FDA Adverse Event Reporting System Research Articles

A real-world pharmacovigilance study of blinatumomab based on the FDA adverse event reporting system.

Blinatumomab, the first CD3/CD19 bispecific antibody, is FDA-approved for relapsed or refractory precursor B-cell acute lymphoblastic leukemia in adults and children. This study evaluates its safety profile through pharmacovigilance analysis of adverse events (AEs) reported in the FDA Adverse Event Reporting System (FAERS). We conducted a disproportionality analysis using four algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS). Data from 2014Q1 to 2023Q4 were analyzed to identify safety signals related to blinatumomab, along with a stratification analysis to examine AE onset timing. A total of 17,131 AE reports were retrieved from the FAERS database, with 6,266 indicating blinatumomab as the primary suspect. We identified 277 preferred terms (PTs) demonstrating significant disproportionality across all algorithms. Notably, unexpected AEs included Graft Versus Host Disease, myelosuppression, and hypokalaemia. Common AEs were consistent across gender and age groups, predominantly occurring within one month of treatment. This pharmacovigilance study utilizing the FAERS database identified potential AE signals associated with blinatumomab, providing essential insights for its safe clinical use.

Post-marketing safety concerns with luspatercept: a disproportionality analysis of the FDA adverse event reporting system.

Luspatercept, approved for treating beta thalassemia, myelodysplastic syndromes (MDS) associated anemia, and MDS with ring sideroblasts or myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis associated anemia, has uncertain long-term safety in large populations. This study analyzed adverse events (AEs) linked to luspatercept using data from the FDA Adverse Event Reporting System (FAERS) with data mining techniques. We collected and analyzed luspatercept-related reports from the FAERS database from the first quarter of 2022 through the first quarter of 2024. Disproportionality analysis was used in data mining to quantify luspatercept-related AE signals. A total of 46 AE signals were detected in 13 SOCs (system organ classes). In addition to the AEs identified during the clinical trial stage, this study also identified some unexpected and important AEs, such as product preparation error, prescribed overdose, product preparation issue, prescribed underdose, and acute hepatitis. Our study provides a comprehensive description of the post-marketing safety of luspatercept and identifies new potential AEs. Healthcare workers must be vigilant in avoiding product preparation errors, an adverse event that highlights the need for enhanced training and the participation of chemists in assessing medication utilization scenarios.

Safety assessment of selinexor: a real-world pharmacovigilance study

ABSTRACT Background Selinexor is approved for the treatment of relapsed or refractory multiple myeloma. However, a comprehensive understanding of adverse events associated with selinexor is lacking. Methods Clinical trials of selinexor in patients with multiple myeloma were reviewed. We investigated selinexor-related adverse events through data of the US Food and Drug Administration Adverse Event Reporting System (FAERS). The disproportionality analysis was conducted. Four algorithms were employed to evaluate the signals of adverse events. The adverse effects of selinexor combined with dexamethasone were compared with bortezomib and dexamethasone. Sensitivity analysis was performed to exclude consumer-reported adverse events. The onset of adverse reactions were calculated. Results A total of 1,698 reports related with selinexor from FAERS were identified. 6 significant system organ class and 42 significant preferred terms (PTs) were found. Unexpected significant adverse events including mania, acute kidney injury, orthostatic hypotension, and embolisms were identified. 14 PTs reported significant signals in treatment of selinexor combined dexamethasone compared with traditional treatment of bortezomib and dexamethasone. 45.2% of adverse events occurred within the first month of starting selinexor. Conclusions Comprehensive analyses of selinexor related adverse events are helpful for clinical detection of adverse events and timely intervention, advancing selinexor’s therapeutic progress in future treatment.

