Real-World Prescription Data for Intrathecal Drug Delivery: A Retrospective Analysis in 32,784 Patients.

OBJECTIVES: Currently, there are three monotherapy drugs approved by the United States Food and Drug Administration (FDA) for use in intrathecal drug delivery systems (IDDS): morphine, ziconotide, and baclofen. In practice, use includes alternate drugs, drug combinations, and drug concentrations. There is a paucity of real-world data examining prescription patterns for IDDS. Our analysis explores a one-year sample of prescription intrathecal (IT) medications from a large pharmaceutical data base to characterize medication usage in IDDS. MATERIALS AND METHODS: Data were provided by an accredited pharmacy as a deidentified data base of IT drug prescriptions. Statistical analyses included rates of monotherapy vs combination therapies, frequencies of various IT prescriptions, use of on- vs off-label medications, and opioid vs nonopioid formulations. RESULTS: Data were extracted from February 1, 2021 to February 14, 2022. No patients were excluded. The initial sample comprised 49,917 individual IT prescriptions for 32,784 patients. Monotherapies constituted 55.0% of all prescriptions (27,475/49,917). Of these, 23,257 prescriptions (84.6%) were opioid based, with the most common medications being morphine (46.5%), hydromorphone (39.4%), and fentanyl (13.5%). Although 29.3% of all prescriptions were for one of the FDA-approved medications, only 7.9% used FDA-approved concentrations; 9865 patients underwent ≥one prescription change in the study period-16.7% of whom were initially prescribed medications that met the approved, on-label indications for the pump before being switched to off-label concentrations or combinations to address clinical needs. CONCLUSIONS: Despite the prevalence of IDDS for managing chronic, intractable pain, minimal data exist on real-world prescription practices. Our study found that FDA-approved IT formulations accounted for the minority of prescriptions, indicating significant practice variation, with off-label prescriptions being common.

MEIBO (perfluorohexyloctane): a novel approach to treating dry eye disease.

Dry eye disease (DED) or keratoconjunctivitis sicca (KCS) is a multifactorial disease that classically develops due to the hyperosmolarity of the tear film. Categorically divided into two types, based on decreased production and increased evaporation of the tear film, DED begins with a spectrum of nonspecific symptoms like pruritus, redness, burning and discomfort, progressively leading to stringy mucus eye discharge, photophobia, twitching, visual fluctuations, and punctate epithelial lesions. This disease has numerous treatment options, including medications, artificial tear inducers, and surgical manoeuvres that prevent water loss from the tear film. However, each of these treatment options has its limitations. The Food and Drug Administration (FDA) has approved another intervention, Meibo (perfluorohexyloctane), as a choice of management for dry eye disease. With its shielding action on the ocular surface, Meibo (perfluorohexyloctane) reduces desiccation stress-induced ocular damage, making it highly specific for treating DED. Available in an eye drop formulation of perfluorohexyloctane (PFHO), these drops can reduce saline evaporation by up to 80%. The methods we used for this analysis are literature searches from PubMed, Medline and Google Scholar. This study aims to scour varying differentials of DED, its aetiology, general interventions, the latest refinements, and clinical efficacy, safety, and trials associated with Meibo (perfluorohexyloctane) in the management of DED.

Tobacco and Nicotine Products Adverse Health Events: Findings From the FDA Safety Reporting Portal.

