Drug Ther Bull. 2025 May 12:dtb-2025-000016. doi: 10.1136/dtb.2025.000016. Online ahead of print.

NO ABSTRACT

PMID:40355247 | DOI:10.1136/dtb.2025.000016

J Ophthalmic Inflamm Infect. 2025 May 12;15(1):44. doi: 10.1186/s12348-025-00484-8.

ABSTRACT

TOPIC: Vogt-Koyanagi-Harada (VKH)-like uveitis is uniquely reported with immune checkpoint inhibitors (ICI) and BRAF/MEK inhibitors. This article aims to provide a comprehensive portrait of the comorbidities, ocular presentations, treatments, and visual outcomes of patients with VKH-like uveitis following ICI therapy.

CLINICAL RELEVANCE: ICIs are increasingly used in cancer therapy, but poorly understood ocular immune-related adverse events (irAEs) can lead to suspension of treatment and be vision-threatening.

METHODS: We conducted a systematic review (PROSPERO #CRD42024558269) according to PRISMA guidelines. MEDLINE, Embase, CENTRAL, and Web of Science were searched for English articles published up to June 28, 2024. All study designs reporting on incident VKH-like uveitis following ICI were included. Risk of Bias was assessed using a tool modified from Murad et al. (2018).

RESULTS: Of 865 articles, we included 42 articles (4 observational studies, 28 case reports, 6 case series, 3 letters, and 1 editorial) from 12 countries, comprising 52 patients. The mean age was 60.0 ± 11.9 years, and 32 (61.5%) were females. Thirty-six (69.2%) had melanoma, and most were undergoing treatment with a PD-1 inhibitor alone (n = 33, 63.5%) or in combination with a CTLA-4 inhibitor (n = 10, 19.2%). The mean duration of ICI treatment before VKH-like uveitis symptoms was 22.2 ± 29.6 weeks, and the mean duration of ocular symptoms was 16.7 ± 18.6 weeks, with wide variation. Overall, 43 patients (73.1%) had imaging or exams suggesting bilateral involvement and 21 cases (40.4%) suggesting panuveitis. Only 31 cases (59.6%) met the acute initial-onset uveitis criteria, and 15 (28.8%) met the chronic phase criteria. Most (n = 47, 90.4%) required systemic or intravitreal steroids, termination of ICI (n = 31, 59.6%), and experienced full resolution or remission of visual symptoms (n = 43, 82.7%). Most articles (n = 40, 95.2%) were judged to be at medium risk of bias.

CONCLUSION: This descriptive systematic review consisted mostly of case reports, but it confirmed that a high proportion of VKH-like uveitis occur with PD-1 inhibitors and melanoma patients. VKH-like uveitis can lead to suspension of treatment. Further collaboration between oncologists and ophthalmologists is needed in the continuum of cancer care.

PMID:40354015 | DOI:10.1186/s12348-025-00484-8

Zhongguo Zhong Yao Za Zhi. 2025 Feb;50(4):853-859. doi: 10.19540/j.cnki.cjcmm.20241025.601.

ABSTRACT

The safety of traditional Chinese medicine(TCM) has always been taken very seriously, and rich and valuable theories and experiences have been developed to ensure the safe and precise use of TCM in clinical practices. In recent years, the cognitive theory of toxicity of TCM, has undergone a profound change. TCM is characterized by the existence of intrinsic toxicity, idiosyncratic toxicity, and indirect toxicity related to organic factors. Therefore, the traditional theories and experiences of TCM, which focus on the prevention and control of intrinsic toxicity, fail to be used for the development of risk prevention and control countermeasures for newly discovered TCM with idiosyncratic toxicity and indirect toxicity. Accordingly, based on the toxicity classification and mechanism characteristics of TCM, this paper proposed a new strategy and method in TCM compatibility for detoxification based on componenttarget-effect interaction. The strategy based on component-target-effect interaction is to carry out TCM compatibility for detoxification by blocking the occurrence of drug-mediated damage and promoting damage repair through component interactions, target interactions,and/or effect interactions. Based on this theory, the paper established a strategy for TCM compatibility that aligned with the cognitive theory of toxicity of TCM, so as to achieve safe and precise use of TCM in clinical practices. The strategy based on component-targeteffect interaction has been exemplarily applied to the development of countermeasures to reduce the toxicity of TCM, including Polygonum Multiflorum, Epimedii Folium, and Psoraleae Fructus, and a new mechanism of Glycyrrhizae Radix et Rhizoma to " harmonize various medicines and detoxify myriad poisons" was illustrated, providing a scientific basis for the safe and precise use of TCM in clinical practice. This paper explained the scientific connotation, application forms, and application examples of componenttarget-effect interaction, aiming to provide a theoretical and methodological basis for guaranteeing the precise use of TCM in clinical practice and innovate the theories and methods of TCM compatibility for detoxification.