Safety profiles of IDH inhibitors: a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database

Abstract Background With the increased use of isocitrate dehydrogenase (IDH) inhibitors in acute myeloid leukemia (AML) and cholangiocarcinoma, the toxicity of these drugs is a growing concern. This study aimed to evaluate the adverse events (AEs) of IDH inhibitors based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods AE reports for IDH inhibitors (enasidenib, ivosidenib, and olutasidenib) were collected and analyzed from the time of launch through the first quarter of 2024. Only IDH inhibitors reported as the target drug and coded as the primary suspect (PS) were included in the analysis. AEs were standardized and classified according to the preferred term (PT) and system organ classification (SOC) in the Medical Dictionary for Regulatory Activities (MedDRA) version 26.0. Disproportionality analyses including the reporting odds ratio and the Bayesian confidence propagation neural network were performed in data mining to assess IDH inhibitor-relatedAEs. Differentiation syndrome was the AE of special interest. Results The reports number of enasidenib, ivosidenib, and olutasidenib was 11 616 357, 10 067 250, and 2 563 464, respectively. A total of 80 enasidenib-related signals involving 15 SOCs, 78 ivosidenib-related signals involving 17 SOCs, and 7 olutasidenib-related signals involving 4 SOCs were obtained. The most signals reported were “blood and lymphatic system disorders,” “infections and infestations,” and “nervous system disorders” in enasidenib. For signals of ivosidenib, the most frequently reported were “gastrointestinal disorders,” “general disorders and administration site conditions,” and “injury, poisoning and procedural complications.” Ivosidenib was the only IDH inhibitor with signals in “cardiac disorders.” Differentiation syndrome events were reported in 89, 40, and 2 cases for enasidenib, ivosidenib, and olutasidenib, respectively. The median time to onset was 26–31 days for ivosidenib and enasidenib. AML was the most common indication in the differentiation syndrome reports. Conclusions Our study identifies potential AE signals associated with IDH inhibitors and provides a broader understanding of the safety. The safety profiles highlight the need for long-term safety monitoring of IDH inhibitor recipients. Promptly monitoring and intervention in specific organ systems depending on the type of IDH inhibitor may improve the overall survival or enhance the quality of life. In the future, it will be necessary to validate our findings in prospective large-scale studies and to investigate the underlying mechanisms.

Safety assessment of rosuvastatin-fenofibrate combination in the treatment of hyperlipidemia based on FDA’s adverse event reporting system database

BackgroundWith the improvement of living standards, an increasing number of patients are presenting with mixed hyperlipidemia. In addition to cholesterol reduction, it is imperative to lower triglyceride levels. The combination of statin and fibrate for reducing lipid levels has commonly been applied in clinical therapy. However, the combination of drugs also increases the risk of adverse events (AEs). In this study, we analyzed the safety signals of rosuvastatin-fenofibrate combination by assessing the publicly available US Food and Drug Administration Adverse Event Reporting System (FAERS), so as to provide a reference for rational clinical use of rosuvastatin and fenofibrate, and reduce the occurrence of related AEs.MethodsReports to the FAERS from 1 January 2004 to 19 March 2020 were analyzed. The proportional report ratio (PRR), reporting odds ratio (ROR), and Bayesian Confidence Propagation Neural Network (BCPNN) analysis were used to extract data from FAERS for suspected signals referring to the combination of rosuvastatin and fenofibrate.ResultsA total of 68 safety signals were detected from the top 250 AEs in 3,587 reports, of which 28 signals were not included in the drug labels. All the detected AEs were associated with 12 System Organ Classes (SOC), such as gastrointestinal, musculoskeletal and connective tissue, general diseases, investigations and nervous system. The most frequent AEs were analyzed, and it was found that women generally have a higher susceptibility to experiencing AEs, including pain, nausea, fatigue, myalgia, diarrhea, dyspnea, headache, weakness, and dizziness.ConclusionClinicians should pay more attention to the AEs of gastrointestinal and muscular system during combination therapy, and it is recommended to strengthen pharmaceutical care during clinical application.

