four weeks of rebamipide. The two main outcome variables were presented as percentages, and the risk differences (RD) and 95% confidence intervals (CI) were calculated for the relative treatment effects. RESULTS: In the primary analysis, the erosion improvement and healing rates after a two-week treatment with fexuprazan were 64.5% and 53.2%, respectively, while a two-week treatment with rebamipide resulted in erosion improvement and healing rates of 43.6% (RD: 21.0%; 95%CI: 9.6-32.3; P < 0.01) and 35.6% (RD: 17.6%; 95%CI: 6.1-29.2; P = 0.003), respectively. In the additional analysis, the erosion improvement and healing rates for the two-week fexuprazan treatment (64.2% and 51.2%, respectively) were similar to those obtained during a four-week treatment with rebamipide (60.6%; RD: 3.6%; 95%CI: -9.8, 17.0; P = 0.600 and 53.5%; RD: -2.3%; 95%CI: -16.1, 11.5; P = 0.744, respectively). CONCLUSION: The two-week fexuprazan treatment was superior to the two-week rebamipide treatment and similar to the four-week rebamipide treatment for patients with gastritis.

Rebamipide gargle and benzydamine gargle in prevention and management of chemo-radiotherapy and radiotherapy-induced oral mucositis in head and neck cancer patients (randomized clinical trial).

OBJECTIVES: This study aimed to evaluate the preventive and therapeutic effects of rebamipide gargle in comparison with benzydamine in head and neck cancer patients undergoing radiotherapy with or without chemotherapy. MATERIALS AND METHODS: Phase III randomized clinical trial was conducted from January 2021 till August 2022 on one hundred patients with head and neck cancer receiving high doses of radiotherapy. These patients were equally allocated into either rebamipide group or benzydamine group, The measured outcomes were the incidence of oral mucositis ≥ grade1, according to the WHO mucositis scale, in addition to the duration, and the onset of oral mucositis. RESULTS: There was no statistically significant difference between the two groups, regarding the incidence of a severe grade of oral mucositis (WHO grades 3), as well as the onset and duration of oral mucositis. Both gargles succeeded to prevent the development of WHO grade 4 oral mucositis. Side effects reported were mainly burning sensation in benzydamine group and nausea in rebamipide group. CONCLUSION: Rebamipide mouthwash was as beneficial as benzydamine mouthwash in minimizing the incidence of severe oral mucositis induced by treatment of head and neck cancer. However, rebamipide gargle proved to be superior to benzydamine in terms of reduction in the severity of the radiation-induced oral mucositis. TRIAL REGISTRATION: The trial was registered in the protocol Registration and Result system of Clinical Trials (Registration ID: NCT04685395)0.28-12-2020.

Enhancing Corneal Drug Penetration Using Penetratin for Ophthalmic Suspensions.

Eye drops, including solutions and suspensions, are essential dosage forms to treat ophthalmic diseases, with poorly water-soluble drugs typically formulated as ophthalmic suspensions. In addition to low bioavailability, suspensions exhibit limited efficacy, safety, and usability due to the presence of drug particles. Improving bioavailability can reduce the drug concentrations and the risk of problems associated with suspended drug particles. However, practical penetration enhancers capable of improving bioavailability remain elusive. Herein, we focused on penetratin (PNT), a cell-penetrating peptide (CPP) that promotes active cellular transport related to macromolecule uptake, such as micropinocytosis. According to the in vitro corneal uptake study using a reconstructed human corneal epithelial tissue model, LabCyte CORNEA-MODEL24, PNT enhanced the uptake of Fluoresbrite® YG carboxylate polystyrene microspheres without covalent binding. In an ex vivo porcine eye model, the addition of 10 µM PNT to rebamipide ophthalmic suspension markedly improved the corneal uptake of rebamipide; however, the addition of 100 µM PNT was ineffective due to potentially increased particle size by aggregation. This article provides basic information on the application of PNT as a penetration enhancer in ophthalmic suspensions, including the in vitro and ex vivo studies mentioned above, as well as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay and storage stability at different pH values.

