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Keywords = adverse drug reaction

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18 pages, 791 KB  
Article
Risks Associated with 5α-Reductase Inhibitor Use: Analysis of Adverse Drug Reactions Reported to EudraVigilance
by Ricardo Alves, Samuel Silvestre and Cristina Monteiro
Pharmaceuticals 2026, 19(6), 939; https://doi.org/10.3390/ph19060939 - 15 Jun 2026
Viewed by 241
Abstract
Background/Objectives: 5α-Reductase inhibitors (5ARIs) are commonly used to treat and prevent androgenic alopecia and benign prostatic hyperplasia. Despite their well-established effectiveness, they are associated with adverse drug reactions (ADRs), highlighting the need for continuous safety assessment. This study aimed to analyze the [...] Read more.
Background/Objectives: 5α-Reductase inhibitors (5ARIs) are commonly used to treat and prevent androgenic alopecia and benign prostatic hyperplasia. Despite their well-established effectiveness, they are associated with adverse drug reactions (ADRs), highlighting the need for continuous safety assessment. This study aimed to analyze the ADRs associated with finasteride and dutasteride, both as monotherapy and in combination therapy. Methods: A retrospective analysis of ADRs associated with finasteride and dutasteride reported to EudraVigilance between 1 January 2005 and 27 March 2023 was performed. A total of 7777 reports were selected, and various variables were examined, including the temporal evolution of ADR reports, reporter profile, and the age group of the affected population. ADRs were categorized based on their seriousness and outcome, with particular focus on the most common reactions and their alignment with the Summary of Product Characteristics (SmPC). Results: The most affected age group, excluding the “Not Specified” category, was “18–64 years.” Overall, finasteride was the most reported. The majority of reported ADRs were classified as “Serious,” with a predominant outcome of “Persists without recovery,” and a significant proportion of these ADRs were not listed in the respective 5ARI SmPCs. Among the ADRs classified as “Serious,” the most frequently reported seriousness criterion was “Clinically important”. Conclusions: The results emphasize how crucial it is to continuously monitor these drugs in order to prevent and mitigate ADRs, ensure population safety, and promote public health. Additionally, more research is required to determine whether the ADRs not included in the SmPC could be new warning signs. Full article
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10 pages, 220 KB  
Article
Perioperative Antibiotic Use in Pediatric Surgical Patients in a Tertiary Care Hospital: A Retrospective Pharmacoepidemiological Study
by Fitim Bexhet Alidema and Zejdush Tahiri
Pharmacoepidemiology 2026, 5(2), 18; https://doi.org/10.3390/pharma5020018 - 9 Jun 2026
Viewed by 149
Abstract
Background and Objective: Perioperative antibiotics are widely used in pediatric surgical practice; however, inappropriate selection and prolonged use may contribute to antimicrobial resistance and unnecessary exposure. Appropriate use of perioperative antibiotics is essential to prevent surgical site infections while minimizing antimicrobial resistance, [...] Read more.
Background and Objective: Perioperative antibiotics are widely used in pediatric surgical practice; however, inappropriate selection and prolonged use may contribute to antimicrobial resistance and unnecessary exposure. Appropriate use of perioperative antibiotics is essential to prevent surgical site infections while minimizing antimicrobial resistance, adverse drug reactions, and unnecessary healthcare costs. Despite existing international recommendations, deviations from guideline-based practice remain frequent in pediatric surgical settings. This study aimed to describe patterns of perioperative antibiotic use and assess the appropriateness of prescribing practices in a tertiary care setting, and to identify factors associated with inappropriate antibiotic use. Methods: A retrospective pharmacoepidemiological study was conducted by reviewing medical records of pediatric patients admitted to a tertiary care hospital in Kosovo between January 2022 and December 2025 (data lock: December 2025). A total of 650 patients aged 0–18 years who underwent surgical interventions and received perioperative antibiotics for prophylaxis or empirical treatment (defined as antibiotic therapy initiated in the presence of suspected infection) were included. Data collected comprised demographic characteristics, surgical diagnoses, type of surgery, antibiotics prescribed, weight-adjusted dosing, route of administration, timing of initiation, and duration of therapy. Appropriateness of antibiotic use was evaluated based on available documentation and compliance with WHO (2018) and CDC (2017) guidelines regarding indication, antibiotic selection, dosage, timing, and duration. Statistical analyses included descriptive statistics, chi-square tests, and multivariable logistic regression to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs), with statistical significance set at p < 0.05. Results: Among the 650 patients, 378 (58.2%) were male and 272 (41.8%) were female, with a mean age of 6.8 ± 4.3 years. The most common types of surgery were abdominal (35.7%), otorhinolaryngological (29.4%), urological (19.1%), and orthopedic (15.8%). Perioperative antibiotics were administered