Drug-induced nasal septum perforation: a disproportionality analysis of the FDA adverse event reporting system database

ABSTRACT Background Nasal septum perforation represents a significant clinical concern, with limited investigations into the role of medications in its etiology. This study utilizes the FDA Adverse Event Reporting System (FAERS) database to identify the drugs associated with nasal septum perforation and assess their risk. Research design and methods This retrospective pharmacovigilance study analyzed drug-induced nasal septum perforation data from January 2004 to December 2023. Disproportionality analysis using reporting odds ratio (ROR) assessed drug associations with nasal septum perforation. Results For 552 identified cases, the most commonly reported drugs were bevacizumab (n = 56), fluticasone propionate (n = 50), methotrexate (n = 34), hydrocodone and acetaminophen (n = 22), and paclitaxel (n = 17). Twenty-six drugs showed positive risk signals, with the top five being azelastine hydrochloride and fluticasone propionate (ROR = 173.82), beclomethasone dipropionate (ROR = 90.91), oxymetazoline (ROR = 53.77), desmopressin (ROR = 51.43), and leucovorin (ROR = 42.83). Intriguingly, 18 of these drugs did not list nasal septum perforation as a known side effect. Conclusion This study provides a comprehensive overview of drug-induced nasal septum perforation from a pharmacovigilance perspective, highlighting the need for further research to clarify these associations and update drug safety information to reduce patient risk.

Associations of acute kidney injury with oral anticoagulants: a disproportionality analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database

ABSTRACT Objective The FDA Adverse Event Reporting System (FAERS) was used to evaluate the associations between oral anticoagulants (OACs) and acute kidney injury (AKI). Methods Disproportionality analysis was applied to data in the FAERS database from January 2004 to December 2023 to detect adverse events (AEs) for various OACs. The adjusted reporting odds ratios (RORs) calculated using multiple logistic regression were used to explore the risk factors for OACs-associated AKI. Results The crude RORs for the associations of AKI with warfarin, rivaroxaban, dabigatran, apixaban, and edoxaban were 1.35, 2.14, 2.98, 1.33, and 3.56, respectively. The risk of OACs-associated AKI was affected by age and sex, being higher in those aged 65 years and males. The adjusted RORs for rivaroxaban, dabigatran, apixaban, and edoxaban were 1.26, 1.67, 0.65, and 2.06, respectively.Nearly 50% of AKI cases occurred within the first 2 months, and each OAC was of the early-failure type. Hospitalization and mortality rates for AKI patients after OACs were 45.53% and 22.98%, respectively. Conclusions The study revealed a strong association between AKI and OACs, emphasizing the need for regular renal function monitoring , especially in elderly male patients. Further in-depth research is needed to confirm these exploratory findings.

Diabetic Ketoacidosis and the Use of New Hypoglycemic Groups: Real-World Evidence Utilizing the Food and Drug Administration Adverse Event Reporting System

Background: Diabetic ketoacidosis (DKA), a life-threatening complication, can occur in individuals with type 2 diabetes during illness, stress, or medication use. This study examines DKA signals in type 2 diabetes, focusing on sodium–glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl-peptidase-4 (DPP-4) inhibitors. Methods: DKA reports from Q1 2019 to Q3 2024 were retrieved from the FDA Adverse Event Reporting System (FAERS). Associations between primary exposure and outcomes were ascertained using four key metrics: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and Information Component (IC). Results: SGLT2 inhibitors exhibited the higher DKA risk in 2019–2021 (ROR: 314.86 [95% CI 301.76–328.53], PRR of 245.69 [95% CI 235.47- 256.36], IC of 6.90, and EBGM of 120), declining in 2022–2024. GLP-1 receptor agonists showed an ROR increase from 2.88 [95% CI 2.56–3.25] in 2019–2021 to 4.64 [95% CI 4.06–5.29] in 2022–2023, slightly declining to 3.95 [95% CI 3.27–4.74] in 2024. DPP-4 inhibitors exhibited a steady ROR rise from 6.81 [95% CI 5.52–8.40] in 2019–2021 to 8.57 [95% CI 6.24–11.76] in 2022–2023 and further to 11.02 [95% CI 6.71–18.10] in 2024. PRR, EBGM, and IC values followed similar trends. The age groups 41–60 and 61–91 years were the most affected, with hospitalization at its highest rate for DPP4-inhibitors in Q1-Q3 of 2024. Hospitalizations were also observed with GLP-1 receptor agonists and SGLT2 inhibitors. Life-threatening events and fatalities were also reported, with physicians contributing to most reports. Conclusions: DKA signals were observed for all three drug classes, particularly among elderly patients, highlighting the need for careful monitoring, especially during periods of illness or stress. However, the risk was higher in the SGLT2 inhibitor group than in the other groups.