High-Performance Liquid Chromatography (HPLC) Method Validation for Identifying and Quantifying Rebamipide in Ethosomes.

Introduction The research aimed to develop a robust, high-performance liquid chromatography (HPLC) analytical method for the quantitative assessment of rebamipide encapsulated in ethosomes. Rebamipide, a quinolinone derivative, holds promise as a therapeutic agent for dry eye, but challenges such as low bioavailability and vision clouding post-installation have prompted innovative approaches. Encapsulation in ethosomes, lipid-based nanovesicles, offers a potential solution to enhance ocular bioavailability. Materials and methods The study focused on creating a specific, linear, accurate, precise, and robust HPLC method, addressing entrapment efficiency (%EE), drug content, and drug release of rebamipide in prepared ethosomes. Statistical validation followed International Conference of Harmonization (ICH) specifications. The method's parameters were evaluated within a concentration range of 4-24 µg/ml, with recovery rates indicating accuracy and low % relative standard deviation (RSD) values confirming precision. Limits of detection (LOD) and quantification (LOQ) for rebamipide were determined. Results After preparing the ethosome dosage form by film hydrating method for rebamipide, the rebamipide entrapment efficiency in ethosomes was established at 76% ± 7, while the drug content was found to be 93% ± 6. The drug release process demonstrated zero-order kinetics and five different models of kinetics were applied for a comprehensive analysis. The method exhibited excellent system suitability, specificity, and linearity. Recovery rates for rebamipide ranged from 90% to 100%, and repeatability was confirmed by low %RSD values. The LOD and LOQ for rebamipide were determined to be 1.04 µg/mL and 3.16 µg/mL, respectively. Conclusion The developed HPLC method proved suitable for the quantitative determination of rebamipide in ethosomes, offering rapid and accurate analysis. The results underscore the method's specificity, accuracy, and precision within the specified concentration range. Overall, the validated method contributes to the advancement of ocular drug delivery systems, providing a reliable analytical tool for pharmaceutical research.

Rebamipide Prevents the Hemoglobin Drop Related to Mucosal-Damaging Agents at a Level Comparable to Proton Pump Inhibitors.

Background/Aims: : The effect of proton pump inhibitors (PPIs) on the lower gastrointestinal (GI) tract is uncertain, with potential to worsen damage. This study aimed to find the best method for protecting the entire GI tract from mucosal damage. Methods: : A retrospective cohort study at Samsung Medical Center (2002-2019) included 195,817 patients prescribed GI mucosa-damaging agents. The primary goal was to assess the effectiveness of GI protective agents in preventing significant hemoglobin drops (>2 g/dL), indicating overall GI mucosal damage. Self-controlled case series and landmark analysis were used to address biases in real-world data. Results: : The incidence rate ratios for rebamipide, PPI, and histamine-2 receptor antagonist (H2RA) were 0.34, 0.33, and 0.52, respectively. Rebamipide showed a significantly lower incidence rate than H2RA and was comparable to PPIs. Landmark analysis revealed significant reductions in hemoglobin drop risk with rebamipide and H2RA, but not with PPI. Conclusions: : Rebamipide, like PPIs, was highly effective in preventing blood hemoglobin level decreases, as shown in real-world data. Rebamipide could be a comprehensive strategy for protecting the entire GI tract, especially when considering PPIs' potential side effects on the lower GI tract.

The Efficacy and Safety of Rebamipide Ophthalmic Suspension (OPC-12759) in Patients with Dry Eye Disease: A Systematic Review of Randomized Controlled Trials.

