US FDA Adverse Event Research Articles

A real-world study of adverse drug reactions of two isocitrate dehydrogenase inhibitor based on the US FDA adverse event reporting system and VigiAccess databases

A real-world study of adverse drug reactions of two isocitrate dehydrogenase inhibitor based on the US FDA adverse event reporting system and VigiAccess databases

Analysis of tirzepatide in the US FDA adverse event reporting system (FAERS): a focus on overall patient population and sex-specific subgroups

ObjectiveTirzepatide, a novel GIP and GLP1 agonist, has been extensively examined in clinical trials. However, specific data on its adverse drug events (ADEs) remain limited. This study aims to comprehensively assess real-world ADEs associated with tirzepatide by mining data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodsADE reports from the FAERS database were retrieved for the second quarter of 2022 through the first quarter of 2024. Significant associations between ADEs and tirzepatide were evaluated using proportional disproportionality analyses, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinkage (MGPS).ResultsA total of 37,827 ADE reports associated with tirzepatide were identified, with 100 significantly disproportionate preferred terms (PTs) recognized by all four algorithms. The top five PTs with the highest reporting rates were incorrect dose administered, injection site pain, off-label use, nausea, and injection site hemorrhage. Additionally, unexpected signals such as starvation ketoacidosis were identified. The median time to onset for all ADEs was 23 days. Furthermore, sex-specific high-intensity signals were found, with males primarily experiencing gastrointestinal disorders and females experiencing general disorders and administration site conditions.ConclusionThis study provides valuable insights into the occurrence of ADEs following tirzepatide administration, potentially supporting clinical monitoring and risk identification efforts.

Mining and analysis of adverse event signals for alendronate based on the real-world data of FDA adverse event reporting system database

ABSTRACT Objective Our study aims to assess alendronate-related adverse events (AEs) from the US FDA adverse event reporting system database. Methods The AE data associated with alendronate between the first quarter of 2004 and the first quarter of 2024 were selected. Various signal quantification methods, including the ROR, PRR, BCPNN, and EBGM, were applied for analysis. Results In 34,943 reports where alendronate was the primary suspected drug for the AE, 24 affected system organ classes and 1046 significant preferred terms were identified in this study. Several significant AEs beyond drug instructions with strong signals were determined, including low turnover osteopathy, fracture delayed union, fracture nonunion, loss of anatomical alignment after fracture reduction, fracture malunion, periprosthetic fracture, carotid bruit, oral fibroma, traumatic occlusion, and phlebolith. The median time to onset of alendronate-related AEs was 306 days (interquartile range [IQR] 12–1,461 days), and the majority of cases occurred 2 years later (18.80%) and within 30 days (14.49%). Conclusions The current study detected multiple potential new AE signals for alendronate, and more clinical researches are required to further validate our results and clarify their associations.

Adverse reaction of specific acute kidney injury caused by atorvastatin: an actual study based on the database of the US FDA adverse event reporting system

ABSTRACT Introduction Atorvastatin, one of the most widely used drugs, has attracted controversy regarding its potential adverse reactions to acute kidney injury(AKI). This study aims to provide evidence in support of the safe use of atorvastatin. Areas Covered Using the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q1 2024), we extracted reports where atorvastatin was the primary suspect and categorized them into five populations: the general population, acute myocardial infarction (AMI), ischemic stroke (IS), type 2 diabetes mellitus (T2DM), and hyperlipidemia (HLD). We performed subgroup analyses by gender and age strata within these populations, assessing positive signals through disproportionality analysis using four criteria: Ratio of Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EGBM). The statistical analysis evaluated differences between adverse drug reaction (ADR) occurrence and nonoccurrence, as well as between high and low induction time groups. Expert Opinion In the general population, evidence for a positive signal of AKI was insufficient. However, the sub-group analysis revealed a risk in males, with older individuals more often affected in both AMI and IS populations. In T2DM, positive signals were evident in younger age groups. For the HLD population, evidence of a positive AKI signal was insufficient across gender and age strata. Overall, atorvastatin is generally safe, but clinical vigilance for AKI is warranted in T2DM, AMI, and IS populations, particularly in older adults (65+ years).