predominantly for prophylaxis (91.5%), while 8.5% of patients received empirical treatment. The most frequently prescribed antibiotics were cefazolin (42.6%), ceftriaxone (34.8%), ampicillin/sulbactam (12.3%), and gentamicin (6.1%). Notably, ceftriaxone was frequently prescribed for prophylactic purposes despite international recommendations generally favoring narrow-spectrum first-line agents for perioperative prophylaxis. Intravenous administration was used in 87.9% of cases. Antibiotic duration was ≤24 h in 61.2% of patients, whereas 38.8% received antibiotics for more than 24 h. Overall, appropriate antibiotic use was identified in 62.9% of cases, while 37.1% were classified as inappropriate. Prolonged antibiotic use beyond 24 h (adjusted OR = 3.87; 95% CI: 2.68–5.58; p < 0.001) and ceftriaxone use (adjusted OR = 2.41; 95% CI: 1.63–3.55; p < 0.001), were independently associated with inappropriate antibiotic use. Conclusions: Perioperative antibiotic use in pediatric tertiary care is highly prevalent, with more than one-third of prescriptions not fully aligned with international recommendations. Prolonged antibiotic duration and the preferential use of broad-spectrum agents, particularly ceftriaxone, were the factors most strongly associated with inappropriate prescribing patterns. These findings highlight the need for improved adherence to guideline-based perioperative antibiotic protocols; however, causal inferences regarding stewardship interventions cannot be drawn from this retrospective study. The findings should be interpreted within the limitations inherent to retrospective observational studies. Full article
22 pages, 1062 KB  
Article
Chemical Motifs Associated with FAERS-Derived Severe Cutaneous Adverse Reaction Disproportionality Signals: An Interpretable Pharmacovigilance-Driven Cheminformatics Study
by Yoshihiro Uesawa, Kaito Inden and Mizuho Asada
Int. J. Mol. Sci. 2026, 27(11), 5062; https://doi.org/10.3390/ijms27115062 - 3 Jun 2026
Viewed by 213
Abstract
Severe cutaneous adverse reactions (SCARs) are rare, life-threatening drug hypersensitivity syndromes. Although pharmacovigilance can identify drugs disproportionately reported with SCARs, it does not reveal which local chemistries recur among them. To address this, we assessed whether drugs with FAERS-derived SCAR disproportionality signals share [...] Read more.
Severe cutaneous adverse reactions (SCARs) are rare, life-threatening drug hypersensitivity syndromes. Although pharmacovigilance can identify drugs disproportionately reported with SCARs, it does not reveal which local chemistries recur among them. To address this, we assessed whether drugs with FAERS-derived SCAR disproportionality signals share interpretable chemical motifs. We screened FAERS data from 2004Q1 to 2024Q3, identified 5523 drugs with available Simplified Molecular-Input Line-Entry System (SMILES) representations, and constructed a signal-enriched dataset of 1676 compounds with nominally significant broad-SCAR associations after excluding predefined therapeutic/supportive confounders. Compounds were assigned to positive-signal [natural logarithm of reporting odds ratio (lnROR) > 0, n = 1219] or non-positive-signal (lnROR ≤ 0, n = 457) classes and encoded with 9753 explicitly mappable atom-centered local substructure descriptors. A LightGBM signal-classification model evaluated using random repeated nested cross-validation (six-fold outer × 50 repeats) achieved moderate internal discrimination (mean area under the receiver operating characteristic curve = 0.7041 ± 0.0337). Descriptor-space cluster-based repeated nested cross-validation, designed to reduce train–test structural leakage, yielded lower but still above-chance performance (mean ROC AUC = 0.6409; permutation p = 0.001), indicating that random-split estimates should be interpreted as optimistic for structurally novel compounds. Sensitivity analyses using minimum SCAR case-count thresholds and retention of predefined therapeutic/supportive drugs showed broadly similar performance and motif rankings. SHapley Additive exPlanations (SHAP) analysis revealed a fragment-level contrast: allylamine-like, ethanolamine-related, and diaminopropane-related motifs were associated with higher positive-signal class probability, whereas phenol and pyrimidine motifs were associated with lower positive-signal class probability. These findings suggest that FAERS-derived broad-SCAR signal direction is not chemically random within the selected dataset. Overall, the proposed framework should be viewed not as a direct predictor of absolute clinical SCAR risk but as an exploratory, pharmacovigilance-driven cheminformatics approach for prioritizing compounds and motif families for further SCAR-focused evaluation. Full article
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13 pages, 1436 KB  
Review
Anaphylaxis to Proton Pump Inhibitor and SARS-CoV-2 Vaccine: What Is the Link? A Case Report and Review of the Literature
by Luca Gammeri, Serena Sanfilippo, Mario Di Gioacchino, Marco Casciaro, Sebastiano Gangemi and Paola Lucia Minciullo
Allergies 2026, 6(2), 20; https://doi.org/10.3390/allergies6020020 - 3 Jun 2026
Viewed by 511
Abstract
The widespread use of proton pump inhibitors (PPIs) in clinical practice has increased the number of related hypersensitivity reactions (HSRs). The active ingredient is not always responsible for the reaction. In some cases, HSRs may be related to the excipients contained in the [...] Read more.
