Expert Opinion on Drug Safety最新文献

Background: Ivabradine is primarily indicated for patients with sinus rhythm and a heart rate ≥ 75 beats/min, who have NYHA class II-IV chronic heart failure with systolic dysfunction. There is currently a lack of large-scale, real-world studies concerning its drug adverse reactions.

Research design & methods: This research assesses the side effects of ivabradine by analyzing reports of adverse events (AEs) from the FDA's Adverse Event Reporting System (FAERS) database. To evaluate the importance of these AEs, four sequential analytic strategies were utilized.

Results: In total, 2,701 ivabradine-related AE reports were identified in the FAERS database. We identified 26 ivabradine-induced AEs, each with more than 20 reports, including some significant AEs not mentioned on the product label. The timing of AEs was also analyzed, with the majority of AEs occurring within the first month of ivabradine use. Gender-specific analysis indicates that female have a higher risk of AEs, such as off-label use, tachycardia, drug effectiveness for unapproved indications, and rash compared to male.

Conclusion: This study provides important information for maximizing the usage of ivabradine, increasing its efficacy, and reducing any possible negative effects. The actual clinical use of the medication will be greatly aided by this knowledge.

Background: The sodium-dependent glucose transporters 2 inhibitors (SGLT-2i) is associated with body weight loss but the composition of the losing weight remains unclear.

Research design and methods: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi- item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of SGLT-2i-associated musculoskeletal and connective tissue disorders AEs.

Results: The search retrieved a total of 3,206 cases of musculoskeletal and connective tissue disorder-related AEs during the reporting period. This included 1,061 cases for Canagliflozin, 1,052 cases for Dapagliflozin, 1,074 cases for Empagliflozin, and 19 cases for Ertugliflozin. Fifteen preferred terms (PTs) with significant disproportionality were retained. No musculoskeletal and connective tissue system-related AE signals were reported for Ertugliflozin. We identified a risk of muscle necrosis with Canagliflozin use, a risk of sarcopenia with Dapagliflozin use, and a chance of muscle atrophy with Dapagliflozin and Empagliflozin prescriptions. Most cases occurred within the first month after SGLT-2i initiation, and AEs can persist beyond 360 days of use.

Conclusions: Our study identified potential new musculoskeletal and connective tissue disorder-related AE signals associated with SGLT-2 inhibitors.

Background: Fluorouracil (5-FU) is widely used to treat metastatic colorectal cancer (mCRC), but real-world safety data is limited. Our study aimed to evaluate 5-FU's safety profile in a large mCRC population using the FAERS database.

Research design and methods: We conducted disproportionality analyses to identify adverse drug events associated with 5-FU use in mCRC patients from 2004 to 2023. Subgroup analyses, gender difference analyses, and logistic regression were also performed.

Results: We identified 1,458 reports with 5-FU as the primary suspected drug, with males accounting for 48.8% of reports. Gastrointestinal disorders were the most common adverse event (864 cases), while pregnancy-related conditions showed the strongest signal intensity (ROR = 2.97). We found 19 preferred terms with positive signals, including ischemic hepatitis (ROR = 59.32), blood iron increased (ROR = 59.32), and stress cardiomyopathy (ROR = 51.94). Males were more susceptible to weight loss and skin toxicity. Most adverse events occurred within the first month of 5-FU administration.

Conclusion: Our study provides a comprehensive analysis of 5-FU's safety profile in mCRC patients, helping healthcare professionals mitigate risks in clinical practice.

Introduction: Despite the public health success of vaccination, there is an ongoing need to build public confidence in vaccines and improve systems to monitor safety while maintaining data security and patient privacy. African countries face multiple challenges in establishing systems for vaccine pharmacovigilance as was demonstrated during COVID-19 mass vaccination. We provide a framework for the development of pharmacovigilance using the COVID-19 vaccination rollout as an exemplar.

Areas covered: We describe the pre-COVID-19 vaccine pharmacovigilance systems in Southern Africa and propose improvements based on our experience of COVID-19 vaccine rollout in South Africa where we implemented systems to evaluate real-world safety and effectiveness of COVID-19 vaccinations. By conducting a PubMed review of the literature on pharmacovigilance with a focus on Africa and from guidance emanating from the World Health Organization (WHO), we evaluate challenges and opportunities to improve pharmacovigilance in our setting.

