Current drug safety最新文献

The drug approval and review process plays a crucial role in the pharmaceutical industry, aiming to ensure that newly marketed drugs are safe, effective, and of high quality. Regulatory authorities overseeing this process, tailored to geographically distinct needs, include the U.S. FDA, EMA, Japan's Pharmaceuticals and Medical Devices Agency (PMDA), China's National Medical Products Administration (NMPA), and India's Central Drugs Standard Control Organization (CDSCO). This analysis offers insight into the various drug approval processes employed by these authorities and examines the International Council for Harmonisation's ongoing efforts to establish a global consensus on drug regulation standards. It also compares regulatory pathways and highlights current harmonization initiatives. The focus is on analyzing operational aspects of drug regulation and identifying challenges arising from these regulations. The ultimate goal is to present a clear understanding of the intricacies and dynamics of the global drug approval process. Regulating the drug approval process is essential to ensure that new drugs are safe for public consumption, as the introduction of a new drug often faces numerous hurdles beyond safety and efficacy. The challenges highlighted include variations in regulations between authorities, the complexity of modern therapeutics, and the balance between safety and speed. This paper provides an overview of innovations in drug development, their impact on regulatory pathways, ongoing harmonization efforts, and potential obstacles that may arise during the regulatory process.

A transdermal drug delivery system is a convenient drug delivery system where the drug enters the systemic circulation through the protective barrier, i.e., skin. Ethosomes are the ethanolic phospholipid vesicles, which are mainly used for transdermal delivery of medicines. They are nano-vesicular carriers for the topical application of the drugs. The major components of ethosomes are phospholipids, ethanol at relatively high concentrations (up to 50%), and water. The vesicles' composition and structure enhance their ability to entrap molecules with numerous physicochemical characteristics and bring them to the skin's deep layers. Because of their enhanced skin penetration, improved drug delivery, and higher drug entrapment efficiency, ethosomes have become more significant in the field of research. Skin acts as a major target and main barrier for topical or transdermal drug delivery and hence several approaches have been developed to weaken this skin barrier. Vesicular systems like ethosomes are the key approaches to increasing the skin penetration of medicines and various cosmetic components. Ethanol has been added to vesicular systems to create elastic nanovesicles because it is an effective penetration enhancer. For stability and simplicity of use, ethosomal dispersions are added to gels, patches, and creams. This review focuses on research using ethosomal formulations containing natural active compounds for the treatment of skin problems that has been done in vitro, in vivo in animal models, and on people in clinical investigations. Ethosomal systems have been shown to effectively control a variety of skin conditions, including bacterial and fungal infections, inflammation, acne vulgaris, arthritis, skin cancer, etc. Furthermore, ethosomes loaded with various naturally occurring components for cosmetic applications are also reported. The conception of new dermal therapies was made possible by the effective treatments, their good safety profile, and their lack of toxicity or irritation.

Acute kidney injury (AKI) is a severe and life-threatening complication of drug therapy, a significant risk to patient well-being, with high morbidity and death rates. An increasing proportion of AKI cases are mainly caused due to drug-induced nephrotoxicity; despite its prevalence, the exact study of causative drugs is still unclear. AKI is often caused by kidney damage, reducing the kidneys' ability to detoxify, eventually leading to nephrotoxicity. Drug-induced nephrotoxicity often happens through various mechanisms such as crystal nephropathy, oxidative stress, reduced flow to the kidneys, damage to kidney cells, and thrombotic microangiopathy. Epidemiology of drug-induced nephrotoxicity focuses on how prevalent it is and the factors that increase the nephrotoxicity. Specific biomarkers have been found to assess nephrotoxicity for early and accurate diagnosis of kidney damage. This review focuses on explaining drug-induced nephrotoxicity mechanisms for commonly used agents such as non-steroidal anti-inflammatory drugs, immunosuppressants, antibiotics, anticancer agents, and antifungals. It also covers specific biomarkers and respective treatment approaches. Additionally, protective agents and their mechanisms in preventing nephrotoxicity are also analyzed, including their antioxidant and anti-inflammatory potential and other drug-based interventions. This review discusses various therapeutic studies using experimental models, offering invaluable insights into the cellular processes and pathways involved in developing prevention strategies. By advancing our understanding of the mechanisms behind drug-induced nephrotoxicity, it is aimed to improve patient care and reduce health-related complications.

