Search Results (425)

Background: Adverse Drug Reactions (ADRs) are a significant public concern because of their impact on healthcare systems. Spontaneous reporting of ADRs is crucial for monitoring drug safety and recognizing possible risk factors. The objective of this study was to characterize ADR reports from the Allergy and Clinical Immunology Unit of the G. Martino University Hospital, Messina, Italy. Methods: A retrospective analysis was conducted, including all ADRs spontaneously reported from patients attending the clinic because of at least one previous ADR, from June 2022 to June 2024. Results: A total of 388 reports were collected, mainly from females (71.1%) and adult patients (84.3%). ADRs were mostly immediate, from antibiotics and anti-inflammatory drugs (61.5%), with a high prevalence of cutaneous and respiratory disorders. Delayed reactions were mostly from endocrine therapies, vaccines, and antiepileptics. Anaphylactic shock was present only in 13 ADR reports (3.35%). A higher risk of developing serious ADRs was found in elderly patients aged ≥65 years (p = 0.012). An original finding was that a positive history of allergies (p = 0.023) and past medical history of ADRs (p = 0.045) were negatively correlated to the occurrence of a serious ADR, probably because patients had been previously followed in an allergy setting and alerted about ADRs. Conclusions: This study underlines the role of ADR follow-up in allergy settings to identify preventable traits and related risk factors; appropriate ADR reporting and collaboration between allergists and pharmacovigilance centers can be a winning strategy for ADR prevention. Full article

Background: This study examined whether adverse drug reaction (ADR)-related hospital admissions or adverse drug events (ADE) in primary care are associated with changes in health-related quality of life (HRQOL), functional decline, and A&E visits, over time, in two separate prospective cohort studies of older adults in Ireland. Methods: The Adverse Drug reactions in an Ageing PopulaTion (ADAPT) (Study 1: N = 230) and the Centre for Primary Care Research (CPCR) (Study 2: N = 605) prospective cohorts were used. Participants completed health outcome questionnaires at baseline and again at 3 months (Study 1) and at 24 months (Study 2). ADR-related admissions and ADEs were assessed at baseline. Multivariable linear, logistic, and ordinal logistic regressions were used to examine associations between ADR-related admissions/ADEs and changes in HRQOL (EQ-5D-5L/3L), functional decline, and A&E visits, adjusting for age, sex, comorbidity, and polypharmacy. Results: In Study 1 (ADAPT cohort), frailty increased and A&E visits decreased over 3 months in both ADR/non-ADR groups (p < 0.01). In Study 2 (CPCR cohort), HRQOL decreased, and functional decline and A&E visits increased for both ADE/non-ADE groups over 24 months (p < 0.05). Individuals with ADEs had lower HRQOL and greater functional decline at both time points (p < 0.001). However, experiencing an ADR or an ADE was not significantly associated with changes in HRQOL, functional decline, or A&E visits over time, after adjustments. Conclusions: There were no substantial differences in the short-term healthcare burden of ADRs, while ADEs had poorer long-term outcomes. Full article

Background: The tyrosine kinase inhibitors (TKIs) asciminib, bosutinib, dasatinib, imatinib, nilotinib, and ponatinib have been approved for chronic myelogenous leukemia (CML) therapy. However, pharmacovigilance reports associated with these drugs are neither consistent nor homogenous, with reports of pulmonary toxicity, which could limit their utilization. To better clarify TKIs’ pulmonary risk, we used the European database EudraVigilance to conduct a study on adverse events suspected to be caused by the TKIs asciminib, bosutinib, dasatinib, imatinib, nilotinib, and ponatinib when used for CML therapy. Methods: Suspected adverse reactions to TKIs in the EudraVigilance database (2020–2024) coming from European countries and the United Kingdom were analyzed and compared through a disproportionality analysis. Results: The most frequent alerts concerned the respiratory disorders “pleural effusion” (PE) and “pulmonary arterial hypertension” (PAH) in relation to dasatinib and bosutinib use. Among the TKIs, the prescription of dasatinib is associated with a higher occurrence of PE and PAH, while the prescription of bosutinib induces PE at a minor frequency that nonetheless carries a significant risk for PAH, occurring more often in women. Conclusions: The results indicate that respiratory disorders induced by the TKIs dasatinib and bosutinib need to be diagnosed in a timely manner, and suggest that caution should be taken when prescribing these TKIs to patients affected by CML and pulmonary comorbidities. Full article