The aim of this paper is to evaluate the efficacy and safety of Rebamipide (REB) ophthalmic suspension in dry eye disease (DED). A systematic review that only included full-length randomized controlled studies (RCTs) reporting the effects of REB ophthalmic suspension in three databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement. The Cochrane risk of bias tool was used to analyze the quality of the studies selected. A total of seven studies were included in this systematic review. Although the overall risk of bias was low, most studies were sponsored by the manufacturer. REB ophthalmic suspension treatment achieved higher improvement than the control group in all reported variables. The mean differences between both groups were in favor of the REB group and were as follows: dry eye-related quality of life score (DEQS) -3.5 ± 2.9 points, tear film break-up time (TBUT) of 0.7 ± 0.6 s, Schirmer test (ST) without anesthesia of 0.3 ± 0.6 mm and total corneal fluorescein staining (tCFS) of -1.2 ± 0.7 points. Adverse events (AEs) were 5.2 ± 7.6% superior in the REB group, with an overall compliance > 95%. Therefore, REB ophthalmic suspension is a safe and effective treatment that could be recommended in patients with DED.

Management of Recurrent Aphthous Stomatitis: An Indian Expert Consensus.

Recurrent aphthous stomatitis (RAS) is characterized by painful, oral mucosal ulcers with wide range of prevalence ranging from 2 to 78%. Etiology of RAS is idiopathic and multifactorial. There are numerous gaps in assessment and management of RAS and the absence of guidelines or a consensus document makes the treatment further difficult. The aim of this document is to provide an Indian expert consensus for management of RAS. Experts from different specialties such as Otorhinolaryngology, Oral Medicine/Dentistry and Internal Medicine from India were invited for face to face and online meetings. After a deliberate discussion of current literature, evidence and clinical practice during advisory meetings, experts developed a consensus for management of RAS. We identify that the prevalence of RAS may lie between 2 and 5%. In defining RAS, we advocate three or more recurrences of aphthous ulcers per year as criterion for RAS. Investigation should include basic hematological (complete blood count) and nutritional (serum vitamin B12, and iron studies) parameters. Primary aim of treatment is to reduce the pain, accelerate ulcer healing, reduce the recurrences and improve the quality of life. In treating RAS, initial choice of medications is determined by pain intensity, number and size of ulcers and previous number of recurrences. Topical and systemic agents can be used in combination for effective relief. In conclusion, this consensus will help physicians and may harmonize effective diagnosis and treatment of RAS.

A novel approach to achieve semi-sustained drug delivery to the eye through asymmetric loading of soft contact lenses.

Soft contact lenses are increasingly being explored as a vehicle for controlled delivery of ophthalmic drugs. However, traditional methods of drug-loading by soaking have limitations such as burst delivery and the release of drugs at the front side of the lens, leading to poor drug efficacy and systemic side effects. This study introduces a new methodology, termed asymmetric drug loading, whereby the ophthalmic drug 'Rebamipide' is attached to and released from the post-lens (=cornea-contacting) surface exclusively. The methodology involves using polymeric microparticles that carry a lipophilic crystalline ophthalmic drug at their surface. These drug-loaded microparticles first transfer the drug to the concave surface of the contact lens, and when worn, the drug is transferred again, now from the lens to the cornea. This is achieved through the diffusion of the drug from one hydrophobic microenvironment (the silicone moieties of the contact lens polymer network) to another hydrophobic microenvironment (the corneal epithelium) over a short pathway. The second drug transfer was observed and studied in experiments using an ex vivo porcine eye model. The results show that the drug amount that was absorbed by the cornea after applying the rebamipide-loaded contact lenses is approximately 3× (10.7 ± 3.1 µg) as much as the amount of rebamipide that gets transferred after the instillation of one eye drop (1% solution (p < 0.001). The new drug-loading method offers a practical and reproducible means of delivering ophthalmic drugs to the cornea through soft contact lenses. The drug payloads achieved are comparable to dosages used during eye drop therapy.

[The effect of the FODMAP and rebamipid diet on the activity of disaccharidases in patients with enteropathy with impaired membrane digestion].