Analysis of ADR reports of cetuximab based on the FDA adverse event reporting system database

This study aims to monitor and identify adverse events (AEs) associated with cetuximab, a drug used to treat various late-stage (metastatic) tumors, to improve patient safety and guide drug use. This study retrospectively analyzed the cases reported in the FDA adverse event reporting system (FAERS) related to the application of cetuximab from 2013 Q1 to 2022 Q4. Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the empirical Bayesian geometric mean (EBGM) algorithms, were employed to quantify the signals of cetuximab-associated AEs. A total of 8364225 reports were contained in the FAERS database, of which 5186 reports of cetuximab were identified as ‘primary suspected (PS)’ AEs. The application of cetuximab resulted in AEs in 22 system organ classes (SOCs), which preserved 176 significant disproportionality preferred terms (PTs) through the computation of four algorithms. The main SOCs (Skin and subcutaneous tissue disorders, investigations, metabolism and nutrition disorders, and blood and lymphatic system disorders) accounted for 58.63%. Some AEs were not on the drug label: speech disorder, intervertebral discitis, glomerulonephritis rapidly progressive and disseminated intravascular coagulation. This study identified new signals of adverse drug reactions (ADRs) other than those mentioned in the specification associated with cetuximab, providing valuable insights into the relationship between ADRs and cetuximab use. The findings highlight the importance of continuous surveillance to detect and manage AEs effectively, ultimately improving patient safety during treatment with cetuximab.

Infectious complications associated with immune and targeted anti-cancer therapies: a retrospective study of the FDA adverse events reporting system (FAERS)

ABSTRACT Background Immune and targeted anti-cancer therapies are associated with an increased risk of infectious complications. The objectives of the present study were to evaluate the infectious complications associated with immune and targeted anti-cancer drugs. Research design and methods This was a retrospective study for immune and targeted anti-cancer drugs submitted to the FDA Adverse Event Reporting System (FAERS) from 1996 to 20 March 2024. The primary outcome was the rate of infectious disease events, and the secondary outcomes were the incidence of febrile neutropenia (FN), all-cause mortality, and the top 10 infections in each class. Results Our study included 14 drug classes comprising 44 drugs. The incidence of infectious complications was 14.31% (110,671/773,130). The highest incidence rate was reported with IL-6 inhibitors (30.89%), the highest incidence of FN was reported with Histone deacetylase inhibitors (8.43%), and the highest all-cause mortality was reported with BCR-ABL tyrosine kinase inhibitors (17.17%). Conclusion Immune and targeted anti-cancer therapies vary in the incidence of infectious complications. Pirtobrutinib, copanlisib, sirolimus, vorinostat, and tocilizumab were associated with high infectious complications (>30%) that warrant emphasis in the clinical guidelines. Thus, clinicians should vigilantly monitor patients undergoing immune and targeted therapies for infectious complications and use antimicrobial prophylaxes when indicated.