Drug–drug interactions (DDIs) can cause adverse reactions or reduce the efficiency of a drug. Using computers to predict DDIs is now critical in pharmacology, as this reduces risks, improves drug outcomes and lowers healthcare costs. Clinical trials are slow, expensive, and require a lot of effort. The use of artificial intelligence (AI), primarily in the form of machine learning (ML) and its subfield deep learning (DL), has made DDI prediction more accurate and efficient when handling large datasets from biological, chemical, and clinical domains. Many ML and DL approaches are bio-inspired, taking inspiration from natural systems, and are considered part of the broader class of biomimetic methods. This review provides a comprehensive overview of AI-based methods currently used for DDI prediction. These include classical ML algorithms, such as logistic regression (LR) and support vector machines (SVMs); advanced DL models, such as deep neural networks (DNNs) and long short-term memory networks (LSTMs); graph-based models, such as graph convolutional networks (GCNs) and graph attention networks (GATs); and ensemble techniques. The use of knowledge graphs and transformers to capture relations and meaningful data about drugs is also investigated. Additionally, emerging biomimetic approaches offer promising directions for the future in designing AI models that can emulate the complexity of pharmacological interactions. These upgrades include using genetic algorithms with LR and SVM, neuroevaluation (brain-inspired model optimization) to improve DNN and LSTM architectures, ant-colony-inspired path exploration with GCN and GAT, and immune-inspired attention mechanisms in transformer models. This manuscript reviews the typical types of data employed in DDI (pDDI) prediction studies and the evaluation methods employed, discussing the pros and cons of each. There are useful approaches outlined that reveal important points that require further research and suggest ways to improve the accuracy, usability, and understanding of DDI prediction models. Full article

Pembrolizumab, an anti-PD-1 monoclonal antibody, showed promising results in the treatment of different types of solid tumors and generally an improvement in overall survival and patients’ outcome. However, as a drug that targets the immune system to enhance the anti-tumor response, it simultaneously increases the risk of autoimmune reactions, producing immune-related adverse events (irAEs). These irAEs might involve any body organ, and in some cases may lead to treatment discontinuation. In this article, we discuss two cases of triple-negative breast cancer (TNBC) patients, who developed irAEs during the course of neoadjuvant pembrolizumab, highlighting the mechanism of the reactions, possible clinical manifestations, and potential management. Full article

Background: Real-world safety profiles of immune checkpoint inhibitors (ICIs) in older adults remain insufficiently characterized. Although ICIs are widely used across tumor types, older patients, particularly those with frailty, multimorbidity, or polypharmacy, are consistently under-represented in clinical trials, limiting the external validity of trial-derived toxicity estimates. Robust real-world data are therefore essential to clarify the incidence, seriousness, and age-related patterns of immune-related adverse events (irAEs) in routine practice. Methods: This is a nationwide retrospective study of spontaneous ICI-related ADRs reported in INFARMED’s Portal RAM (2011–2024). We evaluated the frequency, seriousness, fatality, and organ-specific patterns of ICI-related adverse drug reactions (ADRs) reported to the Portuguese National Pharmacovigilance System. The analytic unit was the ADR case. Endpoints included seriousness (primary), fatality, hospitalization, time-to-onset, and System Organ Class. Multivariable logistic regression adjusted for age, sex, regimen, tumor type, polypharmacy, and calendar period; sensitivity analyses using first ADR per patient were concordant. Results: We identified 2300 eligible ICI-related ADRs (corresponding to 925 patients). Median age at the time of ADR was 65 years (IQR not reported); 33.7% occurred in adults aged ≥70 years, and 62.8% of reports involved male patients. PD-1 inhibitors accounted for 77.5% of ADRs, and monotherapy for 72.9%. Overall, 85.8% of ADRs were classified as serious; 17.9% led to hospitalization and 19.1% were fatal. Serious-event reporting was similar in older and younger adults (≥70 vs. <70 years: 84.5% vs. 86.5%, p = 0.22), and the proportion explicitly labeled immune-related did not differ (9.3% vs. 8.7%, p = 0.56). In contrast, fatal outcomes were significantly more common in older adults (25.3% vs. 16.0%; p < 0.001). Age was associated with distinct organ-specific patterns. Adults ≥ 70 years had higher odds of nervous system disorders (aOR 1.75, 95% CI 1.23–2.48) and immune system disorders (aOR 1.42, 95% CI 1.02–1.98), but lower odds of hepatobiliary (aOR 0.52, 95% CI 0.36–0.76; p = 0.001) and blood/lymphatic disorders (aOR 0.50, 95% CI 0.32–0.79). In multivariable models, age ≥ 70 years did not predict seriousness (aOR 0.98, 95% CI 0.76–1.27), whereas combination therapy remained independently associated with increased seriousness (aOR 1.57, 95% CI 1.13–2.18). Conversely, age ≥ 70 years independently predicted fatal outcomes (aOR 1.66, 95% CI 1.31–2.09). Later calendar periods (2017–2024) were associated with substantially lower fatality (aOR 0.16; 95% CI 0.10–0.27). CTLA-4-containing regimens demonstrated a tendency toward higher fatality (aOR 1.50; 95% CI 0.94–2.37). Conclusions: Chronological age does not seem to increase the likelihood of reporting a serious ICI-related ADR, but, once toxicity occurs, older adults experience higher fatality rates. Age-related phenotypic differences and regimen-specific risks highlight the need for early recognition systems and tailored toxicity management in older populations. Full article

