FDA Adverse Event Reporting System Research Articles

Immune Checkpoint Inhibitor (ICI) Induced Sinonasal Disease: Review of Literature and FDA Database.

Immune checkpoint inhibitors (ICIs) are a rapidly expanding class of oncologic therapies whose mechanism of action can result in unique immune-related adverse events (irAEs) not seen in other cancer therapeutics. The objective of this study was to determine the presence of sinonasal irAEs with these medications. A case report of chronic rhinosinusitis with nasal polyps (CRSwNP) caused by an ICI is presented and was the impetus for this review. Review of the literature using Pubmed and Cochrane Database of Systematic Reviews was performed. Additionally, we searched the FDA adverse event reporting system (FAERS) database for sinonasal AEs in the 7 FDA-approved ICIs. We demonstrate an emerging scientific literature describing cases of CRS associated with multiple ICIs with a particular predilection toward TH2 driven phenotypes. Review of the FAERS also demonstrates a small percentage of patients who report sinonasal complaints after initiating ICI therapy. Sinonasal symptoms and the development of CRS, in particular, are not currently well recognized as potential irAEs for ICIs. Increased awareness and further study may help to elucidate if these are more common than currently reported and if irAE-related CRS is a unique phenotype.

An investigation of broad-spectrum antibiotic-induced liver injury based on the FDA Adverse Event Reporting System and retrospective observational study

Tazobactam/piperacillin and meropenem are commonly used as an empiric treatment in patients with severe bacterial infections. However, few studies have investigated the cause of tazobactam/piperacillin- or meropenem-induced liver injury in them. Our objective was to evaluate the association between tazobactam/piperacillin or meropenem and liver injury in the intensive care unit patients. We evaluated the expression profiles of antibiotics-induced liver injury using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Further, in the retrospective observational study, data of patients who initiated tazobactam/piperacillin or meropenem in the intensive care unit were extracted. In FAERS database, male, age, the fourth-generation cephalosporin, carbapenem, β-lactam and β-lactamase inhibitor combination, and complication of sepsis were associated with liver injury (p < 0.001). In the retrospective observational study, multivariate logistic regression analyses indicated that the risk factors for liver injury included male (p = 0.046), administration period ≥ 7 days (p < 0.001), and alanine aminotransferase (p = 0.031). Not only administration period but also sex and alanine aminotransferase should be considered when clinicians conduct the monitoring of liver function in the patients receiving tazobactam/piperacillin or meropenem.

Data mining and safety analysis of dual orexin receptor antagonists (DORAs): a real-world pharmacovigilance study based on the FAERS database

ObjectiveUsing the Food and Drug Administration Adverse Event Reporting System (FAERS) database, four signal detection methods were applied to mine adverse drug events (ADEs) related to use of dual orexin receptor antagonists (DORAs) to provide reference for safe clinical use.Research design and MethodsData collected from Q3rd 2014 to Q4th 2023 were obtained from the FAERS database. According to the preferred terminology (PT) and systematic organ classification (SOC) of MedDRA v.26.0, the reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN) were used to detect ADE signals.ResultsA total of 11,857 DORAs-related adverse reactions were detected, reported with suvorexant, lemborexant, and daridorexant as the main suspected drugs was 8717584, and 2556, respectively. A higher proportion of females than males were reported (57.27% vs. 33.04%). The top 20 positive PT signals from three DORAs showed that “sleep paralysis” ranked first. “Brain fog” was stronger following daridorexant but was not detected for the other two drugs, and “sleep sex” and “dyssomnia” were stronger in suvorexant but not in the other two drugs. Additionally, some PTs occurred that were not included in drug instructions, such as “hangover” and “hypnagogic hallucination.”ConclusionIn this study, four algorithms (ROR, PRR, BCPNN, and MGPS) were used to mine the safety signals of DORAs. We identified some potential ADE signals that can promote the rational use of DORAs and improve their safety.