AIM: To compare the effect of a diet low in fermentable oligo-, di-, monosaccharides and polyols (fermentable oligosaccharides, disaccharides, monosaccharides and polyols - FODMAP) and rebamipide on carbohydrate tolerance and disaccharidases activity in patients with maldigestive enteropathy (ENMP). MATERIALS AND METHODS: The study included 61 patients with ENMP with reduced small intestine carbohydrases. Their glucoamylase activity was 100 ng glucose/mg tissue × min (quartile 53, 72), maltase - 504 (quartile 258, 708), sucrase - 43 (quartile 25, 58), lactase - 8 (quartile 4, 20). Group 1 included 19 people on a low FODMAP diet. The 2nd group included 42 patients who were on a normal diet and received rebamipide 300 mg/day. Patients were monitored weekly for 8 weeks. RESULTS: In 16 patients of the 1st group, abdominal pain and stool disorders decreased, in 15 patients, swelling and rumbling in the abdomen stopped. Glucoamylase activity increased to 196 (quartile 133, 446, р<0.024) ng glucose/mg tissue × min, maltase activity increased to 889 (quartile 554, 1555, p<0.145), sucrase activity increased to 67 (quartile 43, 175, p<0.039), lactase activity increased to 13 (quartile 9, 21, p<0.02). After the diet was discontinued, intestinal symptoms in patients of group 1 resumed. In 27 patients of the 2nd group after 4 weeks dyspeptic manifestations decreased, in 34 patients the tolerability of products containing FODMAP improved. Continuation of treatment up to 8 weeks contributed to a further improvement in well-being. Glucoamylase activity increased after 4 and 8 weeks to 189 (quartile 107, 357, p<0.013) and 203 (quartile 160, 536, p<0.005), respectively; maltase - up to 812 (quartile 487, 915, p<0.005) and 966 (quartile 621, 2195, р<0.0012); sucrases - up to 60 (quartile 34, 105, p<0.013) and 75 (quartile 52, 245, р=0.003); lactase - up to 12 (quartile 8, 12, p<0.132) and 15 ng glucose/mg tissue × min (quartile 10, 20, р<0.092). CONCLUSION: The clinical symptoms of fermentable carbohydrate intolerance and increased membrane enzyme activity are reduced by a low FODMAP diet in patients with ENMT, but clinical symptoms of food intolerance reappear when switching to a normal diet. Treatment with rebamipide improves food tolerance and consistently increases the activity of TSOTS enzymes after 4 and 8 weeks.

[Pharmacokinetics and pharmacodynamics of rebamipide. New possibilities of therapy: A review].

The MedLine database contains 570 publications, including 71 randomized clinical trials and 6 meta-analyses on the rebamipide molecule in 2022. Indications for the use of rebamipide are gastric ulcer, chronic gastritis with hyperacidityin the acute stage, erosive gastritis, prevention of damage to the gastrointestinal mucosa while taking non-steroidal anti-inflammatory drugs, eradication of Helicobacter pylori. Currently trials are studying the efficacy and safety of the drug in gouty and rheumatoid arthritis, osteoarthritis, Sjögren's syndrome, bronchial asthma, vitiligo, atherosclerosis, diseases of the kidneys and liver; using in traumatology to accelerate bone regeneration; in ophthalmology to improve the regeneration of corneal epithelium; in oncology to reduce inflammatory changes in the oral mucosa after chemoradiotherapy. The review article is about the main pharmacokinetic and pharmacodynamic characteristics of rebamipide. A detailed understanding of pharmacodynamics and pharmacokinetics allows for individual selection of therapy based on the characteristics of the patient's body - gender, age, comorbidities; choose the optimal route of administration and dosing regimen; predict adverse effects and drug interactions; be determined with new clinical indications.

Rebamipide protects against experimentally induced intestinal ischemia/reperfusion-promoted liver damage: Impact on SIRT1/ß-catenin/FOXO1and NFκB signaling.