Mitochondrial dysfunction plays a central role in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Targeted drug delivery to mitochondria represents a promising therapeutic strategy to mitigate neuronal degeneration and preserve mitochondrial function in these devastating conditions. This review provides a comprehensive overview of recent advances in targeted drug delivery solutions for mitochondrial dysfunction in neurodegenerative disorders. The mechanisms underlying mitochondrial dysfunction in AD, PD, HD, and ALS are explored, highlighting the specific challenges and opportunities for therapeutic intervention. Emerging drug delivery technologies are discussed, including mitochondriaresponsive systems, nanoparticles, peptides, and viral vectors, designed to deliver therapeutic agents directly to mitochondria along with suitable case studies. Furthermore, preclinical and clinical studies evaluating the efficacy and safety of mitochondria-targeted therapeutics are reviewed, and future directions and challenges in the field are outlined. By elucidating the intersection of mitochondrial biology and drug delivery, this review aims to inspire further research and innovation toward effective treatments for neurodegenerative diseases.

Background: Thalidomide has emerged as a novel antitumor drug with antiangiogenic and immunomodulatory properties. It was taken off the market in the early 1960s due to its infamous connection with congenital defects. Recently, the FDA approved thalidomide for treating erythema nodosum leprosum, adhering to strict guidelines and safety measures. Sensory peripheral neuropathy and teratogenicity, fatigue, vertigo, headache, gastrointestinal issues, skin eruptions, dizziness, galactorrhoea, decreased libido, and constitutional symptoms like fever, weakness, headaches, and weight loss are the main adverse effects of thalidomide.

Case report: We report a case of a 46-year-old female diagnosed with lepromatous leprosy on multibacillary multidrug therapy presenting with unusual adverse reactions, such as generalized burning sensation, breathlessness, and low backache after the intake of thalidomide.

Conclusion: We describe an unusual adverse reaction to thalidomide that has not previously been reported in the literature and aim to alert clinicians about the unusual, adverse reaction as an uncommon side effect of thalidomide and to always keep in mind if the patient develops any of these symptoms.

Objectives: We aimed to estimate the global prevalence of anti-drug antibodies (ADAb), their impact on response, and associated factors in adults with rheumatoid arthritis (RA) and spondyloarthritis (SpA) treated by TNF alpha inhibitors (TNF-i).

Methods: We searched PubMed, MEDLINE, Cochrane, Web of Science, and Scopus for observational, population-based studies published between Jan 2010 and Sept 2021. We included studies that reported the prevalence of ADAb (our main outcome) and examined their impact on treatment efficacy in adults treated with TNF-i (secondary outcome). To investigate heterogeneity, we used a Q-test and predictive interval.

Results: The overall global prevalence of ADAb in RA was 20.8% (95%CI,6.8-25.5) (95%PI,6.12-51.42) and in SpA 24.8% (95%CI,19.1-31.5) (95%PI,7.31-57.98). There was no significant difference in the prevalence of ADAb between infliximab (IFX) and adalimumab (ADA) in RA (p=0.21) nor in SpA (p=0.46). There was a statistically significant difference between IFX and etanercept (ETN) in RA (p<0.0001) as well as in SpA (p=0.001) and, likewise, between ADA and ETN in RA (p<0.0001) and in SpA (p=0.002). Study by subgroups of the impact of immunogenicity on response, according to the type of TNF-i, showed that the mean OR for ADA was 0.152 (CI 95%, 0.054 to 0.427) and for IFX was 0.144 (CI 95%, 0.055 to 0.378). The pairwise comparison of ADA vs IFX was not statistically significant (p=0.94). In subgroup analysis, according to the disease, the mean OR for RA was 0.149 (IC 95% 0.064 to 0.347) and for SpA was 0.303 (IC95% 0.103 to 0.890). The pairwise comparison of RA vs SpA was not statistically significant. The use of methotrexate tends to reduce the development of ADAb in RA and SpA with an OR=0.472 (CI95%,0.324-0.689) (PI95%,0.16-1.39).

