Expert Opinion on Drug Safety最新文献

Background: Antibody-drug conjugates (ADCs) have demonstrated remarkable therapeutic efficacy in refractory cancers, however, ophthalmotoxicity remains a serious concern. This study aimed to investigate the association between ADCs and ophthalmotoxicity.

Research design and methods: A retrospective pharmacovigilance study was conducted utilizing data extracted from the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) from 2004 to 2023. Disproportionality analyses were performed using the reporting odds ratio (ROR) and information component (IC), with sensitivity analyses and subgroup evaluations by age and sex.

Results: A total of 1992 cases of ophthalmotoxicity linked to ADCs were identified, with a median latency of 40 days. The correlation between ophthalmotoxicity and ADCs was higher than with other medications (IC = 0.67, 95% CI:0.64-0.70). Signal detection revealed 36 adverse events unreported in product labeling. Sensitivity analyses confirmed the robustness of our results on the association between ADCs and ocular toxicity, with higher reporting in females compared to males (OR = 1.25, 95% CI: 1.11-1.40).

Conclusions: ADCs had different profiles of ophthalmotoxicity. Our pharmacovigilance study suggested increased reporting of ophthalmotoxicity associated with ADCs.

Background: Fluconazole, a widely used antifungal agent, has been associated with various adverse events (AEs). This study aimed to analyze the safety profiles of fluconazole using the FDA Adverse Event Reporting System (FAERS) database to provide insights for its safe use.

Research design and methods: Fluconazole-related AEs from 2004 to 2024Q2 were extracted from the FAERS database. The Reporting Odds Ratio (ROR) method was employed to detect and analyze safety signals. Additionally, the impact of COVID-19 on fluconazole safety was also examined.

Results: A total of 7,720 AEs were identified, with 40.3% being serious. The most common AEs involved skin, gastrointestinal, and administration site reactions. High doses of fluconazole were linked to increased teratogenic risks. Weekly dosing regimens and doses below 200 mg/day were associated with fewer severe AEs. During the COVID-19 pandemic, there was a notable rise in reports of drug inefficacy and hepatic/renal damage. Additionally, 45 new adverse reactions were identified. Conclusions: The study highlights the importance of monitoring liver, kidney, and cardiovascular functions during fluconazole use, especially in high-risk populations. The findings underscore the need for careful dosing and consideration of drug interactions, particularly during the COVID-19 pandemic, to ensure safe and effective use of fluconazole.

Background: Adverse events (AEs) suspected to be associated with the three FDA approved medications (eluxadoline, rifaximin, and alosetron) for diarrhea-predominant irritable bowel syndrome (IBS-D) were examined.

Research design and methods: We analyzed all reports in the FDA Adverse Event Reporting System (FAERS) database from each medication's date of FDA approval through 30 June 2024. Reports were excluded if they contained other suspected medications or had a reason for use outside of IBS and/or diarrhea.

Results: Eluxadoline was associated with 1,002 AEs, most commonly abdominal pain (n = 257, 17.0%) and uniquely pancreatitis (n = 174, 11.5%) and sphincter of Oddi dysfunction (n = 39, 2.6%). Rifaximin was associated with 652 AEs, most commonly abdominal pain (n = 64, 7.6%) and uniquely C.difficile and bacterial overgrowth (n = 3, 0.4% each). Alosetron was associated with 3,832AEs, most commonly constipation (n = 2,007, 23.1%) and uniquely colitis (n = 235,2.7%), ischemic colitis (n = 140, 1.6%), obstruction (n = 110, 1.3%), and perforation (n = 26, 0.3%).

Conclusions: Our analysis of the FAERS database showed frequent reports of abdominal pain, constipation, and nausea/vomiting related to the three FDA approved medications for IBS-D. Each raised concerns for distinct and serious AEs including pancreatitis (eluxadoline), C.difficile infection (rifaximin), ischemic colitis (alosetron), and intestinal obstruction/perforation (alosetron).

Background: Cidofovir, an antiviral drug used to treat cytomegalovirus retinitis in AIDS patients. While effective against several viruses, cidofovir's nephrotoxicity and other adverse events (AEs) limit its broader use. This study aims to evaluate the AE profile of cidofovir using data from the FAERS database.