7626 Endocrine Adverse Reactions Of Tyrosine Kinase Inhibitors In Combination With Immune Checkpoint Inhibitors: A Retrospective Analysis Using The US FDA Adverse Event Reporting System

Abstract Disclosure: W. Shao: None. D. Lu: None. K. Yang: None. Y. Gao: None. J. Zhang: None. Y. Zhang: None. Background: Tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) have been recognized to cause multiple endocrine adverse reactions (EARs). However, the combination therapy-associated EARs is still unclear. We aimed to evaluate the clinical characteristics and prognosis of EARs induced by TKI, ICI and TKI+ICI therapy. Methods: Using the US FDA Adverse Event Reporting System, 938464 cases of all adverse events, adult patients, related to the three types of treatments from January 2001 to September 2023 were identified. A total of 22275 cases were EARs and divided into TKI (n=9181), ICI (n=11363) and TKI+ICI group (n=1731). Results: The incidence of EARs was the highest in TKI+ICI group (9.1%), followed by ICI (7.7%), and TKI group (1.2%) (P < 0.05). Among patients with EARs, the proportions of female and Asian patients were significantly greater in TKI+ICI group than in the other groups (P<0.05 for all). TKI+ICI group had a larger proportion of elderly patients compared with TKI group. The most common type of EARs in TKI+ICI group was thyroid dysfunction (TD) (67.5%), followed by glucose metabolism disorder (GMD) (14.0%). Compared with TKI group, TKI+ICI group displayed a higher risk of TD (OR 3.247, 95% CI [2.849-3.701]), pituitary dysfunction (PD) (OR 6.199, 95% CI [4.534-8.474]), and primary adrenal insufficiency (PAI) (OR 4.178, 95% CI [3.470-5.031]), while the risk of GMD was lower (OR 0.136, 95% CI [0.115-0.161]). Compared with ICI group, an increasing trend of TD (OR 2.640, 95% CI [2.328-2.995]) was found in TKI+ICI group, while a lower risk of GMD (OR 0.388, 95% CI [0.328-0.459]) and PD (OR 0.312, 95% CI [0.255-0.383]) was observed in TKI+ICI group. Hypothyroidism and diabetes mellitus were the main types of TD and GMD in all three groups. Patients with polyendocrine glands involvement accounted for the largest proportion in ICI group (11.4%), followed by TKI +ICI (7.9%), and TKI group (2.3%) (P<0.05). In TKI+ICI group, elderly patients, Asians, melanoma patients were more likely to experience multi-glandular EARs. In terms of prognosis, TKI+ICI group presented a higher risk of hospitalization compared to TKI (OR 2.201, 95% CI [1.943-2.492]) and ICI group (OR 1.282, 95%CI [1.139-1.442]). However, the mortality risk of TKI+ICI group was significantly lower (OR 0.717, 95% CI [0.588-0.874]) than TKI group, and there was no significant difference compared to ICI group. Moreover, there was no difference in mortality between patients with polyendocrine and single endocrine gland involvement. Conclusions: EARs were more common in TKI+ICI therapy. The distribution of EARs in different glands varied among combination therapy and monotherapy. Combination therapy associated EARs did not increase the risk of mortality. Key words: Tyrosine kinase inhibitors, Immune checkpoint inhibitors, Combination therapy, Endocrine adverse reactions, Prognosis Presentation: 6/3/2024

Adverse Event Profile of First-line Drugs for Treating Patent Ductus Arteriosus in Neonates: A Disproportionality Analysis Study of USFDA Adverse Event Reporting System.

Acetaminophen, ibuprofen, and indomethacin are widely used as first-line drugs for patent ductus arteriosus (PDA) closure in preterm neonates. However, their relative safety profiles remain unclear. Adverse event reports related to the first-line drugs used in PDA and neonates in general were retrieved from the US Food and Drug Authority (FDA) Adverse Event Reporting System. Deduplicated reports were analyzed using proportional reporting ratios and reporting odds ratios to identify disproportionality safety signals between drugs. A total of 969 unique reports related to the first-line drugs used in PDA and 499 reports in the neonatal period were included. Acetaminophen signals primarily involved the liver, while ibuprofen and indomethacin signals pertained to gastrointestinal, renal, vascular, and mortality outcomes. Higher occurrences of death were reported with indomethacin and ibuprofen compared with acetaminophen. This first comparison of PDA drug safety profiles from spontaneous reports highlights some differences, with acetaminophen potentially conferring a safer adverse effect profile overall. While limitations include missing data and reporting biases, the signals warrant further validation. Given its comparable efficacy to ibuprofen, as demonstrated in other studies, acetaminophen has the potential to be preferred as an initial medical therapy for PDA.

