Current drug safety最新文献

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain relief and inflammation management; however, they can lead to serious upper gastrointestinal (GI) issues, including ulcers, bleeding, and perforations. This review explores various risk factors for NSAID-related GI complications, including medication dosage, duration of treatment, patient age, health history, and interactions with other drugs. It also evaluates existing measures to reduce these risks, such as using proton pump inhibitors (PPIs) and selective COX-2 inhibitors, while discussing their limitations. Emphasis is placed on the value of prediction tools that integrate multiple risk factors to enhance preventive care. The review provides an in-depth analysis of current scoring systems and examines future directions, including the integration of biomarkers, genetic data, and technologies like machine learning to improve prediction and clinical utility. By addressing gaps in existing models, it offers insights into advancing personalized approaches to minimize NSAID-induced GI complications.

Introduction: DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) is a rare adverse drug reaction characterized by cutaneous and systemic manifestations, with a mortality rate of up to 10%. In this study, we describe the case of a 77-year-old man who developed DRESS syndrome with cold agglutination.

Case presentation: A 77-year-old man prescribed phenytoin and carbamazepine for suspected cranial neuralgia after a tooth extraction developed high-grade fever and hemorrhagic crusting on the upper and lower lips and oral mucosa, morbilliform rashes over the chest, abdomen, and back along with facial edema, all occurring over 2 weeks. Clinically significant right-sided submandibular, cervical, and axillary lymphadenopathy was observed. Additional findings, including peripheral blood eosinophilia, hepatitis, and coagulopathy, helped us make a provisional diagnosis of DRESS syndrome. The peripheral blood smear showed an incidental finding of cold agglutination phenomenon at room temperature (16 °C; winter months in North India), which disappeared under warmer conditions. However, gross hemolysis was not confirmed. The patient showed significant response in both clinical and hematological parameters within 24 hours of initiating intravenous dexamethasone, which was continued and gradually tapered over 14 days. Follow-up at one month showed the disappearance of the cold agglutination phenomenon.

Conclusion: Cold agglutination in DRESS syndrome has not been documented in detail in the past. One hypothesis is the agglutination of red blood cells (RBCs) due to the effect of the pathogenetic antibodies in DRESS syndrome directed against RBC antigens. Further molecular research may elucidate the pathways of this rare clinical finding.

Introduction/objective: Biosimilars, a class of biologic medications that are highly similar to reference biologics, have emerged as cost-effective alternatives to their expensive originator counterparts. Due to their complex nature and manufacturing processes, biosimilars differ significantly from small molecule generics and must undergo a rigorous assessment to ensure safety, efficacy, and accessibility. This review explores the regulatory landscape surrounding biosimilars across key markets such as the United States, Europe, and India, with a focus on approval processes and post-marketing pharmacovigilance for patient safety.

Methods: The study conducted a detailed review of regulatory guidelines, approval frameworks, and post-marketing requirements for biosimilars across various countries. Data was collected from official sources such as the European Medicines Agency (EMA), the United States Food and Drug Administration (FDA), and relevant Indian regulatory bodies. The research also analysed guidelines focusing on pharmacovigilance practices, particularly for vulnerable populations like paediatric and geriatric patients.

Results: The analysis found that while regulatory agencies such as the EMA and FDA have established stringent biosimilar approval pathways, India's regulatory framework, though promising, still lacks comprehensive pharmacovigilance guidelines. The harmonization of global biosimilar guidelines has contributed to their widespread adoption in new therapeutic areas and emerging markets, driving market expansion. The study highlights the importance of postmarketing monitoring to ensure continued safety, with particular emphasis on vulnerable populations.

Conclusion: The regulatory landscape for biosimilars is evolving, with increasing global collaboration fostering the harmonization of guidelines. Regulatory agencies such as the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) have established rigorous approval frameworks, ensuring biosimilars meet the necessary standards for safety and efficacy. In emerging markets like India, the biosimilar sector is poised for significant growth, though the regulatory framework is still maturing. Strengthening regulatory infrastructure, particularly in areas such as approval processes and quality control, will be crucial in supporting this expansion. The review emphasizes the importance of robust and clear regulations to facilitate the safe and effective integration of biosimilars into global healthcare systems, ensuring greater accessibility for patients without compromising on quality.