Research design and methods: An analysis of FAERS data from the first quarter of 2004 to the fourth quarter of 2023 was performed. Signal detection was conducted using four algorithms: ROR, PRR, BCPNN, and EBGM. Data were categorized by system organ classes (SOCs) and preferred terms (PTs), and the strength of association between cidofovir and AEs was assessed.

Results: 1,874 AE reports involving 1,266 patients were identified. 'Renal and urinary disorders,' 'Infections and infestations,' and 'Immune system disorders' were the most frequently reported SOCs, with the highest signal detected for 'Renal and urinary disorders.' Off-label use was the most common PT, highlighting the importance of controlling the indication of medication in clinical practice.

Conclusion: This study identified significant signals related to cidofovir, suggesting that clinicians should carefully monitor patients, especially when using cidofovir for off-label purposes to mitigate potential risk outcomes. Further research is needed to optimize the safe and effective use of cidofovir.

Background: Relugolix and degarelix are gonadotropin-releasing hormone antagonist. However, the cardiac safety of relugolix and degarelix in the real world remains uncertain. The purpose of this study was to explore the potential association of relugolix and degarelix with cardiac adverse events (AEs).

Methods: We queried the FAERS database and selected AE reports with relugolix or degarelix as the first suspected drug for analysis. Reporting odds ratio (ROR) and empirical Bayes geometric mean (EBGM) were used to quantify the association between relugolix and degarelix and cardiac AEs.

Results: A total of 5,598 and 372 AEs were reported for relugolix and degarelix, respectively, with 235 and 56 being cardiac AEs. The cardiac AEs associated with relugolix and degarelix predominantly occurred in elderly patients (>65 years). Disproportionality analysis showed that relugolix was significantly associated with electrocardiogram/heart rate abnormality and palpitations, with the strongest signal for electrocardiogram abnormality (ROR = 77.54, EBGM = 68.64). While degarelix was significantly associated with cardiac failure, myocardial Infarction, and arrhythmia, with cardiac failure showing the strongest signal (ROR = 8.62, EBGM = 97.71).

Conclusions: There are differences in the types of cardiac adverse events induced by relugolix and degarelix. Clinicians should consider their differences and enhanced electrocardiogram monitoring when prescribing GnRH antagonists to their patients.

Background: This study aims to systematically evaluate adverse events (AEs) associated with hydrocortisone through the FDA Adverse Event Reporting System (FAERS) database.

Research designs: AE reports associated with hydrocortisone from Q1 2014 to Q4 2023 were extracted from the FAERS database. Multiple disproportionality analysis techniques, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM), were employed for signal detection. In addition, we also analyzed the time to onset of AEs.

Results: Analysis of 7,532 hydrocortisone-associated AEs from the FAERS database revealed significant signals across multiple system organ classes. The strongest associations were found in endocrine disorders (ROR: 13.39), ear and labyrinth disorders (ROR: 3.05), and immune system disorders (ROR: 2.17). Additionally, the study uncovered unexpected AEs such as splenic peliosis and lymphoid tissue hypoplasia. 63.9% of the AEs occurred within 7 days of treatment.

Conclusions: Based on disproportionality analysis of FAERS data, this study provides new insights into the safety of hydrocortisone in the real-world setting. Future prospective studies should be conducted to validate the findings of this investigation.

Background: Bevacizumab combined with FOLFOX improves outcomes in metastatic colorectal cancer (mCRC), but comprehensive safety evaluations remain limited.

Research design and methods: We analyzed adverse drug reactions (ADRs) in the FDA Adverse Event Reporting System (FAERS), comparing FOLFOX monotherapy (366 reports), combination therapy (517 reports), and bevacizumab monotherapy (1,604 reports). Disproportionality analysis using ROR, PRR, BCPNN, and EBGM identified significant ADRs.