Introduction: The FDA oversees regulatory aspects of all U.S. tobacco products. Understanding the impact of emerging health trends and incidents associated with various tobacco and nicotine products is vital for public health. This study utilizes the FDA's Tobacco Product Problem Reports (TPPRs) to characterize and track adverse health events (AHEs) associated with tobacco and nicotine products over time, considering the impact of EVALI and the COVID-19 pandemic. Methods: FDA TPPRs from 2017-2022 provided information on AHEs related to various tobacco products. After data cleaning, 839 reports were categorized by two independent coders based on affected health category, frequency of AHEs reports, and proportion of AHEs per each health category. Additionally, variations in AHEs over time were assessed, considering major health events like EVALI and the COVID-19 pandemic. Results: Among the 839 reports, electronic cigarettes (e-cigarettes) were the primary product of concern, comprising 90.6% (n = 760) of all reports, surpassing traditional cigarettes (5.1%; n = 43) and other products. Notably, 45.6% of reports (n = 383) identified the neurological system as the most frequently mentioned health category, each reporting at least one AHE. This was followed by the respiratory (39.1%; n = 328) and digestive (10.7%; n = 90) systems. Among all reported AHEs, respiratory system issues were most frequent (25.9%; n = 512), closely followed by neurological (25.2%; n = 499) and digestive (6.6%; n = 131) concerns. Most reports occurred in 2019 (65.7%; n = 551), coinciding with the EVALI outbreak, with a subsequent decline post-Q3 2019, highlighting the potential impact of specific health crises on reporting trends. Conclusion: E-cigarettes dominated adverse health reports, particularly affecting the neurological and respiratory systems, with a peak in 2019. Our findings provide insights to regulatory entities and future research, enhancing understanding of AHEs in lesser-explored bodily systems, such as the neurological and digestive systems. This study emphasizes the need for ongoing and improved surveillance of emerging tobacco products to protect public health.

Safety of titanium dioxide (E171) as a food additive for humans.

Titanium dioxide (TiO2), also known as E171, is commonly used as a white colorant in food, pharmaceuticals, cosmetics, and toothpaste. However, in May 2021, the European Food Safety Authority (EFSA) expert panel, in evaluating the safety of titanium dioxide (E171) as a food additive, concluded that a concern for genotoxicity could not be ruled out. This occurred several years after EFSA had previously considered titanium dioxide to be safe as a food additive. EFSA based this new interpretation on the results of genotoxicity tests of TiO2 nanomaterials. EFSA noted that available data are insufficient to define threshold doses/concentrations of TiO2 particles below which genotoxicity will not occur in tissues containing these particles. Here, it is argued that EFSA made a manifest error regarding the safety of titanium dioxide (E171) particles as a food additive for humans. First, the notion of particle size distribution of TiO2 particles is explained. Second, the changing opinions from the various EFSA evaluations in 2016, 2018, 2019 vs. 2021 are discussed. Third, the low toxicity of TiO2 particles is described in rats exposed by oral gavage and feeding studies in rats and mice. Fourth, the importance of low absorption rates from the gastrointestinal tract vs. circulation in rats and humans but not in mice is identified. Fifth, other international health scientists have weighed in on the EFSA (EFSA J, 2021, 19 (5), 6585) decision and generally disagreed with EFSA's opinion on the safety of E171 TiO2. A common theme voiced by the United Kingdom, Canada, Australia, and New Zealand agencies is that it is inappropriate to compare nanoparticle toxicity studies of dispersed/sonicated nanoparticles with the content of E171 TiO2 in foods because the test materials used in key studies considered by EFSA (EFSA J, 2021, 19 (5), 6585) are not representative of E171 TiO2 particles. Finally, a group of experts recently considered the genotoxicity of TiO2 and could not find support for a direct DNA damaging mechanism of TiO2 (nano and other forms). For these reasons, it is suggested that EFSA made a manifest error on the safety of E171 as a food additive.

Real-World Disproportionality Analysis of the Food and Drug Administration Adverse Event Reporting System Database for Asciminib.

INTRODUCTION: Asciminib is primarily utilized for treating Philadelphia chromosome-positive chronic myeloid leukemia in its chronic phase among patients harboring the T315I mutation or those who have been previously treated with at least two tyrosine kinase inhibitors. The safety profile of asciminib across a broad patient population over an extended timeframe remains unverified. This study uses a real-world pharmacovigilance database to evaluate the adverse events (AEs) linked with asciminib, providing valuable insights for clinical drug safety. METHODS: Data from the FDA Adverse Event Reporting System (FAERS) database, spanning from October 2021 to December 2023, served as the basis for this analysis. The extent of disproportional events was assessed using sophisticated metrics such as the reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean. RESULTS: Within the specified period, the FAERS database documented 3,913,574 AE reports, with asciminib being associated with 966 incidents. Reactions to asciminib spanned 27 system organ categories. Utilizing four distinct analytical algorithms, 663 significant preferred terms exhibiting disproportional frequencies were identified. Notably, this investigation uncovered 26 significant AEs linked to off-label asciminib use, encompassing conditions such as gynecomastia, nephrotic syndrome, orchitis, pyelonephritis, hepatotoxicity, and pancreatitis. The median onset time for asciminib-related AEs was 52.5 days, ranging from 17 to 122.75 days. CONCLUSION: The study sheds light on additional potential AEs associated with asciminib use, warranting further research to confirm these findings.

