Search Results (1,602)

Background/Objectives: Anthracycline-induced cardiotoxicity may compromise cancer treatment and long-term outcomes. Although differences in the cardiotoxicity profile of epirubicin and doxorubicin have been reported, direct comparative pharmacovigilance evidence remains limited. This study compared their cardiovascular adverse reaction reporting profiles using EudraVigilance (EV) data. Methods: Aggregated Individual Case Safety Reports submitted up to 12 July 2026 on the European portal were analyzed. Descriptive analyses assessed demographic characteristics, report origin, reporter type, System Organ Class distribution, seriousness, and clinical outcomes. Cardiotoxicity-related preferred terms (PTs) were identified using the Standardized MedDRA Queries “Cardiac failure”, “Cardiomyopathy”, and “Myocardial infarction”. Comparative disproportionality analysis was restricted to reports submitted by healthcare professionals. Reporting odds ratios and 95% confidence intervals were calculated for PTs with at least five reports for each drug. Results: Overall, 52,257 reports for doxorubicin and 31,049 for epirubicin were identified. Cardiac disorders were reported in 4459 doxorubicin cases and 1406 epirubicin cases, with over 97% classified as serious. Among 51 cardiotoxicity-related PTs, doxorubicin showed significantly higher reporting odds for cardiogenic shock, congestive, chronic, acute, and left ventricular cardiac failure, decreased ejection fraction, cardiomyopathy, cardiotoxicity, toxic cardiomyopathy, acute myocardial infarction, myocardial infarction, and increased troponin. The strongest disproportionality signals were observed for cardiogenic shock, toxic cardiomyopathy, cardiomyopathy, and cardiotoxicity. Conclusions: Doxorubicin was associated with a more pronounced pattern of cardiotoxicity-related reporting and disproportionality signals than epirubicin in the EV database. These findings highlight potential differences in the cardiovascular safety profiles of the two anthracyclines and provide signals that warrant further investigation, while underscoring the importance of cardiovascular risk assessment and monitoring in patients receiving anthracycline therapy. However, disproportionality signals do not establish incidence, absolute risk, or causality and require confirmation in prospective comparative studies. Full article

Pharmacogenomics can convert stable DNA variation into prescribing information, but its value in primary care depends on whether a result changes a decision at the right moment. This narrative review critically examines selected actionable gene–drug pairs, implementation models, conflicting evidence, and unresolved questions for family physicians managing multimorbidity and polypharmacy. A targeted search of PubMed/MEDLINE and current pharmacogenomic guideline resources was updated through 14 August 2026, prioritizing clinical guidelines, randomized and pragmatic trials, implementation studies, and primary-care evidence. Guideline actionability describes how an available result can guide treatment; it does not by itself establish that testing should be ordered. Selected examples include clopidogrel, statins, metoprolol, antidepressants, codeine and tramadol, proton-pump inhibitors, nonsteroidal anti-inflammatory drugs, and warfarin, together with shared-care medicines such as thiopurines and carbamazepine. In PREPARE, a defined 12-gene panel linked to prescribing recommendations reduced clinically relevant adverse drug reactions within a specific European workflow. Other trials showed that benefit is drug-, population-, comparator-, and workflow-dependent. Pharmacogenomics does not replace assessment of organ function, interactions, adherence, frailty, or patient preference. This review proposes selective, clinically triggered panel testing as a pragmatic model for primary care, with structured, reusable results and concise decision support. Future work should define who benefits, improve ancestry representation, account for phenoconversion, and demonstrate health-system-specific cost-effectiveness. Pharmacogenomics is best understood as an additional medication-safety input rather than a stand-alone precision-medicine solution. Full article