Real-world safety evaluation of brivaracetam: insights from the US FDA Adverse Event Reporting System

ABSTRACT Background Brivaracetam (BRV) is a novel drug for the treatment of epilepsy. This study aimed to detect and characterize adverse events (AEs) associated with BRV from the first quarter of 2016 to the second quarter of 2024 using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Research design and methods We utilized disproportionality analysis methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), to assess the associations between reported AEs and BRV usage in the FAERS data. Results A total of 1,781 adverse event reports were analyzed, with Brivaracetam as the primary suspected drug. We identified 13 positive system organ classes (SOCs) and 78 positive preferred term signals (PTs), with a particular focus on nervous system disorders, psychiatric disorders, and injury, poisoning, and procedural complications. Exposures related to injury, poisoning, and procedural complications during pregnancy and lactation showed positive signals, including exposure before pregnancy, during breastfeeding, and during pregnancy. These exposures warrant significant attention. Conclusions Based on the FAERS database, we conducted a comprehensive analysis of AEs associated with BRV. This study aims to provide guidance for the clinical application of BRV in epilepsy treatment, thereby improving its safety.

Analysis of immune related adverse events of pembrolizumab using FAERS database

Objective: This study aims to investigate the risk signals associated with pembrolizumab and provide references for its safe and rational clinical use. Methods: Data on adverse events (AEs) related to pembrolizumab, reported from July 2014 to September 2023, were extracted from the US FDA Adverse Event Reporting System (FAERS) database. Data mining was conducted using the Proportional Reporting Ratio (PRR) method. AEs were classified and analyzed according to the System Organ Class (SOC) and Preferred Term (PT) from the Medical Dictionary for Regulatory Activities (version 26.1). Results: A total of 37,511 AE reports related to pembrolizumab were identified, involving 5,259 PTs and 22 SOCs. Using the PRR method, 931 positive signals were detected. The top 10 risk signals for pembrolizumab were all immune-related adverse events (irAEs) and important medical events (IMEs). The five PTs with the highest signal intensity were immune-mediated hypothyroidism, immune-mediated renal disorder, immune-mediated hepatic disorder, immune-mediated gastritis, and immune-mediated hyperthyroidism. The leading SOCs involved in AE reports were general disorders and administration site conditions (8,184; 14.11%), investigations (5,333; 9.19%), gastrointestinal disorders (4,962; 8.55%), respiratory, thoracic, and mediastinal disorders (4,937; 7.57%), and injury, poisoning, and procedural complications (3,611; 6.22%). The median time to onset of AE was 25 days (IQR 6-85 days), with the Weibull distribution test indicating an early failure-type curve. Gender and age analysis revealed that women were more likely to develop hypertension, alopecia, headache, hypothyroidism, and palmar-plantar erythrodysaesthesia syndrome, whereas men were more likely to develop interstitial lung disease, renal impairment, and death. Additionally, neutropenia was more prevalent in patients under 65 years of age, while interstitial lung disease and renal impairment were more common in patients aged 65 and above. Conclusion: Significant age- and gender-related differences were observed in AE signals with pembrolizumab, particularly for irAEs. Clinical attention should be directed towards the potential occurrence of irAEs at the initial stages of drug administration, with appropriate measures implemented as necessary.

A 13-years pharmacovigilance analysis of novel hormonal agents in prostate cancer using the FDA adverse event reporting system database

ABSTRACT Background Novel hormonal agents (NHAs), such as abiraterone, apalutamide, enzalutamide, and darolutamide, play a pivotal role in prostate cancer treatment. However, the toxicity spectrum of NHAs in the real-world has not been fully investigated. This study aims to analyze the adverse events (AEs) linked to NHAs. Methods The safety profiles of NHAs were evaluated by using the United States FDA Adverse Event Reporting System (FAERS) database. Disproportionality analysis methods were applied to compare the safety signals of AEs associated with NHAs. Results Our research has identified significant safety signals for all NHAs in vascular disorders, particularly noting elevated risk in the combined treatment involving docetaxel or poly ADP-ribose polymerase (PARP) inhibitors, specifically in blood and lymphatic system. Apalutamide, enzalutamide, and darolutamide displayed notable safety signals related to nervous system disorders, whereas abiraterone did not. Apalutamide exhibited specific AEs primarily linked to skin and subcutaneous tissue disorders, with severe AEs (SAEs) also concentrated in this category. Enzalutamide’s specific AEs were predominantly associated with gastrointestinal disorders. Meanwhile, abiraterone’s SAEs were mainly related to cardiac and hepatobiliary disorders. Conclusion Our study offers a comprehensive overview of safety signals associated with NHAs, providing a valuable reference for drug selection and future prospective research.

