Search Results (1,359)

People with cystic fibrosis may experience polypharmacy, which can increase the risk of drug induced complications such as adverse events and drug–drug interactions. This study aimed to examine the prevalence of adverse events and to identify potential drug–drug interactions associated with elexacaftor/tezacaftor/ivacaftor (ETI). Three databases, the Australian Therapeutic Goods Administration Database of Adverse Event Notification (TGA DAEN), the Canada Vigilance Adverse Reaction Online Database (CVAROD), and the USA Food and Drug Administration Adverse Event Reporting System (FAERS) Database were searched for spontaneous ETI adverse events between 2019 and 2024. Descriptive analysis of the data was undertaken. The FAERS database was analysed to identify adverse events of interest such as anxiety and depression and concomitant drugs prescribed with ETI. A total of 10,628 ETI associated adverse events were identified in all system organ classes. The incidence of psychiatric adverse events ranged from 7 to 15% across the three databases. Potential drug–drug interactions with CYP 3A4/5 strong inhibitors and strong inducers were identified from the FAERS database and azole antifungals were implicated in several ETI dose modifications. The prevalence and types of ETI adverse events were varied and use of concomitant drugs with potential drug interactions was significant, requiring more research to manage them. Full article

Background: Skin and soft tissue infections (SSTIs) are a major cause of emergency room (ER) visits and hospitalizations. Long-acting lipoglycopeptides (LALs), such as dalbavancin and oritavancin, offer potential for early discharge and outpatient management, especially in patients at risk for methicillin-resistant Staphylococcus aureus (MRSA) or with comorbidities. Methods: We conducted a retrospective observational cohort study from March to December 2024 in an Italian tertiary-care hospital. Adult patients treated in the ER with a single dose of dalbavancin (1500 mg) or oritavancin (1200 mg) for SSTIs were included. Demographic, clinical, and laboratory data were collected. Follow-up evaluations were performed at 14 and 30 days post-treatment to assess outcomes. Results: Nineteen patients were enrolled (median age 59 years; 53% female). Most had lower limb involvement and elevated inflammatory markers. Three patients (16%) were septic. Fourteen patients (74%) were discharged without hospital admission; hospitalization in the remaining cases was due to comorbidities rather than SSTI severity. No adverse drug reactions were observed. At 14 days, 84% of patients had clinical resolution; only 10% had recurrence by day 30, with no mortality nor readmission reported. Conclusions: LALs appear effective and well-tolerated in the ER setting, supporting early discharge and reducing healthcare burden. Broader use may require structured care pathways and multidisciplinary coordination. Full article

Background: Fixed-dose combinations of rosuvastatin and ezetimibe are increasingly used in clinical practice, but real-world data on their effectiveness and safety in large populations remain limited. Methods: This prospective, single-group, open-label, non-interventional observational study was conducted in the Republic of Korea to evaluate the effectiveness and safety of Rovazet^® (a fixed-dose combination of rosuvastatin and ezetimibe). Patients were prospectively enrolled from 235 institutions (50 general hospitals and 185 private clinics) as part of routine clinical practice over a five-year period. Lipid profiles and medication compliance questionnaire results were collected at baseline, 12 weeks, and 24 weeks of treatment. Results: A total of 5527 patients with dyslipidemia, the majority were men (53.0%), and the mean age was 60.4 years. Rovazet^® significantly reduced low-density lipoprotein cholesterol (LDL-C) by 23.5% at 12 weeks (from 117.47 ± 50.65 mg/dL to 81.14 ± 38.20 mg/dL; p < 0.0001) and by 27.4% at 24 weeks (from 117.47 ± 50.65 mg/dL to 74.52 ± 33.36 mg/dL; p < 0.0001). Total cholesterol was significantly reduced by 17.7% at 12 weeks and by 19.8% at 24 weeks. Rovazet^® treatment reduced triglycerides by 4.1% at 12 weeks and by 7.2% at 24 weeks. High-density lipoprotein cholesterol increased by 4.5% at 12 weeks and by 7.9% at 24 weeks following Rovazet^® treatment. These changes in lipid profiles were consistent, regardless of cardiovascular risk profiles. By 24 weeks of treatment with Rovazet^®, 91.8% of patients had reached their target LDL-C goals. Adverse drug reactions were reported in 2.81% of patients, most of which were minor, indicating that Rovazet^® was well tolerated. Conclusions: Rovazet^® was effective in improving lipid profiles and well tolerated in Korean adults with dyslipidemia. Full article

