Expert Opinion on Drug Safety最新文献

Introduction: Left atrial appendage occlusion (LAAO) is a viable alternative to anticoagulation for treatment in patients with non-valvular atrial fibrillation (NVAF) who cannot tolerate anticoagulation. Post-procedure patients are generally prescribed oral anticoagulation (OAC) for 45 days, while the device is undergoing endothelialization, following which patients are continued on antiplatelet agents. Recommendations for antithrombotic agents following LAAO arrived by consensus, which are not tolerated by all patients.

Areas covered: This review covers the safety profile of antithrombotic therapy options after LAAO. We discuss the side effect profiles including device-related thrombosis (DRT), bleeding, and thromboembolic events. The new randomized controlled trials and meta-analysis compared combinations of DOAC with single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), VKA, or only SAPT and studied the incidence of major bleeding, DRT, and thromboembolic events. This review is a comprehensive summary of different antithrombotic agents' combinations along with the duration recommendations and emphasizes the importance of a discussion among involved team members and patients.

Expert opinion: In patients with NVAF undergoing LAAO, initial post-procedural antithrombotic monotherapy with DOAC is associated with low rates of thromboembolism, DRT, and major bleeding followed by DAPT. DAPT is associated with lower incidence of thromboembolic events in comparison to SAPT.

Background: Interstitial lung diseases (ILD) is a serious adverse event (AE) associated with antibody-drug conjugates (ADCs). This study aims to delve deeply into the signals of AE associated with ILD linked to ADCs.

Research design and methods: The AE reports were extracted from the first quarter of 2004 to the fourth quarter of 2023 based on the FDA Adverse Event Reporting System (FAERS) database. Signal mining was performed using the reporting odds ratio (ROR) method and the multi-item gamma Poisson shrinker (MGPS) method. Data management, analysis, and visualization were carried out using Python, R software, and MySQL.

Results: A total of 1389 AE reports related to ILD with 11 types of ADCs as the primary suspected drugs were obtained. The age groups most represented were 61-80 age group. ILD-related AE signals were detected for 11 ADCs in the study. Trastuzumab deruxtecan showed the strongest signals in both for ROR and MGPS methods. The median onset time vary from 8 days to 207 days.

Conclusions: The signals of ILD AE associated with ADCs are notably strong. ILD should be closely monitored and assessed in the clinical use of ADCs taking full account of the efficacy and risks of these drugs.

Introduction: Hyperglycemia in pregnancy, including gestational diabetes mellitus (GDM) and pregestational diabetes, significantly impacts maternal and neonatal outcomes, necessitating effective management strategies. Insulin is the first-line therapy; however, adherence barriers, cost, and route of administration challenges have driven interest in oral agents like metformin and glyburide. These agents offer practical alternatives but raise questions about long-term safety and fetal exposure.

Areas covered: This review evaluates the pharmacokinetics, pharmacodynamics, and clinical outcomes of metformin and glyburide, focusing on their roles in GDM, pregestational diabetes, polycystic ovary syndrome (PCOS), and obesity. Maternal outcomes, neonatal impacts, and long-term offspring health were assessed to determine the safety of these therapies.

Expert opinion: Metformin reduces insulin dependency and weight gain during pregnancy but raises concerns about short and long-term offspring impacts, such as increased SGA rates (22% vs. 5%), altered growth patterns, and offspring neurocognition. Glyburide is effective for glycemic control but carries higher neonatal hypoglycemia risks and lacks robust long-term safety data. Both agents hold promise as alternatives to insulin, particularly in resource-limited settings. However, further research is needed to address knowledge gaps, optimize their use, and ensure safe integration into clinical practice.

Introduction: Medical therapy is crucial in the long-term management of endometriosis, and its clinical efficacy must be balanced with a favorable safety profile.

Areas covered: This review aims to provide a comprehensive overview of available drugs for the treatment of endometriosis, with an emphasis on their safety. A literature search was conducted using MEDLINE. EMBASE. and the Cochrane Library. Reference lists of relevant articles and recent book chapters were also examined.

Expert opinion: First-line therapies include combined contraceptives and progestins, both effective in reducing pain. Combined contraceptives commonly cause breakthrough bleeding, nausea, headaches, breast tenderness, and libido changes. Progestins may lead to depression, decreased libido, weight gain, breast tenderness, and lipid alterations. Gonadotropin-releasing hormone agonists are second-line options but are limited by hypoestrogenic side effects, including vasomotor symptoms, urogenital atrophy, and bone mineral density (BMD) loss. Add-back therapy with norethindrone acetate or low-dose combined contraceptives mitigates these effects. GnRH antagonists provide immediate suppression without flare-up and may improve adherence; however, hot flushes and BMD loss remain concerns. While all hormonal therapies are suppressive rather than curative, optimizing safety and tolerability is essential for sustained use and symptom control.

Objective: By analyzing the signal mining of vandetanib AEs, it provides a reference for the rational clinical use of the drug.

Methods: This study provides signal detection and analysis of AEs associated with vandetanib using the FAERS from Q2 2011 to Q1 2023.