Background/Objectives: Adverse drug reactions (ADRs) caused by drug–drug interactions (DDIs) represent an important problem in pharmacotherapy, especially in patients receiving multiple medications. Most computational approaches to DDI-associated ADR prediction formulate the task as a binary classification, but they do not explicitly consider the severity of adverse reactions. Our study aims to develop structure-based models that predict the severity of ADRs associated with specific drug pairs. Methods: Datasets were generated using DrugMAP as the source of drug pair–ADR associations with annotated severity categories, and TwoSides was used as an additional source to generate conditionally negative examples. The drug pairs were represented using PoSMNA descriptors, which encode pair-specific structural features derived from the molecular structures of both compounds. Predictive models were built using PASS DDI software. Model performance was evaluated using a modified cross-validation procedure that excluded compound-level overlap between the training and test sets, thereby reducing information leakage caused by the repeated occurrence of the same drugs in different pairs. Results: Models were developed for 14 clinically relevant ADR types, including cardiovascular, hepatotoxic, nephrotoxic, hemorrhagic, metabolic, and neurological effects. The unweighted class-level macro-average AUC values ranged from 0.830 for the Major category to 0.911 for the Minor category, while balanced accuracy ranged from 0.776 to 0.857. Predictive performance varied significantly between ADR types and severity categories. Higher accuracy was observed for some ADR types that were better captured by the structure-based descriptors used in this study, whereas complex multifactorial reactions, such as hepatotoxicity, were less accurately predicted. Case-based assessment using clinically documented drug combinations showed that the predicted severity profiles were generally consistent with the expected clinical risk patterns. Conclusions: The proposed approach demonstrates that the PoSMNA descriptors of drug pairs can be used for preliminary prediction of DDI-associated ADR severity. The developed models can help to filter out potentially dangerous drug combinations at an early stage and are implemented in the AdverDDIPred web-application. Full article

Background: Amoxicillin–clavulanate (AC) is the antibiotic most frequently implicated in idiosyncratic drug-induced liver injury (DILI) worldwide, and it characteristically produces a cholestatic or mixed pattern in older adults. A predominantly hepatocellular presentation is distinctly less common in this age group, and reports from the Arabian Peninsula are scarce. Case presentation: A 66-year-old Saudi man developed painless, progressive jaundice after a seven-day course of oral AC (500/125 mg three times daily) prescribed for a thumb laceration. He described a similar self-limiting jaundice after the same antibiotic approximately five years earlier, an episode that was never investigated and had not been entered in his allergy record, so the drug was prescribed again unknowingly. Liver biochemistry, documented as normal four months earlier, showed alanine aminotransferase (ALT) peaking at 587 U/L (14.3 × the upper limit of normal, ULN) and aspartate aminotransferase at 335 U/L, with total bilirubin 249 µmol/L (11.9 × ULN) and a 69% conjugated fraction, whereas alkaline phosphatase (ALP) never exceeded 245 U/L (1.9 × ULN). The R-value at the ALT peak was 19.3 using the same-day ALP, and 7.6 even when the peak ALT is paired with the highest ALP recorded at any point in the illness; the pattern was therefore hepatocellular (R > 5) throughout the injury phase. Hy’s law criteria were met, although the international normalised ratio remained 1.0 and no encephalopathy developed. Peripheral eosinophilia (peak 1.05 × 10⁹/L) was documented. Hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody and HIV serology were non-reactive; antinuclear, anti-smooth-muscle, anti-liver-kidney microsomal type 1 and antimitochondrial antibodies were negative and serum ceruloplasmin was normal; ultrasound with contrast-enhanced triphasic computed tomography excluded biliary obstruction and malignancy. Hepatitis A and E serology and cytomegalovirus/Epstein–Barr studies were unavailable at our institution, which we report as a limitation. AC was withdrawn and management was supportive. Liver biochemistry normalised completely over the following three months (ALT 25 U/L, ALP 103 U/L, and total bilirubin 22 µmol/L). Updated Roussel Uclaf Causality Assessment Method (RUCAM) scoring on the hepatocellular scale gave 7 points (probable); no credit was taken for the historical episode, since RUCAM requires documented enzyme re-elevation for a positive re-administration response. Conclusions: AC can cause hepatocellular, Hy’s-law-positive injury in older adults, not only the cholestatic phenotype emphasised in the literature. The decisive failure here was administrative rather than diagnostic: an adverse drug reaction that is never recorded will be repeated. Full article