PMID:40350805 | DOI:10.19540/j.cnki.cjcmm.20241025.601

Zhongguo Zhong Yao Za Zhi. 2025 Feb;50(3):812-816. doi: 10.19540/j.cnki.cjcmm.20241108.501.

ABSTRACT

Because of the unclear active substances, metabolic pathways, and targets of new drugs of traditional Chinese medicine(TCM), non-clinical safety evaluation often fails to accurately locate the target organs and tissue exposed to medicinal toxicity. The human use experience(HUE) contains important safety information of TCM, while the clinical safety data in the past HUE are few and have not been effectively applied. Standardized prospective HUE studies should be carried out to collect the clinical safety data, in which appropriate physical and chemical indicators(including blood, urine, and stool routine), liver biochemical indicators, kidney biochemical indicators, and cardiovascular biochemical indicators should be selected for safety evaluation, and the detection time point and sample size should be rationally designed. Importance should be attached to the observation of symptoms and signs of adverse events/reactions in patients as well as the safety information of special groups such as the elderly, children, and pregnant women. The adverse events of TCM should be observed, judged, and treated according to the theory and the diagnosis and treatment mode of TCM. The clinical safety information about the HUE should be comprehensively collected for new drugs of TCM to make up for the lack of extrapolation of toxicological test results to humans. The unique advantages of clinical origin of new drugs of TCM should be given full play for cross-reference of the results of toxicological research and the conclusions of HUE safety evaluation. In addition, benefit-risk assessment should be conducted based on HUE, and a panoramic safety evaluation system characterized by macro and micro combination and in line with the characteristics of TCM should be established to improve the success rate in the research and development of new drugs of TCM.

PMID:40350857 | DOI:10.19540/j.cnki.cjcmm.20241108.501

Rinsho Ketsueki. 2025;66(4):228-232. doi: 10.11406/rinketsu.66.228.

ABSTRACT

A 48-year-old man with acute myeloid leukemia underwent HLA-matched related donor peripheral blood stem cell transplantation. He developed chronic graft-versus-host disease (cGVHD) of the liver on day 359, which became dependent on cyclosporine and prednisolone. Long-term administration of cyclosporine led to progressive renal dysfunction. Ibrutinib was started, but was stopped due to acute cardiac failure. Mycophenolate mofetil was then started and liver cGVHD improved. The patient developed bacterial pneumonia and COVID-19 during this period. He began to experience limited range of motion in the shoulder joints beyond 2 years after transplantation, and suffered from progressive symptoms. To prevent additional infections due to myelosuppression, drug-induced liver dysfunction, and progression of renal dysfunction, extracorporeal photopheresis (ECP) was chosen to treat musculoskeletal cGVHD. ECP was started on day 1202 and completed 6 months later following the recommended schedule, without severe adverse events. Shoulder joint symptoms completely resolved with ECP, and the cGVHD score in joints decreased from 2 to 0. ECP is considered a promising treatment option for cGVHD patients who are at risk of infection and liver or renal dysfunction.

PMID:40350272 | DOI:10.11406/rinketsu.66.228

Probl Sotsialnoi Gig Zdravookhranenniiai Istor Med. 2025 May 10;33(2):1606. doi: 10.32687/0869-866X-2025-33-2-263-272.

ABSTRACT

The chronic cardiac deficiency continues to be one of the leading health care problems requiring innovative solutions. The article presents mathematical algorithm to evaluate drug interactions and targeted to minimize side effects and to optimize chronic cardiac deficiency therapy. The mathematical model, elaborated using AI, is based on analysis of fully connected sub-graphs and ranking of side effects of combined application of medications. This approach permits to implement optimal selection of the safest and most effective combinations of medications. This is particularly important with regard for co-morbid conditions when patients take simultaneously several different medications. The proposed approach can significantly improve risk prediction and favor more precise selection of combined therapy. The algorithm surmises necessity for further extension and specification of model, including consideration of wider spectrum of medications and mechanism of their interaction. In the context of rapidly advancing digital medicine, models based on mathematical algorithms and machine learning can complement systems of clinical decision support. These models also can become valuable tool improving treatment of various diseases, especially in co-morbid conditions opening new horizons in medical practice.