Post-marketing safety of antiseizure medications: Focus on serious adverse effects including drug reaction with eosinophilia and systemic symptoms (DRESS).

On November 28, 2023, the U.S. FDA issued a Drug Safety Communication, warning that antiseizure medications (ASMs) levetiracetam and clobazam can cause a rare but serious reaction, drug reaction with eosinophilia and systemic symptoms (DRESS). However, the risk of DRESS from other ASMs remains unclear. This observational study examined post-marketing safety of ASMs focusing on serious adverse events (AEs) reporting including DRESS. This retrospective, cross-sectional study analyzed the U.S. FDA Adverse Event Reporting System (FAERS) data from January 1, 2004, to March 31, 2024. Ten older (valproic acid, carbamazepine, oxcarbazepine, phenytoin, and phenobarbital) and newer (zonisamide, topiramate, lamotrigine, lacosamide, and brivaracetam) frequently used ASMs and three benzodiazepines (lorazepam, chlordiazepoxide, and diazepam) in clinical practice as alternative treatments were examined together with levetiracetam and clobazam, respectively. Disproportionality analysis, reporting odds ratio (ROR), was used to detect reporting risk signals of DRESS along with serious AE, hospitalization, death, and Stevens-Johnson Syndrome (SJS) for levetiracetam/clobazam and alternative treatments. A statistically significant reporting risk signal was detected when the lower boundary of the 95 % confidence interval for the RORs exceeded 1. Levetiracetam had significant reporting risks of serious AE, hospitalization, DRESS, and SJS. Older ASMs including valproic acid, carbamazepine, oxcarbazepine, phenytoin, and phenobarbital all had significant reporting risks of DRESS and SJS. Newer ASMs including zonisamide and lamotrigine had significant reporting risks of DRESS and SJS, while topiramate, lacosamide, and brivaracetam did not exhibit reporting risk for DRESS. Clobazam had significant reporting risks of serious AE, DRESS, and SJS. Lorazepam, chlordiazepoxide, and diazepam did not exhibit reporting risks for DRESS or SJS. Findings highlighted reporting risk signals of DRESS for levetiracetam/clobazam and alternative ASMs. Given the limitations from passive surveillance nature of FAERS, further surveillance and longitudinal studies are essential to evaluate and confirm our findings.

Vancomycin and linezolid: severe cutaneous adverse reactions to drugs

ABSTRACT Background Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and Acute Generalized Exanthematous Pustulosis (AGEP), pose significant therapeutic challenges. Vancomycin and linezolid have been linked to these life-threatening conditions, necessitating a better understanding of their associated risks. Methods We conducted a retrospective analysis using data from the FDA Adverse Event Reporting System (FAERS) database. Disproportionality and Bayesian statistical analyses were applied to evaluate the associations between vancomycin, linezolid, and SCARs, comparing the outcomes induced by these drugs. Results Of the 11,737,133 data, there were a total of 1024 vancomycin-associated SCARs and 125 cases of linezolid-associated SCARs. Vancomycin was strongly associated with DRESS, showing a Reporting Odds Ratio (ROR) of 53.79 (95% CI: 49.75–58.16), Proportional Reporting Ratio (PRR) of 50.38, and Empirical Bayesian Geometric Mean (EBGM) of 2.32. For SJS and TEN, vancomycin reported RORs of 8.04 and 15.63, respectively. Linezolid demonstrated lower associations, with RORs of 5.14 for DRESS and 2.36 for SJS. Conclusions Vancomycin presents a higher risk of SCARs compared to linezolid, particularly for DRESS. Underscoring the need for cautious use and the potential benefit of personalized medicine practices to improve patient safety.