Rebamipide (Reba) is a well-known gastroprotective agent. However, its potential protective efficacy against intestinal ischemia/reperfusion (I/R)-induced liver injury remains elusive. Therefore, this study aimed to assess the modulatory effect of Reba on SIRT1/ß-catenin/FOXO1-NFκB signaling cascade. Thirty-two male Wistar albino rats were randomized into four groups: G1 (sham): rats were subjected to surgical stress without I/R, GII (I/R): rats were subjected to 60 min/4-h I/R, GIII (Reba + I/R): rats received Reba 100 mg/kg/day, p.o. for three weeks, then were subjected to 60 min/4-h I/R, and GIV (Reba + EX527 + I/R): rats received Reba (100 mg/kg/day p.o.) + EX527 (10 mg/kg/day, ip) for three weeks before I/R. Reba pretreatment decreased the serum levels of ALT and AST, improved I/R-induced histological alterations of both intestine and liver, increased hepatic Silent information regulator 1 (SIRT1) expression/content, ß-catenin expression/immunoreactivity, and FOXO1 expression, while suppressed NF-κB p65 expression/protein content. In addition, Reba increased hepatic total antioxidant capacity (TAC), while suppressed malondialdehyde (MDA), tumor necrosis factor (TNFα), and caspase-3 activity. Furthermore, Reba inhibited BAX expression, while upregulated Bcl-2 expression. Reba exhibited a plausible protective effect against intestinal I/R-mediated liver injury by modulating SIRT1/ß-catenin/FOXO1-NFκB signaling mechanisms.

Targeting SIRT1/FoxO3a/Nrf2 and PI3K/AKT Pathways with Rebamipide Attenuates Acetic Acid-Induced Colitis in Rats.

Rebamipide is a quinolone derivative that has been commonly used for the treatment of gastric and duodenal ulcers. However, the molecular mechanisms of rebamipide against acetic acid-evoked colitis have not been adequately examined. Hence, the current study aimed to investigate the ameliorative effect of rebamipide in a rat model of acetic acid-evoked ulcerative colitis and the linked mechanisms pertaining to SIRT1/FoxO3a/Nrf2 and PI3K/AKT pathways. Herein, colitis was induced by the intrarectal administration of 3% acetic acid solution in saline (v/v) while rebamipide was administered by oral gavage (100 mg/kg/day) for seven days before the colonic insult. The colonic injury was examined by macroscopical and microscopical examination. The current findings demonstrated that rebamipide significantly improved the colonic injury by lowering the colonic disease activity index and macroscopic mucosal injury score. Moreover, it mitigated the histopathological aberrations and microscopical damage score. The favorable outcomes of rebamipide were driven by combating inflammation evidenced by dampening the colonic expression of NF-κBp65 and the pro-inflammatory markers CRP, TNF-α, and IL-6. In the same context, rebamipide curtailed the colonic pro-inflammatory PI3K/AKT pathway as seen by downregulating the immunostaining of PI3K and p-AKT(Ser473) signals. In tandem, rebamipide combated the colonic pro-oxidant events and augmented the antioxidant milieu by significantly diminishing the colonic TBARS and replenishing GSH, SOD, GST, GPx, and CAT. In the same regard, rebamipide stimulated the colonic upstream SIRT1/FoxO3a/Nrf2 axis by upregulating the expression of SIRT1, FoxO3a, and Nrf2, alongside downregulating Keap-1 gene expression. These antioxidant actions were accompanied by upregulation of the protein expression of the cytoprotective signal PPAR-γ in the colons of rats. In conclusion, the present findings suggest that the promising ameliorative features of rebamipide against experimental colitis were driven by combating the colonic inflammatory and oxidative responses. In perspective, augmentation of colonic SIRT1/FoxO3a/Nrf2 and inhibition of PI3K/AKT pathways were engaged in the observed favorable outcomes.