Background: Precision medicine refers to the formulation of personalized drug regimens according to the individual characteristics of patients to achieve optimal efficacy and minimize adverse reactions. Additive manufacturing (AM), also known as three-dimensional (3D) printing, has emerged as an optimal solution for precision drug delivery, enabling customizable and the fabrication of multifunctional structures with precise control over morphology and release behavior in pharmaceutics. However, the influence of 3D printing parameters on the printed tablets, especially regarding in vitro and in vivo performance, remains poorly understood, limiting the optimization of manufacturing processes for controlled-release profiles. Objective: To establish the fabrication process of 3D-printed controlled-release tablets via comprehensively understanding the printing parameters using fused deposition modeling (FDM) combined with hot-melt extrusion (HME) technologies. HPMC-AS/HPC-EF was used as the drug delivery matrix and carbamazepine (CBZ) was used as a model drug to investigate the in vitro drug delivery performance of the printed tablets. Methodology: Thermogravimetric analysis (TGA) was employed to assess the thermal compatibility of CBZ with HPMC-AS/HPC-EF excipients up to 230 °C, surpassing typical processing temperatures (160–200 °C). The formation of stable amorphous solid dispersions (ASDs) was validated using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (PLM), and powder X-ray diffraction (PXRD). A 15-group full factorial design was then used to evaluate the effects of the fan speed (20–100%), platform temperature (40–80 °C), and printing speed (20–100 mm/s) on the tablet properties. Response surface modeling (RSM) with inverse square-root transformation was applied to analyze the dissolution kinetics, specifically t_50% (time for 50% drug release) and Q_4h (drug released at 4 h). Results: TGA confirmed the thermal compatibility of CBZ with HPMC-AS/HPC-EF, enabling stable ASD formation validated by DSC, PLM, and PXRD. The full factorial design revealed that printing speed was the dominant parameter governing dissolution behavior, with high speeds accelerating release and low speeds prolonging release through porosity-modulated diffusion control. RSM quadratic models showed optimal fits for t_50% (R² = 0.9936) and Q_4h (R² = 0.9019), highlighting the predictability of release kinetics via process parameter tuning. This work demonstrates the adaptability of polymer composite AM for tailoring drug release profiles, balancing mechanical integrity, release kinetics, and manufacturing scalability to advance multifunctional 3D-printed drug delivery devices in pharmaceutics. Full article

Background: Intravenous vancomycin remains a key agent in the treatment of complex orthopedic infections, particularly those involving methicillin-resistant Staphylococcus aureus (MRSA). However, its use is associated with significant risks, most notably nephrotoxicity. Despite guideline recommendations, standardized dosing and monitoring protocols are often absent in orthopedic settings, leading to inconsistent therapeutic drug exposure and preventable adverse events. This study evaluated the clinical impact of implementing a structured standard operating procedure (SOP) for intravenous vancomycin therapy in orthopedic inpatients. Methods: We conducted a single-center, pre-post cohort study at a university orthopedic department. The intervention consisted of a standard operating procedure (SOP) for intravenous vancomycin therapy, which mandated weight-based loading doses, renal function-adjusted maintenance dosing, trough level monitoring, and defined dose adjustments. Patients treated before SOP implementation (n = 58) formed the control group; those treated under the SOP (n = 56) were prospectively included. The primary outcome was the incidence of vancomycin-associated acute kidney injury (VA-AKI) defined by KDIGO Stage 1 criteria. Secondary outcomes included therapeutic trough level attainment and infusion-related or ototoxic adverse events. Results: All patients in the post-SOP group received a loading dose (100% vs. 31% pre-SOP, p < 0.001). The range of measured vancomycin trough levels narrowed substantially after SOP implementation (7.1–36.2 mg/L vs. 4.0–80.0 mg/L). The proportion of patients reaching therapeutic trough levels increased, although this was not statistically significant. Most notably, VA-AKI occurred in 17.2% of patients in the control group, but in none of the patients after SOP implementation (0%, p = 0.0013). No cases of ototoxicity were observed in either group. Infusion-related reactions decreased after the implementation of the SOP, though not significantly. Conclusions: The introduction of a structured vancomycin protocol significantly reduced adverse drug events and improved dosing control in orthopedic inpatients. Incorporating such protocols into routine practice represents a feasible and effective strategy to strengthen antibiotic stewardship and clinical quality in surgical disciplines. Full article