PMID:40349243 | DOI:10.32687/0869-866X-2025-33-2-263-272

Expert Opin Drug Metab Toxicol. 2025 May 10. doi: 10.1080/17425255.2025.2505637. Online ahead of print.

ABSTRACT

BACKGROUND: Tegoprazan (LXI-15028), a novel potassium-competitive acid blocker, has shown great efficacy in treating acid-related disorders. However, its metabolic and excretion characteristics are not fully understood.

RESEARCH DESIGN AND METHODS: A single oral dose of 50 mg/150 μCi [14C]tegoprazan was administered to six healthy subjects. Blood, urine and fecal samples were collected and measured for total radioactivity (TRA), tegoprazan and metabolites. Its safety was also assessed.

RESULTS: The maximum concentrations (Cmax) of tegoprazan and TRA in plasma were 634 ng/mL and 990 ng eq./mL, respectively, at 0.5 h post dose. Tegoprazan and its N-demethylation metabolite (M1) were the major drug-related compounds in plasma, accounting for 34.84% and 40.10% of TRA, respectively. The half-life (t1/2) of TRA (8.72 h) was longer than that of tegoprazan (4.33 h) in plasma, indicating slower metabolite elimination. Tegoprazan was excreted through both the urine (50.51 ± 3.35%) and feces (47.26 ± 3.06%). The main metabolic pathways of tegoprazan are demethylation, oxidation, glucuronidation and sulfation. There were no serious adverse events observed in this study.

CONCLUSIONS: Tegoprazan is widely metabolized and excreted completely in humans. Tegoprazan and M1 were the primary compounds present in the circulation.

CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05883306.

PMID:40349123 | DOI:10.1080/17425255.2025.2505637

Eur J Hosp Pharm. 2025 May 10:ejhpharm-2025-004597. doi: 10.1136/ejhpharm-2025-004597. Online ahead of print.

NO ABSTRACT

PMID:40348405 | DOI:10.1136/ejhpharm-2025-004597

Clin Transl Sci. 2025 May;18(5):e70246. doi: 10.1111/cts.70246.

ABSTRACT

Pharmacogenomics remains underutilized in pediatric oncology, despite the existence of evidence-based guidelines. Implementation of pharmacogenomics-informed prescribing could improve medication safety and efficacy in pediatric oncology patients, who are at high risk of adverse drug reactions. This study examines the prevalence of high-risk pharmacogenomic phenotypes and the prescription of relevant medications in a diverse Australian pediatric oncology cohort, highlighting the potential impact of pharmacogenomic testing in this unique population. Whole genome sequencing data from 180 patients were analyzed to assess 14 genes with evidence-based pharmacogenomic guidelines relevant to pediatric oncology. Over 90% of patients had at least one high-risk phenotype, with 20% presenting four or more. Ondansetron, mercaptopurine, omeprazole, pantoprazole, and voriconazole were commonly prescribed medications that have pharmacogenomic prescribing recommendations, with the latter three showing the highest actionability rates. High-risk phenotypes were most frequently observed for CYP2C19 and CYP2D6, with 30% of patients having a high-risk phenotype for both genes. This study underscores the potential utility of pharmacogenomics in pediatric oncology patients across a range of pharmacogenes and commonly prescribed medications. The findings support advocacy for implementing broad, pre-emptive pharmacogenomic testing in oncology patients to improve treatment safety and efficacy.

PMID:40347484 | DOI:10.1111/cts.70246

Paediatr Drugs. 2025 May 10. doi: 10.1007/s40272-025-00698-2. Online ahead of print.