Sodium-glucose cotransporter 2 inhibitors and renal cancer in the US FDA adverse event reporting system.

Recent evidence suggests an association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and a higher risk of renal cancer. We conducted a pharmacovigilance analysis using the US FDA Adverse Event Reporting System (FAERS) to investigate the disproportionate association between SGLT2 inhibitors and renal cancer. We used AERSMine to mine data from FAERS, covering the period from 2014 Q1 to 2023 Q3. The control group was treated with other glucose-lowering medications (ATC-A10B). Disproportionality analysis results were performed using a proportional reporting ratio (PRR) with a 95% confidence interval (CI) and an information component (IC) with 95% credible interval. Compared to the control group, the SGLT2 inhibitor group had a higher disproportionate renal cancer reporting frequency (0.92 vs 0.27/1000 reports; PRR 3.38; 95% CI 2.68-4.25; p < 0.001) with an IC of 1.36 (0.60-2.06), comprising dapagliflozin (PRR 4.14; 2.95-5.80; p < 0.001), empagliflozin (PRR 2.74; 1.94-3.89; p < 0.001), and canagliflozin (PRR 3.56; 2.48-5.12; p < 0.001). Consistent results were obtained in the diabetes indication with the primary outcomes only for the SGLT2 inhibitors group (not individual molecule). The results of the sensitivity analysis (excluding hypertension indication or antihypertensive drugs, obesity, smoking, alpha-1 blockers, or anti-renal cancer drugs) were highly consistent with the main outcomes, indicating good robustness of the results. The results from 2004 Q1 to 2023 Q3 were similar to those from 2014 Q1 to 2023 Q3, with the exception of empagliflozin. There was a disproportionate association between SGLT2 inhibitors and renal cancer, which supports the current meta-analysis results indicating an increased risk of renal cancer associated with SGLT2 inhibitors.

A real-world disproportionality analysis of baloxavir marboxil: post-marketing pharmacovigilance data

ABSTRACT Objective Baloxavir marboxil (hereafter referred to as baloxavir) is the only cap-dependent endonuclease inhiabitor approved for the treatment and prevention of influenza. However, as a new drug marketed in 2018, the long-term safety of baloxavir in large sample population was unclear. This study aims to evaluate baloxavir-associated adverse events (AEs) through data mining of the international pharmacovigilance database of US FDA Adverse Event Reporting System (FAERS). Methods Disproportionality analysis was conducted to assess the association between baloxavir and its AEs. Data were collected from FAERS from March 2018 to June 2023. After standardizing the data, signal quantification techniques including ROR, PRR, BCPNN and MGPS were used for analysis. Results A total of 49 significant baloxavir-related preferred terms (PTs) in 20 system organ classes (SOCs) were identified in our data analysis. Compared to baloxavir’s FDA label, some new PTs emerged, with the top 10 being pneumonia, loss of consciousness, rhabdomyolysis, seizure, altered state of consciousness, hepatic function abnormal, delirium, depressed level of consciousness, encephalopathy and cardio-respiratory arrest. Conclusion In clinical application of baloxavir, attention should be paid to the new AE signals in addition to the those recorded in the labels, so as to ensure the safety of the patients.