The widespread use of proton pump inhibitors (PPIs) in clinical practice has increased the number of related hypersensitivity reactions (HSRs). The active ingredient is not always responsible for the reaction. In some cases, HSRs may be related to the excipients contained in the drug. The adverse reactions to anti-SARS-CoV-2 vaccines have drawn the scientific community’s attention to the potential roles of excipients such as polyethylene glycol (PEG) and polysorbate 80. We present a case of a patient with three anaphylactic reactions following the administration of the anti-SARS-CoV-2 vaccine and a history of HSR to omeprazole. Through an in-depth medical history and allergy testing, we found that the patient was sensitized to PEG contained in the vaccine and to the omeprazole formulation used. We also conducted a mini-review of the literature, reporting all cases of reactions to PPIs, both related to the active ingredient and to excipients. Adverse reactions to PPIs are rare but still increasing. To our knowledge, this is the first reported case of anaphylaxis to PPI-related PEG. Some excipients are widely used in commonly used products, including non-pharmaceuticals. Therefore, in patients with multiple episodes of anaphylaxis, it appears necessary to exclude a possible allergy to excipients. This could ensure a greater safety and a better quality of life. Full article
(This article belongs to the Section Drug Allergy)
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23 pages, 450 KB  
Article
Incretin-Based Drugs for Obesity: Common and Drug-Specific Reporting Patterns of Adverse Drug Reactions—A Comparative Disproportionality Analysis Using EudraVigilance Reports Integrating SmPC Data
by Ioana Rada Popa Ilie, Steliana Ghibu, Anca Butuca, Carmen Maximiliana Dobrea, Adina Frum, Calin Homorodean, Adriana Aurelia Chis and Claudiu Morgovan
Pharmaceuticals 2026, 19(6), 876; https://doi.org/10.3390/ph19060876 - 31 May 2026
Viewed by 384
Abstract
Background: With the increasing widespread use of GLP-1 RA and dual GIP/GLP-1 RAs in the treatment of obesity, their safety profile remains a concern for healthcare professionals (HPs). Objective: This study aimed to characterize and evaluate safety data from the EudraVigilance (EV) database [...] Read more.
Background: With the increasing widespread use of GLP-1 RA and dual GIP/GLP-1 RAs in the treatment of obesity, their safety profile remains a concern for healthcare professionals (HPs). Objective: This study aimed to characterize and evaluate safety data from the EudraVigilance (EV) database for semaglutide (SEM), liraglutide (LIR), and tirzepatide (TIR). Methods: A hierarchical pharmacovigilance approach was applied, integrating SOC- and PT-level analyses with SmPC-based evaluation and both frequentist (ROR, 95% CI) and Bayesian (IC025) disproportionality methods. Within each molecule, reporter type–stratified analyses were performed, while across all molecules, disproportionality analyses were conducted separately in HP reports and in the full database to identify reporting patterns and potential safety signals, including those not described in the SmPCs. Results: Some ADRs, listed in the SmPC of only one or two of the three GLP1-RAs were also reported in the EV database for the other agents whose SmPCs do not specify these ADRs including optic ischemic neuropathy (TIR: 0.28% and LIR: 0.17%), alopecia (LIR: 0.81%), headache (TIR: 2.51%), intestinal obstruction (TIR: 1.55%), angioedema (LIR: 0.19%), hypersensitivity (SEM: 0.58% and LIR: 0.73%), etc. Pancreatitis, in particular, showed a significant but low-magnitude signal, being more frequently reported by HPs compared with non-HPs across all three GLP1-RAs. Additionally, statistically significant signals (IC025 > 0) were observed in both the HPs and full datasets. For example, for SEM vs. TIR, signals were identified for optic ischemic neuropathy (0.17; 0.13), gallbladder disorder (0.09; 0.11), and dysesthesia (0.42; 0.43), respectively. For TIR vs. SEM, signals were observed for injection site erythema (0.05; 0.11), injection site pruritus (0.01; 0.11), and injection site reaction (0.02; 0.08). Conclusions: These findings suggest potential safety signals beyond current SmPC information, emphasizing the need for continuous pharmacovigilance and cautious interpretation of reporting biases. Full article
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24 pages, 8840 KB  
Article
Multimodal Collaborative Modeling of Molecular Structures and Biomedical Text for Accurate Drug–Drug Interaction Extraction
by Liumei Yang, Yiyang Shi, Fangfang Han and Yongming Cai
Biomedicines 2026, 14(6), 1231; https://doi.org/10.3390/biomedicines14061231 - 29 May 2026
Viewed by 220
Abstract
Background: Drug–drug interactions (DDIs) account for about 30% of adverse drug reactions and 5–10% of hospital deaths. Combination therapy increases DDI risks, yet extracting DDIs from biomedical text remains challenging: existing methods rely on surface co-occurrence and fail when multiple drugs and [...] Read more.
