Food And Drug Administration Adverse Event Reporting System Database Research Articles

Adverse event signal mining and severe adverse event influencing factor analysis of Lumateperone based on FAERS database.

Lumateperone has been approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia in adults since 2019, however, there is still a lack of data report on adverse reactions in real-world settings. Conducting data mining on adverse events (AEs) associated with Lumateperone and investigating the risk factors for serious AEs can provide valuable insights for its clinical practice. AE reports in the FDA Adverse Event Reporting System (FAERS) from 2019 Q4 (FDA approval of Lumateperone) to 2024 Q1 were collected and analyzed. Disproportionality in Lumateperone-associated AEs was evaluated using the following parameters: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Univariate and multivariate logistic regression analyses were conducted to identify the risk factors for Lumateperone-induced severe AEs. A total of 2,644 reports defined Lumateperone as the primary suspected drug was collected, including 739 reports classified as severe AEs and 1905 reports as non-severe AEs. The analysis revealed that 130 preferred terms (PTs) with significant disproportionality were based on the four algorithms, 67 (51.53%) of which were not included in the product labeling, affecting 6 systems and organs. In addition, dizziness (81 cases) was the most reported Lumateperone-associated severe AEs, and tardive dyskinesia showed the strongest signal (ROR = 186.24). Logistic regression analysis indicated that gender, bipolar II disorder, and concomitant drug use are independent risk factors for Lumateperone-associated severe AEs. Specifically, female patients had a 1.811-fold increased risk compared with male patients (OR = 1.811 [1.302, 2.519], p = 0.000), while patients with bipolar II disorder had a 1.695-fold increased risk compared with patients diagnosed with bipolar disorder (OR = 1.695 [1.320, 2.178], p = 0.000). Conversely, concomitant use of CYP3A4 inhibitors or drugs metabolized by CYP3A4 was associated with a decreased risk of severe AEs (OR = 0.524 [0.434, 0.633], P = 0.000). Collectively, this study provides critical insights into the safety profile of Lumateperone. It highlights the need for cautious use in high-risk populations, such as females and individuals with bipolar II disorder, and emphasizes the importance of monitoring for AEs, including dizziness and tardive dyskinesia. Healthcare also should remain alert to potential AEs not listed in the prescribing information to ensure medical safety.

Investigating drug-induced urinary retention: a pharmacovigilance analysis of FDA adverse event reports from 2004 to 2024

ABSTRACT Background Drug-induced urinary retention (DIUR) can severely impact patient quality of life and complicate treatment. This study investigates the incidence and characteristics of DIUR using data from the FDA Adverse Event Reporting System (FAERS) over 20 years. Methods FAERS reports related to urinary retention (UR) from Q1 2004 to Q1 2024 were analyzed. Potential causative drugs were identified, and the top 30 drugs with the most UR reports were ranked. Statistical disproportionality analyses, including Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR), were conducted to detect significant safety signals. Results Out of 17,703,515 reports in the FAERS database 28,423 cases of UR were identified. Anticholinergics, antidepressants, and opioids were the most frequently implicated drug classes. The highest ROR and PRR values were observed for drugs like ezogabine. Additionally, less commonly associated drugs, such as adalimumab and others, were implicated, suggesting potential under-recognition of this adverse effect. However, these associations should be interpreted with caution, as they do not confirm a direct causal relationship. Conclusion This study underscores the importance of pharmacovigilance in identifying and understanding DIUR. Further research is needed to confirm these findings and develop strategies to manage and reduce the risk, improving patient outcomes.

