Expert Opinion on Drug Safety最新文献

Introduction: Pharmacovigilance (PV) plays a vital role in post-marketing surveillance of drug safety; however, traditional methods are hindered by underreporting, data heterogeneity, and delayed signal detection. Artificial Intelligence (AI) has been increasingly employed to overcome these shortcomings through automation, advanced pattern recognition, and multimodal fusion of patient data.

Areas covered: The regulatory acceptance of these systems rests on explainability, transparency, and auditability, which necessitate the inclusion of explainable AI (XAI) methods. This review thoroughly examines the international regulatory environment for AI in PV and suggests using Shapley Additive Explanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) to build regulatory trust. Research materials, including official guidelines and publications, were systematically sourced from authoritative regulatory websites in the US, Europe, and India, as well as from major academic databases such as Google Scholar, ScienceDirect, and PubMed.

Expert guidance: The EU AI Act classifies PV algorithms as 'high-risk,' imposing strict requirements for human oversight and transparency, aligning with the FDA's GMLP and India's Responsible AI principles. The review emphasizes traceability and governance, recommending convergence with human oversight into a regulatory-fit XAI framework to maximize safety signal detection and foster international trust in AI-based decision-making.

Introduction: Hormonal therapy is the cornerstone of long-term endometriosis management, especially for women deferring surgery. In patients with comorbid migraine - a common, disabling condition - therapeutic choices must balance efficacy with neurological and vascular safety.

Areas covered: This review summarizes hormonal therapies for endometriosis with a focus on safety in migraineurs. A comprehensive literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library up to March 2025.

Expert opinion: Combined hormonal contraceptives (CHCs) and progestins remain first-line options for treating endometriosis-related pain. CHCs are contraindicated in patients with migraine with aura because of the increased risk of ischemic stroke, while their prescription in migraine without aura should be individualized, considering also the fact that evidence in women with concomitant endometriosis is still limited. Progestins generally show better tolerability and may improve migraine outcomes, despite the occurrence of breakthrough bleeding or mood changes. Gonadotropin-releasing hormone (GnRH) agonists and antagonists are second-line options, providing effective pain control, although their effects on migraine are variable and headaches are a frequent adverse event. Add-back therapy is essential to mitigate hypoestrogenic sequelae, particularly about bone health. Overall, treatment should be individualized according to migraine subtype and vascular risk profile to ensure long-term safety, adherence, and therapeutic effectiveness.

Background: Tafamidis emerged as the first FDA-approved drug for treating termed amyloid fibrils. This study aims to analyze adverse events (AEs) related to tafamidis from the second quarter (Q2) of 2019 to the fourth quarter (Q4) of 2023 from the FDA adverse event reporting system (FAERS) database.

Research design and methods: The AE data related to tafamidis from 2019 Q2 to 2023 Q4 were collected and standardized. Various signal quantification techniques, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker, were employed for analysis.

Results: Among the 8742 AE reports with tafamidis as the primary suspected drug, 180 preferred terms of AEs spanning 27 different system organ classes were identified. Unique adverse events to tafamidis included renal and urinary disorders and ear and labyrinth disorders, with not mentioned in the official drug label. Additionally, uncommon but significantly strong AE signals, such as blood culture positive and acquired hemophilia, were observed. Common AEs with relatively high occurrence rates included death, off-label use, fall, hypoacusis, and dysphagia.

Conclusion: These findings offer valuable insights for optimizing the use of tafamidis and reducing potential side effects, thereby facilitating its safe use in clinical settings.

Background: Reactivation of the hepatitis B virus (HBV) induced by drugs is a commonly overlooked but clinically significant complication, posing risks of treatment interruptions, hepatitis exacerbation, liver failure, and even mortality.

Methods: Disproportionality analyses were conducted on the Food and Drug Administration Adverse Event Reporting System (FAERS) database data spanning from January 2017 to December 2023 to detect drugs posing a risk of HBV reactivation (HBV-R). HBV-R cases were identified using the Medical Dictionary for Regulatory Activities (MedDRA), and drug generic names were ascertained from the DrugBank database.