ABSTRACT

The evidence to support the efficacy and safety of pharmacological treatments for chronic non-cancer pain in children is limited. In practice, clinicians are often required to establish therapeutic plans using data extrapolated from adult studies, which may not apply to younger patients. Recent systematic reviews and meta-analyses indicate minimal evidence of benefit for these treatments in children; however, the low quality of studies included in these reviews complicates the conclusions that can be derived from them. In this article, we focus on safety, an outcome as critical as efficacy in clinical trial design but often designated as secondary or even exploratory. Specifically, we examine methods for assessing adverse events in clinical research and propose a practical approach for evaluating these events in everyday practice. Additionally, we outline our strategy to conduct a risk-benefit analysis at the individual patient level, highlighting the importance of using a composite risk-benefit metric rather than assessing these outcomes separately. This approach enables real-time monitoring of both drug-related symptom relief and adverse effects, facilitating clinically meaningful risk-benefit discussions with patients and their families. Finally, we advocate for improvements in clinical trial design for pediatric chronic pain treatments, particularly around adverse events. Future trials should incorporate standardized definitions, comprehensive risk-benefit evaluations, and transparent outcome reporting. Implementing these changes may enhance decision-making by balancing the safety and the effectiveness of pharmacological treatments for children and adolescents with chronic pain.

PMID:40347360 | DOI:10.1007/s40272-025-00698-2

Sci Rep. 2025 May 9;15(1):16188. doi: 10.1038/s41598-025-00004-7.

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality, with limited therapeutic options available for advanced stages of the disease. Treatment strategies for HCC are multimodal and largely depend on the disease stage, liver function, and individual patient factors. Based on the WHO's VigiAccess database, this study employed a retrospective descriptive analysis of adverse drug reaction (ADR) reports associated with four widely used tyrosine kinase inhibitors (TKIs) for HCC, including Sorafenib, Cabozantinib, Lenvatinib, and Regorafenib. The analysis included demographic data such as patient age, gender, and geographical distribution, alongside clinical information on the systems and symptoms associated with ADR reports. A total of 112,975 ADR reports related to the four TKI-targeted drugs were identified. Sorafenib exhibited the highest ADR reporting rate (30.7%), followed by Cabozantinib (29.4%), Lenvatinib (24.5%), and Regorafenib (15.4%). The odds ratio method was employed to assess the statistical correlation between the use of these targeted drugs and the occurrence of ADRs. Notably, Sorafenib (3,746) and Regorafenib (2,496) served to have the highest number of reported palmar-plantar erythrodysaesthesia syndrome. Chi-square analyses suggested that ADRs related to Lenvatinib were reported significantly more frequently in female patients compared to their male counterparts. The findings of this study can enhance public awareness of drug-related adverse events and provide an evidence-based foundation for prioritizing the management of ADRs associated with TKIs in second-line HCC therapy.

PMID:40346128 | DOI:10.1038/s41598-025-00004-7

Front Vet Sci. 2025 Apr 24;12:1558222. doi: 10.3389/fvets.2025.1558222. eCollection 2025.

ABSTRACT

INTRODUCTION: Continuous product monitoring post approval builds on the knowledge gained during clinical studies to aid in understanding a product's safety and efficacy profile. Pharmacovigilance reporting of a medicinal product might be influenced by several factors including duration in the market, geographical region and veterinary practices. The goals of this report are to present the global data accrued for bedinvetmab, the first monoclonal antibody for canine osteoarthritis, and to explore reporting patterns globally and across major markets.

METHODS: Adverse event reports from the Zoetis Global Pharmacovigilance database (from first introduction on 01 February 2021 through 30 June 2024) were collected irrespective of suspected causality or off-label use. Each adverse event was coded using the Veterinary Dictionary for Drug Related Affairs (VeDDRA) terminology. The top 20 most reported VeDDRA terms were identified. Countries were ranked by number of doses distributed and frequency of adverse events.

RESULTS: Globally, 18,102,535 doses of bedinvetmab were sold during the study period with a total of 17,162 adverse events reported in dogs (9.48 events/10,000 treated animals (doses)). Eight clinical signs were considered rare (1-10 events/10,000 treated animals (doses)) with lack of efficacy having the highest rate (1.70) followed by polydipsia, ataxia, polyuria/pollakiuria, anorexia, lethargy, death, and emesis. All other clinical signs were considered very rare (< 1 event/10,000 treated animals (doses)). Median (interquartile range) of dogs' age and body weight were 12 (10-13) years and 26 (16-34.6) kg, respectively. The top eight countries by market size were United States (US), United Kingdom (UK), Germany, Spain, France, Italy, Canada, and Australia; from these, the top five by frequency of adverse events were Canada, US, UK, Australia and Germany. The most reported adverse events following bedinvetmab are considered rare or very rare.