Objective: This review investigates the regulatory framework for dermocosmetic bioactive in functional skincare, focusing on products with both cosmetic and pharmaceutical characteristics. The global regulatory environment, with comparisons between the EU, the US, and India, will be analyzed, emphasizing the duality in regulation. Safety assessments, bioavailability, and toxicity concerns will be key focus areas, especially considering the impact of emerging technologies such as nanotechnology and AI-driven formulation development.

Method: A comprehensive literature search was performed using PubMed and Google Scholar electronic databases. This involves a comparative analysis of regulatory frameworks governing dermocosmetic bioactives across the EU, US, and India, focusing on understanding differences and similarities in their approaches. Additionally, the review will cover safety assessment techniques, including in vitro methods, ex vivo skin permeation models, and bioavailability studies to evaluate product safety and efficacy. The exploration extends to emerging technologies such as nanotechnology and the use of machine learning for predictive toxicology. It also addresses virtual clinical trials and the integration of "-omics" data into safety evaluations, offering new insights into regulatory compliance and risk assessment.

Result: The review highlights the need for adaptive regulations to balance innovation with consumer safety. Regulatory differences in the EU, US, and India reflect varying approaches to dual- function products.

Conclusion: Advances in nanotechnology, AI, and machine learning offer new pathways for formulation development and safety assessments, suggesting a future where regulatory frameworks evolve to accommodate these innovations while ensuring product safety and efficacy.

Process analytical technology has emerged as a possible game-changing platform in the pharmaceutical business to improve process knowledge while also improving product quality and lowering production costs. This paper outlines the underlying principles of PAT, its application in pharmaceutical manufacturing processes, and the impact on assurance of quality and reduction of cost. Real-time monitoring, multivariate data analysis, and process control strategies are three modules that are computed and integrated with PAT to develop robust and efficient manufacturing processes. A number of case studies and examples have been used to illustrate this relationship between the implementation of PAT and a reduction in variability with an improvement in process control and consistency of the product, which finally realizes million-dollar savings. It also debates the regulatory perspectives and challenges involved in PAT adoption, focusing on how stakeholders in the industry and agencies can integrate in developing and implementing innovations that will pass the test of compliance criteria. In general, what this paper presents is that PAT will drive pharmaceutical manufacturing into advancement for higher standards of quality with increased efficiency.

Impurity separation and detection are essential processes in the pharmaceutical industry to preserve the quality of drugs as the impurities have the potential to significantly impair the therapeutic efficacy of an active ingredient and have negative effects on pharmaceutical formulations. The primary determinant of drug development is the creation of products that adhere to the highest standards of quality and safety, with a particular emphasis on effectively managing impurities in the therapeutic ingredients. To ensure that the resulting pharmaceutical possesses a high level of safety, meticulous identification, precise quantification, and stringent management of any extraneous components present in the drug ingredient need to be performed. The literature was compiled from different databases, such as DOAJ, PubMed, Research Gate, Google Scholar, Scopus, and Science Direct. Several organic and inorganic contaminants that are frequently present in final products and active pharmaceutical ingredients (APIs) were covered, along with the crucial section for quality control and fundamental details on their security, toxicity, detection limits, and quantification limitations. Pharmaceutical companies resolve the problem of the presence of impurities by adhering to strict regulatory requirements set by reputable agencies, like the ICH, USFDA, EMA, and PMDA. Also, impurity profiling is required for the regulatory submissions of new drug candidates. In some pharmacopoeias, impurity profiling and reporting are also included. To identify and measure contaminants, a variety of analytical techniques are employed, as discussed in this article. This paper covers the scientific features of contaminants present in pharmaceutical preparations, their prevention strategies, and the application of state-of-the-art analytical techniques for their detection.

Background: Traumatic Brain Injury (TBI) is a significant public health issue, often leading to long-term cognitive, physical, and emotional impairments. Amantadine has emerged as a treatment option due to its potential neuroprotective properties, aiming to enhance recovery. However, its safety profile in TBI patients remains under scrutiny.

