Expert Opinion on Drug Safety最新文献

Background: This study evaluated the safety of compounded glucagon-like peptide-1 receptor agonists (GLP-1 RAs) compared to non-compounded formulations using the U.S. FDA Adverse Event Reporting System (FAERS).

Research design and methods: A retrospective analysis of FAERS from 2018 to 2024 examined adverse events (AEs), medication errors, and product quality issues for liraglutide, semaglutide, and tirzepatide. Reporting odds ratios (RORs) with 95% confidence intervals were calculated with adjustment using logistic regression.

Results: Of the 81,078 GLP-1 RA reports in the FAERS database, 707 involved compounded products. Compounded formulations demonstrated higher RORs for abdominal pain (2.84 [2.29, 3.49]), diarrhea (1.59 [1.25, 1.99]), nausea (1.27 [1.05, 1.52]), suicidality (6.34, [4.32, 8.99]), and cholecystitis (3.39, [1.61, 6.31]). Compounded products showed higher RORs of preparation errors (48.92 [12.63, 189.6]), prescribing errors (4.46, [2.49, 7.98]), contamination (19.00, [4.24, 85.03]), and compounding/manufacturing issues (8.51, [5.17, 14.0]), while lower odds of administration (0.29 [0.16, 0.53]) and dosing errors (0.24, [0.17, 0.32]). The hospitalization odds were higher for compounded products (2.35 [1.94, 2.83]).

Conclusions: Compounded GLP-1 RAs may be associated with a higher odds of AEs, safety concerns, and product quality issues compared to non-compounded products. These findings underscore the importance of cautious prescribing, rigorous quality standards, and enhanced patient monitoring.

Background: Drug-induced nephrolithiasis is a recognized complication in clinical practice. The objective of this study is to identify drugs that are significantly associated with an increased risk of inducing nephrolithiasis based on the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Research design and methods: We collected adverse event reports associated with drug-induced nephrolithiasis from the first quarter of 2004 (2004 Q1) to the fourth quarter of 2023 (2023 Q4) in the FAERS database. Subsequently, we applied 4 disproportionality algorithms to evaluate the connection between drugs and nephrolithiasis.

Results: A total of 32,788 adverse event reports related to nephrolithiasis with primary suspected drugs were identified. The 50 drugs with the highest frequency and the 40 drugs with the strongest signal were identified and counted. The most frequently occurring drug was adalimumab, while the antiretroviral drug indinavir exhibited the strongest signal intensity. The labels for many of these drugs did not mention the risk of nephrolithiasis.

Conclusions: This comprehensive pharmacovigilance study has revealed many drugs potentially associated with an increased risk of nephrolithiasis. Notably, vigilant surveillance for nephrolithiasis risk while using these drugs is crucial in clinical practice.

Introduction: The study aimed to comprehensively evaluate the role of direct oral anticoagulants (DOACs) combined with antiplatelet therapy (APT) in acute coronary syndrome (ACS) patients and those with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) or complicating ACS.

Methods: Data were pooled using the Mantel - Haenszel random-effect models. The risk ratio (RR) value and 95% confidence intervals (CI) calculated were applied to dichotomous outcomes.

Results: In 38,170 ACS patients from 11 studies, DOACs combined with APT significantly reduced major adverse cardiovascular events (MACEs), stent thrombosis (ST), ischemic stroke and all-cause death, accompanied by increased bleeding risks compared with control groups. Among 11,175 participants from 6 studies involving AF patients undergoing PCI or complicating ACS, DOACs plus APT markedly reduced bleeding risksin various definitions, with no significant difference in efficacy outcomes compared with control groups.

Conclusions: The combination of DOACs and APT requires a tailored approach. For ACS patients, therapy should center on balancing ischemic and bleeding risks, favoring those at high ischemic risk but low or manageable bleeding risk. In contrast, for AF patients undergoing PCI or complicating ACS, the regimen is aimed at risk minimization and is most suitable for patients in whom this is the primary concern.Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42025645639.

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.

Objectives: Medroxyprogesterone acetate (MPA), a steroid progesterone, is widely used to treat endometriosis, menstrual disorders, and uterine bleeding in clinical practice. However, the safety profile of MPA requires comprehensive evaluation.

Methods: This study performed a retrospective analysis using real-world data extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Case reports from 2003 to 2023 were analyzed using methods like reporting advantage ratio (ROR), proportional report ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and empirical Bayes geometric mean (EBGM).