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 The Phosphoinositide 3-kinases (PI3Ks) family plays a crucial role in tumorigenesis. Alpelisib (inhibiting PI3Kα), copanlisib (inhibiting PI3Kα andPI3Kδ), duvelisib (inhibiting PI3Kδ and PI3Kγ), and idelalisib (inhibiting PI3Kδ) were developed to target the PI3K pathway. However, the toxicity limits their application to some extent. It’s necessary to investigate the adverse effects (AEs) of these inhibitors. Research design and methods We conducted a comparative analysis of the safety signals of AEs in PI3K inhibitors using disproportionality analysis in the FDA Adverse Event Reporting System database(FAERS). Results Our study identified significant safety signals for metabolic disorders with all PI3K inhibitors. Notable safety signals for gastrointestinal disorders were observed with most PI3K inhibitors, with the exception of copanlisib. Common AEs shared among all PI3K inhibitors included colitis and dehydration. Alpelisib displayed unique AEs associated with metabolic disorders, whereas copanlisib exhibited idiosyncratic AEs linked to cardiac and vascular disorders. Stevens-Johnson syndrome emerged as a common severe adverse event (SAE) among alpelisib, copanlisib, and idelalisib, while febrile neutropenia was prevalent among copanlisib, duvelisib, and idelalisib. Intestinal perforation was solely associated with alpelisib. Conclusions The safety profiles of the five PI3K inhibitors vary concerning adverse events. These findings could guide drug selection and inform future prospective research.

Drug-Related Keratitis: A Real-World FDA Adverse Event Reporting System Database Study.

This study aimed to assess the drug risk of drug-related keratitis and track the epidemiological characteristics of drug-related keratitis. This study analyzed data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from January 2004 to December 2023. A disproportionality analysis was conducted to assess drug-related keratitis with positive signals, and drugs were classified and assessed with regard to their drug-induced timing and risk of drug-related keratitis. A total of 1606 drugs were reported to pose a risk of drug-related keratitis in the FAERS database, and, after disproportionality analysis and screening, 17 drugs were found to significantly increase the risk of drug-related keratitis. Among them, seven were ophthalmic medications, including dorzolamide (reporting odds ratio [ROR] = 3695.82), travoprost (ROR = 2287.27), and brimonidine (ROR = 2118.52), and 10 were non-ophthalmic medications, including tralokinumab (ROR = 2609.12), trazodone (ROR = 2377.07), and belantamab mafodotin (ROR = 680.28). The top three drugs having the highest risk of drug-related keratitis were dorzolamide (Bayesian confidence propagation neural network [BCPNN] = 11.71), trazodone (BCPNN = 11.11), and tralokinumab (BCPNN = 11.08). The drug-induced times for non-ophthalmic medications were significantly shorter than those for ophthalmic medications (mean days, 141.02 vs. 321.96, respectively; P < 0.001). The incidence of drug-related keratitis reached its peak in 2023. Prevention of drug-related keratitis is more important than treatment. Identifying the specific risks and timing of drug-induced keratitis can support the development of preventive measures. Identifying the specific drugs related to medication-related keratitis is of significant importance for drug vigilance in the occurrence of drug-related keratitis.

Association of anxiolytic drugs with Torsade de Pointes: a pharmacovigilance study of the Food and Drug Administration Adverse Event Reporting System.

This study aimed to determine the association of Torsade de Pointes (TdP) with anxiolytic drugs and present a detailed overview of anxiolytic-induced cases of TdP reported to the Food and Drug Administration Adverse Event Reporting System (FAERS). All cases of anxiolytic-induced TdP (n = 260) between 1990 and 2020 were retrieved from the FAERS database using the Preferred Term 'Torsade de Pointes, code: 10044066' from the Medical Dictionary for Regulatory Activities (MedDRA version 22). Four data-mining algorithms were used for disproportionality analysis: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and Information Content (IC). Anxiolytics with ≥3 TdP cases were included. Of a total of eight drugs, this study identified seven signals of TdP, of which six signals were new, namely for alprazolam, bromazepam, lorazepam, meprobamate, midazolam, and oxazepam. Based on disproportionality analysis, among new signals, the highest risk of TdP was observed with bromazepam and midazolam. Alprazolam showed the lowest risk for TdP, while diazepam did not reach significant disproportionality. This study identified six new signals of TdP among anxiolytic drugs, so warranting stringent clinical studies to ascertain the actual risk of TdP and ensure patient safety. This study is registered at ClinicalTrials.gov (NCT.gov ID: NCT04293432).

Rhabdomyolysis associated with concomitant use of colchicine and statins in the real world: identifying the likelihood of drug-drug interactions through the FDA adverse event reporting system.