Conclusion: ADAb were equally prevalent in RA and SpA treated with TNF-i. Immunogenicity was associated with response to treatment and influenced by concomitant use of methotrexate.

Background: Since 2016, Moroccan pharmaceutical companies have been required to report adverse effects linked to their medicines. Initially, reports were submitted using the CIOMS form, sent by normal mail to le Centre Antipoison et de Pharmacovigilance du Maroc, then using XML files in ICH E2B format, sent electronically. In 2021, a "vigiflow e-reporting for industry" standardized online reporting system was implemented. The primary objective of this study was to evaluate the pharmaceutical companies' use of electronic reporting. Secondarily, the study aimed to assess the quality of adverse drug reaction reports by comparing completeness scores across the three reporting means.

Methods: All individual case safety reports sent by pharmaceutical companies from January 1, 2019, to December 31, 2023, were extracted from Vigibase®. A quantitative and qualitative analysis was conducted, and a statistical comparison of data was performed using p-values. VigiGrade completeness score was calculated for a sample size selected.

Results: The highest number of reports were from E-reporting (50%), followed by CIOMS (29%) and E2B (21%). Between 2019 and 2021, CIOMS and E2B notifications decreased along with reporting laboratories. However, after 2021, electronic reporting increased steadily alongside reporting companies. Comparing vigiGrade completeness score across reporting means revealed no statistically significant differences (p = 0.094 > 0.05).

Conclusion: Electronic reporting shows quantitative effectiveness and consistent quality. Its adoption remains limited and requires continuous strengthening, particularly through increased awareness among pharmaceutical companies.

Vericiguat, a novel stimulator of soluble guanylate cyclase (sGC), marks a significant advancement in the management of heart failure with reduced ejection fraction (HFrEF). By enhancing the nitric oxide signaling pathway, it facilitates vasodilation and improves myocardial function. Clinical trials, including the VICTORIA study, have demonstrated that vericiguat effectively reduces the risk of cardiovascular death and hospitalizations associated with chronic HFrEF. The favorable safety profile of this drug, with tolerability comparable to placebo, further supports its suitability for long-term use. Understanding the pharmacodynamics and pharmacokinetics of vericiguat is essential to appreciating its clinical efficacy and its role in current heart failure treatment strategies. This review explores existing research to explore the therapeutic potential of vericiguat, its practical implications for patient care, and the need for further investigation to expand its applications. By addressing unmet needs in heart failure management, vericiguat represents a promising addition to contemporary treatment paradigms.

Background: Capecitabine, an important drug used for solid tumors involving the gastrointestinal tract, is known to be associated with many Adverse Drug Reactions (ADRs) leading to dose modification or discontinuation.

Objective: The objective of this study was to determine the frequency and pattern of adverse drug reactions (ADRs) associated with capecitabine-based chemotherapy regimens (CBCR).

Methods: A prospective observational study was carried out at a regional cancer center in South India. A total of 120 cancer patients receiving CBCR were recruited and interviewed for the occurrence of any ADRs during the complete course of chemotherapy cycles. The adverse drug events were graded for severity as per the CTCAE criteria (v4.03), and causality assessment was done using the WHO and Naranjo scales. The preventability assessment of the ADRs was conducted using the modified Schumock and Thornton scale. The chi-squared test was used to analyze the difference in the frequency of ADRs among cancer types, genders, and chemotherapy regimens.

Results: The majority of ADRs (96.6%) reported throughout the treatment cycles were from the gastrointestinal system, followed by neurology-related events (93.3%). Among the various ADRs detected, skin/nail discoloration and fatigue/weakness were the most frequently reported. Causality analysis classified most ADRs under the "possible" category (50.5% by the WHO scale and 50.9% by the Naranjo scale). Most ADRs were of Grade I severity (54.5%) and were deemed "probably preventable."

Conclusion: CBCR was associated with several ADRs, though most were of Grade I severity and primarily affected the gastrointestinal system. The majority of ADRs were classified as "possible" based on causality analysis, and most were deemed "probably preventable." Future research could focus on ameliorating these ADRs to avoid dose adjustments or discontinuation of chemotherapy.