Machine learning (ML) integrated with metabolomics has emerged as a promising strategy to advance precision pharmacotherapy, enabling data-driven prediction of drug response. This review provides an overview of commonly applied ML methodologies in metabolomics-based pharmacological studies, including supervised models (Random Forest, Extreme Gradient Boosting, Support Vector Machine, Logistic Regression, K-Nearest Neighbors), unsupervised models (K-Means Clustering, Principal Component Analysis), and deep learning approaches. We summarize recent progress in the application of metabolomics-driven ML to personalized medication, with a focus on drug dosage optimization, therapeutic efficacy prediction, and adverse drug reaction assessment. Despite these advances, significant challenges remain, including limited explainability, insufficient prospective clinical validation, lack of standardization and reproducibility, and data dimensionality and quality issues. Addressing these issues will be essential for the clinical translation of ML-metabolomics integration. Looking ahead, continued methodological innovation, large-scale multi-center prospective validation, and integration with other omics platforms will be key to unlocking the full potential of metabolomics combined with ML in precision healthcare. Full article

Background/Objectives: Pharmacogenetics (PGx) may improve drug safety and effectiveness, but its integration into routine care remains heterogeneous across the Spanish National Health System (NHS). This article presents BioFRAM PGx, a multicentre implementation framework that defines the methodological and operational basis for subsequent observational validation in cardiovascular and mental-health care settings. Methods: The framework was developed by healthcare centres from eight Spanish Autonomous Communities through a structured review of PharmGKB/ClinPGx clinical annotations, CPIC and DPWG guidelines, and national regulatory resources. Gene–drug pairs were prioritized according to clinical actionability, therapeutic relevance, applicability to the Spanish population, and analytical feasibility. BioFRAM PGx defines a panel of seven pharmacogenes and 35 drugs, standardized genotyping and phenotype-assignment procedures, pharmacovigilance and clinical variables, healthcare-resource measures, and centralized data management. The proposed non-interventional validation phase includes adults receiving at least one selected drug in hospital or primary-care settings, with a minimum six-month follow-up. PGx results are not returned to clinicians and do not modify treatment. Its primary objective is to assess the predictive value of PGx genotyping for adverse drug reactions (ADRs); secondary objectives include ADR incidence and implementation feasibility. Results: The main outputs are the proposed multicentre observational design, the prioritized gene–drug panel, harmonized analytical and pharmacovigilance workflows, standardized data domains, and a centralized data-management strategy. No patient-level clinical, implementation, or economic outcomes are presented. Conclusions: BioFRAM PGx provides a structured multicentre framework for harmonizing pharmacogenetic procedures across the Spanish NHS. Its clinical effectiveness, influence on prescribing, scalability, and economic outcomes remain to be assessed in subsequent studies. Full article

Acne vulgaris is one of the most prevalent dermatological conditions, affecting up to 85% of individuals aged 11–30 years. Clascoterone cream is the first topical androgen receptor inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of acne vulgaris in patients aged 12 years and older, and the first agent in this class approved for use in both male and female patients. The aim of this narrative review is to summarize the current evidence regarding the efficacy, safety profile, and potential future applications of clascoterone in the treatment of acne vulgaris. A comprehensive literature search was conducted in PubMed/MEDLINE and ClinicalTrials.gov databases up to April 2026. Search terms included “clascoterone,” “cortexolone 17α-propionate,” and “androgen receptor inhibitor acne.” Eligible publications included randomized controlled trials, meta-analyses, open-label extension studies, retrospective analyses, case reports, and relevant review articles published in English. Clinical trial registries and regulatory agency announcements were also searched for ongoing studies and recent approval decisions. Phase 3 trials and meta-analyses demonstrate that twice-daily application of clascoterone 1% cream significantly reduces inflammatory and non-inflammatory lesion counts compared to vehicle, with efficacy sustained up to 12 months of treatment. The safety profile is favorable, with adverse events limited predominantly to mild and transient local skin reactions. Subgroup analyses have shown no significant sex-related differences in efficacy or safety, and the safety profile appears comparable between adolescents and adults. In an exploratory pooled subgroup analysis, lesion-count reductions were greater in adults than in adolescents, whereas the adjusted between-group comparison of IGA success was not statistically significant. Because no formal treatment-by-age interaction test was reported, these findings should be considered hypothesis-generating. Emerging but still incomplete data suggest potential applications in androgenetic alopecia and mild hidradenitis suppurativa. Clascoterone represents a novel addition to the therapeutic armamentarium for acne vulgaris, offering a unique mechanism of action with a favorable safety profile. Further research is warranted to establish its role in combination therapies and in other androgen-dependent dermatoses. Full article