Currently, there remains substantial controversy in research regarding whether the concomitant use of colchicine and statins increases the occurrence of rhabdomyolysis, warranting further substantiation. This study aimed to identify the likelihood drug-drug interactions (DDIs) for the co-administration of colchicine and statins resulting in rhabdomyolysis. A disproportionality analysis was conducted by using data sourced from the US Food and Drug Administration Adverse Event Reporting System (FAERS) to detect rhabdomyolysis signals associated with the combined use of colchicine and statins. The association between (colchicine/statins/colchicine and statins) and rhabdomyolysis were evaluated using information component (IC). DDI signals were calculated based on the Ω shrinkage measure and Bayesian confidence propagation neural network (BCPNN) method. Furthermore, stratification was performed based on colchicine and individual statins agents. In total, 11,119 reports of rhabdomyolysis were identified in the FAERS database, 255 (2.29%) involved both colchicine and statins. Our analysis showed potential DDI signals of rhabdomyolysis (Ω025 = 1.17) among individuals concurrent use of colchicine and statins. Moreover, further drug-specific analysis suggests DDI signals in the colchicine-atorvastatin pair (Ω025 = 1.12), and colchicine-rosuvastatin pair (Ω025 = 1.05), along with a higher proportion of rhabdomyolysis (IC025 = 5.20) and (IC025 = 4.26), respectively. The findings suggest that concomitant use of colchicine and statins may increase the risk of rhabdomyolysis, particularly when combined with atorvastatin or rosuvastatin. Therefore, healthcare professionals should pay special attention to life-threatening AE such as rhabdomyolysis, when co-prescribing colchicine statins.

Risk of Suicide, Hair Loss, and Aspiration with GLP1-Receptor Agonists and Other Diabetic Agents: A Real-World Pharmacovigilance Study.

With the increasing popularity of glucagon-like peptide 1 receptor agonists (GLP1-RAs), numerous safety concerns arose pertaining to suicide, hair loss, and aspiration risks. We attempted to validate these concerns. We queried four pharmacovigilance databases to compare GLP1-RAs to sodium-glucose transporter 2 inhibitors (SGLT2is) with respect to these adverse events (AE): the FDA Adverse Event Reporting System (FAERS), the Australian Database of Adverse Event Notifications (DAEN), the European Medicines Agency's (EudraVigilance), and the World Health Organization-Vigibase. OpenVigil 2.1 was utilized to perform a disproportionality analysis for GLP1-RAs, SGLT2is, dipeptidyl peptidase 4 inhibitors (DPP4is), sulfonylureas, metformin, and insulin. The following indices were extracted from the FAERS database from Q4/2003 until Q3/2023: relative reporting ratio (RRR), proportional reporting ratio (PRR), reporting odds ratio (ROR), and chi-squared (χ2). A positive signal was detected if PRR > 2 and χ2 > 4 for any drug-event pair. No positive signals were observed between GLP1-RAs and either suicide, hair loss, or aspiration risks. Semaglutide [ROR = 0.60 (0.51-0.71)] and liraglutide [ROR = 0.28 (0.23-0.35)] had higher suicidal events than DPP4is and SGLT2is. GLP1-RAs were the most reported class with hair loss [ROR = 0.61 (0.60-0.64)], and semaglutide, liraglutide, and dulaglutide were the three leading medications. GLP1-RAs ranked lower with aspiration events, which were led by sitagliptin and DPP4is as a group. GLP1-RAs exhibit higher reporting of suicide, hair loss, and aspiration events when compared to several other antidiabetic medications despite not meeting the criteria for positive signals yet. This warrants intensive monitoring and reporting.

Safety assessment of anti-B cell maturation antigen chimeric antigen receptor T cell therapy: a real-world study based on the FDA adverse event reporting system database.