A disproportionality analysis of CDK4/6 inhibitors in the FDA Adverse Event Reporting System (FAERS)

ABSTRACT Objective The FDA Adverse Event Reporting System (FAERS) was used to mine and evaluate adverse events (AEs) associated with cyclin-dependent kinase (CDK) 4/6 inhibitors, thereby providing a reference for clinical rational drug use. Methods AE data related to CDK4/6 inhibitors from the first quarter of 2015 to the first quarter of 2023 were acquired from FAERS, while the signal mining was processed using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. Results The number of AE reports for CDK4/6 inhibitors was, respectively, 132,494 for palbociclib, 56,151 for ribociclib, and 7,014 for abemaciclib. The corresponding numbers of AE signals were 319, 517, and 59, with the number of involved System Organ Class (SOC) being 23, 23, and 15, mainly involving blood and lymphatic system disorders, respiratory, thoracic and mediastinal disorders, hepatobiliary disorders, skin and subcutaneous tissue disorders, etc. Conclusion CDK4/6 inhibitors could lead to pulmonary toxicity, myelosuppression, skin reactions, etc. Special attention should be paid to abemaciclib for interstitial lung disease (ILD), erythema multiforme, and thrombosis risk; ribociclib for cardiac toxicity, hepatotoxicity, and musculoskeletal toxicity; palbociclib for neurocognitive impairment and osteonecrosis of the jaw.

Real-world pharmacovigilance analysis of galsulfase: a study based on the FDA adverse event reporting system (FAERS) database

BackgroundAssociated with enzyme deficiencies causing glycosaminoglycans (GAGs) accumulation, mucopolysaccharidosis type VI (MPS VI) is lysosomal storage disorder. In the treatment of MPS VI, galsulfase (Naglazyme) is commonly used as an enzyme replacement therapy (ERT). There remains a need for comprehensive real-world data on its safety and associated adverse events (AEs).ObjectiveAn analysis of the FDA Adverse Event Reporting System (FAERS) database will be conducted to identify potential risks and adverse reactions associated with galsulfase in real-life settings.MethodsThe FAERS database was used to extract data from Q2 2005 to Q4 2023. A total of 20,281,876 reports were analyzed after duplicate elimination, with 3,195 AE reports related to galsulfase identified. The association between galsulfase and AEs was investigated by utilizing four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). The analysis focused on the timing of onset, signs of AEs, and clinical significance.ResultsTwenty seven organ systems were involved, and significant system organ classes (SOCs) included respiratory, thoracic and mediastinal disorders, and infections and infestations. At the PT level, 72 PTs corresponding to 15 SOCs were identified, with some AEs not previously mentioned in the product label. AEs associated with galsulfase had a median onset time of 1,471 days, with over half of the cases occurred within the first 5 years of treatment initiation.ConclusionThis investigation delivers an exhaustive and indicative assessment of galsulfase’s safety profile, grounded in authentic, real-world evidence. The findings emphasis the importance of continuous safety surveillance and the emergence of new AEs. The identification of previously unreported urologic adverse events, such as glomerulonephritis membranous and nephritic syndrome, warrants further investigation. The study emphasizes the need for enhanced pharmacovigilance to ensure patient safety and the effectiveness of galsulfase treatment.

Post-marketing safety concerns with montelukast: A pharmacovigilance study based on the FDA adverse event reporting system.

The United States Food and Drug Administration (FDA) has been warning about the psychiatric disorders associated with montelukast (MTK) for years. To study the characteristics of the presence of MTK-associated adverse events (AEs), we obtained data from the FDA Adverse Event Reporting System database and used a case (MTK) vs. non-case (all other drugs) analysis to investigate the safety signals in a disproportionality study. 27,507 reported AEs from January 2004 to December 2022 were analyzed. Disproportionality analysis shows that psychiatric, respiratory, thoracic, and mediastinal disorders as well as social circumstances are the most commonly reported AEs. In addition, our study found several unreported AEs, such as increased systolic blood pressure, diastolic dysfunction, hypothyroidism, obesity, bursitis, and polycystic ovaries. The timing of AE occurrence indicates that MTK-associated AEs are mainly acute effects. Most importantly, we found that 60.1% of patients reporting AEs in the category of psychiatric disorders were younger than 18 years. In summary, we revealed an age-preference pattern of psychiatric AEs in patients prescribed MTK. Our study is helpful for physicians and health professionals to better evaluate the value and risk of MTK and to achieve the goal of optimal patient care.

Real-world Disproportionality Analysis of the FDA Adverse Event Reporting System (FAERS) Database for Asciminib.