Objective: This study aimed to evaluate the safety of amantadine using the FDA Adverse Event Reporting System (FAERS) database, focusing on identifying novel adverse events to inform clinical decisions.

Methods: We analyzed adverse event reports of amantadine from FAERS (2004-2024), identifying 2766 reports where it was the primary suspect. Signal detection was conducted using ROR, PRR, BCPNN, and MGPS methods, ranked by ROR values. A gender subgroup analysis with Bonferroni correction ensured statistical significance.

Results: Among the 2766 reports, most events were related to nervous (n=2013, ROR=2.9) and psychiatric disorders (n=1631, ROR=3.46). Notable events included hallucinations (n=302, ROR=27.57), falls (n=286, ROR=5.7), and drug inefficacy (n=266, ROR=1.34). Adverse events were more common in patients aged 65+ years (48.5%) and slightly more frequent in females (49.3%). New adverse events identified included falls, drug inefficacy, tremors, and gait disturbances, mostly occurring within the first month of treatment (39.6%).

Conclusion: The study revealed significant safety concerns with amantadine, especially regarding nervous and psychiatric reactions. It highlighted the need for careful monitoring in clinical use and further research to understand mechanisms, enhance therapeutic outcomes, and minimize adverse events.

Background: Antibiotic resistance poses a significant challenge in healthcare, requiring effective management of antibiotic use. This study examines systemic antibiotic consumption at ASST Bergamo Ovest, a northern Italian hospital, from January 2022 to June 2023, with a focus on Healthcare-Associated Infections (HAIs) and prescription appropriateness.

Objective: This retrospective observational study aims to analyze antibiotic usage trends and to evaluate prescribing practices against national guidelines.

Methods: Data on systemic antibiotic consumption were reviewed, categorized by the AWaRe classification system (Access, Watch, Reserve), and analyzed using the Defined Daily Dose per 100 patient-days metric.

Results: The study observed a 7% overall reduction in antibiotic use, including a 5% decrease in the AWaRe Watch category. Despite this progress, the appropriateness of prescribing remained consistently low. These findings suggest partial alignment with the Italian Plan against Antibiotic Resistance but highlight the need for improvement in prescribing practices.

Conclusion: While ASST Bergamo Ovest has reduced antibiotic consumption and the use of higher-risk antibiotics, low prescribing appropriateness underscores the need for enhanced real-time monitoring and more effective stewardship programs. Targeted interventions are essential to improve prescribing practices, combat multidrug-resistant infections, and meet European antibiotic stewardship standards.

Background: Limited clinical evidence exists regarding the safety profile of amiodarone therapy in patients with heart failure (HF) who already have underlying cirrhosis.

Objective: The present study aimed to investigate the safety profile of amiodarone in patients with cirrhosis and HF concomitantly.

Methods: This was a retrospective cohort study with the TriNetX database using ICD-10 codes. Patients aged > 18 years with HF and cirrhosis receiving amiodarone for atrial fibrillation/flutter or ventricular tachycardia/fibrillation were compared with those not receiving amiodarone as a control group. Patients with end-stage renal disease were excluded. The primary outcome was a composite of all-cause mortality or all-cause hospitalization/emergency room visits.

Results: No significant differences in the primary outcome were found between the amiodarone and non-amiodarone groups (OR: 1.125 [95% CI: 0.956, 1.324]; P=0.158). The time-to-event analysis also revealed no significant differences in the primary outcome between the two groups (HR 0.949 [95% CI 0.816, 1.103], P=0.499). There were no significant differences in all-cause hospitalization/ emergency room visits (OR: 1.013 [95% CI: 0.880, 1.166]; P= 0.121), all-cause mortality (OR: 1.031 [95% CI: 0.901, 1.179]; P=0.656), and worsening hepatic function between two groups (OR: 0.943 [95% CI: 0.798, 1.115]; P=0.494).

Conclusion: The amiodarone therapy in patients with underlying cirrhosis and heart failure may be reasonable with close liver function monitoring if the benefits outweigh the risks of amiodarone therapy.