J Eval Clin Pract. 2025 Jun;31(4):e70164. doi: 10.1111/jep.70164.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADRs) are unintended and harmful responses to medications. Although clinicians and researchers often focus on the clinical aspects and prevention of ADRs, consumers-the patients themselves-experience and interpret these events in personal, social, and cultural contexts. Understanding consumers' perspectives on ADRs is essential to improving communication, therapeutic decision-making, and patient safety strategies.

OBJECTIVE: This study aimed to explore consumers' views and experiences of ADRs, including their perceptions of risk, attribution of causes, and the impact on medication adherence and trust in healthcare providers.

METHODS: A qualitative research design was employed. Purposive sampling was used to recruit adult participants who had experienced at least one ADR or were caregivers of someone with an ADR experience. Four focus group discussions (FGDs) were conducted (n = 28). A semi-structured discussion guide elicited participants' personal accounts and interpretations of ADRs. Data were transcribed verbatim and analyzed using thematic analysis.

RESULTS: Six major themes emerged: (1) Understanding and Knowledge of ADRs, (2) Severity and Impact on Daily Life, (3) Trust and Communication with Healthcare Providers, (4) Self-Medication Practices and ADR Risk, (5) Emotional and Psychological Responses, and (6) Recommendations for Improved ADR Awareness and Reporting. Participants expressed anxiety about the unpredictability of ADRs, citing both mild and severe reactions. Many shared difficulties with navigating information sources, feeling that healthcare professionals sometimes minimized or overlooked their concerns. The emotional toll of ADRs ranged from worry and frustration to lowered trust in medical recommendations.

CONCLUSION: Consumers' experiences of ADRs are deeply personal, often influenced by prior knowledge, trust in healthcare providers, and the perceived severity of reactions. Patient-centered communication strategies, clearer information on risks and benefits, and robust ADR reporting mechanisms are recommended to empower consumers and enhance medication safety. Understanding the consumer perspective is pivotal for healthcare policy and practice to reduce the burden of preventable ADRs and to improve patient-centered care.

PMID:40492956 | DOI:10.1111/jep.70164

Front Immunol. 2025 May 26;16:1605958. doi: 10.3389/fimmu.2025.1605958. eCollection 2025.

ABSTRACT

BACKGROUND: Nivolumab, a human immunoglobulin IgG4 monoclonal antibody targeting PD-1 receptor, received initial FDA approval in 2014 for treating unresectable or metastatic malignant melanoma (MM), followed by approval for metastatic squamous and non-squamous non-small cell lung cancer (NSCLC) in 2015. With expanding clinical applications of nivolumab, comprehensive evaluation of its safety profile in real-world healthcare settings becomes increasingly crucial.

METHODS: We compiled a real-world safety dataset of nivolumab from the FDA Adverse Event Reporting System (FAERS) database, encompassing reports from Q4-2014 through Q2 2024. To evaluate the association between nivolumab and adverse events (AEs), we employed four distinct disproportionality analysis methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multi-item Gamma Poisson Shrinker (MGPS) and Bayesian Confidence Propagation Neural Network (BCPNN). Additionally, we utilized Weibull distribution modeling to characterize the temporal risk patterns of identified adverse events.

RESULTS: Our analysis identified 64,627 AEs reports associated with nivolumab. The most frequently reported AEs included fatigue, dyspnea, musculoskeletal pain, decreased appetite, cough, nausea, and constipation. Notably, we detected several potential safety signals not currently listed in the prescribing information: Malignant neoplasm progression, weight decreased, sepsis myocarditis, encephalitis and hypotension.

CONCLUSIONS: Our large-scale pharmacovigilance study identified significant safety signals associated with nivolumab, including previously unrecognized adverse drug reactions. The identification of these safety signals underscores the importance of ongoing post-marketing surveillance for immune checkpoint inhibitors. Future studies should investigate the mechanisms underlying these associations and develop targeted monitoring protocols.

PMID:40491923 | PMC:PMC12146392 | DOI:10.3389/fimmu.2025.1605958

Front Immunol. 2025 May 26;16:1596842. doi: 10.3389/fimmu.2025.1596842. eCollection 2025.

ABSTRACT

BACKGROUND: Tislelizumab is an anti-programmed cell death protein 1(anti-PD-1) monoclonal antibody, which was approved by the Food and Drug Administration(FDA) on March 14, 2024. However, clinical studies are often limited by small sample sizes, and thus a more comprehensive evaluation of the safety of Tislelizumab, particularly its immune-related adverse reactions, is urgently needed.