A pharmacovigilance study assessing risk of angioedema with angiotensin receptor blockers using the US FDA Adverse Event Reporting System

ABSTRACT Background Angiotensin receptor blockers (ARBs) are widely used for treating hypertension and heart failure. Angioedema has been reported as a controversial adverse effect of ARBs and the evidence on individual ARB risks is limited. This study aimed to assess signals of angioedema with different ARBs using the US FDA Adverse Event Reporting System (AERS) database. Research design and methods Reports of angioedema from 2004 to 2024 in AERS with an ARB as the primary suspect were extracted using Medical Dictionary for Regulatory Activities queries. Disproportionality analyses including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network and multi-item gamma Poisson shrinker were conducted to identify safety signals for individual ARBs. Results A total of 3,683 unique reports met the selection criteria. Irbesartan and losartan generated signals in all statistical measures, followed by telmisartan and candesartan in some measures. Valsartan had the highest report count. Most reports reported hospitalization, prolonged hospitalization or life-threatening outcomes consequent to angioedema. Conclusion This pharmacovigilance study using AERS highlights potential higher risks of angioedema with losartan and irbesartan compared to other ARBs, warranting validation through prospective epidemiological studies to characterize individual ARB safety profiles.

Eye disorders associated with selective serotonin reuptake inhibitors: a real-world disproportionality analysis of FDA adverse event reporting system

ABSTRACT Background Selective serotonin reuptake inhibitors (SSRIs) are widely used in depression and other psychiatric disorders. Despite their efficacy, there is a growing concern about the risk of eye disorders. This study aims to explore the potential correlation between eye disorders and SSRIs utilizing real-world data. Research design and methods The data were extracted from the US FDA Adverse Event Reporting System database from 2004Q1 to 2023Q3. The analysis focused on the clinical characteristics, the ranking of adverse reactions, the time-to-onset, and the severity proportion of SSRI-related eye disorders. Results Our analysis revealed that SSRIs were significantly associated with eye disorders, with a higher risk of vision blurred with escitalopram, angle closure glaucoma with citalopram, and photopsia with paroxetine. The most common eye disorders were vision blurred, visual impairment, mydriasis, etc. Most of these adverse events occurred within the first 30 days of treatment. The reported incidence of severe eye disorders was 38.6% for SSRIs, with fluoxetine exhibiting the highest rate at 45.9%. Conclusion Our study demonstrates a significant association between SSRIs and the risk of eye disorders. These findings provide crucial insights for clinicians when prescribing SSRIs and underscore the need to monitor eye health in patients receiving these medications.

Safety of TNF-α inhibitors: A real-world study based on the US FDA Adverse Event Reporting System Database.

As a common treatment for rheumatoid arthritis (RA), the adverse reactions of TNF-α inhibitors (TNFis) in practical application have garnered attention. This study aims to investigate the adverse drug events (ADEs) associated with TNFi in RA patients as reported in the FDA Adverse Event Reporting System, to offer insights for clinical use. Cases related to RA and primarily involving TNFi were extracted from the FDA Adverse Event Reporting System database and compared by gender stratification. Screening was conducted based on reporting odds ratio and information component to identify positive ADEs for different TNFis and evaluate common and unique ADEs among various TNFis. There are 4 common ADEs among TNFis, including pulmonary tuberculosis, infection, hypersensitivity, and herpes zoster, as described in the package inserts. However, each TNFi has unique positive ADEs. Adalimumab has 63 unique positive ADEs, including lower respiratory tract inflammation, systemic lupus erythematosus rash, vascular dementia, ovarian neoplasm, adhesion, sarcoma, coccidioidomycosis, etc. Golimumab has 6 unique positive ADEs, including pneumonia cryptococcal, device deployment issue, pneumonia bacterial, polyneuropathy, device malfunction, device issue, etc; certolizumab has 24 unique positive ADEs, including maternal exposure before pregnancy, premature rupture of membranes, exposure via breast milk, staphylococcal sepsis, erysipelas, low birth weight baby, herpes virus infection, premature delivery, etc; etanercept has 180 unique positive ADEs, including joint destruction, chondrolysis, finger deformity, ankle deformity, joint warmth, etc; infliximab has 60 unique positive ADEs, including Hodgkin's disease, metastatic neoplasm, non-Hodgkin's Lymphoma, etc. Although the aforementioned 5 TNFis share common ADEs such as herpes zoster, clinicians must exercise caution when selecting specific medications, especially for RA patients concurrently suffering from malignancies. The analysis indicates that infliximab is associated with 60 unique positive ADEs, including Hodgkin's disease, metastatic neoplasm, and non-Hodgkin's lymphoma; therefore, these patients should use infliximab with greater caution. Similarly, certolizumab should be used with increased caution in pregnant and postpartum women.