Asciminib is primarily utilized for treating Philadelphia chromosome-positive chronic myeloid leukemia in its chronic phase among patients harboring the T315I mutation or those who have been previously treated with at least two tyrosine kinase inhibitors. The safety profile of asciminib across a broad patient population over an extended timeframe remains unverified. This study uses a real-world pharmacovigilance database to evaluate the adverse events (AEs) linked with asciminib, providing valuable insights for clinical drug safety. Data from the FDA Adverse Event Reporting System (FAERS) database, spanning from October 2021 to December 2023, served as the basis for this analysis. The extent of disproportional events was assessed using sophisticated metrics such as the reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean. Within the specified period, the FAERS database documented 3,913,574 AE reports, with asciminib being associated with 966 incidents. Reactions to asciminib spanned 27 system organ categories. Utilizing four distinct analytical algorithms, 663 significant preferred terms exhibiting disproportional frequencies were identified. Notably, this investigation uncovered 26 significant AEs linked to off-label asciminib use, encompassing conditions such as gynecomastia, nephrotic syndrome, orchitis, pyelonephritis, hepatotoxicity, and pancreatitis. The median onset time for asciminib-related AEs was 52.5 days, ranging from 17 to 122.75 days.

Signal mining and gender differences analysis of adverse events in NMIBC treatment with gemcitabine and BCG bladder instillation based on the FAERS database

ABSTRACT Objective To explore safety differences and perform a gender-based analysis of adverse events related to gemcitabine and Bacillus Calmette-Guérin (BCG) vaccine using the U.S. FDA Adverse Event Reporting System (FAERS) database. Methods Using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods, adverse events associated with gemcitabine and BCG were mined from FAERS database reports spanning from Q1 2004 to Q3 2023. Results The study extracted 37,855 reports with gemcitabine and 5,455 reports with BCG as the primary suspected drugs. Adverse events were more prevalent in males (male-to-female ratio: gemcitabine 1.10, BCG 4.25). Differences in high-frequency adverse events among the top 20 signals were detected for both drugs. Both drugs affected similar organ systems, including potential pulmonary, ocular, and renal toxicity, with gemcitabine showing a broader range of adverse events. Gender analysis revealed fewer adverse reactions to gemcitabine in females, while males had fewer adverse reactions to BCG. Conclusion Differences in high-frequency adverse events between gemcitabine and BCG, including some not listed on drug labels, were observed. Both drugs affect similar organ systems, with gemcitabine showing a broader range of adverse events. Gender differences in adverse events were notable.

Adverse Event Profiles of Adalimumab in Children: A Disproportionality Analysis

Background: Adalimumab has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult rheumatoid arthritis (RA), and subsequently approved for pediatric treatment of various autoimmune diseases in children of different ages. Due to genetic differences between children and adults in terms of physiology and immunity, there is a need to explore the safety of adalimumab in children in the real world. The aim of this study is to identify potential adverse event (AE) signals associated with the use of adalimumab in pediatric patients (&lt;18 years old) using data from the FDA Adverse Event Reporting System (FAERS). Methods: AEs associated with adalimumab in pediatric patients reported in the FAERS database from the first quarter (Q1) of 2017 to the third quarter (Q3) of 2022 were systematically gathered. Reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC), and the empirical Bayes geometric mean (EBGM) were used to assess the relationship between adalimumab and AEs in children. Results: Out of 8,363,304 reports collected from the FAERS database during the study period, 3819 reports on children on adalimumab were identified. Adalimumab-related AEs reports were concentrated on 10 toxicity areas and a total of 202 positive signals were detected, of which injection site papule (ROR = 261.97) and intestinal fistula (ROR = 122.09) had the strongest signals. Unexpected significant AEs, including intestinal obstruction, immunodeficiency, abdominal abscess, and Takayasu’s arteritis might also occur. In comparison with patients of all ages in the same time window, the median onset time of children was shorter (99 vs. 149 days). Most of the AE cases occurred in children within the first 1 (1.71%), 2 (8.12%), and 3 months (8.39%) and had early failure types after adalimumab initiation. Methotrexate, folic acid, prednisone, azathioprine, and mesalamine were the top five drugs used concomitantly for adalimumab-associated AEs. Conclusions: When adalimumab is used in children, especially in the first 3 months of treatment, in addition to the AEs recorded in the drug package insert, close attention should be paid to the new potential AEs off-label to ensure the safety of adalimumab in children.