METHOD: Disproportionality analysis was used in this study to assess the safety of Tislelizumab in clinical practice by analyzing all adverse event reports from the FDA Adverse Event Reporting System database, starting from the first quarter of 2024, where Tislelizumab was identified as the primary suspected drug. Two disproportionality analysis methods, reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN), were utilized to investigate the adverse reactions related to Tislelizumab. Additionally, the Weibull distribution was employed to examine the time-dependent changes in the incidence of adverse events.

RESULTS: Consistent with the drug label, this study identified significant positive signals for adverse reactions, including myelosuppression, hepatic dysfunction, pruritus, rash, and exfoliative dermatitis. Notably, this study also identified several adverse reactions not documented in the drug label, including palmar-plantar erythrodysaesthesia syndrome, immune-mediated cystitis, and renal cysts. Adverse reactions associated with Tislelizumab generally manifested within the first month of treatment. In terms of immune-related adverse reactions, Tislelizumab demonstrated lower signal values compared to other immune checkpoint inhibitors.

CONCLUSION: This study comprehensively reviews the safety profile of Tislelizumab, thereby providing clinicians with crucial safety information for prescribing this drug. Due to its relatively low risk of immune-related adverse events (irAEs), Tislelizumab may serve as a promising candidate for combination therapy with other immune checkpoint inhibitors (ICIs). Novel combination strategies involving Tislelizumab and other ICIs are anticipated to provide new therapeutic opportunities for patients experiencing irAEs.

PMID:40491908 | PMC:PMC12146294 | DOI:10.3389/fimmu.2025.1596842

Clin Res Hepatol Gastroenterol. 2025 Jun 7:102635. doi: 10.1016/j.clinre.2025.102635. Online ahead of print.

ABSTRACT

BACKGROUND: The efficacy and clinical application of glucocorticoids (GCs) in patients with drug-induced liver injury (DILI) remain controversial.

AIMS: To determine the efficacy and suitable population of GCs in patients with DILI.

METHODS: This was a single-center, retrospective study. Patients with moderate-to-severe DILI who met the diagnostic criteria from January 1, 2009 to December 31, 2024 were enrolled. Patients in the GC group and the non-GC group were matched 1:1 by propensity score-matched (PSM), and the reduction of disease severity and biochemical parameters were compared between the two groups. According to the level of TB, the patients with DILI were divided into three groups, and the efficacy of GCs in each subgroup was compared.

RESULTS: Patients with DILI in our study were evaluated by the updated RUCAM causality assessment scale. All patients had RUCAM scores≥6 and causal relationship graded as " probable" or " highly probable". The use of GC treatment differs according to the severity of patients, especially the baseline level of TB (% in patients with TB <5 ULN, % in patients with 5ULN≤TB≤10ULN, and % in TB≥10ULN). After PSM analysis, 163 patients were included in each group. After PSM, the time of severity reduction was faster in the GC group than the non-GC group (P=0.022). The adjusted cumulative rate of severity reduction was 62% in the GC group and 43.6% in the non-GC group. The cumulative rates of reaching 50% reduction in AST, ALP, TB level was higher in the GC group than in the non-GC group (P<0.001, P=0.0086 and P=0.003). Patients were divided into three subgroups according to baseline TB level. We found the cumulative rates of who achieved severity reduction and 50% reduction in liver biochemical parameters at discharge was higher in the GC group than in the non-GC group in patients with 5ULN≤ TB level ≤10ULN but not in patients with TB <5ULN and TB>10ULN. Multivariate analysis showed that sex, age, treatment group and severity were significantly associated with disease severity reduction of patients with DILI. After PSM, there were 56 patients with drug-induced autoimmune hepatitis (DI-AIH) and 270 patients with DILI with no autoimmune features cases in our cohort. The cumulative rate of severity reduction at discharge in the GC group was higher than that in the non-GC group in patients with DI-AIH (P=0.049). Although the incidence of side effects in the GC group was higher than that in the non-GC group, the adverse reactions were basically relieved with the withdrawal of GCs.

CONCLUSIONS: GCs accelerated the reduction of disease severity and liver biochemical parameters, especially in patients with 5ULN≤baseline TB level≤10ULN. Sex, age, treatment group and severity were significantly associated with disease severity reduction of patients with DILI.

PMID:40490247 | DOI:10.1016/j.clinre.2025.102635

Eur J Pharmacol. 2025 Jun 7:177820. doi: 10.1016/j.ejphar.2025.177820. Online ahead of print.