Association between antipsychotics and pulmonary embolism: a pharmacovigilance analysis.

BACKGROUND: Previous studies have documented an increased risk of pulmonary embolism (PE) in patients with schizophrenia taking antipsychotics (APs). However, specific data from real-world studies remain limited. This study aims to investigate the potential relationship between APs and PE. RESEARCH DESIGN AND METHODS: In the Food and Drug Administration Adverse Event Reporting System (FAERS), from the first quarter of 2018 to the first quarter of 2023, all PE cases suspected of being induced by APs were collected for disproportionality analysis, and the reporting odds ratio (ROR) was used to evaluate associations. Mortality, life-threatening events, and hospitalizations were also analyzed for each APs. RESULTS: A total of 1,676 cases of PE related to APs were included. APs were significantly associated with PE (ROR 2.00, 1.91-2.10), including chlorpromazine (n = 41), haloperidol (n = 164), loxapine (n = 37), olanzapine (n = 461), paliperidone (n = 161), quetiapine (n = 526), risperidone (n = 274), aripiprazole (n = 254), and clozapine (n = 234). The median onset time of PE was 29 days. Among all cases, 347 (20.7%) resulted in death, with haloperidol (53.2%) having a higher mortality rate than other APs. CONCLUSIONS: APs may increase the risk of PE in patients with schizophrenia.

Differential times of submission and approval of CFTR modulators for the treatment of Cystic Fibrosis in the United States and the European Union.

BACKGROUND: The objective of this study was to assess the differential times of submission and approval of CFTR modulators in the United States (US) and the European Union (EU). METHODS: By collecting publicly available data from the websites of the Food and Drug Administration and the European Medicines Agency, we quantified differential times in submission, review duration, and approvals of initial marketing authorization and variation of indications of CFTR modulators in the US and the EU by December 31, 2023. RESULTS: Applications regarding marketing of 4 CFTR modulators were submitted 103 (SD ±143) days later in the EU than in the US: 31 (SD ±39) days later for initial approval, and 124 (SD ±155) days for supplemental indications. The regulatory review process was completed in 181 days [IQR, 179 - 182] in the US and 325 days [IQR, 276 - 382] in the EU: 167 days [IQR, 102 - 232] in the US and 346 days [IQR, 302 - 400] in the EU for first approvals, 181 days [IQR, 181 - 182] in the US and 324 days [IQR, 264 - 382] in the EU for supplemental indication approvals. CFTR modulators were approved 267 (SD 143) days later in the EU than in the US: 220 (SD ±76) days for initial approval and 280 (SD ±157) days for supplemental indications. CONCLUSION: We found significant differences in times of submission and for approval of CFTR modulators between the US and EU, whereby initial approvals and subsequent indication approvals were always first granted in the US.

A review on recent advancements in pharmaceutical technology transfer of tablets from an Indian perspective.

OBJECTIVE: The healthcare sector is a paramount and rapidly expanding industry in India. The pharmaceutical field in India has experienced substantial growth and transformation in recent times, making significant contributions to the global healthcare market. This comprehensive review delves into the most recent innovations in pharmaceutical technology transfer (TT), particularly in the context of tablet formulations from an Indian standpoint. SIGNIFICANCE: The pharmaceutical sector has grappled with various challenging issues, including the escalating costs of medications and the demand for patient-friendly products. METHODS: In this technological progress era, various cutting-edge pharmaceutical technologies, such as artificial intelligence (AI), and 3D and 4D printing, play pivotal roles in drug development. Tablets, the most promising and widely utilized dosage form worldwide, require a sophisticated approach to TT. Achieving a successful TT necessitates a dedicated team with well-defined objectives, improved documentation, and effective communication. RESULTS: The Indian Pharmaceutical Industry (IPI) possesses the potential to make significant contributions to the global healthcare sector. Moreover, we delve into the various phases of TT, highlighting the pivotal role of formulation development and process optimization in ensuring product quality, efficiency, and cost-effectiveness along with different models of TT. Additionally, we examine the challenges associated with TT and potential solutions, as well as the initiatives of the Indian government to bolster the Indian pharmaceutical sector's position as the "Pharmacy of the World". CONCLUSION: It is concluded that there is a need to contextualize and institutionalize the tech transfer policies for successful implementation for the benefit of the global population.