Background: Mental health issues among medical students have gained increasing attention globally, with studies indicating a high prevalence of psychological disorders within this population. The use of antidepressants and anti-anxiety medications has become a common response to these mental health challenges. However, it is crucial to understand the extent of their usage and associated effects on students’ mental health and academic performance. This cross-sectional study explored the use of antidepressants and anti-anxiety drugs and their impact on the mental health of medical students in Saudi Arabia. Methods: A cross-sectional survey of 561 medical students from 34 universities was conducted between March and July 2024. An anonymous online questionnaire was used to collect sociodemographic, mental health, and medication usage-related information. Results: Most of the participants were female (71.5%) and aged 21–25 years (62.7%). Approximately 23.8% of them used antidepressants, 5.6% reported using anti-anxiety medications, and 14.0% used both types of medication. Among the medication users, 71.7% were using selective serotonin reuptake inhibitors (SSRIs), and 28.3% were using other medications. Adverse drug reactions were reported by 58.8% of the participants, and 39.6% changed drugs with inadequate efficacy. Notably, 49.0% of the respondents who have ever used medications discontinued their medication without consulting a healthcare professional. Despite these challenges, 62.0% of the participants felt that their medications had a positive impact on their academic performance, 73.4% believed that the benefits outweighed the drawbacks, and 76.2% expressed a willingness to continue taking their medication. In particular, 77.6% agreed that treatment with these drugs could prevent mental breakdowns. Sleep duration, physical activity, and family history of psychiatric disorders were significantly associated with medication use, with p values of 0.002, 0.014, and 0.042, respectively. Conclusions: These results shed light on the need to understand the prescribing practices of antidepressant and anti-anxiety drugs among medical students while promoting the appropriate use of these medications among the students. There is a need to incorporate mental health interventions into counseling services and awareness programs to support students. Future longitudinal studies are needed to explore long-term trends. Full article

Background: Oral lichen planus is a chronic, potentially malignant disorder affecting the mucous membrane. As the etiology remains not fully understood, the treatment of this condition is mainly symptomatic, involving corticosteroids and other immunosuppressive agents, e.g., calcineurin inhibitors. One of the alternative therapeutic approaches includes platelet concentrates, which are autologous bioactive materials. The aim of this review was to evaluate the effects of platelet concentrates in the treatment of oral lichen planus and to compare them to other therapeutic strategies. Methods: The electronic databases PubMed/Medline, Web of Science, and Cochrane Library were searched for articles published up to 30 March 2025, describing clinical studies focused on oral lichen planus and treatment with platelet concentrates. Results: Fourteen studies describing the effects of oral lichen planus therapy with three types of platelet concentrates (injectable platelet-rich plasma, injectable platelet-rich fibrin, and platelet-rich plasma gel) were included in this review. Comparative strategies included steroids and immunosuppressive agents. The treatment duration ranged from 3 weeks to 2 months. The follow-up period varied from 4 weeks to 6 months. In most of the studies, comparable efficacy was achieved for platelet derivatives and alternative treatments. Two of the studies demonstrated more beneficial effects for platelet concentrates compared to controls, while in one of the studies, more severe adverse reactions were revealed in the platelet group compared to the controls. Conclusions: Autologous platelet concentrates showed comparable efficacy in achieving clinical improvement in patients with oral lichen planus to steroids and immunosuppressive drugs. Platelet derivatives could be considered as an alternative treatment to topical immunosuppressives, especially in steroid-refractory cases. Full article