ABSTRACT

BACKGROUND: Visual blurring is one of the most common symptoms in ophthalmology, and one of the important causes of secondary visual blurring is drug-related. This study assesses the risk of drug-related visual blurring using a large real-world database.

METHODS: We analyzed adverse event reports from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database between January 2004 and September 2024. Disproportionality analysis algorithm were used. Drugs related with positive signals for visual blurring were categorized, and the risk levels, number of reports, and drug-induced onset times were quantified.

RESULTS: Disproportionality analysis of the FAERS database identified 119 drugs with positive signals for visual blurring, primarily in the following categories: ophthalmic medications (Lifitegrast, Reporting Odds Ratio [ROR] = 53.24; 95% Confidence Interval [CI]: 49.19-57.61), endocrine medications (Semaglutide, ROR = 3.26 [2.84-3.75]), nervous system medications (Pregabalin, ROR = 4.15 [3.93-4.37]), oncology medications (Encorafenib, ROR = 5.38 [4.37-6.62]), antimuscarinic medications (Fesoterodine, ROR = 6.77 [5.08-9.03]), and other medications (Dupilumab, ROR = 8.39 [8.16-8.64]). The top three drugs associated with the highest incidence of blurred vision as an adverse event are lifitegrast, oxymetazoline, and olopatadine. Antimuscarinic Medications had the shortest drug-induced onset time. Women (63.87%) and middle-aged to elderly individuals [Age (mean ± standard deviation): 53.59 ± 18.79] were the main populations affected by drug-related visual blurring.

CONCLUSION: Preventing drug-related vision issues is vital. Early risk assessment and intervention with personalized medication can reduce side effects, ensure safety, and improve quality of life.

PMID:40490170 | DOI:10.1016/j.ejphar.2025.177820

Adv Exp Med Biol. 2025;1475:77-102. doi: 10.1007/978-3-031-84988-6_5.

ABSTRACT

Graft-versus-host disease (GVHD) limits the curative potential of allogeneic hematopoietic cell transplant (HCT). This immune-mediated disease can result in multisystem organ morbidity, chronic debility, or mortality. Prevention of GVHD is a primary objective when treating patients with allogeneic HCT. While many factors are considered in transplant planning, the choice of GVHD prophylaxis is a critical and modifiable factor that impacts the risk of GVHD. Each regimen is associated with variable GVHD risk, immune reconstitution, infection risk, graft-versus-tumor effect, and drug-related adverse events. Furthermore, the utility of a specific regimen must be considered in the context of the transplant platform such as conditioning regimen and donor choice. In this chapter, we review the current state of GVHD prophylaxis, highlighting the historical standard approach of calcineurin inhibitor-based regimens, as well as the emerging standard of post-transplant cyclophosphamide.

PMID:40488825 | DOI:10.1007/978-3-031-84988-6_5

Surg Laparosc Endosc Percutan Tech. 2025 Jun 9. doi: 10.1097/SLE.0000000000001384. Online ahead of print.

ABSTRACT

INTRODUCTION: The WIRELESS trial compared the postoperative analgesic effect of the bilateral transversus abdominis plane patient-controlled analgesia (TAP-PCA) with that of epidural patient-controlled analgesia (E-PCA) using ropivacaine 0.25%.

METHODOLOGY: A hundred patients aged between 18 and 85 years and planned for upper midline laparotomy (Class I and II wounds) under general anesthesia were randomized into TAP-PCA (50) and E-PCA (50) groups. The PCA pump used for the study was designed to deliver a baseline infusion rate of 5 mL/hour (0.25%). The patients were instructed to press the PCA button, as and when required to deliver an additional dose of 2 mL, with 15-minutes lockout period. Both groups received 1 g of paracetamol infusion every 8 hours. The pain score was evaluated at 3, 6, 12, and 24 hours and then every 12 hours till 72 hours postoperatively. The requirements of rescue analgesia (injection tramadol), out-of-bed mobilization, and recovery of bowel function were recorded. Drug-related side effects and catheter-related complications were also noted.

RESULTS: Five (10%) patients in the TAP arm and 17 (34%) patients in the epidural arm could not complete the study due to complications/failure. The intention-to-treat analysis indicates that VAS scores were similar in both groups (47 in the epidural PCA group and 48 in the TAP-PCA group) at 3, 12, 24, 36, 48, 60, and 72 hours. Rescue analgesia (tramadol) was similar in both groups (0.21, 0.58 vs. 0.13, 0.44). There were no significant differences observed between the 2 groups in terms of out-of-bed mobilization and pulmonary complications. Nonetheless, the TAP arm showed the earlier passage of the first flatus and a shorter hospital stay compared with the epidural arm.