Characteristics of eye disorders induced by atypical antipsychotics: a real-world study from 2016 to 2022 based on Food and Drug Administration Adverse Event Reporting System.

Background: Common atypical antipsychotics include risperidone, paliperidone, olanzapine, lurasidone, quetiapine, clozapine, aripiprazole, ziprasidone, asenapine, brexpiprazole, and cariprazine. Previous studies on ocular adverse reactions of antipsychotics were mainly focused on typical antipsychotics. Systematic research on atypical antipsychotics remains limited. Objective: This study aimed to evaluate the potential risks of different atypical antipsychotics causing ocular side effects by mining the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Extract reports from the FAERS from the first quarter of 2016 to the fourth quarter of 2022 were obtained. Data mining of eye disorders associated with atypical antipsychotics was carried out using The Reporting Odds Ratio (ROR) method and The Medicines and Healthcare Products Regulatory Agency (MHRA) method to determine positive signals. Results: FAERS reports for 9913783 cases were included in these 28 quarters. 64 defined ocular adverse events were classified into 10 categories according to High-Level Group Terms (HLGT). Conclusions: There were differences in the types and severity of ocular-related adverse events associated with atypical antipsychotics. Ocular neuromuscular-related adverse events were found among all 11 atypical antipsychotics. Olanzapine had the highest signal intensity in oculogyric crisis. Aripiprazole had the highest signal strength in blepharospasm. Cariprazine was associated with cataract-related ocular adverse reactions. In terms of the types of adverse events, our study found that aripiprazole was associated with 28 types of ocular adverse events, followed by quetiapine. Clozapine was only associated with two types of ocular adverse events.

An update on nonhuman primate usage for drug and vaccine evaluation against filoviruses.

INTRODUCTION: Due to their faithful recapitulation of human disease, nonhuman primates (NHPs) are considered the gold standard for evaluating drugs against Ebolavirus and other filoviruses. The long-term goal is to reduce the reliance on NHPs with more ethical alternatives. In silico simulations and organoid models have the potential to revolutionize drug testing by providing accurate, human-based systems that mimic disease processes and drug responses without the ethical concerns associated with animal testing. However, as these emerging technologies are still in their developmental infancy, NHP models are presently needed for late-stage evaluation of filovirus vaccines and drugs, as they provide critical insights into the efficacy and safety of new medical countermeasures. AREAS COVERED: In this review, the authors introduce available NHP models and examine the existing literature on drug discovery for all medically significant filoviruses in corresponding models. EXPERT OPINION: A deliberate shift toward animal-free models is desired to align with the 3Rs of animal research. In the short term, the use of NHP models can be refined and reduced by enhancing replicability and publishing negative data. Replacement involves a gradual transition, beginning with the selection and optimization of better small animal models; advancing organoid systems, and using in silico models to accurately predict immunological outcomes.

Cardiovascular toxicities of selective ret-specific tyrosine kinase inhibitors: a pharmacovigilance study based on the United States Food and Drug Administration Adverse Event Reporting System database.