DISCUSSION: The reported clinical signs generally aligned with expected adverse events or were anticipated within the population receiving bedinvetmab. Reporting rates and patterns in general and for specific VeDDRA terms greatly varied between countries and were not related to market size. Most dogs for which adverse events were reported were considered older and in fair clinical condition. Reporting to pharmacovigilance contributes to the understanding of the safety profile of a medicinal product.

PMID:40343372 | PMC:PMC12061024 | DOI:10.3389/fvets.2025.1558222

Front Pharmacol. 2025 Apr 24;16:1498191. doi: 10.3389/fphar.2025.1498191. eCollection 2025.

ABSTRACT

OBJECTIVE: Although numerous drugs have been associated with cataracts, the risk for most drugs remains unclear. This study aimed to investigate the risk factors for drug-induced cataracts by analyzing large-scale data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

METHODS: We used the reporting odds ratio (ROR) to evaluate reports of drug-induced cataracts in FAERS from the first quarter of 2004 to the third quarter of 2024. A univariate analysis, LASSO (least absolute shrinkage and selection operator) regression, and a multivariate regression analysis were performed to identify drug-related risk factors for cataracts, and Bonferroni correction was applied for multiple comparisons.

RESULTS: Multivariate logistic regression ultimately identified 15 drugs as independent risk factors, including immunomodulators (6/15), antineoplastic drugs (3/15), psychotropic drugs (1/15), respiratory drugs (1/15), gastrointestinal drugs (1/15), orthopedic drugs (1/15), metabolic regulators (1/15), and ophthalmic drugs (1/15). The median time to onset of drug-induced cataracts was 449 days (interquartile range [IQR]: 150-901 days), with approximately 75% of adverse events occurring within 747 days.

CONCLUSION: These findings may help clinicians detect drug-related cataracts at an early stage and provide valuable insights for future research on the mechanisms of drug-induced cataracts.

PMID:40343006 | PMC:PMC12058479 | DOI:10.3389/fphar.2025.1498191

Front Immunol. 2025 Apr 24;16:1544312. doi: 10.3389/fimmu.2025.1544312. eCollection 2025.

ABSTRACT

Immune checkpoint inhibitors (ICIs) have become a standard treatment for various cancers, but their use is often associated with immune-related adverse events (irAEs), including cutaneous irAEs (cirAEs). Here, we report a rare case of subacute cutaneous lupus erythematosus (SCLE) induced by sintilimab, a PD-1 inhibitor, in a 30-year-old woman undergoing neoadjuvant chemo-immunotherapy for gastric cancer. The patient presented with erythema, macules, papules, and vesicles, with positive ANA (108U/mL) and strongly positive anti-SSA/Ro. After discontinuation of sintilimab and treatment with corticosteroids, hydroxychloroquine, and intravenous immunoglobulin (IVIG), her symptoms improved. This case represents the first reported instance of drug-induced lupus caused by sintilimab and emphasizes the importance of distinguishing between paraneoplastic lupus and ICI-induced lupus.

PMID:40342412 | PMC:PMC12058751 | DOI:10.3389/fimmu.2025.1544312

Pharmacol Res Perspect. 2025 Jun;13(3):e70102. doi: 10.1002/prp2.70102.

ABSTRACT

Pharmacovigilance plays a significant role in guaranteeing the safety of medications for patients. Over the last three decades, China has significantly advanced its pharmacovigilance practices, yet the factors that drive the quality of pharmacovigilance remain unclear. This study aimed to investigate how multiple factors interactively influence the quality of pharmacovigilance and identify pathways for achieving high-quality pharmacovigilance practices. A unique sample of pharmacovigilance-specific inspection reports from 13 representative companies in China was adopted in analysis. Given the qualitative nature of the inspection reports, we utilized crisp-set qualitative comparative analysis (csQCA) with five factors structure based on the technology-organization-environment (TOE) theoretical framework. The csQCA enabled us to elucidate the interactions among the antecedents of pharmacovigilance quality through quantitative univariate necessity analysis and configuration analysis. Three pathways contributing to high-quality pharmacovigilance were identified, and "Dedicated and Qualified Person for Pharmacovigilance (DQPPV)" was shown to be involved in all three pathways. Upon examining the manner in which multiple variables influence the quality of pharmacovigilance, it becomes evident that the DQPPV represents a factor that warrants further investigation. The results of the configuration allow companies to implement targeted measures to enhance the functionality of the pharmacovigilance system and to improve the quality of the system. Further research could explore the influence of additional factors on pharmacovigilance efforts, which could then contribute to marketing authorization holders' (MAHs') pharmacovigilance efforts.