CONCLUSION: PCA through the TAP route is not inferior to the epidural route for managing postoperative pain. Because of fewer contraindications and complications, TAP-PCA can be considered an alternative to epidural PCA.

PMID:40488448 | DOI:10.1097/SLE.0000000000001384

Case Rep Oncol. 2025 Apr 29;18(1):667-674. doi: 10.1159/000545957. eCollection 2025 Jan-Dec.

ABSTRACT

INTRODUCTION: Enfortumab vedotin (EV) has been approved for the treatment of many types of cancer, and its use is still expanding. It is an essential drug used as a standard treatment for advanced and metastatic urothelial carcinoma but is known to cause various adverse events (AEs).

CASE PRESENTATION: We report a patient with metastatic urothelial carcinoma who experienced multiple AEs associated with diabetic ketoacidosis (DKA) during EV treatment. The onset of DKA during EV treatment has been reported to be associated with poor prognosis. Although strict management was required in the intensive care unit, we were able to save the patient's life.

CONCLUSION: Although the detailed mechanism that induced insulin resistance remains unclear, the patient required high-dose insulin because of a marked increase in insulin resistance. If hyperglycemia is observed during EV therapy, DKA may lead to the occurrence of serious AEs. We report on the pathogenesis and management of drug-induced DKA caused by EV based on our case and a literature review.

PMID:40487556 | PMC:PMC12143863 | DOI:10.1159/000545957

Toxicol Rep. 2025 May 10;14:102047. doi: 10.1016/j.toxrep.2025.102047. eCollection 2025 Jun.

ABSTRACT

The liver is an essential organ crucial for metabolism, detoxification, and maintaining homeostasis, faces growing global health challenges such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), hepatitis, cirrhosis, and liver cancer. These conditions collectively account for significant morbidity and mortality worldwide. Although traditional treatments help control symptoms and slow disease progression, they are frequently hindered by issues such as drug resistance, side effects, and high costs, especially in areas with limited resources. Drug-induced liver injury (DILI) continues to be a significant concern. Traditional medicine offers a promising avenue for addressing these limitations, with numerous plants demonstrating hepatoprotective properties through their bioactive compounds, including alkaloids, glycosides, and flavonoids. These natural agents not only mitigate hepatic damage but also provide immune modulation and chronic disease management. This review examines liver injury mechanisms and highlights the therapeutic potential of traditionally used medicinal plants in treating and preventing the liver diseases, emphasizing the integration of traditional knowledge with modern pharmacological advancements.

PMID:40487380 | PMC:PMC12142353 | DOI:10.1016/j.toxrep.2025.102047

Oncol Lett. 2025 Mar 21;29(5):241. doi: 10.3892/ol.2025.14987. eCollection 2025 May.

ABSTRACT

Venetoclax, an orally administered B-cell lymphoma 2 inhibitor, requires dose adjustments when coadministered with cytochrome P450 inhibitors in patients with acute myeloid leukemia (AML). The present study retrospectively analyzed data on progression-free survival (PFS), overall survival (OS) and drug-related adverse events in patients with AML who received adjusted low-dose venetoclax with antifungal agents, compared with those receiving conventional chemotherapy regimens (I3A7, LDAC, and I2A5), at a single hospital. In total, 45 patients with AML who were treated between January 2015 and December 2021 were retrospectively included. A significantly longer median OS time was observed in the group receiving idarubicin [12 mg/m2 intravenous (IV) on days 1-3] and cytarabine (100 mg/m2 continuous IV infusion on days 1-7) (I3A7 group) (median not reached) compared with that in the venetoclax group [10.7 months; 95% confidence interval (CI), 6.3-20.8], the low-dose cytarabine (LDAC) group (4.7 months; 95% CI, 0.8-18.7) and the group receiving idarubicin (12 mg/m2 IV on days 1-2) with cytarabine (100 mg/m2 continuous IV infusion on days 1-5) (I2A5 group) (2.3 months; 95% CI, 0.5-2.3). Similarly, the median PFS time was significantly longer in the I3A7 group (29.0 months; 95% CI, 1.1-29.0) compared with that in the venetoclax (8.0 months; 95% CI, 0.8-10.8), LDAC (2.1 months; 95% CI, 0.1-6.4) and I2A5 (0.9 months; 95% CI, 0.1-4.7) groups. Grade 3 or higher adverse hematological events were common across all treatment groups. Cardiovascular events and grade 3 or higher tumor lysis syndrome occurred only in the venetoclax group (14 and 7%, respectively). In conclusion, low-dose venetoclax combined with antifungal agents appears to be less effective than standard treatment but superior to both LDAC and the I2A5 treatment regimens. Venetoclax also demonstrates a relatively low infection risk. However, careful monitoring for cardiovascular events and tumor lysis syndrome during venetoclax administration is crucial, particularly in patients with relevant medical histories.