Results: A total of 2596 adverse event reports (AERs) were found to be related to drug-induced HBV-R.According to the disproportionality analysis, the top five drugs with the highest ROR and PRR were daklinza, vocabria, doxorubicin, sovaldi, and ribavirin. The top 40 drugs causing drug-induced HBV-R can be roughly divided into three categories: anti-tumor drugs, immunosuppressive drugs, and antiviral drugs. Among them, 23 drugs do not explicitly mention the risk of HBV-R in their drug instructions.

Conclusions: It was observed that some pharmaceuticals do not adequately address the risk of HBV-R in their drug documentation. These findings could assist healthcare providers in promptly recognizing drug-induced HBV-R.

Background: Trastuzumab deruxtecan (T-DXd) is a novel generation antibody-drug conjugate. However, current evidence for the safety of T-DXd is mostly limited to clinical trials. Therefore, we mine and analyze adverse events (AEs) caused by T-DXd based on the FAERS database and to provide reference for the safe use of drug in clinical practice.

Research design and methods: AEs associated with T-DXd were analyzed in the FAERS database from December 2019 to December 2023, and four disproportionality methods were combined to identify and evaluate reports.

Results: A total of 4651 AE reports of T-DXd as the 'primary suspect' were collected. The median time to onset of T-DXd-related AEs was 25 days. The proportion of serious AEs was 69.40%. Death (24.19%) accounted for the highest occurrence frequency of clinical serious outcomes. The top three AEs in both frequency and signal intensity were interstitial lung disease. We also found 12 novel AEs not recorded in the drug label.

Conclusion: This study indicate the importance of timely mining and updating information of adverse drug reactions. Drug evaluation should be performed well before using T-DXd, and timely intervention measures should be taken to avoid related injury caused by AEs.

Background: Inclisiran is a novel inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9). This study aimed to explore its safety profiles.

Research design and methods: Reports from FDA Adverse Event Reporting System were collected and analyzed from January 2021 to September 2023. The ROR method was employed to detect safety signals. Comparative analysis was conducted at levels of SOCs, HLGTs, and PTs with other PCSK9 inhibitors.

Results: A total of 136 safety signals were identified, and the majority were novel. In comparison with other PCSK9 inhibitors, inclisiran had a greater number of adverse drug events in 'Gastrointestinal disorders' and 'Infections and infestations.' 'Gastrointestinal symptoms and motility' and 'respiratory and urinary tract infections' are the principal causes for the aforementioned safety issues. Nevertheless, inclisiran demonstrates potential advantages in terms of safety, particularly in 'Eye disorders,' 'Skin and subcutaneous tissue disorders' and 'General disorders and administration site condition.'

Conclusion: Due to distinctive pharmacological mechanism of action, the safety issues of inclisiran merit meticulous consideration. There are some safety profile tendencies that differ from other PCSK9 inhibitors. Therefore, special attention should be paid to its administration in high-risk populations. Additionally, some results remain uncertain, requiring further verification.

Background: Based on real data from the FDA Adverse Event Reporting System (FAERS), we explored and evaluated the adverse reactions (ADRs) of sulfasalazine (SSZ) in the first quarter of 2004-2023 to provide a reference basis and early warning for the safe use of SSZ in the clinic.

Research design and methods: The reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the empirical Bayesian geometric mean (EBGM) were used as measures of SSZ-associated adverse events (AEs) signals, mining for potential positive signals between SSZ and AE.

Results: In this study, a total of 5327 case reports related to SSZ in the last 20 years involving 25 system organ classes (SOCs) were collected in FAERS. The AEs of SSZ were mainly focused on Immune system disorders (n = 1621, IC025 = 2.86), Blood and lymphatic system disorders (n = 638, IC025 = 2.4), and others. In addition, we found 41 adverse reactions not mentioned in the specification, including oculomucocutaneous syndrome (n = 12, IC025 = 4.86), wegener's granulomatosis(n = 6, IC025 = 4.05) and reproductive system aspects.

Conclusion: Significant new AEs signals were observed in this study and may provide important support for clinical monitoring and risk identification in SSZ.

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.