Expert opinion: There are ongoing efforts to improve pharmacovigilance on the African continent with improved coordination at a national level with the support of the WHO, the national regulatory authorities, and national departments of health. COVID-19 vaccine rollout provided an opportunity to improve pharmacovigilance by integrating national vaccine platforms with active and passive surveillance including hospital and death registries.

This study investigated the patterns of hematological adverse events related to daptomycin (DAP), tigecycline (TIG), vancomycin (VAN) and linezolid (LIN) in the FDA Adverse Event Reporting System (FAERS). Adverse event associations were analyzed through calculating reporting odds ratio (ROR), proportional reporting ratio (PRR), multiple gamma Poisson shrinkage (MGPS), and Bayesian confidence propagation neural network (BCPNN). A comprehensive descriptive analysis was also conducted considering factors such as age, gender, daily dose, cumulative dose, and time to onset. The leading hematologic adverse events were eosinophilia for daptomycin, coagulation abnormalities and thrombocytopenia for tigecycline, thrombocytopenia, neutropenia, and anemia for linezolid, and thrombocytopenia, eosinophilia, and neutropenia for vancomycin. Most of the affected patients were over 55 years old. Daily doses for the tigecycline and daptomycin groups exceeded the standard daily dose. The times to onset were 14.00 days for daptomycin (interquartile range [IQR], 4.00-21.00), 6.00 days for tigecycline (IQR, 2.00-9.00), 10.00 days for linezolid (IQR, 4.00-16.5), and 10.00 days for vancomycin (IQR,5.00-20.00). It is essential to intensify early monitoring and identification of these adverse events, especially in the context of off-label dosages and for elderly patients and individuals taking medication for over one week.

Introduction: People with severe mental illness have poor cardiometabolic health. Commonly used antidepressants and antipsychotics frequently lead to weight gain, which may further contribute to adverse cardiovascular outcomes.

Areas covered: We searched MEDLINE up to April 2023 for umbrella reviews, (network-)meta-analyses, trials and cohort studies on risk factors, prevention and treatment strategies of weight gain associated with antidepressants/antipsychotics. We developed 10 clinical recommendations.

Expert opinion: To prevent, manage, and treat antidepressant/antipsychotic-related weight gain, we recommend i) assessing risk factors for obesity before treatment, ii) monitoring metabolic health at baseline and regularly during follow-up, iii) offering lifestyle interventions including regular exercise and healthy diet based on patient preference to optimize motivation, iv) considering first-line psychotherapy for mild-moderate depression and anxiety disorders, v)choosing medications based on medications' and patient's weight gain risk, vi) choosing medications based on acute vs long-term treatment, vii) using effective, tolerated medications, viii) switching to less weight-inducing antipsychotics/antidepressants where possible, ix) using early weight gain as a predictor of further weight gain to inform the timing of intervention/switch options, and x) considering adding metformin or glucagon-like peptide-1 receptor agonists, or topiramate(second-line due to potential adverse cognitive effects) to antipsychotics, or aripiprazole to clozapine or olanzapine.

Background: Interleukin-6 (IL-6) monoclonal antibodies are commonly acknowledged for their efficacy in managing coronavirus disease 2019 (COVID-19); however, there remains a paucity of comprehensive studies on their potential adverse effects.

Research design and methods: This is a retrospective pharmacovigilance investigation. We employed FAERS using OpenVigil FDA to detect adverse reactions linked to the interleukin-6 antagonist tocilizumab and sarilumab.

Results: Completely 67,976 reports were identified as 'primary suspected (PS)' adverse events (AEs) for tocilizumab, and 12,560 reports for sarilumab. 109 significant disproportionality preferred terms (PTs) of tocilizumab and 158 PTs of sarilumab were retained. A higher incidence of adverse reactions occurred in females aged 45-64 years, with a higher rate of subsequent hospitalization. Both drugs exhibited adverse reactions consistent with previously reported side effects, such as leukopenia, elevated liver enzymes, and hypercholesterolemia. Additionally, there was a strong correlation with gastrointestinal issues. Unexpected significant adverse events, including diabetes, fluctuations in blood pressure, drug ineffectiveness, malignancies, and disorders of the nervous system, were also observed. Gender and age differences existed in AEs signals related to IL-6RAs.