PMID:40341821 | DOI:10.1002/prp2.70102

Arch Esp Urol. 2025 Apr;78(3):325-333. doi: 10.56434/j.arch.esp.urol.20257803.44.

ABSTRACT

BACKGROUND: Drug-related problems (DRPs) are prevalent among older cancer patients. This study aimed to investigate the impact of pharmaceutical services on DRP, disease knowledge, health-related quality of life, and satisfaction among older patients with prostate cancer (PCa).

METHODS: The clinical data of 86 elderly patients with PCa admitted during June 2021-June 2024 were retrospectively analyzed. Descriptive statistics and univariate analysis were used to evaluate the effectiveness of the clinical application of the pharmacy service carried out in our hospital, including the incidence of DRP, knowledge of disease, health-related quality of life score, and satisfaction. The general content of pharmaceutical services is as follows: Arrange hospital pharmacists to directly participate in patient treatment, conduct drug reviews, identify DRPs, and discuss with prescribing doctors based on problems to optimize medication plans. At the same time, it provides disease knowledge education, medication consultation, and primary care guidance.

RESULTS: At admission, 55 patients (63.95%) had DRP, with the most common classification being drug selection, with an incidence rate of 36.36% (20/55). At discharge, the proportion of DRP in patients receiving pharmaceutical services was lower than that in patients refusing pharmaceutical services, and the DRP status was better than that of patients refusing pharmaceutical services (p < 0.05). Patients who received pharmaceutical services had higher level of disease knowledge mastery (p < 0.001), Short-Form-36 (SF-36) score in some dimensions (p < 0.05), and satisfaction (p < 0.05) than those who refused pharmaceutical services.

CONCLUSIONS: Hospital pharmaceutical services can effectively reduce the occurrence of DRP during hospitalization of elderly patients with PCa, help them to acquire knowledge of the disease and health-related quality of life, and have high patient satisfaction.

PMID:40340998 | DOI:10.56434/j.arch.esp.urol.20257803.44

Inflammopharmacology. 2025 May 8. doi: 10.1007/s10787-025-01766-2. Online ahead of print.

ABSTRACT

Ototoxicity, the property of certain drugs to cause hearing loss, is a significant concern in medical treatments, particularly with the use of chemotherapeutic agents like cisplatin and aminoglycosides. These drugs can lead to permanent sensorineural hearing loss (SNHL), affecting a substantial proportion of patients. Existing strategies to alleviate these side effects are limited, prompting interest in natural products as potential protective agents. Natural products are being investigated for their ability to counteract these mechanisms through anti-inflammatory and antioxidant properties. The review seeks to highlight the potential of these natural products as complementary therapies to conventional ototoxic medications, emphasizing their protective roles, which are involved in cochlear cellular damage and programmed cell death. Further research is essential to establish standardized protocols for their use and to ensure their integration into clinical practice as effective therapeutic options.

PMID:40338449 | DOI:10.1007/s10787-025-01766-2

Cochrane Database Syst Rev. 2025 May 8;5:CD014585. doi: 10.1002/14651858.CD014585.pub2.

ABSTRACT

RATIONALE: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed medicines, commonly used to mitigate pain, inflammation, and cardiovascular prevention, among others. Chronic NSAID consumption increases the risk of acute renal failure, stroke, myocardial infarction, and gastrointestinal toxicity, ranging from mild dyspepsia to serious ulcer complications such as bleeding, obstruction, and perforation. Proton pump inhibitors (PPIs) may exert a gastroprotective effect from NSAID gastroduodenal injury by reducing gastric acid secretion.

OBJECTIVES: To assess the effects of proton pump inhibitors on the prevention of dyspepsia and ulcers in people with chronic consumption of non-steroidal anti-inflammatory drugs.

SEARCH METHODS: We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid), and two trial registers up to 23 October 2023, as well as reference checking, citation searching, and contact with study authors to identify additional studies.

ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs comparing PPIs taken orally versus placebo, histamine 2-receptor antagonists, misoprostol, or sucralfate in adults and children with chronic consumption of NSAIDs for four weeks or longer.

OUTCOMES: Our outcomes were global symptoms of dyspepsia, incident ulcer, adverse events, ulcer complications, and quality of life.

RISK OF BIAS: We used the Cochrane RoB 2 tool for RCTs and the tool extension for cluster-RCTs.

SYNTHESIS METHODS: We conducted meta-analyses using random-effects models to calculate risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes and mean differences (MD) and 95% CIs for continuous outcomes. Due to statistical heterogeneity, we conducted meta-analyses for all but two outcomes. We summarised the certainty of evidence according to GRADE methods.

INCLUDED STUDIES: We included 12 studies with 8760 participants. All studies were conducted in an outpatient setting in Africa, Asia, Europe, North America, Central America, South America, and Australia. They were published between 1996 and 2014. All studies measured outcomes in the short term (up to 12 months).

SYNTHESIS OF RESULTS: PPI versus placebo PPIs may have little to no effect on global symptoms of dyspepsia assessed as a dichotomous outcome, but the evidence is very uncertain (meta-analysis was not possible due to high and unexplained statistical heterogeneity and point estimates of RR ranged from 0.36 to 1.13; 8 studies; 4944 participants; very low-certainty evidence). PPIs probably result in a slight reduction in global symptoms of dyspepsia assessed as a continuous outcome (MD -0.56, 95% CI -0.74 to -0.38; 2 studies, 1149 participants; moderate-certainty evidence). PPIs probably result in a reduction in incident ulcers compared to placebo (RR 0.29, 95% CI 0.23 to 0.36; 11 studies, 7022 participants; moderate-certainty evidence). PPIs may have few or no adverse events, but the evidence is very uncertain (meta-analysis was not possible due to high and unexplained statistical heterogeneity and point estimates of RR ranged from 0.67 to 6.35; 12 studies, 7530 participants; very low-certainty evidence). PPIs may reduce ulcer complications compared with placebo (RR 0.33, 95% CI 0.10 to 1.07; P = 0.30; I2 = 18%; 5 studies, 4394 participants; low-certainty evidence). PPIs probably result in a slight increase in quality of life (MD 0.39, 95% CI 0.23 to 0.55; 2 studies, 1149 participants; moderate-certainty evidence). PPI versus histamine 2-receptor antagonists PPIs may increase incident ulcers (RR 2.00, 95% CI 0.21 to 19.44; 1 study, 26 participants; low-certainty evidence). The included study did not report data on global symptoms of dyspepsia, adverse events, ulcer complications, or quality of life. PPI versus misoprostol PPIs may increase incident ulcers (RR 2.32, 95% CI 1.25 to 4.30; 1 study, 402 participants; very low-certainty evidence) and may have fewer adverse events (RR 0.38, 0.25 to 0.57; 1 study, 402 participants; very low-certainty evidence), but the evidence is very uncertain. The included study did not report data on global symptoms of dyspepsia, ulcer complications, or quality of life. No studies compared PPI against sucralfate. Most included studies were at overall high risk of bias or overall some concerns of risk of bias. Imprecision in the effect estimates was also a concern.

AUTHORS' CONCLUSIONS: Compared with placebo, PPIs may have no effect on the presence of global symptoms of dyspepsia and probably result in a slight reduction in global symptoms of dyspepsia scales. PPI probably reduces incident ulcers and may have little to no effect on adverse events. PPIs may reduce ulcer complications and probably slightly increase quality of life. Compared with histamine 2-receptor antagonists, PPIs may increase incident ulcers. The evidence for this comparison came from only one study. Compared with misoprostol, PPIs may increase incident ulcers and may reduce adverse events, but the evidence is very uncertain. The evidence for this comparison came from only one study. The certainty of the evidence for most outcomes and comparisons was low or very low, except for global symptoms of dyspepsia measured as a continuous outcome, incident ulcer, and quality of life in the comparison of PPI versus placebo. Further research is needed to assess the effect of PPIs compared to other active treatments such as sucralfate, misoprostol, or histamine 2-receptor antagonists. Well-designed and reported studies focussing on patient-important outcomes and addressing the methodological limitations found in the present included studies would be informative. These could include different baseline ulcer risks, ages, and types of NSAIDs. Long-term follow-up would be beneficial.