Efficacy and safety of topical 2% rebamipide ophthalmic suspension in dry eye disease at tertiary care centre.

Purpose: To evaluate the effect and side effects of topical 2% rebamipide ophthalmic suspension in dry eye disease. Method: This prospective randomized case control study included total 80 patients (40 cases and 40 controls) of dry eye. Symptoms were graded according to OSDI scoring system and specific tests for dry eye included Tear film breakup time (TBUT), Schirmer's test, Fluorescein corneal staining (FCS), Rose Bengal staining) were performed. Case group received 2% rebamipide ophthalmic suspension four times daily and control group given carboxymethylcellulose 0.5% four times daily. The follow ups had done at two, six and twelve weeks. Results: The maximum numbers of patients were between 45-60 years. Patient with mild moderate and severe OSDI Score shows marked improvement. Mild TBUT score showed improvement but statistically not significant (P value-0.34). In moderate and severe TBUT Score statistically significant improvement (P value- 0.0001, 0.0001). In all grade FCS shows statistically significant improvement with p value-0.0001, 0.0001, and 0.028 respectively. Schirmer's test score in all cases had shown improvement but statistically not significant and P value were 0.09, 0.07, and 0.07 respectively. In mild, moderate and severe Rose Bengal staining statistically significant improvement (P value -0.027, 0.0001, and 0.04) .The only side effect was dysgeusia (10% patients). Conclusion: Rebamipide 2% ophthalmic suspension showed significant improvement in symptoms and signs of dry eye. It able to modify epithelial cell function, improve tear stability, and suppress inflammation suggests that it may be a first drug of choice for severe dry eye disease.

The Development of Super-Saturated Rebamipide Eye Drops for Enhanced Solubility, Stability, Patient Compliance, and Bioavailability.

The present study aimed to develop clear aqueous rebamipide (REB) eye drops to enhance solubility, stability, patient compliance, and bioavailability. For the preparation of a super-saturated 1.5% REB solution, the pH-modification method using NaOH and a hydrophilic polymer was employed. Low-viscosity hydroxypropyl methylcellulose (HPMC 4.5cp) was selected and worked efficiently to suppress REB precipitation at 40 °C for 16 days. The additionally optimized eye drops formulation (F18 and F19) using aminocaproic acid and D-sorbitol as a buffering agent and an osmotic agent, respectively, demonstrated long-term physicochemical stability at 25 °C and 40 °C for 6 months. The hypotonicity (<230 mOsm) for F18 and F19 noticeably extended the stable period, since the pressure causing the REB precipitation was relieved compared to the isotonic. In the rat study, the optimized REB eye drops showed significantly long-lasting pharmacokinetic results, suggesting the possibility of reducing daily administration times and increasing patient compliance (0.50- and 0.83-times lower Cmax and 2.60- and 3.64-times higher exposure in the cornea and aqueous humor). In conclusion, the formulations suggested in the present study are promising candidates and offer enhanced solubility, stability, patient compliance, and bioavailability.

Further insights into the impact of rebamipide on gentamicin-induced nephrotoxicity in rats: modulation of SIRT1 and ß-catenin/cyclin D1 pathways.