PMID:40486085 | PMC:PMC12142305 | DOI:10.3892/ol.2025.14987

Expert Opin Drug Saf. 2025 Jun 7. doi: 10.1080/14740338.2025.2518234. Online ahead of print.

ABSTRACT

BACKGROUND: Clozapine is the best treatment for treatment-resistant schizophrenia (TRS) but is associated with metabolic adverse drug reactions (ADRs).

RESEARCH DOSING/METHODS: The international pharmacovigilance database (VigiBase) uses the information component (IC) as a disproportionality analysis. On 1 July 2024, we studied in VigiBase: 1) the myocardial infarction (MI) ICs for antipsychotics and 2) clozapine reports for MI since clozapine's introduction. After excluding 298 patients with incomplete data, 1490 adults were studied for fatal outcomes using logistic regression with adjusted odds ratios (aOR) and survival analysis.

RESULTS: Clozapine was associated with the highest IC (IC = 0.903; IC025 = 0.835). Olanzapine (IC = 0.524; IC025 = 0.398) showed a lower but significant association. The ICs for quetiapine, risperidone and haloperidol were non-significant or negative. Mortality in 1490 adult clozapine-treated patients with MI was 68%. Using as a baseline age 18-44 years, age 45-64 years had a significant (p < 0.001) aOR = 1.87 with CI 1.43-2.44 while age ≥65 years had a significant (p < 0.001) aOR = 4.07 with CI 2.77-5.97. High clozapine doses (>600 mg/day) displayed an aOR = 2.18 for fatal outcomes.

CONCLUSION: A MI IC around 0.9 is higher than that of other antipsychotics, but we cannot rule out that it is explained by TRS present in clozapine-treated patients.

PMID:40481717 | DOI:10.1080/14740338.2025.2518234

Arch Dermatol Res. 2025 Jun 6;317(1):799. doi: 10.1007/s00403-025-04300-0.

ABSTRACT

Anti TNFα agents can induce cutaneous adverse events in both adults and children. While drug-related alopecia was reported in adults treated with TNFα inhibitors for various indications, pediatric data are scarce. To describe clinical characteristics and outcomes in pediatric patients with TNFα inhibitor-induced alopecia we conducted a single center retrospective study (0748-21-RMC, retrospectively registered on January 2nd 2022) including all patients aged < 18 years who were treated with TNFα inhibitors for any indication and developed drug-induced alopecia between the years 2018-2023. A comprehensive literature review was also performed. Twenty patients were included (mean age 12.9 ± 3.1 years, male:female ratio 1:1.4). Fourteen were diagnosed with Crohn's disease, three with ulcerative colitis, and three with juvenile idiopathic arthritis. Half of the patients were treated with adalimumab and half with infliximab. Overall, alopecia was observed after 14.8 ± 10.8 months of treatment. Eighteen (90.0%) patients presented with psoriatic-like inflammatory alopecia, and two with alopecia areata-like lesions. Seventeen (85.0%) patients discontinued their anti-TNFα therapy due to the alopecia, all presented hair regrowth within six months. Hair regrowth was not recorded in three patients who continued TNFα inhibitors. Literature review of pediatric TNFα inhibitor-induced alopecia revealed comparable patients' demographics and response to treatment discontinuation. In conclusion, TNFα inhibitor-induced alopecia is a rare adverse event in children, occurring mainly in adolescents with inflammatory bowel diseases. Our relatively large cohort provides further evidence for the need for TNFα inhibitor cessation to improve drug-induced alopecia in pediatric patients.

PMID:40481366 | DOI:10.1007/s00403-025-04300-0

Acta Pharmacol Sin. 2025 Jun 6. doi: 10.1038/s41401-025-01573-z. Online ahead of print.