Results: Twenty-one ADRs were significantly associated with FOLFOX-bevacizumab combination therapy, predominantly infections (e.g. febrile infection) and gastrointestinal disorders (e.g. anastomotic leak, ulcerative gastritis). The combination exhibited comparable but fewer ADRs than monotherapies, excluding pneumothorax and hypertension. Certain ADRs showed higher incidence and shorter median onset time (3 days post-treatment).

Conclusions: Combination therapy demonstrates manageable safety with early monitoring, though stricter criteria for ADR detection may overlook rare events. Key risks align with monotherapy profiles, emphasizing vigilance for infection-related and gastrointestinal complications. Further studies are warranted to validate these pharmacovigilance findings.

Background: EGFR and HER2 dual TKIs have been approved for the treatment of advanced breast cancer in patients who are HER2-positive for second and/or third-line treatment. However, there is a lack of attention to the cardiovascular adverse events (AEs) caused by EGFR and HER2 dual TKIs.

Research design and methods: We analyzed data spanning between March 2007 and June 2024 using the FAERS database and the reporting odds ratio, proportional reporting ratio, and Bayesian confidence propagation neural network to perform disproportionality analysis.

Results: Compared with non-cardiovascular AEs, cardiovascular AEs were associated with more severe clinical outcomes, such as higher rates of hospitalization, life-threatening events, disability, and death. Our analysis revealed that lapatinib had a higher-than-expected reporting rate for three SMQs, including cardiac failure, embolic and thrombotic events, and cardiomyopathy. No significant cardiovascular signals were observed for neratinib.

Conclusion: Disproportionality analysis results revealed a positive signal for cardiac failure, embolic and thrombotic events, and cardiomyopathy of lapatinib, and no positive signal for neratinib. We should pay attention to high-risk signals in clinical practice and monitor them appropriately.

Background: Type Ib MET Tyrosine Kinase Inhibitors (TKIs), such as capmatinib, tepotinib, and savolitinib, are used to treat MET-amplified and MET exon 14 deletion mutant non-small cell lung cancer. This pharmacovigilance study analyzed data from the FDA Adverse Event Reporting System (FAERS) between September 2014 and March 2024 to assess adverse events (AEs) for these FDA-approved drugs.

Research design and methods: We conducted a systematic search of AEs using MedDRA SMQs by SOC and PT, and performed disproportionality analysis to identify safety signals, calculating ROR, PRR, EBGM, and IC.

Results: The analysis identified significant safety signals: capmatinib showed signals for ear and labyrinth disorders, neoplasms, general disorders, and hepatobiliary disorders; tepotinib for renal and urinary disorders, ear and labyrinth disorders, metabolism and nutrition disorders, and general disorders; savolitinib for hepatobiliary disorders. Key PT signals included protein deficiency, scrotal edema, and chylothorax for capmatinib; edema and decreased blood albumin for tepotinib; and abnormal hepatic function for savolitinib.

Conclusion: The study highlights differences in the safety profiles of Type Ib MET TKIs, underscoring the need for further regulatory review and possible updates to product labels to better inform clinicians and patients.

Background: Diroximel fumarate (DRF) is an oral fumarate used to treat relapsing forms of multiple sclerosis (RMS). This study comprehensively analyzed the adverse events (AEs) associated with DRF for treating RMS based on data from the FDA Adverse Event Reporting System (FAERS) database.

Research design and methods: This study collected data on AEs associated with DRF treatment of RMS from the FAERS database between 2019 and 2024. We used reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) for signal detection.

Results: This study collected 7,944,554 AE reports, of which 7,868 were associated with DRF. A total of 120 preferred terms (PTs) were included in the analysis, relating to 27 system organ classes (SOCs). This study identified several clinically significant new potential AEs, including decreased immune responsiveness (n = 26, ROR 4.45, PRR 4.45, IC 2.15, EBGM 4.43), female breast cancer (n = 50, ROR 4.07, PRR 4.07, IC 2.02, EBGM 4.05), transient blindness (n = 19, ROR 7.27, PRR 7.26, IC 2.85, EBGM 7.21) and others.

Conclusions: Our study identified several potentially important AEs that were not mentioned in the DRF instructions. However, further epidemiologic studies are needed to validate these findings.