Background: Drug–drug interactions (DDIs) account for about 30% of adverse drug reactions and 5–10% of hospital deaths. Combination therapy increases DDI risks, yet extracting DDIs from biomedical text remains challenging: existing methods rely on surface co-occurrence and fail when multiple drugs and interactions coexist in a sentence. Prior multimodal approaches simply concatenate text, molecular, or knowledge features without deep alignment, leading to misclassification of structurally similar but non-interacting drug pairs. Methods: We propose MultiMod-DDI, a framework that constructs a ternary evidence chain of “molecular structure–biological entities–DDI text”. Unlike existing work, MultiMod-DDI introduces (1) PS-AEGNN, a molecular graph network with ProbSparse self-attention to capture long-range chemical dependencies; (2) an adaptive position interaction vector that dynamically weights distant semantic links between drug entities; and (3) a multi-stage adaptive fusion module that sequentially applies subgraph-molecule attention and text-guided gating. These components are co-designed to enforce structured semantic alignment among heterogeneous modalities, effectively addressing the specific challenge of matching drug pairs to their correct interaction types in complex, multi-drug sentences. Results: On SemEval-2013 Task 9, MultiMod-DDI achieves 85.57% F1macro and 85.20% F1micro, outperforming state-of-the-art models. Conclusions: Through multimodal deep semantic alignment, MultiMod-DDI effectively resolves the mismatch between drug pairs and their interaction types in complex biomedical texts. The integration of multimodal features greatly improves DDI extraction accuracy, offering a reliable method for intelligent DDI mining from biomedical literature. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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10 pages, 222 KB  
Article
Management of Rituximab-Associated Hypersensitivity Reactions with Successfully Applied Desensitization Protocols: A Clinical Experience of 46 Infusions in 11 Patients
by Ömer Candar, Vildan Özkocaman, Raziye Tülümen Öztürk, Tuba Ersal, Esra Gülderen, Cumali Yalçın, Sinem Çubukçu, Tuba Güllü Koca, Fazıl Çağrı Hunutlu, Şeyma Yavuz, Dane Ediger and Fahir Özkalemkaş
J. Clin. Med. 2026, 15(11), 4164; https://doi.org/10.3390/jcm15114164 - 28 May 2026
Viewed by 207
Abstract
Objective: This study aimed to evaluate patients who developed hypersensitivity reactions (HSRs) during rituximab treatment and report the outcomes of desensitization protocols implemented to allow treatment continuation. Methods: We retrospectively reviewed the institutional data of 76 patients who received rituximab therapy at the [...] Read more.
Objective: This study aimed to evaluate patients who developed hypersensitivity reactions (HSRs) during rituximab treatment and report the outcomes of desensitization protocols implemented to allow treatment continuation. Methods: We retrospectively reviewed the institutional data of 76 patients who received rituximab therapy at the Adult Hematology Department between January 2022 and September 2023. Among these, 11 patients who experienced immediate hypersensitivity reactions during infusion were analyzed. The overall frequency of rituximab-associated HSRs was 14.47% (11 out of 76 patients). Demographic data, underlying diseases, timing and type of HSRs, and details of the desensitization protocols were recorded. Results: The overall frequency of rituximab-associated HSRs was 14.47% (11 out of 76 patients). Among the 11 patients, eight were male and three were female, with a median age of 56 years (range: 19–72). Eight patients had CD20-positive non-Hodgkin lymphoma (NHL) and three had acute B-lymphoblastic leukemia (B-ALL). HSRs occurred during the first rituximab exposure in nine patients, at the fourth dose in one patient, and at the eighth dose in another. Symptoms included widespread rash, pruritus, flushing, chills, shivering, dyspnea, dysphagia, back pain, dizziness, syncope, and throat discomfort. All the patients were consulted by the Allergy and Immunology Clinic. Based on prick and intradermal test (IDT) results and the planned rituximab dose, desensitization protocols consisting of a three-dilution/12-step and a four-dilution/16-step regimen were prepared. Overall, 46 desensitization procedures were successfully completed in 11 patients. Notably, no severe anaphylactic events or treatment discontinuations due to drug toxicity occurred during the implementation of the protocols. Conclusions: Although the number of patients was limited, our findings indicate that in patients with hematologic malignancies receiving rituximab who develop early HSRs, desensitization represents a safe and effective strategy before considering treatment modification. These results support that, in appropriately selected patients, desensitization protocols are an important approach to continue therapy without interruption while minimizing adverse reactions. Full article
(This article belongs to the Section Hematology)
16 pages, 2269 KB  
Article
Monogenic Syndromes as a Cause of Adverse Drug Reactions in the Russian Population
by Anastasiia A. Buianova, Valery V. Cheranev, Anna O. Shmitko, Iuliia A. Vasiliadis, Alina F. Samitova, Oleg N. Suchalko, Zhanna A. Repinskaia, Mikhail Iu. Kuznetsov, Vera A. Belova and Dmitriy O. Korostin
Int. J. Mol. Sci. 2026, 27(11), 4851; https://doi.org/10.3390/ijms27114851 - 28 May 2026
Viewed by 220
Abstract
Adverse drug reactions (ADRs) remain a major public health issue, and genetic factors contribute importantly to interindividual variability in drug response. Pharmacogenetic testing helps reduce ADR risk by optimizing drug selection and dosage, particularly in monogenic disorders. Whole-exome sequencing of 6739 samples from [...] Read more.