A Real-World Disproportionality Analysis of Histamine H2-Receptors Antagonists (Famotidine): A Pharmacovigilance Study Based on Spontaneous Reports in the FDA Adverse Event Reporting System.

Famotidine is an H2 receptor antagonist and is currently used on a large scale in gastroenterology. However, Famotidine may also cause severe toxicity to organ systems, including the blood system, digestive system, and urinary system. The objective of this study was to scientifically and systematically investigate the adverse events (AEs) of Famotidine in the real world through the FDA Adverse Event Reporting System (FAERS) database. A disproportionality analysis was used to quantify the signals of AEs associated with Famotidine in FAERS data from the first quarter of 2004 to the first quarter of 2023. The clinical features, onset time, oral and intravenous administration and severe consequences of Famotidine induced AEs were further analyzed. Among the four tests, we found several AEs that were not mentioned in the drug label. For example, abdominal pain upper, abdominal discomfort, dyspepsia, liver disorder, gastrooesophageal reflux disease, and rhabdomyolysis. These AEs are consistent with the drug instructions. Interestingly, we found several unreported AEs, such as: cerebral infarction, hypocalcaemia, hallucination, visual, hypomagnesaemia, hypoparathyroidism, diabetes insipidus, vulvovaginal candidiasis, retro-orbital neoplasm, neuroblastoma recurrent, and malignant cranial nerve neoplasm. Most of our findings are consistent with clinical observations and drug labels, and we also found possible new and unexpected AEs signals, which suggest the need for prospective clinical studies to confirm these results and explain their relationships. Our findings provide valuable evidence for further safety studies.

Cyclin-dependent kinase 4/6 inhibitor-associated pulmonary toxicity: a disproportionality analysis from 2015 to 2023 based on the FAERS database

ABSTRACT Objectives This study aimed to describe the pulmonary toxicity of cyclin-dependent kinase 4/6 inhibitors (CDK 4/6 inhibitors) (palbociclib, ribociclib, and abemaciclib) in patients being treated for breast cancer using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Research design and Methods Disproportionality analysis was performed to assess pulmonary toxicity associated with CDK 4/6 inhibitors. Clinical characteristics, onset time, sensitivity analysis, subgroup analyses, drug combinations, comorbidities, and co-reported events were performed. Results Out of 83,505 CDK 4/6 inhibitor-related adverse events (AEs) documented in the FAERS database during the study period, 437 cases of pneumonitis, 555 cases of pulmonary edema, and 181 cases of pulmonary thrombosis related to CDK 4/6 inhibitors were analyzed. Pneumonitis and pulmonary thrombosis had the strongest signal strength in abemaciclib, pulmonary edema had the strongest signal strength in ribociclib. The median latency for pneumonitis, pulmonary edema, and pulmonary thrombosis was 66-173.5 days 27-131 days, and 68-279 days), respectively. Pulmonary toxicity is statistically significant disproportionality in females as well as in patients over 60 years old. Conclusion Abemaciclib was most strongly associated with pneumonitis and pulmonary thrombosis. Ribociclib was most strongly associated with pulmonary edema. The correlation with pulmonary toxicity was, in descending order, abemaciclib, ribociclib, and palbociclib.

Pharmacovigilance analysis of drug-induced hypofibrinogenemia using the FDA Adverse Event Reporting System.