On April 18, 2024, the U.S. Food and Drug Administration officially required updating of the "boxed warning" for T cell malignancies for all chimeric antigen receptor T cell (CAR-T) therapies. Given the clinical significance of these therapies, a rigorous safety assessment is paramount. However, comprehensive real-world safety studies have been lacking for the newly marketed CAR-T products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), which target B cell maturation antigen, especially regarding the risk of secondary malignancies. Therefore, we aimed to thoroughly analyze the adverse events (AEs) information in the FDA Adverse Event Reporting System (FAERS) database to comprehensively understand the safety risks of ide-cel and cilta-cel. We extracted AE reports related to ide-cel and cilta-cel from the FAERS database (https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html.) from January 1, 2019 to December 31, 2023. Disproportionality analysis and Bayesian analysis were used to identify risk signals across subgroups and specific cases (including for death and secondary malignancies). Weibull distribution analysis was employed to determine the time to AE onset. A total of 695 AE reports for ide-cel and 848 for cilta-cel were included in the FAERS database. This analysis identified 81 positive signals for ide-cel and 74 for cilta-cel. Notably, comparisons with the drug labels revealed "unexpected signals," including febrile bone marrow aplasia (reporting odds ratio=69.10; confidence interval 39.12-122.03) and plasma cell myeloma (12.45; 8.18-18.95) for ide-cel, and increased serum ferritin (24.98; 8.0-77.58) and large intestine perforation (18.57; 5.98-57.69) for cilta-cel. Both drugs showed a higher AE incidence among male recipients and patients aged ≥65 years, although female recipients faced a greater risk. Most AEs occurred at the early stage of administration. However, secondary malignancies were detected for both drugs, primarily occurring one-year post-administration. This study provides a foundation for understanding the safety profile of CAR-T cell therapy, particularly in relation to the emergence of secondary malignancies. Such insights are helpful for clinical decision-making and the safe and effective utilization of these therapeutic agents.

Real-world safety profile of eculizumab: an analysis of FDA adverse event reporting system and systematic review of case reports

ABSTRACT Background Most of the safety data regarding eculizumab came from clinical trials, while its safety information in the real world is still limited. Research design and methods The data of eculizumab in the FDA Adverse Event Reporting System (FAERS) database (from the first quarter of 2007 to the first quarter of 2023) was collected and analyzed. The case reports of adverse drug reactions (ADRs) related to eculizumab in PubMed, Embase and Web of Science before May 2023 were systematically reviewed. Results A total of 464 ADRs of eculizumab were identified in the FAERS database. The top five ADRs with the highest proportional reporting ratio (PRR) are total complement activity decreased, extravascular hemolysis, hemoglobinuria, total complement activity increased and breakthrough hemolysis. Fifty-one cases of ADR related to eculizumab were identified from 44 publications. The number of reported cases of eculizumab associated Neisseria gonorrhoeae infection in case reports was observed to be comparable to the number of cases of Neisseria meningitidis infection. Conclusions Clinicians must pay close attention to the risk of infections in patients receiving eculizumab, including severe N. meningitidis infection and other potentially fatal infections such as N. gonorrhoeae infection. In addition, The possible emergence of new ADRs should be vigilant during clinical medication.

Drug-induced erectile dysfunction: a real-world pharmacovigilance study using the FDA adverse event reporting system database.

The comprehensive quantitative and comparative risk data of drug-induced erectile dysfunction (ED) are still lacking, and this study aims to supplement this information. We reviewed all the ED reports in the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2023 and summarized a potential ED culprit-drug list and its corresponding reporting frequency. The reporting odds ratio (ROR) method was used to conduct disproportionality analysis. A total of 20,098 ED reports were retrieved from the FAERS database, which recorded 734 different ED culprit-drugs, involving 74 drug classes. Finasteride was the drug with the highest reporting frequency, and urologicals was the drug class with the highest reporting frequency. In disproportionality analysis, 209 drugs with positive signals showed a close relationship with ED occurrence, among which finasteride was the drug with the highest signal strength. Among 209 drugs with positive signals, 27 were compound preparations, and the risk level of compound preparations was usually higher than their single active ingredient. Our study integrated quantitative and comparative ED risk data of 734 drugs by using the FAERS database, which can provide reference information for regulators, medical personnel, and others involved in drug management and use.

