Expert Opinion on Drug Safety最新文献

Background: Amivantamab has been approved for EGFR exon 20 insertion-mutated non-small-cell lung cancer. The aim of this study was to perform an in-depth analysis of its safety profile.

Research design and methods: Safety reports were collected from the database of the Food and Drug Administration Adverse Event Reporting System from April 2021 to September 2023, and the reporting odds ratio (ROR) method was used to detect potential safety signals. Mobocertinib, an agent with similar properties to amivantamab, served as a control for comparison.

Results: A total of 88 safety signals were detected, most of which were novel. In comparison with mobocertinib, amivantamab appeared to cause more injury, poisoning, and procedural complications (ROR = 15.54, 95% CI 10.25-23.58); respiratory, thoracic, and mediastinal disorders (ROR = 1.92, 95% CI 1.57-2.34); infections and infestations (ROR = 1.39, 95% CI 1.09-1.76); blood and lymphatic system disorders (ROR = 9.57, 95% CI 6.17-14.84); and immune system disorders (ROR = 6.41, 95% CI 3.14-13.12). Moreover, amivantamab was associated with higher risks of thrombosis events, bone marrow suppression, skin and soft tissue infection, deterioration of respiratory symptoms, and noninfectious pneumonitis.

Conclusion: The safety profile of amivantamab requires attention; particularly, monitoring of the adverse drug events described above is necessary during its administration.

Objective: The trastuzumab emtansine, trastuzumab deruxtecan, and sacituzumab govitecan are antibody-drug conjugates (ADCs) that have demonstrated efficacy in the treatment of breast cancer. Nonetheless, these ADCs can also induce severe toxicities in various organ systems, particularly the hematological system. Therefore, this study evaluated the hematological toxicities associated with ADCs in breast cancer based on real-world data.

Methods: Data were extracted from the FDA Adverse Event Reporting System (FAERS) database, spanning from 2014 Q1 to 2023 Q3. Further analysis was done on the hematological toxicities related with ADCs, including their features, onset time, and fatality proportion.

Results: Out of 10,976 adverse event reports, 1895 hematotoxicity reports (17.26%) were analyzed. All ADCs exhibited positive safety signals for hematological toxicities, as indicated by reporting odds ratios and the information component. Unexpected significant adverse events, including splenomegaly, immune thrombocytopenia, hemolytic anemia, and hemolytic anemia, that were discovered in the medication label transpired during our data mining. The median time-to-onset of these toxicities was 13 days (interquartile range [IQR] 7-54.75), and the fatality proportion associated with hematological toxicities and ADCs was 17.41%.

Conclusion: The study indicated that hematological toxicities caused by ADCs preferentially emerge early and may have catastrophic consequences. Early detection and management of these hematological toxicities associated with ADC is essential.

Background: Statin-associated autoimmune hepatitis (AIH) is a rare but potentially life-threatening adverse event. Currently, no studies have investigated the associationbetween AIH and different statins.

Research design and methods: This retrospective analysis of statin-associated AIH utilized the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q1 2024) and a systematic literature review. Disproportionality and Bayesian analyses were used to detect potential AIH signals associated with statin use.

Results: Among 3,581 AIH reports in the FAERS database, 337 (9.41%) were associated with statins. Among all statins, fluvastatin exhibited the strongest signal, with a relative odds ratio (ROR) of 54.85 (95% CI: 32.32-93.10). Stratified analysis revealed stronger signals in patients ≥65 years (ROR 16.83 vs 9.45) and females (ROR 13.88 vs 9.00) compared to patients <65 years and males, respectively. Statins showed a higher risk of AIH compared to evolocumab, and a similar or lower risk when compared to ezetimibe and fenofibrate. Additionally, 30 cases reported in 20 independent studies were summarized.

Conclusion: This study demonstrates a significant association between AIH and the use of statins, particularly among older patients and females. Further research is needed to explore additional risk factors for statin-associated AIH.

Background: The aims of this study were to promote the rational use and supervision of dextromethorphan (DM). This study analyzed serious adverse events such as addiction and mental disorders caused by DM in Shenzhen and the behavioral characteristics of people suspected of abusing DM on the Internet.

Methods: Adverse drug reaction/event (ADR/E) reports from 2017 to 2023 were extracted from the National Pharmaceutical Adverse Reaction Monitoring System database. The sales data from 2017 to 2022 were extracted from an Internet platform of selling DM in Shenzhen. Various signal detection methods were used for retrospective analysis and descriptive analysis.

Results: Signal detection results (ROR = 299830.00, 95%CI = 26475.78 -573,184.22) found a high association between DM abuse and addiction. Dextromethorphan abusers have behavioral characteristics such as low age, long duration of abuse, and withdrawal difficulties. Online sales data showed that the number of purchases (P < 0.01), total doses (P < 0.01), and duration of purchases (P < 0.01) in the suspected abuse group were significantly higher than those in the normal group.

Conclusion: The result is possible to provide more accurate portraits of individuals who were suspected of abusing dexmedetomidine and therefore has significant implications in terms of promoting practices that enable rational use of this medication.

Background: Dry eye syndrome (DES) significantly affects quality of life. Meibomian Gland Dysfunction (MGD) is a primary contributor to DES and may be drug-induced.