Adverse drug reactions (ADRs) significantly affect patient safety and healthcare spending worldwide. Hospital pharmacists are uniquely positioned to address ADRs due to their crucial role in medication management. However, underreporting remains a global concern, especially in developing countries, where pharmacovigilance systems are inadequately developed. Therefore, this pilot study aimed to evaluate and compare the knowledge, attitudes, perceived barriers, and facilitators regarding ADR reporting by hospital pharmacists in a developed (US) and a developing (Pakistan) country. A cross-sectional survey was conducted, using a pre-validated questionnaire. The pharmacists, possessing a minimum of one year’s hospital experience, were selected via convenience sampling. Out of 151 respondents, included in the final analysis (US: n = 51; Pakistan: n = 100), the majority were female (62.3%), aged 29–35 years (38%), and possessed a Pharm. D degree (49.7%). The knowledge (US: 6.03 ± 0.27 vs. Pakistan:5.69 ± 0.25, p-value = 0.193) and attitude scores (US: 32.02 ± 0.73 vs. Pakistan: 32.63 ± 0.67; p-value = 0.379) exhibited no significant differences between the groups. Nonetheless, barriers at both the individual and systemic levels were more pronounced in the developing country. Important facilitators reported were mobile applications for ADR reporting, specialized training, and intuitive reporting tools. In conclusion, we found that pharmacists in both settings exhibit comparable knowledge and positive attitudes towards ADR reporting, though specific contextual barriers are present. Interventions customized to the local hospital infrastructure are crucial for enhancing ADR reporting, particularly in resource-constrained settings. Full article

Epilepsy is a chronic neurological disease with a relatively high incidence in the pediatric population. Anti-seizure medication (ASM) may cause adverse drug reactions (ADRs), which may occur repeatedly. Objective: This study aimed to analyze the recurrence of ADRs caused by ASMs over a period of 122 months in hospitalized Mexican pediatric epilepsy patients. The patients were under monotherapy or polytherapy treatment, with valproic acid (VPA), phenytoin (PHT), and levetiracetam (LEV), among others. A total of 313 patients met the inclusion criteria: 211 experienced ADRs, whereas 102 did not. Patient sex, age, seizure type, nutritional status and related drugs were considered explanatory variables. Methods: Four statistical models were used to analyze recurrent events that were defined as “one or more ADRs occurred on a single day”, considering both the classification of ADR seriousness and the ASM causing the ADR. Results: A total of 499 recurrence events were identified. The recurrence risk was significantly greater among younger patients for both nonsevere and severe ADRs and among those with focal seizures for nonsevere ADRs. Interestingly, malnutrition was negatively associated with the risk of nonsevere ADRs, and obesity was positively associated with the risk of severe ADRs. Finally, LEV was associated with a significantly greater risk of causing nonsevere ADRs than VPA. However, LEV significantly reduced the risk of severe ADRs compared with VPA, and PHT increased the risk in comparison with VPA. In conclusion, this study offers a robust clinical tool to predict risk factors for the presence and recurrence of ASM-ADRs in pediatric patients with epilepsy. Full article