Conclusion: Our study identified significant new AE signals for interleukin-6 receptor antagonists, potentially supporting clinical monitoring and risk identification for this class of drugs.

Background: This study aims to evaluate the relationship between voriconazole (VRC) and central nervous system (CNS) toxicity based on the real world data.

Research design and methods: The reports of FAERS from January 2004 to March 2022 were included in our study. The CNS toxicity events were identified by using Medical Dictionary for Regulatory Activities terms. Reporting odds ratios corresponding to 95% confidence intervals were employed to quantify the signals of VRC-associated CNS events.

Results: The overall RORs (95%CI) for psychiatric disorders, nervous system disorders, and eye disorders were 1.84 (1.70, 2.00), 1.09 (1.01, 1.18), and 3.84 (3.48, 4.23), respectively (p < 0.05). The median time to the CNS events of VRC was 1(IQR 0-5) day. Top six signals were macular opacity, chloropsia, scintillating scotoma, toxic optic neuropathy, corneal bleeding, and dyschromatopsia, all of them grouped as eye disorders. Compared with itraconazole, fluconazole, posaconazole, and isavuconazole, VRC shows significant relationship and higher incidence rate of psychiatric disorders, nervous system disorders, and eye disorders, respectively (p < 0.05).

Conclusions: VRC was significantly associated with the CNS toxicity. Dosing adjustment, model-based individualized treatment project, and the therapeutic drug monitoring-guided individualized medication regime could be good strategies for efficacy improvement and the adverse events of reducing of VRC.

Background: This study aims to analyze the adverse event reports (AERs) to vericiguat using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) and provide evidence for the clinical use.

Methods: AERs due to vericiguat from 2021Q1 to 2024Q1 identified as the primary suspect were screened, with duplicate reports subsequently eliminated. Various quantitative signal detection methods, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and multi-item gamma poisson shrinker, were then employed for data mining and analysis. Signal strength is represented by the 95% confidence interval, information component (IC), and empirical Bayesian geometric mean (EBGM).

Results: A total of 617 vericiguat-related AERs were identified. Strong signals were observed in 21 system organ classes. Furthermore, the most frequently reported preferred terms (PT) was hypotension (n = 86, ROR 25.92, PRR 24.11, IC 4.59, EBGM 24.07), followed by dizziness (n = 52, ROR 6.44, PRR 6.20, IC 2.63, EBGM 6.20), malaise (n = 25, ROR 3.59, PRR 3.54, IC 1.82, EBGM 3.54), blood pressure decreased (n = 23, ROR 20.00, PRR 19.64, IC 4.29, EBGM 19.61), and anemia (n = 21, ROR 6.67, PRR 6.57, IC 2.72, EBGM 6.57).

Conclusions: This study extended the adverse reactions documented in the FDA instruction and provided supplementary evidence regarding the clinical safety of vericiguat.

Background: The safety of neonatal sildenafil use remains uncertain. This study aimed to investigate adverse events (AEs) associated with sildenafil use in neonates.

Research design and methods: We collected data on AEs associated with sildenafil use in neonates from the US Food and Drug Administration Adverse Event Reporting System database, spanning from its inception of the database in 2004 to 2023. Disproportionality measures were employed to analyze the correlation between AEs and sildenafil.

Results: Sildenafil was identified as the primary suspect drug in 75 AE reports, involving 214 AEs. Three system organ classes, namely, eye disorders, hepatobiliary disorders, and vascular disorders were associated with sildenafil use. Six preferred terms, namely, flushing, retinopathy of prematurity, hyperbilirubinemia, pulmonary hemorrhage, hypotension, and diarrhea were associated with sildenafil use. Notably, hyperbilirubinemia and pulmonary hemorrhage were previously unreported AEs associated with sildenafil use.

Conclusion: The results highlight the ongoing uncertainty surrounding the safety of neonatal sildenafil use and provide vital support for risk monitoring and identification in neonates receiving sildenafil. Additionally, the study underscores the need for continuous safety surveillance in neonates treated with sildenafil and suggests further exploration of the precise causal relationships between AEs and sildenafil.