Results: Disproportionality analyses were conducted using the ROR and the MHRA method, with AEs categorized and described based on SOC and PT from the MedDRA. A total of 1,721 AEs reports identified vandetanib as the primary suspect. The analyses yielded 187 AEs signals across 20 SOCs categories, with 47 signals not previously reported in the vandetanib labeling. Additionally, the study analyzes factors influencing AEs. The results are as follows: There are significant differences in Investigations based on gender and nationality (p < 0.05); skin and subcutaneous tissue disorders and gastrointestinal disorders exhibit differences based on gender, age, and nationality (p < 0.05).

Conclusion: Common AEs signals identified align with those documented in the drug labeling. However, AEs such as tumor lysis syndrome, skin discoloration, and pigmentary disorders, which are not listed in the labeling, warrant special attention. It is essential that abnormalities in patients' skin and laboratory indicators are closely monitored and addressed promptly to safeguard medication safety.

Background: The primary objective of this research is to conduct an exhaustive evaluation of rimegepant with the Food and Drug Administration Adverse Event Reporting System (FAERS) repository.

Research design and methods: This study downloaded the reporting files related to rimegepant from the second quarter of 2020 to the first quarter of 2024. Disproportionality analysis was utilized to explore the relationship between rimegepant and adverse drug events (ADEs).

Results: This study analyzed 6659 ADE reports associated with rimegepant as the primary suspected (PS) drug. In the disproportionate analysis of system organ classes (SOCs), the significant signal for rimegepant was general disorders and administration site conditions.On the preferred terms level, 35 ADEs were identified following the exclusion. The top five ADEs with high signal strengths were medication overuse headache, nasal edema, tension headache, performance status decreased, and motion sickness. The most frequent ADEs were nausea, feeling abnormal, abdominal pain upper, somnolence, and hypersensitivity. In addition, we need to pay attention to the ADEs not mentioned in the instruction and clinically significant: vertigo, hyperacusis, somnolence, Raynaud's phenomenon, motion sickness, panic attack, and fear.

Conclusions: This study highlights previously unrecognized safety concerns associated with the use of rimegepant. These novel safety aspects suggest that while these treatments can be effective, additional risks may need further exploration.

Introduction: The integration of artificial intelligence (AI) into pharmacovigilance (PV) has advanced rapidly in recent years. AI tools have the potential to transform signal management by enabling faster and more accurate signal management and decision-making. However, the regulatory landscape governing these technologies remains complex.

Areas covered: This article presents available AI tools for signal management, provides an overview of the regulatory landscape of these tools, and explores stakeholder perspectives on the challenges and opportunities posed by AI regulations. On 23 July 2024, we conducted a Google search of the top 2,000 results using the query 'AI pharmacovigilance service provider.' Two searches were performed in Ovid MEDLINE to identify articles published between 1 January 2022, and 23 July 2024, using ad hoc queries.

Expert opinion: AI tools are now available to support all critical activities in signal management. However, regulatory discrepancies and variations persist across different regions. The findings underscore the urgent need for ongoing international collaboration to harmonize regulatory frameworks and ensure the safe and ethical implementation of AI in PV. As AI technologies continue to evolve, addressing these regulatory and operational challenges will be essential to fully realize their potential in enhancing drug safety and improving healthcare outcomes worldwide.

Background: Panitumumab has been extensively applied in antitumor therapy, and the regulation of its adverse drug reactions (ADRs) has become extremely important. This study utilized the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database to extract real-world panitumumab ADR signals and provide relevant information for drug safety.

Research design and methods: ROR, PRR, BCPNN, and MGPS were used to identify real-world ADR signals associated with panitumumab.

Results: Analysis of 9,033 patients identified 263 ADR signals across 20 MedDRA System Organ Classifications. New signals including peripheral sensory neuropathy, gene mutation, decreased neutrophil count, polyneuropathy, ileus, neutropenia, and febrile neutropenia. Age and sex subgroup analyses revealed specific risks, such as polyneuropathy and gene mutation in those under 65 years of age, decreased neutrophil count and peripheral sensory neuropathy in those over 65 years of age, and febrile neutropenia in men. Ileus was highlighted as a novel ADR in gastrointestinal disorders, with no significant age or sex differences.

Conclusion: This study identified new signals of ADR associated with panitumumab, providing valuable information for the clinical use of panitumumab.

Background: The increasing prevalence of statin use for cardiovascular disease management has raised concerns regarding their safety profile, particularly regarding the potential risk of diabetes. Our study aims to analyze diabetic adverse event reports related to statins using a large pharmacovigilance database to provide timely insights into this significant issue.

Methods: We analyzed data from the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2023. Disproportionality analyses were performed to detect signals of diabetic adverse events associated with the three most commonly prescribed statins: atorvastatin, rosuvastatin, and simvastatin.

Results: We identified 11,364 cases of statin-related diabetic adverse events across the three statins. Disproportionality analyses revealed a significant association between these statins and four specific diabetic adverse events: type 2 diabetes mellitus, impaired glucose tolerance, diabetic neuropathy, and diabetic retinal edema. Notable sex differences emerged, with females exhibiting an overall significantly higher propensity for diabetes-related adverse events.

Conclusions: Our study is timely and relevant as it addresses growing concerns about the safety of widely prescribed statins and their association with diabetes. By highlighting these critical issues, the study seeks to contribute valuable insights to practitioners, ultimately guiding better clinical practices and enhancing pharmacovigilance efforts.