Background: Ibuprofen is one of the most accessible non-steroidal anti-inflammatory drugs (NSADs), exhibiting non-selective reversible inhibition on COX-1 and COX-2. A series of common adverse reactions have been mentioned through the years: gastrointestinal (gastritis, ulceration, hemorrhage, or perforation), renal, hematologic, and cardiovascular. Objective: The aim of this study was to assess the real-world impact of ibuprofen regarding cardiovascular safety, utilizing an established pharmacovigilance database. Methods: Descriptive and disproportionality-based methods were used. Forty specific descriptors of cardiovascular effects were selected. Eight other NSADs and the combination of ibuprofen and pseudoephedrine were used as comparators. Results: A total of 58,760 cases were identified as being associated with ibuprofen in EudraVigilance. Stroke was reported for ibuprofen with a lower probability compared with etoricoxib (ROR: 0.34; 95% CI: 0.21–0.55), celecoxib (ROR: 0.07; 95% CI: 0.06–0.10), meloxicam (ROR: 0.25; 95% CI: 0.14–0.43), acetylsalicylic acid (ROR: 0.07; 95% CI: 0.05–0.09), and ibuprofen/pseudoephedrine (ROR: 0.11; 95% CI: 0.05–0.25). Thrombosis was reported for ibuprofen with a higher probability only relative to ketoprofen (ROR: 2.95; 95% CI: 1.71–5.09). Hypertension was reported for ibuprofen as being more probable than for acetylsalicylic acid (ROR: 1.58; 95% CI: 1.43–1.76). Myocardial infarction was reported as being more probable for ibuprofen than ketoprofen (ROR: 2.31; 95% CI: 1.57–3.40) or nimesulide (ROR: 2.43; 95% CI: 1.25–4.73). Conclusions: Overall, according to our study, the probability of reported cardiovascular adverse reactions is lower than those determined for the rest of the NSAIDs; however, taking into consideration the inherent limitations of the study, further clinical investigations would contribute to a better understanding of the cardiovascular safety of ibuprofen. Full article

Background and Aims: Ornidazole, a nitroimidazole antibiotic, is widely used for protozoal and anaerobic infections and is generally considered safe. However, ornidazole-induced liver injury (OILI) is an underrecognized yet potentially severe adverse reaction. This multicenter study aims to characterize the clinical features, histopathology, and outcomes of OILI to improve the awareness and management of this rare entity worldwide. Methods: We conducted a retrospective analysis of 101 patients with OILI from eight tertiary centers between 2006 and 2023. Cases were included based on liver enzyme elevations temporally linked to ornidazole and the exclusion of other causes. Causality was assessed using the Roussel Uclaf Causality Assessment Method (RUCAM) score. Clinical data, laboratory parameters, autoantibody profiles, histology, treatments, and outcomes were evaluated. Results: OILI was classified as highly probable in 42.6% of cases (n = 43), probable in 51.5% of cases (n = 52), and possible in 5.9% (n = 6) of cases. The predominant pattern was acute hepatocellular injury (83.2%) (n = 84). Autoimmune-like hepatitis occurred in 5% of cases (n = 5), with ANA positivity in 16.8% of cases (n = 17). Corticosteroids were used in 24.8% of cases (n = 25) and were associated with higher ANA positivity and a 20% (n = 5) relapse rate post-discontinuation. Recovery was achieved in 87.7% of cases (n = 88), while 7.9% of cases (n = 8) required liver transplantation and 4% (n = 4) died. Conclusions: Ornidazole can cause serious idiosyncratic liver injury, including autoimmune phenotypes, and should be considered in the differential diagnosis of acute hepatitis. Given the notable risk of liver failure and death, early recognition, drug discontinuation, and close monitoring are essential. In select cases, corticosteroids and plasmapheresis may be beneficial, though the evidence remains limited. Full article