FUNDING: This Cochrane review had no dedicated funding.

REGISTRATION: Protocol (2022): doi.org/10.1002/14651858.CD014585.

PMID:40337979 | DOI:10.1002/14651858.CD014585.pub2

Curr Drug Saf. 2025 May 7. doi: 10.2174/0115748863367086250420011411. Online ahead of print.

ABSTRACT

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely accepted for managing Type 2 diabetes mellitus. However, numerous drug-related problems (DRPs) have recently been reported about GLP-1 RAs.

OBJECTIVES: The present descriptive study aimed to compile and report the DRPs of various GLP-1 RAs.

METHODS: The DRPs reported for all the GLP-1 RAs, including exenatide, lixisenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide, were extracted from the category of injury, poisoning, and procedural complications of VigiAccess. The Pharmaceutical Care Network Europe Association (PCNE) classification for drug-related problems (version 9.1) was used to categorize the DRPs into patient-related, healthcare practice-related, and patient- or healthcare practice- related.

RESULTS: Overall, 315952 potential side effects (PSEs) were reported regarding GLP-1 RAs in VigiAccess under injury, poisoning, and procedural complications. Out of 315952 PSE reports, 83210 were DRPs of GLP-1 RAs. Most of them belong to Dulaglutide (23861; 28.68%), followed by tirzepatide (23274; 27.97%), exenatide (18449; 22.17%), semaglutide (11790; 14.97%), and liraglutide (5767; 6.93%). Among the patient-related DRPs, incorrect dose administered (17797; 42.42%), and most of the reports documented for tirzepatide (9993; 23.82%), dulaglutide (4581; 10.92%), and exenatide (2557; 6.10%); however, semaglutide (414; 0.99%), and liraglutide (249; 0.59%), have minor reports documented. Off-label use (13600), most of which were from tirzepatide (4945; 17.59%), followed by semaglutide (4176; 14.85%), liraglutide (1853; 6.59%), exenatide (1530; 5.44%), and dulaglutide (1087; 3.87%).

CONCLUSION: Qualified healthcare practitioners must educate the patients administering the GLP- 1 RAs to minimize preventable DRPs. Also, careful and frequent monitoring of GLP-1 RAs improves therapeutic outcomes by ruling out DRPs. Healthcare practitioners should comply with approved therapeutic guidelines to enhance the quality of GLP-1 RAs treatment.

PMID:40337971 | DOI:10.2174/0115748863367086250420011411

Rom J Ophthalmol. 2025 Jan-Mar;69(1):3-9. doi: 10.22336/rjo.2025.02.

ABSTRACT

OBJECTIVES: The primary aim of this article is to present cystoid macular oedema as one of the side effects of Paclitaxel (Taxol) chemotherapy. Paclitaxel is used as a treatment option in patients with different types of solid carcinomas. The potential loss of vision, already altered by the disease, further compromises their quality of life, a contributing factor to overall psychological and mental decline.

CASE PRESENTATION: A 69-year-old woman developed a drop in visual acuity that was painless, bilateral, and accompanied by wavy lines. This occurred six months after starting Paclitaxel chemotherapy for metastatic breast cancer. The diagnosis of cystoid macular oedema caused by Paclitaxel was made. The visual acuity significantly improved after Paclitaxel was discontinued, and the symptoms subsided.

DISCUSSION: Paclitaxel is a chemotherapy drug used to treat various types of cancers and has been associated with cystoid macular oedema (CMO) in rare cases. CMO is thought to result from the disruption of the normal blood-retinal barrier. The specific mechanism remains incompletely understood, and multiple mechanisms have been postulated. In typical CMO, leakage from parafoveal capillaries is demonstrated on fluorescein angiograms in a classic petaloid pattern. However, in Taxane-Drug Induced CMO (TDICMO), there is no evidence of fluorescein leakage on angiography. TDICMO is a rare drug side effect of breast cancer treatment, described just 14 times in the English literature.

CONCLUSION: It is crucial to reiterate that if a patient undergoing Paclitaxel treatment experiences any vision changes, it is imperative to consult an ophthalmologist for a thorough evaluation and appropriate management. This step is essential for the patient's well-being and to ensure the best possible outcome.

PMID:40330966 | PMC:PMC12049643 | DOI:10.22336/rjo.2025.02