Catatonia related to tacrolimus: a real world pharmacovigilance study of FDA adverse event reporting system (FAERS) database

ABSTRACT Background Emerging case reports have highlighted that catatonia may be a complication that is easily misdiagnosed. Our study aimed to summarize the clinical characteristics of patients with tacrolimus-induced catatonia and assess the association between tacrolimus and catatonia through disproportionality analysis. Research design and methods We conducted a retrospective pharmacovigilance study using the FAERS database, analyzing data up to the third quarter of 2023. The clinical characteristics of the reported cases were summarized using descriptive statistics. Information component (IC) and reporting odds ratio (ROR) were used to evaluate the association between tacrolimus and catatonia. Results There were 66 reports of tacrolimus-related catatonia, with the majority of cases occurring in the United States (78.79%). The risk signal for tacrolimus-related catatonia was significantly higher compared to all other drugs (ROR 3.222 [2.524, 4.111], IC 1.632 [1.273, 1.991]). A significant association was detected in both male and female, while the risk signal of tacrolimus-associated catatonia was only found in the subgroups aged over 40 years. Conclusions Our study identified a safety signal for the association between tacrolimus and catatonia compared to all other drugs in FAERS database, particularly in patients aged 40 and above.

Ocular adverse events associated with antibody-drug conjugates in oncology: a pharmacovigilance study based on FDA adverse event reporting system (FAERS).

Antibody-drug conjugates (ADCs) have emerged as the focus and hotspots in the cancer field, yet the accompanying ocular toxicity has often been underestimated. We aimed to comprehensively and comparatively analyze the risk of ocular toxicity associated with various ADCs using the FDA Adverse Event Reporting System (FAERS) database. Data were extracted from the FAERS database from Q3 2011 to Q3 2023. We analyzed the clinical characteristics of ADCs-related ocular adverse events (AEs). These data were further mined by proportional analysis and Bayesian approach to detect signals of ADCs-induced ocular AEs. Moreover, the time to onset of ocular toxicity was also evaluated. A total of 1,246 cases of ocular AEs were attributed to ADCs. Ocular toxicity signals were observed in patients treated with belantamab mafodotin, brentuximab vedotin, enfortumab vedotin, mirvetuximab soravtansine, sacituzumab govitecan, trastuzumab deruxtecan, and trastuzumab emtansine. Of these, belantamab mafodotin, trastuzumab emtansine, and mirvetuximab soravtansine, whose payloads are microtubule polymerization inhibitors, were more susceptible to ocular toxicity. The ten most common ADCs-related ocular AEs signals are keratopathy [ROR = 1,273.52, 95% CI (1,129.26-1,436.21)], visual acuity reduced [ROR = 22.83, 95% CI (21.2-24.58)], dry eye [ROR = 9.69, 95% CI (8.81-10.66)], night blindness [ROR = 259.87, 95% CI (228.23-295.89)], vision blurred [ROR = 1.78, 95% CI (1.57-2.02)], photophobia [ROR = 10.45, 95% CI (9.07-12.05)], foreign body sensation in eyes [ROR = 23.35, 95% CI (19.88-27.42)], ocular toxicity [ROR = 144.62, 95% CI (117.3-178.32)], punctate keratitis [ROR = 126.21, 95% CI (101.66-156.69)], eye disorder [ROR = 2.71, 95% CI (2.21-3.32)]. In terms of onset time, sacituzumab govitecan displayed an earlier onset of 21days, while trastuzumab deruxtecan exhibited the latest onset of 223days. ADCs may increase the risk of ocular toxicity in cancer patients, leading to serious mortality. With the widespread application of newly launched ADCs, combining the FAERS data with other data sources is crucial for monitoring the ocular toxicity of ADCs. In addition, novel ocular toxicity signals not documented in product labeling were detected. Further research will be necessary to validate our findings in the future.

Post-marketing drug safety surveillance of enfortumab vedotin: an observational pharmacovigilance study based on a real-world database.

Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) that has been approved by the FDA for patients with locally advanced or metastatic urothelial carcinoma (UC). This study presents a comprehensive pharmacovigilance analysis of the post-marketing safety profile of EV in the real-world based on the US Food and Drug Administration Adverse Event Reporting System (FAERS). Adverse event (AE) reports regarding EV between January 2020 and December 2023 were obtained from the FAERS database. The standardized MedDRA query (SMQ) narrow search AEs on the preferred term (PT) level were used. Disproportionality analysis was performed to identify the AE signals for EV with the reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN). A total of 2,216 reports regarding EV were included in the present study. SMQ analysis results indicated that a stronger strength signal was found in severe cutaneous adverse reactions, retroperitoneal fibrosis, and peripheral neuropathy. A total of 116 significant disproportionality PTs referring to 14 system organ classes (SOCs) were retained by disproportionality analysis, with 49 PTs not listed on the EV drug label. Frequently reported EV-related AEs included rash, peripheral neuropathy, decreased appetite, alopecia, and pruritus. The time to onset of the majority of EV-related AEs was within 30 days (66.05%), with only 0.73% events occurring after 1 year. The disproportionality analysis highlights that dermatologic toxicity and peripheral neuropathy were the major AEs induced by EV. The potential AEs not listed on the drug label were mainly related to gastrointestinal, hepatic, and pulmonary events. Further research is needed to confirm and explore the EV-related AEs in clinical practice.

Reassessment of pioglitazone and bladder cancer based on FAERS database

ABSTRACT Background The association between pioglitazone (PLZ) and bladder cancer (BC) remains controversial in several randomized control trials, meta-analyses of multiple prospective studies, and large-scale observational studies. Research design and methods Adverse event (AE) data from 1 January 2004 to 31 March 2024 were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analysis were applied to quantify the signals of PLZ related BC. Results In total, 17,627,524 AE reports were recorded in the FAERS database, of which 1366 were PLZ-related BCs. More male than female patients were reported. The median age of patients was 70 years old. The peak in the annual report occurred in 2011. A total of 602 AEs reported time to onset (TTO) and the median TTO was 1023 days. In this study, BC and BC recurrence were strong signal, whereas BC stage 0 (with cancer in situ), stage ii and iii were weak signals. Conclusions This study comprehensively demostrated the PLZ-induced risk of BC in patients with diabetes mellitus using the FAERS database. The results demonstrated that the patients treated with PLZ were more likely to develop BC. The male and aging attributed more cases to BC-related reports of PLZ treated patients.

Systematic analysis of the adverse effects of commonly used clinical tetracycline drugs based on the FAERS database

ABSTRACT Background Tetracyclines are a class of antibacterial drugs commonly used in clinical practice, but there is no systematic analysis of the adverse effects (AEs) of these drugs. We performed such pharmacovigilance analyses using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database to explore tetracycline-related AEs. Research design and methods We used the pharmacovigilance analysis tool Open Vigil 2.1 to access FAERS data and obtained AE reports from January 2004 to June 2023, including doxycycline, minocycline, tigecycline, omadacycline, sarecycline, and eravacycline as the top suspect drugs. The signal value of the AE of the analyzed drug was calculated by the reporting odds ratio (ROR). Results A total of 15,020 cases were identified by analyzing drugs. In terms of adverse signals, doxycycline caused gastrointestinal mucosal necrosis (ROR = 1699.652); minocycline was reported to cause bone hyperpigmentation (ROR = 30976.223); tigecycline is responsible for blood fibrinogen decreased (ROR = 1714.078). Conclusions AE reports of tetracycline drugs varied significantly. We found some AEs not mentioned in the instruction, such as the ototoxicity of tetracyclines. Doxycycline was associated with psychiatric side effects; minocycline presented in thyroid and skin tissue-associated tumors; abnormal signals were detected with eravacycline in the blood system.

Detection and analysis of the safety profile of talazoparib based on FAERS database

ABSTRACT Background Talazoparib was approved for the treatment of breast cancer. However, the safety of talazoparib in a large population sample over an extended period remained uncertain. The objective of this study is to offer guidance for the secure utilization of talazoparib in clinical settings. Methods Four algorithms were used to quantify the signals of talazoparib associated adverse events(AEs), using data from the food and drug administration adverse event reporting system(FAERS) between fourth quater of 2018 and second quater of 2023. Results A total of 7,186,517 records were reported, with 737 indicating talazoparib as the primary suspected (PS) AEs. A total of 40 significant preferred terms (PTs) that adhere to the four algorithms were simultaneously retained. There is a possibility of experiencing unforeseen and noteworthy AEs, including embolism(0.46%), pulmonary embolism(1.06%), hyponatremia(0.46%), hypokalemia(0.40%), hematuria(0.33%), and pericardial effusion(0.26%). Most of the AEs related to talazoparib occurred within the initial month of starting the medication, with a median onset time of 79 days (IQR: 22–207 days). Conclusion Results of our study were consistent with clinical observations, and we also found potential new and unexpected AEs signals for talazoparib, suggesting prospective clinical studies were needed to confirm these results and illustrate their relationship. Our results may provide valuable evidence for further safety studies of talazoparib.