Comparing the Differences in Adverse Events among Chimeric Antigen Receptor T-Cell Therapies: A Real-World Pharmacovigilance Study

In this study, we compared the similarities and differences in adverse events (AEs) among CAR T-cell products through signal mining via the FDA Adverse Event Reporting System (FAERS) and identified unknown AEs to provide a reference for safe clinical medication. Data from the FAERS database spanning from the fourth quarter of 2017 to the first quarter of 2024 were extracted. Signals were identified using the reporting odds ratio (ROR) method and the Medicines and Healthcare Products Regulatory Agency (MHRA) method. A total of 11,386 AE reports related to six CAR T-cell products were selected. The top three categories of AEs reported were nervous system disorders, immune system disorders, and general disorders and administration site conditions. However, there were variations in the AE spectra among the different CAR T-cell products. The BCMA-targeting drugs idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (Cilta-cel) were found to be associated with parkinsonism, which were not observed in CD19-targeting drugs. Tisagenlecleucel (Tisa-cel) and axicabtagene ciloleucel (Axi-cel) exhibited cerebrovascular accident-related AEs, graft versus host disease, and abnormal coagulation indices. Cilta-cel was associated with cerebral hemorrhage, intracranial hemorrhage, cranial nerve disorder, and facial nerve disorder. Cardiopulmonary toxicity, including hypoxia, tachypnoea, cardiorenal syndrome, and hypotension, exhibited strong signal intensities and considerable overlap with CRS. The number of positive signals for cardiopulmonary toxicity associated with drugs targeting CD-19 is greater. Clinicians should assess patients prior to medication and closely monitor their vital signs, mental status, and laboratory parameters during treatment.

Fluoroquinolones-related psychiatric adverse events: a real‑world retrospective and pharmacovigilance database analysis

ABSTRACT 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.

Central serous chorioretinopathy secondary to drugs: a real-world pharmacovigilance study of the FDA adverse event reporting system (FAERS)

ABSTRACT Background The objective of this study was to evaluate the reporting associations between Central serous chorioretinopathy (CSCR) and many available drugs using FAERS. Research design and methods FAERS reports from 2004 to 2023 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify CSCR cases. Reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs) for the reporting associations between available drugs and CSCR were calculated. A reporting association was considered statistically significant when the lower limit of the 95% CI was > 1.0. Results There were 1002 reports of 110 drugs with suspected drug-associated CSCR based on the ‘primary suspects’ role code in the FAERS database found to have statistically significant signals. Among the top 20 ROR drugs, the most frequently reported drugs were dermatological drugs (ATC:D, 210 cases, 64.41%), followed by antitumor agents and immunological agents (ATC:L,77 cases, 23.62%), Systemic Hormonal Preparations, Excl. Sex hormones and Insulins (ATC:H, 19 cases, 5.80%) and sensory organ drugs (ATC:S, 9 cases, 2.76%). The top 3 drugs associated with CSCR were Prednisolone (144 cases, 44.17%), Fluticasone (29 cases, 8.90%), and Methylprednisolone (27 cases, 8.28%). Conclusions This is the first real-world study using FAERS database to investigate drug-induced CSCR. Clinicians and pharmacist must keep in mind CSCR is a serious ocular complication associated with glucocorticoids, tyrosine kinase receptor inhibitor, and other drugs that can cause CSCR.

Disproportionality analysis of data from VigiBase and other global product safety databases on toxicity of iron chelating agents

ABSTRACT Background Iron chelators; deferasirox, deferiprone, and deferoxamine; used to treat iron toxicities due to excessive ingestions or blood transfusions, may cause serious adverse reactions. Research design and methods This study investigates pharmacovigilance data to uncover unknown safety information. Disproportionality analysis was conducted using VigiBase, the WHO global database of individual case safety reports, to known safety profile of products and the FDA Adverse Event Reporting System, reviewing over 117.000 iron chelator cases between 2010 and 2020. Results Commonly reported adverse events for iron chelators are general disorders and administration site conditions and GI-related disorders. Reporting Odds Ratio was calculated for iron chelator associations to headache (common), blurred vision (rare) and sepsis (serious). Strong association between deferoxamine and blurred vision (ROR: 2.47 in VigiBase and 3.04 in FAERS), deferiprone and sepsis (ROR; 5.95 in VigiBase and 1.24 in FAERS) were identified. However, results showed some inconsistent associations, such as headache and deferiprone, blurred vision and deferasirox association as per FAERS data; sepsis and deferasirox and deferoxamine association as per VigiBase data. Forty-five new potential signals with different associative values were suggested. Conclusion The study identified strong associations between specific iron chelators and adverse events, though some inconsistencies were observed in the data. These findings, including the 45 new potential signals, suggest areas for further review and validation with additional data.