Results: In the case reports spanning from 2003 to 2023, showed 26,437 adverse events (AEs) related to MPA, mostly in females (25,639). Disproportionality analysis identified 116 ADRs across 19 system organ class (SOC) levels, including expected AEs like 'female breast cancer'(n = 8717) and 'ovarian cancer' (n = 459). Unexpected AEs, such as 'acquired diaphragmatic eventration'(n = 3), were also noted.

Conclusion: Our study identifies potential new and unexpected ADR signals linked to MPA, which align with clinical observations. Additional research is necessary to confirm these associations and address previously unrecognized safety concerns. This research provides a novel and distinctive approach to exploring drug-related AEs.

Background: In recent years, β-blockers such as metoprolol have been upgraded to first-line antihypertensive drugs. However, metoprolol demonstrates poor prognosis effects on diseases such as stroke. Further clinical application may expand the possibility of its related adverse reactions. Currently, there is a lack of comprehensive research on the overall safety of metoprolol.

Research design and methods: Statistical analysis and signal mining were conducted on adverse event reports related to metoprolol obtained from the FAERS database. Signal mining was conducted using the proportional reporting ratio, the report margin method, the bayesian confidence propagation neural network, and empirical Bayesian geometric mean in the measures of disproportionality to detect potential adverse reaction signals.

Results: The results showed 16,853 reports related to metoprolol use, identifying 506 preferred terms (PTs) covering 23 system organ classes (SOCs). In addition, some new potential adverse reactions appeared among the top 30 PTs ranked by signal strength, such as 'orthostatic intolerance' (IC025 = 3.00), 'trigemino-cardiac reflex' (IC025 = 4.30), 'decorticate posture' (IC025 = 3.34), etc. Notably, there was a strong association between 'suspected suicide' (IC025 = 5.59) and the drug signal.

Conclusions: This study identified unexpected signals of serious adverse reactions, suggesting the importance of continuous post-marketing surveillance of metoprolol to understand its potential risks.

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.

Introduction: Obesity is one of the most common chronic conditions that raises the risk of cardiometabolic issues. Because of their ability to encourage weight loss through urine glucose excretion, sodium - glucose cotransporter 2 (SGLT2) inhibitors, which were first approved for the treatment of type 2 diabetes, have become a viable off-label option for managing obesity.

Areas covered: This review examines the safety profile of SGLT2 inhibitors for weight reduction in non-diabetic, overweight/obese adults. A comprehensive search on PubMed, EMBASE, the Cochrane Library, and Scopus (January 2015 - January 2025) for RCTs, systematic reviews, and meta-analyses was performed. It details the potential adverse effects of these medications, including euglycemic ketoacidosis, moderate hypotension, vaginal and urinary tract infections, and worries regarding lower limb amputations and renal function. There are still unknowns about the long-term impacts on cardiovascular outcomes, lipid profiles, and bone health, which emphasizes the need for further extensive, focused studies in non-diabetic individuals.

Expert opinion: SGLT2 inhibitors offer a modest but clinically meaningful avenue for weight management in select individuals. Broader adoption in routine obesity care will likely require further research to clarify benefits versus risks, develop patient-specific treatment algorithms, and ensure robust monitoring of potential adverse events.

Background: Autoimmune encephalitis (AE) is a neuroimmune disorder that presents significant diagnostic challenges. The FDA Adverse Event Reporting System (FAERS) database can help explore the relationship between drugs and AE, but comprehensive studies are lacking. This study aims to analyze the association between drugs and AE using the FAERS database, providing insights for clinical practice and pharmacovigilance.

Research design and methods: Adverse event reports in the FAERS database were analyzed, focusing on the incidence of drug-induced AE, as well as characteristics such as gender and age. Multiple statistical methods were employed to assess the association between drugs and adverse reactions.

Results: The study revealed that drug-induced AE predominantly occurred in individuals aged 41 and above, with a higher prevalence among female patients. Nivolumab and pembrolizumab were among the drugs most frequently reported for adverse drug reactions. However, only a minority of drug labels mentioned these adverse reactions.

Conclusion: This study underscores the potential risk of drug-induced AE, advocating for close monitoring in clinical practice. Further epidemiological investigations are warranted to elucidate the exact relationship between drugs and these disorders. While the FAERS database provides crucial leads for such research, additional studies and validation are necessary.