Amiodarone-Induced Anaphylaxis.

Background: Amiodarone-induced anaphylaxis is seldom reported. The mechanism of this anaphylaxis is unknown. Methods: A literature search was carried out with keywords "Amiodarone" and "Anaphylaxis" and "polysorbate 80" or "hypotension." A search using "amiodarone" in the FDA Adverse Event Reporting System (FAERS) from 1969 to 2024 was also conducted. Results: There are a total of 10 cases of amiodarone-induced anaphylaxis in the literature. Six patients were male. Ages ranged from 15 to 86years old. Nine cases were triggered by intravenous injection (IV) and one by oral administration. Eight patients did not have previous exposure to amiodarone. The trigger times for IV amiodarone were immediate to 90 minutes. All nine cases of IV amiodarone resulted in hypotension (90%), with an immeasurable blood pressure (70%). Presentations included bronchospasm or a skin rash (60%), angioedema (40%), and unconsciousness (20%). Only one patient had a history of allergy to penicillin and sulfonamide. An amiodarone skin test was positive on one patient. Increased blood tryptase (4 cases), positive basophil activation test to amiodarone (2 cases), increased eosinophil count (1 case), and increased serum IgE (1 case) were reported. Amiodarone was terminated in 80% of the patients. Epinephrine, norepinephrine, antihistamine-1, or steroids were used to rescue patients. Four patients were intubated. All patients fully recovered. In the FAERS database, 89 cases of amiodarone-associated anaphylaxis were reported, resulting in 14 deaths. Conclusions: Solvent polysorbate 80, amiodarone, and iodide may contribute to amiodarone-induced anaphylaxis. Prompt treatment is the key to saving patients.

Indications and adverse events of teriparatide: based on FDA adverse event reporting system (FAERS).

Teriparatide is approved for osteoporosis. Post-marketing surveillance is critical given its widespread use. To investigate adverse events (AEs) associated with teriparatide using the FAERS database, compare association strengths for key AEs, and explore potential applications to provide clinical reference. FAERS data from 2004 to 2023 were analyzed. Reports where teriparatide was the primary suspect drug were included. Adverse events were mapped to System Organ Classes and Preferred Terms. Disproportionality analysis using ROR, PRR, BCPNN and EBGM algorithms was conducted to detect safety signals. Out of 107,123 reports with teriparatide as the primary suspect, key AEs identified included pain in extremity (PRR: 4.54), muscle spasms (PRR: 5.11), fractures (PRR range: 17.67-552.95), and increased calcium levels (PRR: 50.73). Teriparatide exhibited a stronger association with increased calcium levels (PRR: 50.73) compared to fractures (PRR range: 17.67-552.95). Notably, only 10.86% of AE reports were submitted by physicians and another 10% by other health professionals. Subset analyses showed a higher consistency of reported AEs from health professionals compared to the general dataset. Off-label uses were noted in conditions such as arthritis (0.57%) and cancer (0.12%). For osteoporosis, main AEs were pain (18.2%), fractures (12.4%), muscle spasms (7.7%), and nausea (6.5%), while glucocorticoid-induced osteoporosis AEs included fractures (24.1%), pain (13.2%), decreased bone density (9.8%), and nausea (5.1%). Our findings provide real-world safety data on teriparatide, revealing key AEs and their association strengths. The low proportion of reports by healthcare professionals suggests the need for cautious interpretation. Continuous vigilance and further research are imperative to guide teriparatide's clinical use.

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

Using 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. Data 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. A 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." In 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.

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.