Drug-induced hypofibrinogenemia has received increasing scrutiny; however, the specific drugs involved remain poorly characterized. Hypofibrinogenemia can have significant clinical implications, including increased bleeding risks. This study aimed to utilize the FDA Adverse Event Reporting System (FAERS) to identify and analyze drugs frequently implicated in drug-induced hypofibrinogenemia. A disproportionality analysis was conducted using FAERS data from January 2004 to March 2024. Various statistical tools were used, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio, Medicines and Healthcare Products Regulatory Agency metrics, and Bayesian confidence propagation neural network. The analysis included 17,627,340 cases involving 52,373,206 adverse events, with 1,661 cases identified as hypofibrinogenemia. The top five drugs associated with hypofibrinogenemia by case number were methotrexate (124 cases), tigecycline (119 cases), tocilizumab (100 cases), pegaspargase (83 cases), and alteplase (57 cases). The drugs ranked by signal strength based on ROR includederavacycline (ROR 2173.84, 95% CI 1208.80-3909.30), tigecycline (ROR 747.34, 95% CI 619.03-902.24), crotalidae polyvalent immune Fab (ROR 407.67, 95% CI 291.07-570.99), pegaspargase (ROR 216.06, 95% CI 173.15-269.61), and asparaginase (ROR 184.93, 95% CI 132.18-258.72). This analysis of FAERS data identified 52 drugs associated with hypofibrinogenemia, most (88.5%) of which do not mention this risk in their prescribing information. These findings demonstrate the need for the monitoring of blood fibrinogen and may serve as a reference for the explore of the characteristics and underlying mechanism of drug-induced hypofibrinogenemia in the real world.

Adverse events of Capmatinib: A real-world drug safety surveillance study based on the FDA adverse event reporting system (FAERS) database.

The present study aims to evaluate the adverse events associated with Capmatinib using real-world data, providing a reference basis for its rational use in clinical practice. Relevant data from the Food and Drug Administration adverse event reporting system database was mined. Next, reporting odds ratio and Bayesian confidence propagation neural network method were used to analyze real-world adverse events associated with Capmatinib. The study revealed significant adverse event signals of Capmatinib, primarily involving general disorders and administration site conditions, cardiac disorders, gastrointestinal disorders, respiratory, thoracic and mediastinal disorders, neoplasms benign, malignant and unspecified (including cysts and polyps) and investigations, among others. A total of 79 signals were identified, with 13 of them not mentioned in the drug's specifications. Taken together, our comprehensive analysis of the Food and Drug Administration adverse event reporting system database enhances the understanding of Capmatinib's safety profile, thereby contributing to informed decision-making in its clinical application and facilitating the timely management of associated adverse reactions.

Vancomycin Drug Reaction with Eosinophilia and Systemic Symptoms: Meta-Analysis and Pharmacovigilance Study

Background: Drug reaction with eosinophilia and systemic symptoms is a severe cutaneous reaction with a high mortality rate. It is challenging to diagnose due to its similar presentation to infectious disease syndromes, variation with the culprit drug, and lack of awareness. Methods: We searched PubMed, and Embase, for RegiSCAR-scored observational studies, the FDA Adverse Events Reporting System (FAERS) for adverse event reports, and the Allele Frequency Net Database (AFND) for HLA allele frequency. In our meta-analysis, we employed a random effects model to subgroup patients by ethnicity to determine the proportion of DRESS cases compared with various associated medications. Additionally, we identified a correlation between the proportion of cases and the presence of the HLA*A-32:01allele, which is suspected to predispose individuals to DRESS. Results: Twenty-one studies on 1949 DRESS cases in vancomycin and 2558 antimicrobial DRESS reports in the FAERS database were analyzed. Meta-analysis showed a 27% incidence of vancomycin-DRESS, with Caucasians having the highest proportion at 36%. The median latency for symptom onset was 21 days, with no female predisposition. The proportional incidence of vancomycin-DRESS did not correlate with the HLA-A*32:01 allele. The adjusted ROR for vancomycin was 2.40 compared to other antimicrobials, and the risk increased by 77% with concurrent antimicrobials. Piperacillin/tazobactam had a similar DRESS reporting risk at 0.95 (95%CI: 0.88–1.02). Conclusion: Vancomycin significantly contributes to the incidence of DRESS and is more closely related to ethnicity than to allele frequency, indicating that the HLA-A*32:01 allele may not be directly involved. Furthermore, the use of other antimicrobials can influence the reaction, underscoring the need to minimize antimicrobial use for better coverage.