BACKGROUND: Selective RET-specific tyrosine kinase inhibitors (RET-TKIs) treat RET fusion-positive non-small cell lung cancer (NSCLC), but studies on their cardiovascular toxicities are limited. This study aimed to characterize the cardiovascular toxicities associated with selective RET-TKI in real-world settings. RESEARCH DESIGN AND METHODS: Data from the United States Food and Drug Administration Adverse Event Reporting System database from 1 January 2020 to 30 June 2023, were analyzed. Two disproportionality methods, information component and reporting odds ratio (ROR) were used. RESULTS: Both pralsetinib and selpercatinib showed positive signals for hypertension (pralsetinib: ROR: 5.25, 95% CI: 4.40-6.26; selpercatinib: ROR: 2.68, 95% CI: 1.87-3.82). Additionally, pralsetinib showed a positive signal for ischemic heart disease (ROR: 3.92, 95% CI: 2.94-5.23), and selpercatinib for torsade de pointes/QT prolongation (ROR: 2.65, 95% CI: 1.74-4.04). The median time to onset(TTO) of cardiovascular toxicities was 33 days (IQR: 9-73 days) for pralsetinib and 15 days (IQR: 10-50 days) for selpercatinib. The proportion of deaths, life-threatening events, and hospitalizations due to cardiovascular toxicities were 8.57%, 1.19%, and 31.43%, respectively, for total selective RET-TKI. CONCLUSIONS: Selective RET-TKIs are related to multiple cardiovascular toxicities. Pralsetinib was linked to ischemic heart disease, and selpercatinib to torsade de pointes/QT prolongation and thrombotic events.

Recent and anticipated novel drug approvals (3Q 2024 through 2Q 2025).

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Health-system pharmacists play a crucial role in monitoring the pharmaceutical pipeline to manage formularies, allocate resources, and optimize clinical programs for new therapies. This article aims to support pharmacists by sharing new and anticipated novel drug approvals. SUMMARY: Selected drug approvals anticipated in the 12-month period covering the third quarter of 2024 through the second quarter of 2025 are reviewed. The analysis emphasizes drugs expected to have significant clinical and financial impact in hospitals and clinics selected from 54 novel drugs awaiting US Food and Drug Administration approval. New cell therapies for treating cancers continue to enter the drug pipeline, while novel targeted therapies for biliary tract, gastric, pancreatic, and breast cancers, as well as 3 subcutaneous versions of already approved drugs given intravenously, are awaiting approval. Additionally, many novel drugs are being developed for treatment of rare and ultra-rare diseases such as hereditary angioedema, macular telangiectasia, congenital adrenal hyperplasia, and Barth syndrome. Two new subcutaneous drugs for hemophilia, a new oral medication for hereditary angioedema, a novel monoclonal antibody for atopic dermatitis, and the first oral penem antibiotic are also in the pipeline. CONCLUSION: New drugs with various indications for cancers and rare diseases continue to strengthen the drug pipeline.

Prostate-Specific Membrane Antigen Expression in Patients with Primary Prostate Cancer: Diagnostic and Prognostic Value in Positron Emission Tomography-Prostate-Specific Membrane Antigen.

Prostate cancer represents a significant public health challenge, with its management requiring precise diagnostic and prognostic tools. Prostate-specific membrane antigen (PSMA), a cell surface enzyme overexpressed in prostate cancer cells, has emerged as a pivotal biomarker. PSMA's ability to increase the sensitivity of PET imaging has revolutionized its application in the clinical management of prostate cancer. The advancements in PET-PSMA imaging technologies and methodologies, including the development of PSMA-targeted radiotracers and optimized imaging protocols, led to diagnostic accuracy and clinical utility across different stages of prostate cancer. This highlights its superiority in staging and its comparative effectiveness against conventional imaging modalities. This paper analyzes the impact of PET-PSMA on prostate cancer management, discussing the existing challenges and suggesting future research directions. The integration of recent studies and reviews underscores the evolving understanding of PET-PSMA imaging, marking its significant but still expanding role in clinical practice. This comprehensive review serves as a crucial resource for clinicians and researchers involved in the multifaceted domains of prostate cancer diagnosis, treatment, and management.

New Oncologic Drugs from 2008 to 2023-Differences in Approval and Access between the United States, Europe and Brazil.