Adverse drug reactions (ADRs) remain a major public health issue, and genetic factors contribute importantly to interindividual variability in drug response. Pharmacogenetic testing helps reduce ADR risk by optimizing drug selection and dosage, particularly in monogenic disorders. Whole-exome sequencing of 6739 samples from the Russian population was performed on the DNBSEQ-G400 platform (MGI). Variants in 48 genes were examined, focusing on inherited arrhythmias, enzyme deficiencies (Glucose-6-Phosphate Dehydrogenase Deficiency [G6PDD], Porphyrias), Dravet Syndrome (DS) and Malignant Hyperthermia (MH). Variants reported as pathogenic (P), likely pathogenic (LP), or variants of uncertain significance (VUS) in ClinVar were manually re-evaluated using ACMG criteria. A total of 75 unique variants in 18 genes were observed in 119 individuals (1.77%), including 21 carriers and 13 women with a G6PD mutation. Of these, 44 variants were classified as P, 24 as LP, and 7 as VUS. Missense variants accounted for the largest proportion (73.33%). The most affected genes were KCNQ1 (24/119), which exhibited the highest number of unique variants (18), G6PD (20/119), SCN1A (15/119), and RYR1 (14/119). Regarding associated conditions, mutations linked to arrhythmias were found in 51 individuals, MH in 27, G6PDD in 20, DS in 15, and Porphyrias in 6. Integrating common and rare clinically actionable genetic variants with attention to penetrance and clinical validity may improve medication safety, reduce preventable ADRs, and enhance personalized pharmacotherapy. Full article
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12 pages, 432 KB  
Article
Comparative Analysis of L-Carnitine and Coenzyme Q10 Adverse Reaction Reports Using the EudraVigilance Database: Implications for Health and Sports Supplementation
by Debora Di Mauro, Fabrizio Calapai, Ilaria Ammendolia, Mariaconcetta Currò, Fabio Trimarchi and Carmen Mannucci
Nutrients 2026, 18(11), 1716; https://doi.org/10.3390/nu18111716 - 27 May 2026
Viewed by 303
Abstract
Background/Objectives: L-carnitine and Coenzyme Q10 (CoQ10) are widely used in health and sports supplementation settings to improve energy metabolism, reduce fatigue, and support recovery. Although generally perceived as safe, their safety profiles are mainly based on pre-marketing studies and [...] Read more.
Background/Objectives: L-carnitine and Coenzyme Q10 (CoQ10) are widely used in health and sports supplementation settings to improve energy metabolism, reduce fatigue, and support recovery. Although generally perceived as safe, their safety profiles are mainly based on pre-marketing studies and selected clinical populations, while real-world pharmacovigilance evidence remains limited. This study aimed to evaluate and compare the adverse drug reaction (ADR) reporting patterns associated with L-carnitine and CoQ10 using the EudraVigilance database. Methods: A retrospective pharmacovigilance analysis was conducted using spontaneous individual case safety reports (ICSRs) retrieved from the EudraVigilance database. ADRs associated with L-carnitine and CoQ10 were analyzed and compared at the System Organ Class (SOC) level. Disproportionality analyses were performed using the reporting odds ratio (ROR) and proportional reporting ratio (PRR). Results: A total of 257 ICSRs for L-carnitine and 271 for CoQ10 were identified. Serious cases accounted for 34.2% of L-carnitine reports and 74.5% of CoQ10 reports. For L-carnitine, the most frequently reported SOC categories were gastrointestinal disorders, skin and subcutaneous tissue disorders, general disorders and administration site conditions, and nervous system disorders. For CoQ10, the most commonly reported SOC categories were general disorders and administration site conditions, nervous system disorders, investigations, and gastrointestinal disorders. Comparative disproportionality analysis showed higher reporting frequencies for CoQ10 in blood and lymphatic system disorders (ROR 3.04; PRR 2.99), musculoskeletal and connective tissue disorders (ROR 2.63; PRR 2.52). Conclusions: Real-world pharmacovigilance data suggest partially different ADR reporting patterns for L-carnitine and CoQ10 compared with those described in pre-marketing studies. CoQ10 was associated with a higher proportion of serious reports and greater disproportionality signals for selected SOC categories; however, these findings should be interpreted cautiously, as reporting patterns may be influenced by reporting bias, comorbidities, concomitant therapies, and differences in the populations using these compounds. Continuous pharmacovigilance monitoring and periodic reassessment of their benefit–risk profile remain essential given their widespread use in health and sports supplementation settings. Full article
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45 pages, 5910 KB  
Review
Pharmacomicrobiomics of Non-Antibiotic Drugs: Mechanisms and Clinical Consequences of Gut Microbiota Alterations
by Caterina Nela Dumitru, Alina Oana Dumitru, Larisa Goroftei, Elena Niculet, Mariana Daniela Ignat, Liliana Baroiu, Aurel Nechita and Gabriela Balan
Pharmaceutics 2026, 18(6), 651; https://doi.org/10.3390/pharmaceutics18060651 - 26 May 2026
Viewed by 350
Abstract
Background: The gut microbiota constitutes a metabolically active “second genome” that profoundly modulates drug pharmacokinetics, pharmacodynamics, and adverse reaction profiles. Beyond antibiotics, widely prescribed non-antibiotic pharmacotherapies exert clinically relevant pharmacomicrobiomic effects with implications for therapeutic optimisation and pharmacovigilance. Methods: This narrative [...] Read more.
