Expert Opinion on Drug Safety最新文献

Introduction: Antithyroid drugs (ATDs) constitute the treatment option for the management of pregnant women with hyperthyroidism of Graves' disease. The risk of teratogenic side effects to the use of ATDs in pregnancy has challenged the clinical recommendation on the choice of drug and treatment strategy.

Areas covered: Overview and methodological discussion of the evidence gathered within the last 50 years on the teratogenic risk of ATDs based on sources of real-world data (RWD) and different study designs.

Expert opinion: The level of evidence has evolved within the last century and current state of the art points toward a teratogenic role of Methimazole and Carbimazole. On the other hand, evidence to substantiate the teratogenic role of PTU is less comprehensive and less clear. The findings challenge clinical guidance, and uncertainties prevail for recommendations on the choice of ATD and individual patient management in and around early pregnancy. Future research should focus on the combined use of different sources of RWD in large cohorts and across populations. Detailed assessment of exposure and outcome and considerations on other thyroidal and non-thyroidal related factors in the associations observed are important to inform and support the clinical guidance.

Background: This study aimed to investigate the association between phosphodiesterase-5 inhibitors (PDE-5i) and hearing impairment adverse events (HIAEs) while providing an overview of the characteristics of drug-related HIAEs.

Research design and methods: We conducted a detailed pharmacovigilance analysis using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, covering 2004 to 2022. By calculating the reporting odds ratio (ROR) and the information component (IC), we identified signals that indicate the association between PDE-5i use and HIAEs.

Results: Among the 191,398 reports related to PDE-5i, we identified 2,608 cases of HIAEs. Signals were observed for both PDE-5i monotherapy and polytherapy, indicating combinations of drugs. Avanafil exhibited the strongest signal (ROR: 4.35, 95% CI: 2.56-7.41, IC: 2.09, 95% CI: 0.10-3.51), while vardenafil showed the weakest signal (ROR: 2.69, 95% CI: 2.21-3.28, IC: 1.14, 95% CI: 0.74-2.04). Sildenafil had the highest reported cases (ROR: 3.03, 95% CI: 2.82-3.24, IC: 1.57, 95% CI: 1.34-1.80).

Conclusion: These findings highlight a significant correlation between PDE-5i use and HIAEs, emphasizing the need for careful evaluation in clinical practice and providing appropriate guidance to patients before initiating treatment.

Background: Randomized clinical trials have reported some safety profiles in inclisiran, but adverse events in real-world remain insufficient. We aim to evaluate the safety of inclisiran in real-world by collecting the data from the FDA Adverse Event Reporting System database.

Methods: Disproportionality analysis was performed by utilizing both Frequency method and Bayesian method to mine adverse event signals of inclisiran. A positive signal was deemed significant when adverse event met the criteria of the aforementioned methods simultaneously.

Results: We gathered a total of 2309 adverse event reports. Among these cases, adverse events were more common in females and ≥ 65 years age group. After data analysis, 51 positive signals from 11 system organ classes were identified, involving "Musculoskeletal and connective tissue disorders," "General disorders and administration site conditions," "Gastrointestinal disorders," etc. At the preferred term level, the top three frequently reported adverse events were arthralgia, injection site pain and myalgia. We also found some uncommon but significantly strong adverse event signals (bladder discomfort and sinus pain) which should be taken prudently.

Conclusions: In this study, we analyzed the real-world adverse events of inclisiran more comprehensively and reported some new adverse events, hoping that can offer more safety information for clinical medication.

Background: Bosentan is associated with adverse hepatic effects. To minimize such risk, regulators implemented risk minimization measures (RMMs), including testing for liver injury biomarkers (alanine and aspartate transaminase and bilirubin) prior to therapy initiation and monthly throughout therapy. This study aimed to examine the adherence to hepatic monitoring requirements.

Research design and methods: This retrospective cohort study collected data about bosentan new-users from the Real-world Evidence Research Network from 2016 to 2022. We ascertained hepatic tests from laboratory files. Adherence to RMM definition was performing the required tests within 90 days before initiation and categorized adherence to monthly testing requirement based on the expected number of tests throughout therapy as low (<50%), moderate (50-74%), and high (≥75%).

Results: One hundred patients entered the study cohort and 71% were females, with a median age of 25 years. Adherence to testing prior to bosentan initiation was 60%. Adherence to monthly testing was low in the majority of patients (58.2%).

Conclusions: Adherence to bosentan RMMs relevant to minimizing risk of hepatotoxicity either before starting or throughout therapy was low. Our findings could be used as a baseline for monitoring trends in implementation of RMMs over time or to compare performance of various minimization strategies.

Objective: The purpose of this study was to evaluate the pharmacovigilance and clinical characteristics of psychiatric adverse events(AEs) related to Fluoroquinolones(FQs), and to determine the risk factors for timely management.

Methods: Data about AE reporting comes from the FDA Adverse Event Reporting System (FAERS) database, which was used for pharmacovigilance assessments. In addition, we also analyzed the cases of psychiatric AEs related to FQs retrospectively.