Research design and methods: This study analyzed data from the FDA Adverse Event Reporting System (FAERS) between January 2004 and September 2023 using the Ratio of Odds Ratios (ROR) and Proportional Reporting Ratio (PRR) to detect potential drug-induced MGD signals. Drugs were categorized by therapeutic class.

Results: Among 289 MGD cases, the average patient age was 51.69 years, with 65.44% female. MGD reports have increased over time, peaking in 2023, primarily from the United States and Europe. Of 148 drugs, nine showed significant associations with MGD, including those in ophthalmology, oncology, immunomodulation, dermatology, and the urogenital system.

Conclusion: This real-world study identifies drugs potentially linked to MGD, offering valuable insights for drug safety surveillance. These findings support the development of pharmacovigilance strategies and optimized clinical practice to mitigate ocular risks.

Background: This study aims to utilize the FDA's Adverse Event Reporting System (FAERS) for data analysis to explore the potential adverse events associated with Droxidopa in real-world settings, thereby providing reference information for clinical practice.

Methods: Adverse event reports where Droxidopa was the primary suspected drug were collected from the FAERS database from the third quarter of 2014 to the fourth quarter of 2023. Multiple signal quantification techniques were employed, including ROR, PRR, BCPNN, and MGPS.

Results: A total of 19,295 reports directly related to Droxidopa were screened, encompassing 94 Preferred Terms and involving 27 System Organ Classes. In addition to the adverse events already mentioned in the drug's labeling, this study identified new and valuable adverse event signals, such as Gastrointestinal disorders, Infections and infestations, and Musculoskeletal and connective tissue disorders. Notably, Urinary tract infection, Urinary tract infection pseudomonal, and Pneumonia aspiration were associated with Infections and infestations, indicating the need for heightened vigilance when using Droxidopa in clinical settings. These new signals provide a basis and direction for future research.

Conclusion: This study highlights new potential adverse events related to Droxidopa, emphasizing the need for caution, especially concerning Infections and infestations. Further research is warranted to validate these findings.

Background: Adverse events (AE) in dupilumab-induced ocular surface diseases (DIOSD) have raised concerns regarding its safety. The objective of this study was to evaluate DIOSD by employing database analysis and clinical case review, along with mechanism analysis.

Research design and methods: Database AE data were extracted from FAERS from 2017 Quarter 1 (Q1) to 2023 Q1. Disproportionality analyses were performed to identify the risk signals associated with DIOSD. Case reports/case series reported on DIOSD from March 2017 to June 2023 were collected for a literature review. The mechanisms of DIOSD were investigated through disease-gene interaction network analysis.

Results: A total of 85 signals related to DIOSD were detected from FAERS. The most reported AE was 'dry eye' (n = 3503, ROR 20.32, 95% CI: 19.53-21.14). There were 36 articles, including 201 cases showing the evidence of DIOSD, with an average age of 43 years. About 64.18% patients suffered from severe atopic dermatitis, and 48.26% were reported with a previous ocular history. The mechanisms study suggested that tumor necrosis factor plays an important role in DIOSD.

Conclusions: Our findings support that dupilumab use is associated with exacerbation or new-onset OSD. Particular attention should be focused on eye symptoms during dupilumab use.

Background: Gabapentinoids, including gabapentin and pregabalin, are commonly used for neuropathic pain but have safety concerns. This study analyzed U.S. Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) data to assess risks of psychiatric disorders as adverse effects.

Research design and methods: Data from 2004 to 2023 were extracted for disproportionality analysis using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and the Multi-Item Gamma Poisson Shrinker (MGPS) to evaluate the association between gabapentinoids and psychiatric AEs. Kaplan-Meier and log-rank tests assessed the incidence and onset profiles, while chi-square examined mortality and hospitalization rates differences.

Results: Of 174,321 AE reports, 22.67% involved psychiatric disorders. Gabapentinoids increased psychiatric disorder incidence at SOC level, with events like anxiety and suicidal ideation. Differences in incidence and health outcomes between gabapentin and pregabalin were significant (p < 0.05).

Conclusion: There is a correlation between the use of gabapentinoids and psychiatric disorders. Further research is needed into the mechanisms and prevention strategies for these adverse effects.

Introduction: Endometriosis and pelvic inflammatory disease (PID) are gynecological conditions affecting women of reproductive age and causing pain symptoms. The symptoms caused by these conditions are similar; thus, the differential diagnosis may be challenging. The treatment of these conditions is very different because PID is treated with antibiotic therapy, while endometriosis is treated with hormonal therapies suppressing estrogen levels.

Areas covered: A narrative review was conducted through a comprehensive literature search on endometriosis and PID. The search strategy incorporated relevant keywords and MeSH terms related to these topics.

Expert opinion: The antibiotics used to manage PID have high efficacy and safety profiles. Commonly prescribed regimens include a combination of ceftriaxone, doxycycline, and metronidazole. These antibiotics are generally well-tolerated, with most adverse effects being mild and manageable (gastrointestinal disturbances or hypersensitivity reactions). Hormonal therapies are a cornerstone in the management of endometriosis; they include combined oral contraceptives (COCs), progestins, gonadotropin-releasing hormone (GnRH) agonists, and antagonists. COCs and progestins are generally well-tolerated with a favorable safety profile, though they may cause side effects (breakthrough bleeding and mood changes). Oral GnRH antagonists have emerged as a noteworthy option, offering partial estrogen suppression and thereby overcoming the limitations associated with previously used GnRH agonists.