ABSTRACT

The adverse events associated with antitumour drugs have recently emerged as an increasingly significant clinical concern. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) serve as pivotal therapeutic agents for non-small cell lung cancer (NSCLC). However, considerable interindividual variability exists in drug exposure, along with a high incidence and severity of adverse events. In this study, we quantitatively investigated the impacts of EGFR TKI exposure and other covariates on the severity of the maximum grade of drug-related adverse events (MDRAE) in NSCLC patients treated with EGFR TKIs. Data were collected from 277 patients treated with gefitinib, icotinib, afatinib or osimertinib. Population pharmacokinetic (PopPK) models were constructed for each drug, and individual exposure metrics were derived through model simulations. Normalized individual exposures to different EGFR TKIs based on their IC50 values and MDRAE data were integrated to develop an ordinal logistic regression model for an exposure-safety analysis. A user-friendly nomogram was subsequently designed. The probability of high-grade MDRAE was significantly associated with normalized exposure levels, a history of EGFR TKI treatment, sex and other factors. Model simulations revealed substantial interindividual variability in drug exposure and the probability of different grades of MDRAE for the same treatment regimen. This study quantitatively elucidates the influences of drug exposure and other critical factors on safety, thereby contributing to the formulation of individualized treatment strategies to prevent and promptly address drug safety-related issues.

PMID:40481213 | DOI:10.1038/s41401-025-01573-z

Drug Ther Bull. 2025 Jun 6:dtb-2025-000021. doi: 10.1136/dtb.2025.000021. Online ahead of print.

NO ABSTRACT

PMID:40480797 | DOI:10.1136/dtb.2025.000021

Anesthesiol Perioper Sci. 2023;1(2):16. doi: 10.1007/s44254-023-00018-2. Epub 2023 Jun 14.

ABSTRACT

The list of drugs patients may be exposed to during the perioperative and postoperative periods is potentially extensive. It includes induction agents, neuromuscular blocking drugs (NMBDs), opioids, antibiotics, sugammadex, colloids, local anesthetics, polypeptides, antifibrinolytic agents, heparin and related anticoagulants, blue dyes, chlorhexidine, and a range of other agents depending on several factors related to individual patients' clinical condition and progress in the postoperative recovery period. To avoid poor or ultrarapid metabolizers to a particular drug (for example tramadol and codeine) or possible adverse drug reactions (ADRs), some drugs may need to be avoided during or after surgery. This will be the case for patients with a history of anaphylaxis or other adverse events/intolerances to a known drug. Other drugs may be ceased for a period before surgery, e.g., anticoagulants that increase the chance of bleeding; diuretics for patients with acute renal failure; antihypertensives relative to kidney injury after major vascular surgery; and serotonergic drugs that together with some opioids may rarely induce serotonin toxicity. Studies of germline variations shown by genotyping and phenotyping to identify a predisposition of genetic factors to ADRs offer an increasingly important approach to individualize drug therapy. Studies of associations of human leukocyte antigen (HLA) genes with some serious delayed immune-mediated reactions are ongoing and variations of drug-metabolizing cytochrome CYP450 enzymes, P-glycoprotein, and catechol-O-methyltransferase show promise for the assessment of ADRs and non-responses to drugs, particularly opioids and other analgesics. Surveys of ADRs from an increasing number of institutions often cover small numbers of patients, are retrospective in nature, fail to clearly identify culprit drugs, and do not adequately distinguish immune-mediated from non-immune-mediated anaphylactoid reactions. From the many surveys undertaken, the large list of agents identified during and after anesthesia and surgery are examined for their ADR involvement. Drugs are classified into those most often involved, (NMBD and antibiotics); drugs that are becoming more frequently implicated, namely antibiotics (particularly teicoplanin), and blue dyes; those becoming less frequently involved; and drugs more rarely involved in perioperative, and postoperative adverse reactions but still important and necessary to keep in mind for the occasional potential sensitive patient. Clinicians should be aware of the similarities between drug-induced true allergic type I IgE/FcεRI- and pseudoallergic MRGPRX2-mediated ADRs, the clinical features of each, and their distinguishing characteristics. Procedures for identifying MRGPRX2 agonists and diagnosing and distinguishing pseudoallergic from allergic reaction mechanisms are discussed.

PMID:40476920 | PMC:PMC10264870 | DOI:10.1007/s44254-023-00018-2

Clin Pharmacol Ther. 2025 Jun 6. doi: 10.1002/cpt.3738. Online ahead of print.