Background: The gut microbiota constitutes a metabolically active “second genome” that profoundly modulates drug pharmacokinetics, pharmacodynamics, and adverse reaction profiles. Beyond antibiotics, widely prescribed non-antibiotic pharmacotherapies exert clinically relevant pharmacomicrobiomic effects with implications for therapeutic optimisation and pharmacovigilance. Methods: This narrative review, conducted following PRISMA 2020 reporting principles (without PROSPERO pre-registration), searched PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Library (January 2015–December 2024) for evidence on proton pump inhibitors (PPIs), metformin, NSAIDs, statins, SGLT2 inhibitors, and oral iron. Evidence tables included clinical human studies with molecular microbiota characterisation (16S rRNA or shotgun metagenomics), ≥20 participants, and a control arm; preclinical data informed mechanistic synthesis. Results: Of 68 eligible studies, 20 met criteria for the evidence tables. PPIs significantly remodelled gut microbiota composition with enrichment of oral-origin taxa (“oralisation of the gut”), associating with Clostridioides difficile infection and SIBO. Metformin enriched Akkermansia muciniphila and butyrate producers, contributing causally to glycaemic efficacy. NSAIDs compromised barrier integrity, with synergistic dysbiosis under PPI co-prescription. Statins correlated with reduced prevalence of the dysbiotic Bact2 enterotype. SGLT2 inhibitor data remained discordant. Oral iron consistently enriched Enterobacteriaceae at the expense of beneficial commensals. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
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38 pages, 3776 KB  
Article
An Updated 16-Year Pharmacovigilance Analysis of Neuropsychiatric Safety Profiles of Ciprofloxacin, Levofloxacin, and Moxifloxacin Using FAERS Data
by Aura Rusu, Ioana-Maria Stroia and Marius Călin Cherecheș
Pharmaceuticals 2026, 19(6), 820; https://doi.org/10.3390/ph19060820 - 23 May 2026
Viewed by 517
Abstract
Background/Objectives: Fluoroquinolones (FQNs) are widely prescribed broad-spectrum antibiotics but are associated with central and peripheral nervous system adverse reactions (ARs). Regulatory agencies have issued multiple safety warnings regarding their neuropsychiatric effects; however, large-scale, comparative evaluations across individual FQNs remain limited. This study [...] Read more.
Background/Objectives: Fluoroquinolones (FQNs) are widely prescribed broad-spectrum antibiotics but are associated with central and peripheral nervous system adverse reactions (ARs). Regulatory agencies have issued multiple safety warnings regarding their neuropsychiatric effects; however, large-scale, comparative evaluations across individual FQNs remain limited. This study aimed to comprehensively characterise and compare neuropsychiatric profiles associated with Ciprofloxacin, Levofloxacin, and Moxifloxacin using pharmacovigilance data. Methods: A retrospective pharmacovigilance study was conducted using reports from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) between 2010 and 2025. Neuropsychiatric ARs were identified using MedDRA terms, including neurological and psychiatric manifestations. Reporting trends, demographic characteristics, and event frequencies were descriptively analysed. Signal detection was performed using the Information Component (IC), Proportional Reporting Ratio (PRR), and Reporting Odds Ratio (ROR). Results: A total of 95,968 individual case safety reports involving neuropsychiatric ARs were included. Levofloxacin accounted for the highest number of reported events, followed by Ciprofloxacin and Moxifloxacin. Disproportionality analyses identified peripheral neuropathy as the strongest neurological signal for Levofloxacin and Moxifloxacin, while Ciprofloxacin showed stronger central nervous system associations. Psychiatric ARs were drug-specific, with anxiety predominating for Ciprofloxacin and Moxifloxacin, and insomnia for Levofloxacin. All major signals were statistically robust (IC025 > 0), confirming distinct compound-specific neuropsychiatric risk profiles. Conclusions: The large-scale 16-year analysis demonstrates distinct, drug-specific neuropsychiatric risk profiles. The available evidence supports a non-interchangeable safety profile among FQNs and emphasises the importance of drug-specific risk–benefit assessment in clinical practice. Full article
(This article belongs to the Special Issue Fluoroquinolones, 2nd Edition)
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20 pages, 1608 KB  
Article
Motif-Level Graph Learning Enables Interpretable Prediction of Drug-Induced QT Prolongation via Cooperative Substructural Determinants
by Wulin Long, Shengqiu Zhai, Yuheng Liu, Menglong Li and Zhining Wen
Int. J. Mol. Sci. 2026, 27(11), 4706; https://doi.org/10.3390/ijms27114706 - 23 May 2026
Viewed by 272
Abstract
Drug-induced QT interval prolongation is a critical safety concern in drug development, yet accurate and mechanistically interpretable prediction from chemical structure remains challenging due to the limited substructural resolution of existing approaches. Here, we present a motif-level graph learning framework for interpretable QT [...] Read more.