Exploring Novel Adverse Events of Nefecon

BackgroundNefecon, the first innovative drug approved by both the US FDA and European EMA for IgA nephropathy, lacked comprehensive real-world assessments of its adverse events (AEs). MethodsWe leveraged post-marketing data of Nefecon from the US FDA Adverse Event Reporting System, employing disproportionate analysis to detect positive signals at the system organ class (SOCs) and preferred terms (PTs) levels. Duplicate AEs related to budesonide and those previously reported in studies were excluded through the use of the Medical Dictionary of Regulatory Activities. Our analysis encompassed time to onset (TTO), Weibull shape parameter (WSP) evaluation, cumulative incidence, clinical prioritization evaluation and subgroup analysis based on gender and age. ResultsA total of 1515 individuals with IgA nephropathy were included. Eight positive SOC signals and 23 positive PT signals were identified, including four PTs (asthenia, malaise, product dose omission issue, and anxiety) representing novel AEs newly identified in this study. None of the positive PTs were classified as high clinical priority, with only acne, hypertension, swelling face, and weight increased considered as moderate clinical priority events. The median time to TTO was 31 days. All WSP test results indicated an early failure type profile. Lastly, subgroup analysis provided further insights into the relative risk of specific AEs. ConclusionsNefecon demonstrates a favorable safety profile, with no high-priority clinical events identified. The identification of novel AEs and subgroup-specific high-risk events fills a gap in existing studies and offers valuable insights for early clinical vigilance.

Analysis of Inclisiran in the US FDA adverse event reporting system (FAERS): a focus on overall patient population and Sex-specific Subgroups.

ABSTRACT Background our study aimed to identify inclisiran-related adverse events(AEs) for primary hypercholesterolemia and arteriosclerotic cardiovascular disease(ASCVD) from the US FDA Adverse Event Reporting System (FAERS) database, analyzing its links to AEs in the overall patient population and sex-specific subgroups to improve medication safety. Methods We analyzed inclisiran-related AEs signals by using statistical methods like Reporting Odds Ratio (ROR), Proportional Reporting Ratios (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma-Poisson Shrinker (MGPS). Results Analyzing 2,400 AE reports with inclisiran as the primary suspected drug in the FAERS database, we identified 70 AE signals over 13 organ systems using the above four methods. Notable findings were strong signals for systemic diseases and various reactions at the site of administration (ROR 1.49, 95% CI 1.41-1.57), and Various musculoskeletal and connective tissue diseases (ROR 4.07, 95% CI 3.83-4.03) in overall and gender-specific populations. Myalgia, a new ADE signal not in the drug insert, was a top signal by intensity and frequency (ROR 14.76, 95% CI 12.84-16.98). Conclusion Our study revealed the strongest AE signals associated with inclisiran in both the overall population and gender subgroups, highlighting potential risks in clinical medication use and guiding balanced clinical decision-making.

Post-marketing risk analysis of bendamustine: a real-world approach based on the FAERS database.

Objective: Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application. Methods: We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA's Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0. Results: 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the "primary suspected" drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia-all documented on bendamustine's label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug's label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0-59 days, predominantly occurring on the first day post-initiation. The β of bendamustine-related AEs suggested risk reduction over time. Conclusion: Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use.

Is the Fast Track Safe? A Safety Evaluation of the COVID-19 Drugs with Real-World Data.

The US FDA has given emergency use authorization to multiple Covid-19 drugs. We conducted disproportionality analysis to detect adverse reaction rates (ADRs) in the US FDA's Adverse Event Reporting System. We discovered not only severe ADRs but also unique ADRs and effectiveness that might be explained by pharmacokinetics. This shows that real-time safety reviews could be effective methods for comparing the safety and efficacy of fast-track authorized drugs.

Enhancing Transparency in Defining Studied Drugs: The Open-Source Living DiAna Dictionary for Standardizing Drug Names in the FAERS.