Post-marketing safety concern of PI3K inhibitors in the cancer therapies: an 8-year disproportionality analysis from the FDA adverse event reporting system

ABSTRACT Background ThePhosphoinositide 3-kinases (PI3Ks) family plays a crucial role intumorigenesis. Alpelisib (inhibiting PI3Kα), copanlisib (inhibiting PI3Kα andPI3Kδ), duvelisib (inhibiting PI3Kδ and PI3Kγ), and idelalisib (inhibitingPI3Kδ) were developed to target the PI3K pathway. However, the toxicity limitstheir application to some extent. It’s necessary to investigate the adverseeffects (AEs) of these inhibitors. Research designand methods We conducted acomparative analysis of the safety signals of AEs in PI3K inhibitors usingdisproportionality analysis in the FDA Adverse Event Reporting System database(FAERS). Results Our studyidentified significant safety signals for metabolic disorders with all PI3Kinhibitors. Notable safety signals for gastrointestinal disorders were observedwith most PI3K inhibitors, with the exception of copanlisib. Common AEs shared amongall PI3K inhibitors included colitis and dehydration. Alpelisib displayedunique AEs associated with metabolic disorders, whereas copanlisib exhibitedidiosyncratic AEs linked to cardiac and vascular disorders. Stevens-Johnsonsyndrome emerged as a common severe adverse event (SAE) among alpelisib,copanlisib, and idelalisib, while febrile neutropenia was prevalent amongcopanlisib, duvelisib, and idelalisib. Intestinal perforation was solelyassociated with alpelisib. Conclusions The safety profiles of the five PI3K inhibitorsvary concerning adverse events. These findings could guide drug selection andinform future prospective research.

Post-marketing safety surveillance of fostamatinib: an observational, pharmacovigilance study leveraging FAERS database

ABSTRACT Objective Fostamatinib, an FDA-approved oral small-molecule spleen tyrosine kinase (SYK) inhibitor, is used to treat thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have not responded to previous treatments. However, comprehensive safety data is lacking. This study uses the FDA Adverse Event Reporting System (FAERS) database to explore real-world adverse events (AEs) related to fostamatinib, aiming to inform its clinical use. Methods The FAERS database was retrospectively queried to extract reports associated with fostamatinib from 2019 to 2023. To identify and evaluate potential AEs in patients receiving fostamatinib, various disproportionality analyses such as 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) were employed. Results A total of 23 AE signals were included in our analysis. Among them, hypertension, blood pressure increase, blood pressure abnormality, hepatic enzyme increase, and diarrhea were consistent with the common AEs described for fostamatinib in clinical trials. In addition, unexpected serious AEs were detected including cerebral thrombosis and necrotizing soft tissue infection. The median time to onset of fostamatinib-related AEs was 86 days. Conclusion Our investigation revealed several possibly emergent safety concerns associated with fostamatinib in real-world clinical practice, which might provide essential vigilance evidence for clinicians and pharmacists to manage the safety issues of fostamatinib.

Mortality and Serious Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System

Mortality and Serious Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System

Drug-associated porphyria: a pharmacovigilance study

BackgroundThe potentially fatal attacks experienced by porphyria carriers are triggered by various porphyrinogenic drugs. However, determining the safety of particular drugs is challenging.MethodsWe retrospectively used the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) to identify drugs associated with porphyria as an adverse event (AE) extracted from data from January 2004 to March 2022. The associated search terms included “Porphyria,” “Porphyria screen,” “Porphyria non-acute,” “Porphyria acute,” “Acquired porphyria,” and “Pseudoporphyria.” Signal mining analysis was performed to identify the association between drugs and AEs by four algorithms, namely the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker.ResultsFAERS reported 1470 cases of porphyria-related AEs, and 406 drugs were screened after combining trade and generic names. All four algorithms identified 52 drugs with signals. The characteristics of all the reports and signaling drugs were analyzed.ConclusionsThis is the first report of drug-associated porphyria that provides critical information on drug porphyrogenicity, facilitating rational and evidence-based drug prescription and improving the accuracy of porphyrogenicity prediction based on model algorithms. Moreover, this study serves a reference for clinicians to ensure that porphyrinogenic drugs are not prescribed to carriers of porphyria genetic mutations.