Drug-induced QT interval prolongation is a critical safety concern in drug development, yet accurate and mechanistically interpretable prediction from chemical structure remains challenging due to the limited substructural resolution of existing approaches. Here, we present a motif-level graph learning framework for interpretable QT risk prediction. In this framework, molecules are decomposed into chemically meaningful motifs, enabling representation at an intermediate structural scale between atoms and predefined structural alerts. Motif features are encoded using a pre-trained chemical language model, and inter-motif relationships are modeled via attention-based graph learning with cross-scale integration. The model is trained and evaluated on two clinically grounded datasets derived from regulatory drug labeling (DIQTA) and real-world pharmacovigilance data (FAERS), achieving strong and consistent predictive performance with robust generalization across data sources. Importantly, motif-level attention reveals that QT liability is associated with the cooperative organization of compact cationic centers and heteroatom-rich, conformationally adaptable scaffolds, rather than isolated functional groups. These patterns are consistent with known determinants of human ether-à-go-go-related (hERG) channel blockade while providing a more structured and chemically specific interpretation beyond conventional structural alerts. Overall, this work establishes a generalizable and interpretable framework for QT risk prediction and highlights motif-level graph learning as an effective strategy for structure-based modeling of adverse drug reactions. Full article
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14 pages, 632 KB  
Article
Allergy in the Elderly: A Broad Clinical Spectrum Beyond Atopy
by Fikriye Kalkan, Begum Gorgulu Akin, Sarpcan Maden, Makbule Seda Bayrak Durmaz, Betul Ozdel Ozturk, Orhun Efe and Sadan Soyyigit
Medicina 2026, 62(6), 1010; https://doi.org/10.3390/medicina62061010 - 23 May 2026
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Abstract
Background: This study aimed to evaluate referral reasons, distribution of allergic diseases, atopic status, and comorbidity associations among patients aged 65 years and older presenting to a tertiary allergy clinic. Methods: This retrospective study included all geriatric patients (≥65 years) who attended the [...] Read more.
Background: This study aimed to evaluate referral reasons, distribution of allergic diseases, atopic status, and comorbidity associations among patients aged 65 years and older presenting to a tertiary allergy clinic. Methods: This retrospective study included all geriatric patients (≥65 years) who attended the Immunology and Allergy outpatient clinic at Ankara Bilkent City Hospital between January 2024 and December 2025. Demographic characteristics, comorbidities, referral complaints, and allergic diagnoses were recorded. Allergen sensitization was assessed using skin tests and/or allergen-specific IgE measurements. Results: A total of 1302 geriatric patients were included (mean age 70.9 years; 59.8% female). At least one comorbidity was present in 62.6% of patients, with hypertension being the most common(39.4%). The leading referral complaints were rhinorrhoea/sneezing (22.8%), pruritus (19.1%), drug allergy/adverse drug reactions (14.8%), and chronic urticaria (10.9%). The most common diagnoses were rhinitis (63.2% non-allergic), non-allergic pruritus, drug allergy, and chronic urticaria. Among inhalant allergens, pollen sensitivity (42.2%) was most frequent, followed by house dust mite (32.5%). The most frequently implicated drug groups were antibiotics (42.4%) and analgesics (21.7%). Chronic urticaria and ACE inhibitor-associated angioedema showed significant gender differences: 68.6% female (p = 0.001) and 66.7% male (p = 0.008), respectively. Patients with asthma, rhinitis, or angioedema frequently had comorbid conditions (91.1%, 55.8%, and 83.7%, p = 0.001, p = 0.013, and p = 0.001, respectively). Conclusions: Allergy clinic presentations in elderly patients reflect a broad clinical spectrum, including non-allergic conditions, frequent drug-related reactions in elderly patients with multiple comorbidities, and age-related immunological changes alongside atopic diseases. A comprehensive, individualized diagnostic approach is essential when evaluating allergic complaints in the geriatric population. Full article
(This article belongs to the Section Hematology and Immunology)
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14 pages, 311 KB  
Review
Fixed Dose Combinations as an Advantage for the Treatment of Pediatric Tuberculosis: A Narrative Review
by Susanna Esposito, Beatrice Rita Campana, Gaia Giorgia Arnesano and Nicola Principi
Pharmaceuticals 2026, 19(6), 806; https://doi.org/10.3390/ph19060806 - 22 May 2026
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Abstract
Background: Pediatric tuberculosis (TB) remains a major global health concern, accounting for a substantial proportion of TB-related morbidity and mortality worldwide. Treatment in children is particularly challenging due to age-specific pharmacokinetics, difficulties in drug administration, poor palatability, and reliance on caregivers for adherence. [...] Read more.