ABSTRACT

Osteoporosis is a common metabolic bone disease with aging, characterized by low bone mineral density (BMD) and higher fragility fracture risk. Although current pharmacological interventions provide therapeutic benefits, long-term use is limited by side effects and comorbidities. In this study, we employed driver signaling network identification (DSNI) and drug functional networks (DFN) to identify repurposable drugs from the Library of Integrated Network-Based Cellular Signatures. We constructed osteoporosis driver signaling networks (ODSN) using multi-omics data and developed DFN based on drug similarity. By integrating ODSN and DFN with drug-induced transcriptional responses, we screened 10,158 compounds and identified several drugs with strong targeting effects on ODSN. Mendelian randomization assessed potential causal links between cis-eQTLs of drug targets and BMD using genome-wide association study data. Our findings indicate four drugs, including Ruxolitinib, Alfacalcidol, and Doxercalciferol, may exert anti-osteoporosis effects. Notably, Acebutolol, a β-blocker for hypertension, has not previously been implicated in osteoporosis therapy. For validation, zebrafish osteoporosis models were established using Dexamethasone-induced bone loss, followed by treatment with Acebutolol hydrochloride and Alfacalcidol. Both compounds demonstrated significant protective effects against osteoporosis-related bone deterioration. Furthermore, a population-based data set, utilizing propensity score matching and analyzed via a generalized linear model, revealed that individuals taking β-blocker drugs exhibited significantly higher BMD than users of other cardiovascular medications. In summary, this study integrates multi-omics approaches, experimental validation, and real-world population data to propose acebutolol as a novel candidate for osteoporosis treatment. These findings warrant further mechanistic studies and clinical trials to evaluate its efficacy in osteoporosis management.

PMID:40476595 | DOI:10.1002/cpt.3738

Int J Cardiol Heart Vasc. 2025 May 10;59:101702. doi: 10.1016/j.ijcha.2025.101702. eCollection 2025 Aug.

ABSTRACT

BACKGROUND: Although the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score is a validated mortality risk tool in heart failure (HF), its utility in assessing drug-related adverse events (DAEs) associated with sacubitril/valsartan initiation remains unclear. This study evaluated the association between the MAGGIC risk score and DAEs related to sacubitril/valsartan initiation in a Japanese multicenter cohort.

METHODS: We analyzed 787 patients with HF initiated on sacubitril/valsartan 100 mg/day between August 2020 and August 2021. Patients were stratified into tertiles based on MAGGIC risk scores. The primary outcome was DAEs within 90 days of initiation, defined as hypotension, hyperkalemia, renal events, or angioedema. Secondary outcomes included drug discontinuation and clinical outcomes.

RESULTS: DAEs occurred in 22.7 % patients. Higher MAGGIC risk scores were significantly associated with increased DAEs (adjusted odds ratio [OR] for highest vs. lowest tertile: 2.64, 95 % confidence interval [CI]: 1.66-4.25, p for trend < 0.001) and sacubitril/valsartan discontinuation (21.3 % of patients; adjusted OR for highest vs. lowest tertile: 2.68, 95 % CI: 1.69-4.32, p for trend < 0.001). Time-dependent Cox proportional hazard analyses revealed that the association between DAEs and clinical outcomes varied across the MAGGIC risk score tertiles, with significant interactions between the composite outcome and hospitalization for HF, particularly in lower-risk groups.

CONCLUSIONS: The MAGGIC risk score was associated with DAEs risk following sacubitril/valsartan initiation in patients with HF. The impact of DAEs on outcomes varied across risk tertiles, suggesting potential utility for risk stratification and monitoring approaches in HF management.

PMID:40476175 | PMC:PMC12138916 | DOI:10.1016/j.ijcha.2025.101702

Clin Respir J. 2025 Jun;19(6):e70054. doi: 10.1111/crj.70054.

ABSTRACT

BACKGROUNDS: Pulmonary embolism (PE) is a common disease and a common cause of death. However, it is currently unclear which clinically common drugs can lead to PE.

METHODS: We collected, organized, and analyzed reports from the first quarter of 2018 to the fourth quarter of 2022. We performed disproportionality analysis algorithms to calculate reporting odds ratio (ROR), which could quantify the signal values of different adverse events (AEs).