Background/Objectives: Local anesthetics (LAs) are used in a variety of different contexts, from loco-regional anesthesia to analgesia. In cardiothoracic surgery, fascial plane blocks are deserving of attention, including erector spinae plane block (ESPB). In this context, ropivacaine is convenient, due to its peculiar pharmacokinetic/pharmacodynamic properties. Nevertheless, LAs can still cause systemic toxicity (LAST), due to erroneous injection and/or variable systemic adsorption/distribution. This interindividual pharmacokinetic variability can be intensified by the tendency to use a fixed ropivacaine dose in ESPB. The aims of this work were investigating systemic exposure to ropivacaine during ESPB in the context of cardiac and thoracic surgery, comparing it to the literature-reported maximum tolerated concentrations, and identifying potential predictors of exposure. Methods: Patients receiving ultrasound-guided injection of 40 mL of ropivacaine 0.375% solution for ESPB were enrolled. Arterial blood was sampled at 5, 15, 30, 45, 60, 120, and 180 min after the injection, and total and free concentrations of ropivacaine were determined by means of LC-MS/MS analysis of arterial plasma. Results: Concentrations showed wide variability, particularly during the first hour post-dose. Significant differences were observed between patients undergoing cardiac and thoracic surgery, with the latter showing higher concentrations, potentially above the cutoff values predictive of LAST. Pharmacokinetic differences were mainly explained by anthropometric (body weight and BSA) and clinical/hemodynamic (NYHA score) characteristics. Conclusions: This study shows that about 5% of patients could reach arterial plasma concentrations of ropivacaine above the cutoff level for LAST after ESPB with a 150 mg dose. Considering patients’ weight could be beneficial to maintain exposure below the toxicity cutoff. Full article

Treatment-resistant mental health conditions are common in primary care and challenging for clinicians. Trial-and-error prescribing can prolong morbidity and increase adverse drug reactions (ADRs). Pharmacogenomic (PGx) testing enables individualised prescribing by identifying gene–drug interactions affecting psychotropic response. Thirty adults with treatment-resistant mental health conditions underwent PGx testing using a commercial panel (one lost to follow-up [n = 29]). Patients received PGx-guided treatment (n = 8) or standard care (n = 21). Phenotypes were assigned per CPIC and DPWG guidelines, with prescribing guided by clinical experience where guidelines were unavailable. Medication histories were reviewed for gene–drug concordance, ADRs, and treatment failures. Clinical improvement at eight weeks was defined as “marked” or “moderate” improvement and/or ADR resolution. Actionable genotypes were common, particularly CYP2D6 (27.5% poor/intermediate drug metabolising phenotype) and CYP2C19 (37.9%). Guideline-actionable gene–drug interactions occurred in 37% of patients, and eleven patients possessed actionable phenotype at multiple loci. Gene–drug interactions were identified in nine patients and guidance was fully implemented in six. Clinical benefit at 8 weeks was achieved in 6/8 patients with genotype-guided changes versus 8/21 receiving standard care. PGx-guided prescribing may support improved antidepressant response and tolerability while reducing trial-and-error prescribing for treatment-resistant patients in primary care. Full article