Background: Ticagrelor is a reversible, direct inhibitor of the platelet adenosine diphosphate (P2Y12) receptor, widely used in combination with acetylsalicylic acid (ASA) as dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) to prevent cardiovascular events. Despite its well-established efficacy, ticagrelor may cause adverse effects ranging from common ones (e.g., bleeding, dyspnea) to rare but potentially serious reactions such as bradyarrhythmias. These rare events are likely related to elevated adenosine levels secondary to inhibition of the human equilibrative nucleoside transporter 1 (hENT1). Methods: We describe two clinical cases of ticagrelor-associated bradyarrhythmia observed in patients following ACS. Both cases were analyzed in terms of clinical presentation, ECG findings, management strategy, and outcomes after discontinuation of the drug. Results: The first case concerns a 67-year-old woman with non-ST-segment elevation myocardial infarction (NSTEMI) who developed complete atrioventricular block (third degree) with a 45 s asystolic pause and syncope. The second case involves a 67-year-old man with anterior ST-segment elevation myocardial infarction (STEMI) who experienced recurrent sinus pauses lasting up to 5 s. In both cases, symptoms resolved following ticagrelor discontinuation and theophylline administration. No recurrence of arrhythmia was observed after switching to prasugrel. Conclusions: Ticagrelor-induced bradyarrhythmias, although rare, represent an important and reversible adverse effect that clinicians should be aware of, particularly during the early post-ACS phase. Prompt recognition and drug withdrawal may prevent severe outcomes and avoid unnecessary interventions such as pacemaker implantation. Further studies are warranted to identify patient-specific risk factors predisposing to ticagrelor-related conduction disturbances. Full article

Background/Objectives: The use of linezolid in drug-resistant tuberculosis has shown good effectiveness but has a high risk of adverse drug reactions (ADRs). Linezolid-related ADRs have been widely reported and may affect their therapeutic effect. This systematic review aimed to describe linezolid-related ADRs in drug-resistant tuberculosis. Methods: This literature review was conducted on PubMed, Scopus, ProQuest, and Sage without year limitation, up to June 2023. Study quality was assessed using the JBI checklist to evaluate method quality and risk of bias in the included articles. Inclusion criteria included studies assessing linezolid-correlated ADRs in drug-resistant tuberculosis patients with individual regimens, having access to the full text, and using the English or Indonesian language. Potential reporting bias was minimized by comprehensive database search and duplicate screening. Results: Initially, we identified 650 potential studies. Upon further assessment for relevance and eligibility, seven articles were selected for analysis. From seven articles, it was shown that all articles were reporting about linezolid-correlated ADRs. The three main ADRs are hematologic toxicity, peripheral neuropathy, and optic neuritis. In addition, gastrointestinal disorder and hyperlactatemia are reported as ADRs too. Varied doses of linezolid were used in the seven articles; they range from 300 mg to 1200 mg, with 600 mg/twice daily and 1200 mg/day being dominant. Conclusions: Linezolid-associated ADRs are dose- and duration-dependent. Hematological toxicity most commonly occurs at the beginning of treatment, while peripheral neuropathy and optic neuritis appear after long-term use. Therefore, intensive monitoring and therapeutic drug monitoring are essential to ensure the safety of linezolid therapy. Full article