In refining drug safety signals, defining the object of study is crucial. While research has explored the effect of different event definitions, drug definition is often overlooked. The US FDA Adverse Event Reporting System (FAERS) records drug names as free text, necessitating mapping to active ingredients. Although pre-mapped databases exist, the subjectivity and lack of transparency of the mapping process lead to a loss of control over the object of study. We implemented the DiAna dictionary, systematically mapping individual free-text instances to their corresponding active ingredients and linking them to the World Health Organization Anatomical Therapeutic Chemical (WHO-ATC) classification. We retrieved all drug names reported to the FAERS (2004-December 2022). Using existing vocabularies and string editing, we automatically mapped free text to ingredients. We manually revised the mapping and linked it to the ATC classification. We retrieved 18,151,842 reports, with 74,143,411 drug entries. We manually checked the first 14,832 terms, up to terms occurring over 200 times (96.88% of total drug entries), to 6282 unique active ingredients. Automatic unchecked translations extend the standardization to 346,854 terms (98.94%). The DiAna dictionary showed a higher sensitivity compared with RxNorm alone, particularly for specific drugs (e.g., rimegepant, adapalene, drospirenone, umeclidinium). The most prominent drug classes in the FAERS were immunomodulating (37.40%) and neurologic drugs (29.19%). The DiAna dictionary, as a dynamic open-source tool, provides transparency and flexibility, enabling researchers to actively shape drug definitions during the mapping phase. This empowerment enhances accuracy, reproducibility, and interpretability of results.

Strong opioids-induced cardiac, neurologic, and respiratory disorders: a real-world study from 2004 to 2023 based on FAERS.

Opioids are mainly used as adjuncts to the induction and maintenance of general anesthesia, postoperative analgesia, and treating moderate to severe cancer pain and chronic pain. However, the hazards of these drugs to various organ organs still need to be further explored. This study used the US FDA Adverse Event Reporting System (FAERS) database to determine whether commonly receiving opioids was higher than the baseline risk for all other medications. FAERS was asked about adverse events (AEs) for the opioids "morphine," "fentanyl," "oxycodone," "hydromorphone," "sufentanil," and "remifentanil" from the first quarter of 2004 (2004Q1) through the second quarter of 2023 (2023Q2). Disproportionality signaling analysis was performed by calculating reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). AEs with system organ classes (SOCs) of "cardiac disease," "neurologic disease," and "respiratory, thoracic, and mediastinal disease" were then screened. The statistical analysis included 12,819,518 reports in the FAERS database from 2004Q1 to 2023Q2, of which 236,619 AEs were reported as "primary suspect" for the six drugs mentioned above, which were selected as "cardiac disorders," "nervous system disorders," and "respiratory, thoracic and mediastinal disorders." Some AEs identified in this study are consistent with the drug labeling, such as bradycardia, respiratory depression, and somnolence. In addition, some unexpected and significant acute adverse drug reactions (ADRs), such as toxic leukoencephalopathy and coma, may occur. This study identified potential new and unexpected ADRs for opioids, providing valuable evidence for safety studies of opioids.

1783. Acute Kidney Injury Associations with Antibiotics: A Pharmacovigilance Study of the US FDA Adverse Event Reporting System