INTRODUCTION: Advancements in oncology have revolutionized cancer treatment, with new drugs being approved at different rates worldwide. Our objective was to evaluate the approval of new oncological drugs for solid tumors by the Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Brazilian Health Regulatory Agency (ANVISA) since 2008. METHODS: Data were collected from public and online databases by searching for the date of submission, the date of the procedure, the date of approval, clinical indication, and drug characteristics. The distribution was tested using the Shapiro-Wilk, test and comparisons were made using the Mann-Whitney U test; the data are reported using median days and interquartile range (IQR1-IQR3). RESULTS: In total, 104 new oncologic drugs for the treatment of solid tumors were approved by the three agencies: 98 by the FDA, 90 by the EMA, and 68 by ANVISA. The cancer types with the highest number of first indications were lung cancer (n = 24), breast cancer (n = 15), and melanoma (n = 15). Most approvals were for oral medications (n = 63) and tyrosine-kinase inhibitors or other small-molecule inhibitors (n = 54). Time to approval after submission was as follows: the FDA-224 days (167-285); the EMA-364 days (330-418); and ANVISA-403 days (276-636) (p < 0.00001 for the FDA to the EMA and the FDA to ANVISA). The difference between submission dates among the agencies was as follows: EMA-FDA: 24 days (0-85); ANVISA-FDA: 255 (114-632); and ANVISA-EMA: 260 (109-645). The difference in approval dates between the agencies was as follows: EMA-FDA: 185 days (59-319); ANVISA-FDA: 558 (278-957); and ANVISA-EMA: 435 days (158-918). CONCLUSIONS: New oncologic drugs are submitted to the FDA and EMA for approval on similar dates; however, the longer appraisal period by the EMA pushes the approval date for Europe to approximately 6 months later. The same steps at ANVISA delay the approval by 1.5 years. Such procedures cause a significant difference in available medications between these regions.

Efficient analysis of adverse drug events and toxicological mechanisms of newly marketed drugs by integrating pharmacovigilance and network toxicology: selumetinib as an example.

Objective: To integrate pharmacovigilance and network toxicology methods to explore the potential adverse drug events (ADEs) and toxic mechanisms of selumetinib, and to provide a reference for quickly understanding the safety and toxicological mechanisms of newly marketed drugs. Methods: Taking selumetinib as an example, this study integrated pharmacovigilance methods based on real-world data and network toxicology methods to analyze its ADE and its potential toxicological mechanism. First, the ADE reports of selumetinib were extracted from the US Food and Drug Administration (FDA) adverse event reporting system (FAERS), and the ADE signals were detected by reporting odds ratio (ROR) and UK medicines and healthcare products regulatory agency (MHRA) methods. The ADE signals were classified and described according to the preferred terms (PTs) and system organ class (SOC) derived from the Medical Dictionary for Regulatory Activities (MedDRA). The network toxicology method was used to analyze the toxicological mechanism of the interested SOCs. The specific steps included predicting the potential targets of selumetinib using TOXRIC, STITCH, ChEMBL, CTD, SwissTargetPreditcion, and Super-PRED databases, collecting the targets of SOC using GeneCards database, conducting protein-protein interaction (PPI) analysis through STRING database, conducting gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis through DAVID database, and testing the molecular affinity using AutoDock software. Results: A total of 1388 ADE reports related to selumetinib were extracted, and 53 positive signals were detected by ROR and MHRA methods, of which 20 signals were not mentioned in the package insert, including ingrowing nail, hyperphosphatemia, cardiac valve disease, hematuria, neutropenia, etc. Analysis of the toxicological mechanism of six SOCs involved in positive ADE signals revealed that the key targets included EGFR, STAT3, AKT1, IL6, BCL2, etc., and the key pathways included PI3K/Akt pathway, apoptosis, ErbB signaling pathway, and EGFR tyrosine kinase inhibitor resistance, etc. Molecular docking assays showed spontaneous binding of selumetinib to key targets in these pathways. Conclusion: The pharmacovigilance analysis identified some new potential ADEs of selumetinib, and the network toxicology analysis showed that the toxic effects of selumetinib may be related to PI3K/Akt pathway, apoptosis, ErbB signaling pathway, EGFR tyrosine kinase inhibitor resistance and other pathways.

Association between age and onset of daptomycin-induced adverse events using the U.S. food and drug administration adverse event reporting system.