Cancer pain seriously damages the quality of life of patients, and its management urgently needs new strategies with both efficacy and safety. This review deeply analyzes the clinical limitations of WHO’s third-order analgesic strategy in cancer pain management, especially emphasizes the unique value of integrated traditional Chinese and Western medicine in synergy and reduction in adverse reactions, and summarizes the network interaction of related drugs through the regulation of multi-target analgesic mechanisms such as inflammatory factors, ion channels, neurotransmitters, and even glial cells and osteoclast activity in the tumor microenvironment. Building on this foundation, the article systematically analyzed the clinical advantages and limitations of drug delivery systems (DDS): oral sustained and controlled drug delivery system, mucosal drug delivery system (MDDS), transdermal drug delivery system (TDDS), and intrathecal targeted drug delivery (ITDD) in the treatment of cancer pain for the first time. The development prospects of new DDS: microneedles, disposable intrathecal drug delivery, and nano-drug delivery system (NDDS) in cancer pain were summarized in detail. Looking ahead, research into the analgesic mechanisms of drugs holds promise for providing a theoretical foundation for cancer pain management. Collaborative strategies integrating Chinese and Western medicine, coupled with precision delivery technologies, are expected to advance more efficient and safer pain control, offering new approaches and methods for achieving superior pain management outcomes. Full article

Background: Tyrosine kinase inhibitors (TKIs) are crucial to treating endocrine-related malignancies, including advanced thyroid cancers and neuroendocrine tumors, but their benefit is tempered by cutaneous adverse events (CAEs) that impair adherence and quality of life. Objective: To summarize the dermatologic toxicities of TKIs used in endocrine oncology and provide practical, multidisciplinary guidance for prevention and management. Methods: Narrative synthesis of clinical trial reports, post-marketing studies, and specialty guidelines pertinent to lenvatinib, vandetanib, cabozantinib, and other commonly used TKIs, integrating dermatologic and endocrine perspectives on mechanisms and care pathways. Results: VEGFR-targeted TKIs frequently cause hand–foot skin reaction, xerosis, fissuring, paronychia, and impaired wound healing; multikinase inhibition also produces alopecia, pigmentary changes, and mucositis. Epidermal growth factor receptor (EGFR) and rearranged during transfection (RET) inhibition with vandetanib is associated with acneiform eruption, photosensitivity, and nail fragility. Pathogenesis reflects on-target inhibition of VEGF/EGFR signaling leading to keratinocyte dysfunction, vascular fragility, and altered eccrine mechanics. Early risk stratification, patient education, and bundle-based prophylaxis (emollients, keratolytics, urea-based creams, sun protection) reduce incidence and severity. Grade-based algorithms combining topical corticosteroids/antibiotics, dose interruptions or reductions, and short systemic courses (e.g., doxycycline, antihistamines) enable symptom control while maintaining anticancer intensity. Close coordination around procedures minimizes wound-healing complications. Conclusions: Dermatologic toxicities are predictable, mechanism-linked, and manageable with proactive, multidisciplinary care. Standardized prevention and treatment pathways tailored to specific TKIs—particularly lenvatinib, vandetanib, and cabozantinib—can preserve dose intensity, optimize quality of life, and sustain antineoplastic efficacy. Full article

Background/Objectives: Drug hypersensitivity reactions (DHRs) are an important cause of morbidity in hospitalized patients, but their epidemiology and management in the inpatient setting are not well defined. Mislabeling of drug allergies may lead to inappropriate treatment and reduced antimicrobial stewardship. This study aimed to characterize the clinical profile, diagnostics, and management of inpatients referred for suspected drug allergy in a tertiary care hospital. Methods: We retrospectively reviewed all adult inpatients (≥18 years) at Luigi Sacco Hospital (Milan, Italy) who received allergology consultation between 1 June 2022 and 31 May 2025. Data on demographics, reaction type, culprit drugs, investigations, and management were collected. Immediate reaction severity was graded using the United States Drug Allergy Registry (USDAR) scale; delayed reactions were classified as severe cutaneous adverse reactions (SCARs) or non-SCARs. Logistic regression identified predictors of severity. Results: Among 35,438 admissions, 334 patients (0.9%) were evaluated; median age was 65 years, 51.2% were female, 67.4% had atopic comorbidities, and 55.1% reported prior drug allergy. Immediate reactions occurred in 49.1%, delayed in 43.7%. Cutaneous involvement was present in 86.8%, anaphylaxis in 6.6%, and SCARs in 3.9%. Antibiotics—particularly β-lactams—were most often implicated. In multivariate analysis, antibiotic exposure and older age were linked to more severe immediate reactions, while the absence of atopy predicted SCARs. Desensitization was successfully performed in 16.2% of patients. Conclusions: DHRs in inpatients are frequent and often involve high-risk drugs. Structured inpatient allergology services and an “allergy stewardship” approach may reduce DHR-related risks, support optimal therapy, and improve antimicrobial use strategies in tertiary care settings. Full article