Background/Objectives: Proactively informing the patient prior to initiating medication and implementing preventive strategies are essential for mitigating the risk of developing medication-related osteonecrosis of the jaw (MRONJ). This study evaluated the awareness of MRONJ among a group of dental faculty patients who were scheduled to use, were using, or had previously utilized bisphosphonate and/or denosumab. Methods: A structured questionnaire-based survey was used as the survey tool to evaluate the patients’ awareness of MRONJ. A non-probability convenience sampling method was employed throughout a one-year period. Results: Throughout the study period, 202 participants were included, with a response rate of 97.58%. Only 35 (17.3%) of the patients had awareness of the risk of MRONJ, and 23 (11.4%) reported that their prescribing physicians had informed them about the potential side effects of their medication before the commencement of treatment. Univariate logistic regression, which was performed to elucidate the elements affecting awareness, revealed a significant odds ratio for healthcare professionals as a source of knowledge (29.229, p < 0.001), information of side effects given by a prescribing physician (25.343, p < 0.001), dental consultation (2.592, p = 0.018), and regular dental visits (3.205, p = 0.004). In the multivariate logistic regression analysis, “Healthcare professional as source of knowledge” was significantly associated with awareness (OR = 21.956, p < 0.001). “Information of side effects given by a prescribing physician” was also a significant predictor (OR = 11.450, p < 0.001), indicating that participants informed by prescribing physicians about the side effects were more likely to have awareness. Conclusions: This study revealed that despite patients’ limited awareness of MRONJ, the dissemination of information by healthcare professionals positively influenced their awareness and understanding of the risk factors associated with MRONJ. In particular, receiving information from healthcare professionals and prescribing physician-provided information about side effects appeared to be the strongest predictors of awareness. Full article

Background/Objectives: Concerns regarding the psychiatric safety profile of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have increased since the 2023 European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA) reviews. However, it remains unclear whether this signal is uniform across the drug class or concentrated in specific compounds. This study aimed to characterize and compare, in a systematic manner, the global reporting patterns of psychiatric adverse drug reactions (ADRs) associated with the main GLP-1 RAs using the World Health Organization (WHO) VigiBase global pharmacovigilance database. Methods: A descriptive, cross-sectional pharmacovigilance study was conducted on individual case safety reports (ICSRs) retrieved from VigiAccess (January 2000–2026) for semaglutide, liraglutide, dulaglutide, exenatide, tirzepatide, and lixisenatide. A disproportionality analysis was performed within the MedDRA “Psychiatric disorders” System Organ Class (SOC) using the Reporting Odds Ratio (ROR) with 95% confidence intervals (CIs). This study adhered to the STROBE and READUS-PV guidelines. Results: A total of 537,519 ADR reports were analyzed across the five drugs with sufficient reporting volume (lixisenatide was excluded owing to n = 22 psychiatric events). Psychiatric disorders accounted for 24,899 reports, with marked intraclass heterogeneity in both the proportion of psychiatric reports (6.73% for semaglutide versus 3.12% for tirzepatide) and in disproportionality estimates. Signals of disproportionate reporting were identified exclusively for semaglutide (ROR 1.55; 95% CI 1.50–1.59) and liraglutide (ROR 1.19; 95% CI 1.15–1.23), whereas tirzepatide, dulaglutide, and exenatide showed point estimates below unity. Conclusions: The psychiatric safety profile of GLP-1 RAs is not homogeneous within the therapeutic class. The disproportionality signal is concentrated on semaglutide and, to a lesser extent, liraglutide. These findings extend previous WHO-based analyses limited to suicidality and support active clinical surveillance of psychiatric symptoms in patients treated with these specific agents. Full article

Elite athletes experience diverse biological, psychological, and social challenges during injury rehabilitation, yet few qualitative studies have explored these experiences and their interactions from a biopsychosocial perspective. This exploratory qualitative study investigated the biopsychosocial experiences of elite athletes during injury rehabilitation and the interactions among these experiences through semi-structured interviews with five participants, using inductive content analysis. Athletes reported biological experiences including musculoskeletal symptoms, limitations in daily activities, adverse drug reactions, psychosomatic symptoms, and physical development; psychological experiences including negative emotions (anger, anxiety, and depression) and positive experiences (restoration and psychological resilience); and social experiences including informational, instrumental, and emotional support, as well as negative social influences such as blame and pressure to return to play. Participants perceived that these biological, psychological, and social experiences were closely interconnected throughout rehabilitation. Biological experiences, such as pain and physical impairment, were perceived to contribute to negative emotions, including anxiety, whereas negative emotions were associated with stress-related psychosomatic symptoms, such as gastrointestinal symptoms and headaches. Emotional support was associated with positive emotional experiences, whereas negative social influences, including blame and pressure to return to play, were associated with negative emotional responses. These findings contribute to an understanding of the multidimensional experiences of injured elite athletes and may inform development of integrated rehabilitation approaches that address biological, psychological, and social aspects of recovery. Full article