BACKGROUND: Daptomycin is a lipopeptide antibiotic with a broad spectrum of activity against gram-positive bacteria. Although information on daptomycin-induced adverse events can be found in clinical trials, data regarding the impact of age on these events are insufficient. Therefore, we evaluated whether age affects the occurrence of daptomycin-induced adverse events using adverse drug event reports in post-marketing stages provided by the U.S. Food and Drug Administration (FDA). METHODS: A total dataset of 7307 reports of patients treated with daptomycin in the FDA's Adverse Event Reporting System were analyzed. The patients were divided into seven age groups: 0-28 days, >28 days-23 months, 2-11 years, 12-17 years, 18-64 years, 65-80 years, and >80 years. A disproportionality analysis was conducted to calculate the reporting odds ratio, with a 95 % confidence interval. The univariate regression analysis was conducted using the percentage of each adverse event and age groups. RESULTS: Compared with the number of reports aged 18-64 years, there were significantly increased reports of eosinophilic pneumonia in patients aged 65-80 years and >80 years, anaphylactic reaction and pseudomembranous colitis in patients aged 12-17 years, and acute renal failure in patients aged 65-80 years. The regression coefficient for the reporting proportion of eosinophilic pneumonia was significantly positive. CONCLUSIONS: Our findings revealed age-related trends in daptomycin-induced adverse events, supporting the idea that implementing age-dependent follow-up and supportive care helps in the continuation of daptomycin therapy.

Real-world study of adverse events associated with gepant use in migraine treatment based on the VigiAccess and U.S. Food and Drug Administration's adverse event reporting system databases.

Background: This study aimed to investigate the real-world profile of adverse events (AEs) associated with gepant medications in the clinical treatment of migraines by analyzing data collected from the VigiAccess database and the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. As novel migraine therapies, gepants act by targeting the calcitonin gene-related peptide (CGRP) pathway, demonstrating effective control of migraine attacks and good tolerability. Nonetheless, comprehensive real-world studies on the safety of gepants are still lacking, particularly regarding their safety in large populations, long-term use, and potential adverse reactions in specific groups, which necessitates further empirical research. Leveraging these two international adverse event reporting system databases, we systematically gathered and analyzed reports of AEs related to gepant medications, such as rimegepant. Our focus encompasses but is not limited to severe, new, and rare adverse reactions induced by the drugs, as well as safety issues pertaining to the gastrointestinal, cardiovascular, hepatic, and renal systems. Through descriptive statistical analyses, we assessed the incidence and characteristics of AEs, compared AEs among gepants, and uncovered previously unknown AE information, all with the goal of providing a reference for the selection of clinical treatment regimens and AE monitoring. Methods: By extracting all AE reports concerning "rimegepant", "atogepant", and "ubrogepant" from the VigiAccess and FAERS database since its establishment up to 31 March 2024, a retrospective quantitative analysis was conducted. The reporting odds ratio (ROR) method were used to compare AEs among the three gepants. Results: In the VigiAccess and FAERS databases, 23542 AE reports in total, respectively, were identified as being related to gepant medications. Among gastrointestinal system AEs, rimegepant had the greatest proportion and greatest signal strength; nausea was most severe and had the strongest signal in rimegepant AEs, whereas constipation was most prominent and had the strongest signal in atogepant AEs. In skin and subcutaneous tissue disorders, rash and pruritus were more frequently observed with rimegepant, followed by ubrogepant. Alopecia emerged as a novel AE, being more severe in rimegepant and secondarily in atogepant. Regarding cardiac disorders, the three gepants showed comparable rates of cardiac AEs, yet rimegepant exhibited the strongest AE signal. In musculoskeletal and connective tissue AEs, ubrogepant presented the most positive signals for skeletal muscle AEs. Furthermore, among the rare blood and lymphatic system disorder AEs, rimegepant had the highest number of reports of Raynaud's phenomenon and the strongest signal. The study also revealed that while reports of AEs involving liver diseases were scarce across the three gepants, severe AEs were detected in clinical trials, highlighting the need for continued, enhanced monitoring of liver system AEs through large-scale datasets. Conclusion: Gepant medications exhibit similarities and differences in their safety profiles. Analysis of the two databases indicated the presence of AEs across various systems, including gastrointestinal disorders, skin and subcutaneous tissue diseases, musculoskeletal and connective tissue disorders, organ-specific effects, and liver diseases. However, each drug displays distinct incidences and signal intensities for these AEs. Additionally, the study revealed a rare AE in the form of Raynaud's phenomenon. These findings suggest that during clinical use, individualized medication selection and AE monitoring should be based on the patient's physiological condition and specific characteristics.