Pharmacovigilance approaches have conventionally focused on the use of epidemiological data to detect emergent adverse drug reactions (ADRs). Recent advances in the use and availability of real-world data have expanded opportunities to detect ADR signals in medical records. We provide a limited review of pharmacovigilance practices and tools we have specifically considered implementing into our comprehensive medication management clinic and associated research programs. Use of pharmacogenomic variants has proven useful only on a limited scale as such data are reliant on low-dimensional approaches matching variants to drugs, often with small effect sizes. As such, most ADRs go unrecognized, undocumented, and unactionable. We posit that an idealized pharmacovigilance framework that relies on artificial-intelligence-assisted reporting with adjudication by pharmacovigilance experts and new models of ambulatory pharmaceutical practice would establish the following attributes: (1) all metadata relating to medication use would be available in the medical record in computable and interoperable data models, (2) digital surveillance tools would detect most ADR events with attributed pharmacological contributions, (3) all events would be characterized using standard adjudication rubrics, and (4) all events would iteratively inform an ADR knowledgebase and improve models to advance detection and prediction of ADR during the course of patient care with a focus on having the necessary tools for clinicians to prevent ADRs. This review provides a limited and focused framework for more systematic documentation of ADRs and tactics to mitigate the idiopathic nature of most ADRs. Full article

Background: Iodinated contrast agents are widely used in computed tomography (CT) imaging; however, they can cause adverse drug reactions (ADRs) ranging from mild hypersensitivity to severe anaphylaxis. While several clinical risk factors have been identified, large–scale studies incorporating environmental variables remain limited. This study aimed to assess the prevalence and predictors of contrast agent-related ADRs over a 10-year period. Methods: We retrospectively analyzed 221,962 adult outpatients who underwent contrast-enhanced CT between January 2014 and December 2023 at a single tertiary center: Patient characteristics, clinical conditions (e.g., hypertension, allergy history), contrast agent types, premedication status, seasonal trends, temperature, and humidity were examined. ADRs were categorized as mild, moderate, or severe based on American College of Radiology (ACR) guidelines. Logistic regression was used to identify independent predictors. Results: The overall prevalence of ADRs was 0.64% (1423 cases). ADRs were more frequent in females, younger patients, and those receiving premedication. Seasonal and environmental patterns were evident: higher ADR rates occurred in summer and autumn, with positive correlations to ambient temperature and humidity. Among contrast agents, Ioversol (1.4%) and Iomeprol (1.2%) showed the highest ADR rates. The prevalence of mild ADRs increased in the post–COVID-19 period, while that of moderate reactions declined. Conclusions: This real–world study identified multiple clinical and environmental factors associated with ADRs to iodinated contrast agents in CT imaging. The findings suggest the importance of individualized risk assessment and the consideration of environmental factors when planning contrast administration. Full article

Background: Clinical pharmacy services (CPS) have been shown to confer significant advantages in patient care. It remains to be clarified how CPS resources are allocated across routine care settings. It remains to be clarified which recommendations are made to resolve the drug-related problems (DRP) identified by CPS and which adverse drug reactions (ADR) actually arise from the identified DRP. Methods: Following positive ethical approval, patient chart analyses, evaluation of pharmacy documentation on CPS and pharmacist interviews were performed to characterize CPS at all medical departments of the Bundeswehr Hospital Hamburg. We developed and pre-tested instruments for standardization: A Standard Operating Procedure (SOP) for the practical exercise and documentation of CPS by the pharmacists performing them, a standardized form (checklist) for retrospective data collection as part of this study, and a standardized questionnaire for conducting the pharmacist interviews including a risk assessment according to the NCC-MERP score. Results: In total, 1000 CPS were documented in 504 patients (mean age: 69.95 years; 229 female) on 16,705 treatment days. A total of 66.87% CPS was initiated when pharmacists participated in ward rounds. In all CPS, “Indications” was the topic addressed most frequently (37.70%). “Agents for obstructive respiratory diseases” was the most frequently involved drug class (11.32%). The most frequent processing time per CPS was 16–30 min (48.61%). The number of CPS ranged from 0.36/100 treatment days in dermatology to 12.47 in oncology. Severity of 358 DRP was classified “very severe” (5.03%), “severe” (42.74%), “moderate” (34.36%), “low” (15.08%), “very low” (1.40%), or “without impact” (1.40%). The probability of DRP occurrence was classified as “high” in 13.13% and “very high” in 3.35%. In 15.36% of the DRP, an ADR actually occurred. In 504 patients, 932 specific recommendations were forwarded to solve the DRP identified during CPS. Of those, 53.97% were implemented. Conclusions: In almost all CPS, a considerable number of DRP with serious clinical consequences were identified. Half of the forwarded recommendations were implemented. Full article