Results: Both of the FAERS database analysis and literature reports show that the proportion of FQs-related psychiatric AEs reported in females were higher (51.11% VS 33.44% and 53.23% VS 46.77%). Both of them show that the proportion of psychiatric AEs caused by FQs was higher in the age groups of 19-44 (28.08% and 40.32%) and 45-64 (28.17% and 25.81%). Most psychiatric AEs occurred within 10 days after FQs administration. Literature shows that 67.74% of the psychiatric AEs disappeared within 3 days after drug withdrawal (some cases were accompanied by other drug).

Conclusion: Psychiatric AEs caused by FQs are serious, and there are many important safety signals that have not been mentioned in the label or previous studies. It is very important to identify and manage psychiatric AEs in time for the safe use of FQs.

Background: In this study, physicians' awareness of phytovigilance and their knowledge of safety processes for herbal products were evaluated for the first time in Türkiye.

Research design and methods: A descriptive quantitative study was conducted using face-to-face interview techniques with physicians working in a training and research hospital in Türkiye. A total of 268 (35.2%) questionnaires with appropriate data quality were analyzed with IBM SPSS Statistics 23.0. The factors that had the strongest effect on phytovigilance awareness were determined by binary logistic regression analysis. Values of p < 0.05 were accepted as statistically significant.

Results: The survey results revealed that 45.5% of physicians were aware of the concept of phytovigilance. Physicians who knew that adverse effects were reported due to the use of herbal products, physicians who asked about the use of herbal products while taking their patients' medical history, and specialist physicians had higher awareness of the concept of phytovigilance. Only 30.2% of participants were aware that feedback on adverse reactions from herbal products was being collected and only 27.2% were aware that there was a phytovigilance contact point in the hospital.

Conclusion: The awareness of physicians regarding phytovigilance should be increased. Physicians should ask about the use of herbal products while taking medical history, identify possible adverse effects associated with herbal products, and provide feedback.

Background: Finerenone was approved for the treatment of type 2 diabetes patients with chronic kidney disease. However, the post-marketing safety of finerenone in the real world is unknown.

Methods: The quarterly reported data related to finerenone from the third quarter of 2021 to the second quarter of 2023 were collected by using the FAERS database. Two disproportionality analysis methods were estimated by using Reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN).

Results: A total of 1067 adverse events (AEs) were included. Twenty-four kinds of system organ classes (SOCs) were classified for the organs and systems involved and 39 AEs with significant safety signals were identified using ROR and BCPNN at the preferred terms (PTs) level. Most AEs originated from the United States, and the median time to onset of AEs was 13 days. Three hundred and fifty-one (55.5%) reported serious outcome. The proportion of medication combinations was 29.0%. The most commonly reported AEs were the glomerular filtration rate decreased. Safety signals have also been observed in new and unexpected AEs.

Conclusion: The analysis of the AE signals may contribute to minimizing the risks associated with its use.

Background: Intravesical chemotherapy and immunotherapy are common adjuvant treatments for non-muscle invasive bladder cancer post-surgery. Analyzing adverse events linked to these therapies, can assist in clinical decision-making and risk assessment.

Study design and methods: Disproportionality analysis was conducted to analyze data from the Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the first quarter of 2024, exploring potential positive signals between Bacillus Calmette-Guérin, mitomycin-C, epirubicin, gemcitabine, and adverse events.

Results: The database retrieved 2018, 140, 31, and 85 adverse event reports associated with Bacillus Calmette-Guérin, mitomycin-C, epirubicin, and gemcitabine, respectively. Adverse reactions not mentioned in the label, such as aortic aneurysm and ocular congestion, were observed in preferred term level related to Bacillus Calmette-Guérin. Mitomycin-C exhibited specificity in skin and subcutaneous tissue diseases not reflected in the package insert. Gemcitabine-induced adverse drug reactions showed signals in vascular and lymphatic diseases meeting the screening criteria of all 4 indicators, with capillary leakage syndrome being the preferred term with the highest signal intensity.

Conclusion: This study observed new adverse event signals, providing important assistance for drug selection in adjuvant therapy for non-muscle invasive bladder cancer postoperatively.

Background: To investigate the pharmacovigilance (PV) and make pairwise comparisons on reporting proportion, seriousness, and severity of outcomes of major adverse cardiovascular events (MACE) among poly(ADP-ribose) polymerase-inhibitors (PARPis) in treating ovarian cancer, fallopian tube carcinoma, and primary peritoneal cancer (collectively named EOC) from the US Food and Drug Administration Adverse Event Reporting System (FAERS).

Research design and methods: Data on adverse cardiovascular events reports related to EOC treatment submitted to FAERS from the first quarter of 2015 to the second quarter of 2023 were harvested. Three PARPis were identified: olaparib, niraparib, and rucaparib.

Results: Eventually, a total of 258,596 eligible records were enrolled with 12,331 reports including 5,292 reports of MACE and 7,039 reports of other cardiovascular events. For the primary composite endpoint, a PV signal associated with MACE was detected in niraparib (ROR = 1.12; IC₀₂₅ = 0.03), whereas it was not detected in olaparib and rucaparib; For the secondary endpoint, PV signals associated with other cardiovascular events were detected in niraparib (ROR = 1.17;IC₀₂₅ = 0.04), but not in olaparib and rucaparib.

Conclusions: For EOC patients, close monitoring of blood pressure, heart rate, and coagulation function should be conducted when selecting niraparib for treatment.