Gentamicin (GM) is an effective antibiotic administered to treat acute Gram-negative infections. Nevertheless, its clinical application is limited due to nephrotoxicity. Therefore, our research aimed to investigate the potential renoprotective impact of rebamipide (RBM), a gastroprotective drug, on GM-induced kidney damage in rats, as well as putative nephroprotective pathways. RBM was orally administered (100 mg/kg/d for 14 d) commencing 7 d before the administration of GM (100 mg/kg/d, intraperitoneally). Nephrotoxicity was elucidated, and the silent information regulator 1 (SIRT1) and ß-catenin/cyclin D1 pathways were assessed. GM induced a significant elevation in the serum levels of creatinine, blood urea nitrogen (BUN), and kidney injury molecule-1 (KIM-1), as well as the relative kidney index. In addition, GM increased lipid peroxidation and lowered total antioxidant capacity (TAC) level and superoxide dismutase (SOD) activity. GM administration also demonstrated a significant amplification in tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), nuclear factor-κappa B p65 (NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), and caspase-3 kidney levels, as well as B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax)/Bcl-2 ratio. Notably, RBM treatment amended all these changes induced by GM. Furthermore, the potential role of SIRT1 and ß-catenin-dependent signaling pathways in GM-induced renal injury was assessed. Our findings showed that GM-treated rats demonstrated a substantial decrease in SIRT1, nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) along with an increase in ß-catenin, forkhead box O-3a (FOXO-3a), and cyclin D1 protein expressions. RMB treatment markedly attenuated the deterioration caused by GM on these pathways. Additionally, RBM alleviated the GM-induced deleterious kidney tissue histopathology. In conclusion, our findings have verified that RBM can halt GM-induced renal injury by partly modulating SIRT1 and ß-catenin pathways.

Pharmaceutical analysis for a patient with rebamipide-induced Stevens-Johnson syndrome by clinical pharmacists / 中国药房

OBJECTIVE To provide reference for the diagnosis and treatment of Stevens-Johnson syndrome caused by rebamipide， and to explore the predisposing factors of Stevens-Johnson syndrome. METHODS Clinical pharmacists analyzed the treatment process of a patient with gastrointestinal diseases and evaluated the correlation between the drug used and adverse reactions， in order to determine the suspected allergenic drug causing Stevens-Johnson syndrome. The predisposing factors of patients with Stevens-Johnson syndrome were explored. RESULTS & CONCLUSIONS The suspected allergenic drugs that caused the patient to develop Stevens-Johnson syndrome included Ilaprazole enteric-coated tablets， Rebamipide tablets and Kangfuxin liquid. In summary， the suspect drug was identified as Rebamipide tablets according to the causality evaluation method of the National Center for Adverse Drug Reaction Monitoring， Naranjo’s scoring method and the algorithm of drug causality for epidermal necrolysis scoring criteria. Hypoproteinemia， competitive binding of plasma proteins between drugs， advanced age， bacterial and viral infections were the predisposing factors of Stevens-Johnson syndrome. Therefore， before using rebamipide in clinical practice， it is necessary to inquire about the patient’s allergy history in detail. During the use process， it is necessary to strengthen the patient’s medication monitoring and be alert to the occurrence of serious adverse reactions. If any abnormalities are found， the medication should be stopped immediately and symptomatic treatment should be given as soon as possible to ensure the safety and effectiveness of the patient’s medication.

Effect of Rabeprazole and Rebamipide in the Treatment of Upper Gastrointestinal Hemorrhage Associated with Dual Antiplatelet Therapy in Elderly Patients with Coronary Heart Disease.

To investigate the therapeutic effect of rabeprazole and rebamipide on patient age over 60 with dual antiplatelet therapy (DAPT)-related upper gastrointestinal hemorrhage following percutaneous coronary intervention (PCI). A total of 360 patients age over 60 undergoing PCI were recruited for antiplatelet therapy involving a combined treatment of aspirin (100 mg/d) and clopidogrel (75 mg/d). The enrolled patients were divided into 4 groups: the control group, the rabeprazole group, the rebamipide group, and the rabeprazole + rebamipide group. The incidence and severity of any upper gastrointestinal hemorrhage and the incidence of major adverse cardiac events (MACEs) were observed 6 months after the operation. The incidence of upper gastrointestinal hemorrhage in the 4 groups was 11.1%, 3.3%, 8.9%, and 1.1%, respectively, and the differences were statistically significant (P < 0.05). On comparing the groups, the differences between the control group and the rabeprazole group, those between the control group and the rabeprazole + rebamipide group, and those between the rebamipide group and the rabeprazole + rebamipide group were found to be statistically significant (P < 0.05). The severity of the upper gastrointestinal hemorrhage in the rabeprazole group and the rabeprazole + rebamipide group was significantly lower than that in the control group. The 4 groups exhibited no significant differences in the incidence of MACEs (P > 0.05). For patients age over 60 receiving DAPT following PCI in our study population, treatment with rabeprazole or a combination of rabeprazole and rebamipide could reduce the risk of upper gastrointestinal hemorrhage, as well as reduce its severity.