Abstract Background Antibiotic-associated acute kidney injury is found to be associated with many antibiotics like vancomycin, fluoroquinolones, penicillin combinations, and trimethoprim–sulfamethoxazole. Other antibiotics may also lead to acute kidney injury. Still, no study has systemically compared the cases of acute kidney injury reported to the US FDA Adverse Event Reporting System (FAERS) with the many available antibiotics. Therefore, the study aimed to evaluate the reporting associations between acute kidney injury and different classes of antibiotics through the analysis of the US FDA Adverse Event Reporting System (FAERS). Methods FAERS reports from 1 January 2015 to 31 December 2022 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify AKI cases. Reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs) for the reporting associations between antibiotics and AKI were calculated. A reporting association was considered statistically significant when the lower limit of the 95% CI was &amp;gt; 1.0. Results A total of 2,042,801 reports (including 20,138 AKI reports) were considered. Colistin had the greatest proportion of acute kidney injury reports, representing 25% of all colistin reports. acute kidney injury RORs (95% CI) for antibiotics were, in descending order: colistin 33.10 (21.24–51.56), aminoglycosides 17.41 (14.49–20.90), vancomycin 15.28 (13.82–16.90), trimethoprim–sulfamethoxazole 13.72 (11.94–15.76), penicillin combinations 7.95 (7.09–8.91), clindamycin 6.46 (5.18–8.04), cephalosporins 6.07 (5.23–7.05), daptomycin 6.07 (4.61–7.99), macrolides 3.60 (3.04–4.26), linezolid 3.48 (2.54–4.77), carbapenems 3.31 (2.58–4.25), metronidazole 2.55 (1.94–3.36), tetracyclines 1.73 (1.26–2.36), and fluoroquinolones 1.71 (1.49–1.97). Conclusion This study found 14 classes of antibiotics having significant reporting associations with AKI. Among the antibiotics evaluated in this study, colistin had the highest acute kidney injury ROR and moxifloxacin had the lowest. Disclosures All Authors: No reported disclosures

A real-world analysis of tyrosine receptor kinase inhibitor-related toxicities in cancer treatment.

Background: This study analyzed real-world data from 2004 to 2023 to evaluate the toxicity profile of tyrosine receptor kinase (TRK) inhibitor therapy. Method: A retrospective analysis of USFDA Adverse Event Reporting System data was conducted to identify adverse events in patients receiving TRK inhibitor therapy. Result: Entrectinib demonstrated toxicities primarily in the cardiovascular and nervous systems, followed by the renal and urinary system. Common adverse effects included dizziness, renal impairment, constipation, heart failure and taste disorders. Larotrectinib induced adverse events mainly in the hepatobiliary and nervous systems, with peripheral neuropathy, myalgia, renal impairment and increased alanine aminotransferase commonly reported. Conclusion: Careful monitoring and supportive care strategies are essential for managing adverse events associated with TRK inhibitor therapy.

Rhabdomyolysis associated with newer-generation anti-seizure medications (ASMs): a real-world retrospective and pharmacovigilance study.

Objective: Rhabdomyolysis is a potentially fatal adverse reaction mostly triggered by certain medications. Few real-world studies have shown a clear association between newer-generation anti-seizure medications (ASMs) and rhabdomyolysis. We sought to quantify the risk and evaluate the clinical features and management of rhabdomyolysis associated with newer-generation ASMs. Methods: Data were retrieved from the US FDA Adverse Event Reporting System database (FAERS) from 2018 to 2022 on newer-generation ASMs to identify rhabdomyolysis events, and disproportionality analyses were conducted by estimating the reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs). Furthermore, case reports from 2012 to 31 December 2022 on newer-generation ASMs-induced rhabdomyolysis were retrieved for retrospective analysis. Results: A total of 1,130 rhabdomyolysis reports from the FAERS database were considered. Levetiracetam had the greatest proportion and the highest positive signal values of rhabdomyolysis. The RORs (95% CIs) for newer-generation ASMs were, in descending order, levetiracetam 8.01 (7.26-8.84), lamotrigine 3.78 (3.25-4.40), oxcarbazepine 3.47 (2.53-4.75), pregabalin 2.75 (2.43-3.12), lacosamide 1.85 (1.29-2.65), topiramate 1.64 (1.25-2.15), and gabapentin 1.32 (1.13-1.55). Twenty-six case reports showed evidence of rhabdomyolysis, and levetiracetam (65.4%) was the most frequently reported agent. The median age was 32years; typical initial symptoms included muscle weakness (34.8%), myalgia (34.8%), backache (17.4%), fatigue (13.0%) and leg pain (8.7%). The median time to onset of rhabdomyolysis was 2days. All cases had elevated creatine phosphokinase (CPK), and some cases were accompanied by elevated creatinine (57.1%) and myoglobinuria (53.8%). Cessation of ASMs could lead to complete clinical remission. The median time for creatine phosphokinase (CPK) normalization was 8days. Conclusion: This study identified 7 newer-generation ASMs with significant rhabdomyolysis reporting associations. Prescribers should be more aware of this risk and teach patients to recognize rhabdomyolysis signs/symptoms early.