A safety signal for congenital strabismus associated with valproic acid: A pharmacovigilance analysis utilizing the FDA Adverse Event Reporting System database.

This pharmacovigilance study investigated the relationship between antiepileptic drugs and congenital strabismus, utilizing the FDA Adverse Event Report System database between 2014 and 2023. Out of 28 347 889 reports of adverse events in 10 937 764 cases, we identified 1104 reports of strabismus and 67 of congenital strabismus. Valproic acid was the most frequently implicated primary suspect drug (95 and 14 cases, respectively). Ninety-five reports involved transplacental valproic acid exposure, yielding an information component (IC) of 7.06 (IC-2 × standard deviation: 5.50). A multivariate analysis showed that transplacental exposure to valproic acid correlated with strabismus (adjusted odds ratio: 8.47, 95% CI: 6.74-10.65). We revealed a robust safety signal linking valproic acid to congenital strabismus.

Signal mining of adverse reactions in the antiemetic drug ondansetron during pregnancy:A Real-World analysis of the FDA adverse Event Reporting System (FAERS)

ABSTRACT Background The aim of this study is to assess the risks associated with the use of ondansetron in pregnant women in real-world based on the Food and Drug Administration adverse Event Reporting System (FAERS). Methods The FAERS data from the 2017Q1 to the 2023Q1, which was used by the ratio-of-reporting (ROR) and Bayesian confidence interval progressive neural network (BCPNN) to assess the safety of ondansetron in pregnancy. Results A total of 15,727 pregnancy population reports were reported, with a total of 1,064 reports of adverse reactions with ondansetron as the primary suspected drug. Ondansetron was involved in a total of 10 system organ classifications (SOCs) of signal generation, and the top three signal intensities were Congenital, familial and genetic disorders (ROR=19.1, ROR025=17.03; IC=1.23, IC025=1.16), Ear and labyrinth disorders (ROR=17.11, ROR025=12.46; IC=1.22, IC025=1.03), and Cardiac disorders (ROR=9.48, ROR025=8.38; IC=1.12, IC025=1.03); signals of adverse reactions obtained of 216, of which the main ones were Anhedonia (IC=1.34, IC025=1.08), Injury (IC=1.34, IC025=1.19), Left-to-right cardiac shunt (IC=1.33, IC025=1.05). Conclusion The adverse reactions of Ondansetron involve multiple systems and organs, which should cause clinical vigilance. However, due to the limitations of the data, the causal relationship and risk level of adverse reactions cannot be accurately inferred.

Cytokine release syndrome associated with immune checkpoint inhibitors: a pharmacovigilance study based on spontaneous reports in FAERS

ABSTRACT Objective To describe cytokine release syndrome (CRS) associated with immune checkpoint inhibitors (ICIs) reported in the FDA Adverse Event Reporting System (FAERS). Methods We obtained ICIs adverse event (AE) reports from January 2011 to September 2023 from the FAERS database. The preferred term (PT) ‘cytokine release syndrome’ from the Medical Dictionary for Regulatory Activities (MedDRA) 26.1 was used to identify cases with ICIs-related CRS. The reporting odds ratio (ROR) of the disproportionality method was performed to quantify the association between CRS and ICIs treatment strategy. Results Three hundred and ninety-five cases were gathered. 42.03% of the patients were aged 18 to 65. Male patients outnumbered female patients (53.67% vs. 34.94%). The prevalent potential cancer types were lung cancer (33.42%) and skin cancer (20.51%). Japanese were responsible for the majority of ICIs-related CRS cases (176 cases). The combination of nivolumab and ipilimumab resulted in the most CRS cases (138 cases), and the ICIs combination therapy had the highest ROR signal value (ROR = 11.95 [10.14–14.06]). ICIs-related CRS had a median time to onset of 14 days (interquartile range [IQR] 7–43.25). Conclusions ICIs-related CRS is an increasingly important immune-related AE. Our study provided helpful information to help medical professionals learn more about ICIs-related CRS.