The covalent conjugation of pharmaceutical compounds to polymeric carriers represents an effective strategy for enhancing drug properties, including improved bioavailability, targeted delivery, and sustained release, while reducing systemic toxicity and adverse effects. By exploiting the physicochemical characteristics of biopolymers—particularly molecular charge and weight—we engineered a polymeric platform for glucocorticoid delivery with precisely controlled parameters including particle size, surface charge, targeting capability, and release kinetics. This study reports a linker-free synthesis of hyaluronic acid-dexamethasone (HA-DEX) conjugates through Steglich esterification, catalyzed by 4-dimethylaminopyridine (DMAP), which facilitates the acylation of sterically hindered alcohols. The reaction specifically couples carboxyl groups of hyaluronic acid with the C21 hydroxyl group of dexamethasone. Incorporation of hydrophobic dexamethasone moieties induced self-assembly into nanoparticles featuring a hydrophobic core and negatively charged hydrophilic shell (−20 to −25 mV ζ-potential). In vitro characterization revealed pH-dependent release profiles, with 80–90% dexamethasone liberated in mildly acidic phosphate buffer (pH 5.2) versus 50–60% in phosphate-buffered saline (pH 7.4) over 35 days, demonstrating both sustained release and inflammation-responsive behavior. The conjugates exhibited potent anti-inflammatory activity in a human tumor necrosis factor-α (TNFα)-induced inflammation model. These findings position HA-DEX conjugates as promising candidates for targeted glucocorticoid delivery to specific anatomical sites including ocular, articular, and tympanic tissues, where their combination of CD44-targeting capability, enhanced permeability and retention effects, and stimulus-responsive release can optimize therapeutic outcomes while minimizing off-target effects. Full article

Plasmodium falciparum is the causative agent of malaria, a parasitic disease that affects millions of people in terms of prevalence and is associated with hundreds of thousands of deaths. Current antimalarial medications, in addition to exhibiting moderate to serious adverse reactions, are not efficacious enough due to factors such as drug resistance. In silico approaches can speed up the discovery and design of new molecules with wide-spectrum antimalarial activity. Here, we report a unified computational methodology combining a perturbation theory machine learning model based on multilayer perceptron networks (PTML-MLP) and the fragment-based topological design (FBTD) approach for the prediction and design of novel molecules virtually exhibiting versatile antiplasmodial activity against diverse P. falciparum strains. Our PTML-MLP achieved an accuracy higher than 85%. We applied the FBTD approach to physicochemically and structurally interpret the PTML-MLP, subsequently extracting several suitable molecular fragments and designing new drug-like molecules. These designed molecules were predicted as multi-strain antiplasmodial inhibitors, thus representing promising chemical entities for future synthesis and biological experimentation. The present work confirms the potential of combining PTML modeling and FBTD for early antimalarial drug discovery while opening new horizons for extended computational applications for antimicrobial research and beyond. Full article

Pharmacogenomics (PGx) has emerged as a powerful tool to personalize drug selection and dosing based on a patient’s genetic profile. However, there are a range of challenges that impede uptake in current clinical practice. For example, clinicians often express frustration with commercially available PGx panel tests, which fail to consistently include all key actionable PGx genes (according to the Clinical Pharmacogenetics Implementation Consortium (CPIC), Food and Drug Administration (FDA) PGx guidelines, or The Dutch Pharmacogenetics Working Group (DPWG) guidelines) and instead are too long with clinically unimportant information (unvalidated genotypes). Additionally, the lack of EMR integration, clinician education and awareness of the benefits of PGx impedes uptake. This paper examines key challenges identified in clinical practice and proposes future directions, focusing on limiting PGx reports to essential data, providing point-of-prescription alerts, and establishing reimbursement pathways that encourage adoption. Future directions include leveraging large language models, integrating point-of-prescription alerts and phenoconversion calculators into the electronic medical record, increasing the genomic diversity of PGx study populations, and streamlining coverage by payers. Full article

Biologic therapeutics, particularly monoclonal antibodies (mAbs), have revolutionized disease treatment paradigms; however, their clinical success is often hindered by immunogenicity. Host immune recognition of these biologics can induce anti-drug antibody (ADA) formation, leading to reduced therapeutic efficacy, altered pharmacokinetics and serious adverse events, such as infusion reactions and loss of response. Overcoming these immunogenicity challenges is essential to maximize the clinical effect of biologics and ensure patient safety. This paper offers an overview of the mechanisms underlying the formation of anti-drug antibodies and explores potential nanotechnology-based strategies to reduce or eliminate these responses. Specifically, the review examines how the immune system recognizes biologics and develops ADAs, which can impact drug efficacy and safety. The review then investigates various nanotechnology approaches aimed at mitigating ADA formation, potentially improving the therapeutic outcomes of biologic drugs. Full article