Background: Personalized precision medicine adapts therapeutic strategies to individual characteristics. In psychiatry, suboptimal outcomes with antipsychotics are often related to adverse drug reactions, poor adherence and therapeutic failure. Pharmacogenetics, particularly CYP2D6 genotyping, can improve clinical outcomes through genotype-guided therapy. This study aimed to design and implement a pharmacogenomic and pharmacokinetic testing program for long-acting injectable (LAI) antipsychotics within the Galician Health Service to enhance personalized psychiatric care. Methods: The pilot program encompasses pharmacogenetic and pharmacokinetic testing. Inclusion criteria were broad, covering patients initiating or receiving LAI antipsychotic therapy, as well as those with prior adverse reactions in order to explore scenarios where pharmacogenetic and/or pharmacokinetic data could help with clinical decisions. Structured workflows, interdisciplinary training and integration of results into the electronic health record supported implementation. A pharmacogenetic panel was specifically designed for psychiatric care, targeting clinically relevant variants in CYP2D6, CYP3A4 and ABCB1. Results: A total of 540 patients were included, with primary testing reasons being clinical follow-up (54.6%) and oral-to-LAI transition (38.5%). The CYP2D6 phenotypes were 55% normal, 34% intermediate, 6.3% poor and 4.3% ultrarapid metabolizers. Atypical metabolism was observed in 6.7% of patients for CYP3A4 and in over half for ABCB1. Plasma drug levels were within the therapeutic range for most patients, though some measurements were above or below expected values. Conclusions: This pilot demonstrates a scalable, evidence-based approach to precision psychiatry for LAI antipsychotics, integrating pharmacogenetic and pharmacokinetic testing into routine care. The framework facilitates genotype-guided decision-making and supports broader adoption of pharmacogenomics in psychiatric practice. Full article

Background/Objectives: Cutaneous adverse drug reactions (CADRs) account for approximately 45% of all adverse drug reactions. Although most are self-limiting, some may progress to severe cutaneous adverse reactions (SCARs). In children, delayed rashes associated with antimicrobial therapy, particularly beta-lactams, are often misclassified as drug allergies, leading to unnecessary antibiotic avoidance and potentially suboptimal antimicrobial prescribing. This study aimed to characterize delayed antimicrobial-associated CADRs in children and to investigate reporting patterns and factors associated with their clinical management across age groups. Methods: Real-world data from pediatric patients hospitalized in 2023 at the “Ospedale dei Bambini Vittore Buzzi” (Milan, Italy) were integrated with Individual Case Safety Reports from the FDA Adverse Event Reporting System (FAERS). Only cases with documented treatment durations were included. Clinical characteristics, antimicrobial exposure patterns, and factors associated with the reporting of delayed rashes were evaluated. Results: Five pediatric patients developed delayed CADRs after 19–22 days of antimicrobial therapy. Infectious and immunological investigations were negative, and symptoms resolved following drug discontinuation. FAERS analysis identified 97 delayed rash reports, associated with prolonged treatment duration, frequent polytherapy, and higher reporting rates for vancomycin, teicoplanin, and beta-lactam combination regimens. Logistic regression showed that age and polypharmacy were significantly associated with reporting patterns of delayed rash and therapy continuation among reported cases. Conclusions: Among reported cases, delayed antimicrobial-associated CADRs were associated with age and polypharmacy. Improved recognition of these reactions may facilitate appropriate clinical management, support more informed prescribing decisions, and reduce inappropriate antibiotic allergy labeling. Further studies are needed to validate these findings and refine risk-based management strategies in pediatric patients. Full article