RESULTS: We have screened a total of 3091 drugs, with AE containing "PE" and calculated the ROR signal values of the top 30 drugs reported and ranked them. TESTIM (ROR = 32.03[28.77-35.66]), BARICITINIB (ROR = 23.48[20.55-26.83]), and NUVARIANG (ROR = 19.89[17.13-23.10]) are the drugs with the strongest correlation with PE. In addition, among the 30 drugs with the strongest correlation with PE, most of which are Biologics & Immunomodulators. Therefore, when using these 30 drugs, it is necessary to be alert to the possible risk of PE.

CONCLUSION: In our study, we filtered 30 common drugs that could cause PE through the FAERS public database, which provides theoretical support for drug selection in the treatment of malignant tumors and IMID.

PMID:40474339 | DOI:10.1111/crj.70054

J Intensive Care. 2025 Jun 5;13(1):31. doi: 10.1186/s40560-025-00803-0.

ABSTRACT

Diarrhea is common in critically ill patients and can lead to malnutrition, electrolyte imbalance, and dehydration. While its direct impact on outcomes, such as mortality or intensive care unit (ICU) stay, remains unclear due to inconsistent definitions, it often results from drug-induced causes, such as antibiotics and antacids. These agents can also contribute to dysbiosis and increase the risk of infections including Clostridioides difficile infections (CDI) and ventilator-associated pneumonia (VAP).Probiotics, defined as live beneficial microorganisms, can counteract dysbiosis by modulating immune responses, restoring microbial balance, and reducing intestinal inflammation. Evidence suggests that probiotics may help prevent diarrhea and secondary infections. Clinical trials and meta-analyses have shown that probiotics may reduce the incidence of VAP, length of ICU stay, duration of mechanical ventilation, and potential in-hospital mortality in critically ill patients.However, evaluating probiotic efficacy remains challenging due to the lack of standardized markers and the influence of confounding factors like antacid use. In a randomized controlled trial, synbiotic therapy was associated with improved fecal microbiota and reduced infections; however, the role of antacids was not addressed.Probiotics are generally safe, although rare adverse events, such as probiotic-associated bacteremia, have been reported, particularly in immunocompromised individuals.The 2024 Japanese Critical Care Nutrition Guidelines included a systematic review and meta-analysis supporting the potential benefits of probiotics in critically ill patients. However, due to significant heterogeneity in strains, dosing, duration, and concurrent antibiotic/antacid use, a weak recommendation (GRADE 2C; low certainty) was issued.Future research should focus on the standardized evaluation of diarrhea and microbiota changes, the use of objective markers-such as fecal pH and short-chain fatty acid levels-and clarification of the interactions of probiotics with other medications. Comprehensive bowel management, including the cautious use of antibiotics and antacids, may be essential to fully recognize the therapeutic potential of probiotics in critical care settings.

PMID:40474303 | DOI:10.1186/s40560-025-00803-0

Br J Gen Pract. 2025 Jun 5:BJGP.2024.0806. doi: 10.3399/BJGP.2024.0806. Online ahead of print.

ABSTRACT

Background Pharmacogenetics has the potential to optimise drug therapy and reduce adverse drug effects (ADEs) by tailoring treatment to a patient's genotype, particularly for chronic disorders managed in general practice (GP). However, the adoption of pharmacogenetics in GP remains slow. Aim This study aimed to evaluate the reproducibility of previously reported associations between genomic variants and medically important adverse drug effects (MIADEs) associated with high-risk medications in GP. Design and setting A retrospective study using data from the UK Biobank (UKBB), a population-based cohort of over 500,000 community-based participants. Method We identified high-risk medications prescribed in GP by linking serious ADEs from the Yellow Card database with English GP prescription data. These high-risk medications were then cross-examined with genomic variants associated with MIADEs from the Pharmacogenomics Knowledgebase (PharmGKB), to select variant-drug pairs for investigation within the UKBB. Results From 78 high-risk medications prescribed in GP and 56 PharmGKB annotations linked to MIADE risk, SLCO1B1 rs4149056 was the only variant with guideline-based prescribing recommendations. This variant, along with others of lower evidence levels, was analysed in the UKBB. No genotype-treatment interaction was observed for SLCO1B1 rs4149056 and statin-related muscle toxicity. Similarly, no interactions were detected for the remaining variants in either secondary or exploratory analyses. Conclusion No statistically significant genotype-treatment interactions were observed for MIADE risk associated with high-risk medications in GP. However, the limited predictive value of the assessed variants may reflect underlying phenotypic imprecision and methodological limitations. Hence, further research is needed to validate these results.

PMID:40473432 | DOI:10.3399/BJGP.2024.0806