The effect of rebamipide on non-steroidal anti-inflammatory drug-induced gastro-enteropathy: a multi-center, randomized pilot study.

BACKGROUND/AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly-used medications, and ailments such as arthritis or heart disease, require long-term use of these drugs, which can induce gastroenteropathy with bleeding and ulcers. This study investigated the associations between efficacy, safety, and gastrointestinal symptoms linked to rebamipide and proton pump inhibitor administration in patients requiring long-term NSAID use. METHODS: This study was a multi-center, randomized, open-labeled, pilot design. RESULTS: Thirty-three patients were included. Of these, 15 were included in the study group and 18 were in the control group. NSAID-induced gastric ulcers, which were the primary outcome of this study, did not occur in either the study or control group. Changes in the number of small bowel erosions and ulcers were -0.6 ± 3.06 in the study group and 1.33 ± 4.71 in the control group. The number of subjects with mucosal breaks (defined as multiple erosions and/or ulcers) was three (20%) in the study group and six (40%) in the control group (p = 0.427). No serious adverse events occurred in either group. However, dyspepsia and skin rashes occurred in six patients (31.58%) in the study group and 13 (65%) in the control group (p = 0.036). CONCLUSION: Although statistically significant differences were not generated, possibly as a result of the small sample size, mucosal breaks observed via capsule endoscopy revealed that rebamipide was likely to be more effective than lansoprazole in preventing small intestine damage caused by NSAIDs. Furthermore, fewer side-effects emerged with rebamipide.

[Erosive and ulcerative lesions of the digestive tract: optimization of diagnosis and management tactics].

Erosive and ulcerative lesions of the digestive tract are one of the most pressing problems in the clinic of internal diseases due to the extremely widespread prevalence, the presence of severe complications, often fatal, diagnostic difficulties due to the presence of a large number of asymptomatic pathologies and difficulties in the rational choice of therapy. Particularly noteworthy is the data that during the global pandemic of Covid-19 infection, it is capable, quite often, of causing the development of erosive and ulcerative lesions of the gastrointestinal tract. In this regard, it seems important to use drugs that can not only prevent the occurrence of erosive and ulcerative lesions and strictures throughout the gastrointestinal tract, but also effectively achieve epithelialization of injuries to the mucous membrane of the oral cavity, esophagus, stomach, small and large intestine. One of them is Rebamipid-CZ, which has a fairly high safety and efficacy profile. It seems important to consider the issues of optimizing the prevention and treatment of erosive and ulcerative lesions of various parts of the gastrointestinal tract of various etiologies, taking into account the possibility of using rebamipide both as part of complex therapy and in isolation.

[Epithelial protective therapy in comorbid diseases. Practical Guidelines for Physicians].

This document was produced with the support of the National Medical Association for the Study of Comorbidities (NASС). In 2021 the first multidisciplinary National Consensus on the pathophysiological and clinical aspects of Increased Epithelial Permeability Syndrome was published. The proposed guidelines are developed on the basis of this Consensus, by the same team of experts. Twenty-eight Practical Guidelines for Physicians statements were adopted by the Expert Council using the "delphic" method. Such main groups of epithelial protective drugs as proton pump inhibitors, bismuth drugs and probiotics are discussed in these Guidelines from the positions of evidence-based medicine. The clinical and pharmacological characteristics of such a universal epithelial protector as rebamipide, acting at the preepithelial, epithelial and subepithelial levels, throughout gastrointestinal tract, are presented in detail.