Background: Pediatric tuberculosis (TB) remains a major global health concern, accounting for a substantial proportion of TB-related morbidity and mortality worldwide. Treatment in children is particularly challenging due to age-specific pharmacokinetics, difficulties in drug administration, poor palatability, and reliance on caregivers for adherence. Objectives: This narrative review aims to evaluate the advantages and limitations of fixed-dose combinations (FDCs) in the treatment of pediatric TB, with a focus on adherence, pharmacological considerations, clinical outcomes, and implementation challenges. Methods: A narrative review of the literature was conducted, including clinical studies, pharmacokinetic analyses, programmatic data, and international guidelines related to the use of FDCs in pediatric TB management. Results: Evidence indicates that pediatric FDCs significantly improve treatment adherence by reducing pill burden and simplifying dosing regimens. They also decrease the risk of medication errors and inadvertent monotherapy, thereby contributing to the prevention of drug resistance. The availability of dispersible, child-friendly formulations has enhanced acceptability and ease of administration. However, limitations persist, including reduced flexibility in dose individualization, challenges in identifying the causative agent in adverse drug reactions, and variable access across settings. Pharmacokinetic concerns, particularly regarding rifampicin exposure, have been addressed in newer WHO-recommended formulations. Conclusions: FDCs represent a critical advancement in pediatric TB management and are strongly supported by international guidelines. Further research is needed to optimize formulations, ensure equitable access, and evaluate long-term clinical outcomes in diverse pediatric populations. Full article
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22 pages, 815 KB  
Review
Iodinated Contrast Media in Oncologic CT: A Narrative Review of Safety, Risk Stratification, and Practical Considerations
by Sabina-Oana Vasii, Florin-Gabriel Crișan, Sandra-Monica Lazăr, Claudiu Ioniță, Dan Iliescu, Ioana Ioniță, Daniel-Claudiu Malița, Mirela Voicu, Adrian Voicu and Lucreția Udrescu
Diagnostics 2026, 16(10), 1507; https://doi.org/10.3390/diagnostics16101507 - 15 May 2026
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Abstract
Background: Iodinated contrast media are essential for oncologic imaging but raise specific safety concerns because cancer patients are often exposed to repeated contrast-enhanced computed tomography, nephrotoxic drugs, immune-modulating therapies, and, in selected cases, radioiodine-dependent diagnostic or therapeutic pathways. Methods: We performed a narrative [...] Read more.
Background: Iodinated contrast media are essential for oncologic imaging but raise specific safety concerns because cancer patients are often exposed to repeated contrast-enhanced computed tomography, nephrotoxic drugs, immune-modulating therapies, and, in selected cases, radioiodine-dependent diagnostic or therapeutic pathways. Methods: We performed a narrative review based on an exploratory search followed by a focused search targeting iodinated contrast use in oncology-related settings. Studies were included if they addressed renal risk and post-contrast acute kidney injury, hypersensitivity and acute adverse reactions, or thyroid dysfunction with radioiodine-related implications. We also considered clinically relevant studies on drug interactions, isotope studies, and laboratory confounding. Results: The evidence base was methodologically heterogeneous, with renal safety as the predominant domain. Kidney injury after contrast-enhanced imaging in cancer patients appeared frequently multifactorial, supporting the broader concept of post-contrast acute kidney injury rather than automatic attribution to contrast alone. Hypersensitivity reactions to modern nonionic iodinated contrast media were generally uncommon, with severe reactions rare, although immune-modulating therapies may alter risk. Thyroid-related effects were usually transient but relevant in patients with thyroid autonomy and in differentiated thyroid carcinoma, where contrast exposure may affect scintigraphy and radioiodine planning. Conclusions: In oncology, iodinated contrast use requires individualized, field-specific risk stratification instead of reflexive avoidance. Full article
(This article belongs to the Special Issue Clinical Applications of CT and MRI)
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