Pharmacovigilance Analysis of Vinorelbine: Cardiopulmonary and Pediatric Safety Profiles Based on FAERS and VigiBase Data

Pharmacovigilance Analysis of Vinorelbine: Cardiopulmonary and Pediatric Safety Profiles Based on FAERS and VigiBase Data | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Pharmacovigilance Analysis of Vinorelbine: Cardiopulmonary and Pediatric Safety Profiles Based on FAERS and VigiBase Data Ye Zhang, Mengnan Shuai, Dan Huang, Minghua Yang, Shengfeng Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8245600/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Vinorelbine is a widely used vinca alkaloid chemotherapeutic agent. Although its hematologic and gastrointestinal toxicities are well characterized, its cardiopulmonary safety profile remains insufficiently defined, and evidence in pediatric populations is limited. This study aimed to systematically evaluate vinorelbine-associated adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS) and WHO VigiBase databases, with particular focus on cardiopulmonary events and pediatric safety. AEs from FAERS (2004 Q1-2024 Q4) and VigiBase (up to 2024 Q4) were analyzed using disproportionality methods including reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) to identify potential safety signals. Among 1,712 FAERS and 16,175 VigiBase reports listing vinorelbine as the primary suspected drug, 210 significant signals were detected across multiple system organ classes. Strong associations were found not only with blood and lymphatic system disorders but also with respiratory, thoracic and mediastinal disorders, and cardiac disorders, indicating notable cardiopulmonary safety concerns. Most AEs occurred within 30 days after administration. In pediatric patients, vinorelbine showed a significant association with endocrine disorders. These findings underscore the need for enhanced monitoring of cardiopulmonary effects during vinorelbine treatment, particularly during combination therapy, and heightened vigilance for endocrine-related AEs in pediatric patients. Health sciences/Cardiology Health sciences/Diseases Biological sciences/Drug discovery Health sciences/Medical research Vinorelbine FAERS database VigiBase database Pharmacovigilance Cardiopulmonary Events Figures Figure 1 Figure 2 Figure 3 Introduction Vinorelbine is a semisynthetic vinca alkaloid chemotherapeutic agent with a higher affinity for mitotic microtubules, demonstrating superior efficacy in treating non-small cell lung cancer and breast cancer compared to vincristine and vinblastine [ 1 ] . Despite its widespread clinical application, the safety concerns associated with vinorelbine cannot be overlooked. Among the adverse drug events (AEs) of vinorelbine, hematologic and gastrointestinal reactions have been extensively documented. However, increasing attention has been drawn to its cardiopulmonary adverse effects in recent years. More and more studies suggest that cardiopulmonary adverse reactions to vinorelbine may be more common than previously anticipated [ 2 , 3 ] . Furthermore, the safety profile of vinorelbine in pediatric patients remains inadequately characterized, as current prescribing information and clinical guidelines provide limited guidance for this population. Given these concerns, this study conducted a systematic analysis of vinorelbine-associated AEs using real-world data from the FDA Adverse Event Reporting System (FAERS) and the WHO VigiBase database. The primary focus was to assess the incidence and signal strength of cardiopulmonary AEs, and to further explore the temporal distribution of these events as well as the occurrence of AEs in pediatric patients. In addition to addressing known adverse reactions, this study also identified potential under-recognized drug risks, providing a more comprehensive safety assessment. The findings offer important insights into the safety of vinorelbine and provide valuable data to support the risk management and monitoring strategies in clinical practice. Methods Data Sources The data utilized in this study was sourced from FAERS and WHO VigiBase databases. As for FAERS, the database is updated quarterly [ 4 ] .Raw data from the first quarter of 2004 to the fourth quarter of 2024 was extracted. Each quarterly dataset includes seven tables: the Demographics (DEMO) table, Adverse Event (REAC) table, Drug Usage (DRUG) table, Outcome (OUTC) table, Report Source (RPSR) table, Therapy (THER) table, and Diagnosis (INDI) table. And for the WHO VigiBase database, data were retrieved via the VigiBase public interface using Python 3.10, encompassing all publicly accessible drug-related data up to December 2024. Importantly, VigiBase provides only aggregated reporting-level data rather than individual case safety reports (ICSRs). This constraint precludes granular demographic analyses but facilitates robust disproportionality assessments, aligning with the core objectives of pharmacovigilance signal detection. Data Processing Duplicate reports were handled via a deduplication algorithm where in the report with the most recent FDA receipt date (FDA-DT) was retained for the cases with matching CASEID. In instances where CASEID and FDA-DT were identical, the record with the higher PRIMARYID was chosen. Adverse event terms were processed and categorized using the Standardized MedDRA Queries (SMQs). Data from the VigiBase platform were yielded in JSON format, which were subsequently processed and analyzed via the Pandas library for data wrangling and quality validation. Standardization procedures included: harmonization of adverse event terminology using MedDRA (version 26.0) for consistent coding; mapping of drug names to BASENAME entries in the WHO Drug Dictionary to ensure nomenclature uniformity; and standardization of date formats across the two databases to facilitate cross-dataset comparability. Furthermore, to refine the signa detection analysis, we excluded reports of events that are inherently non-pharmacological, including but not limited to various injures, procedural complications, and congenital or hereditary diseases. Data Standardization The terminology for AEs was standardized and translated using the 26.0 version of the Medical Dictionary for Regulatory Activities (MedDRA). AEs belonging to the same preferred term (PT) were consolidated, and the PTs were categorized and organized according to the System Organ Class (SOC). Data Extraction Adverse event reports in which vinorelbine, either by its generic or brand name, was the primary suspected drug were extracted. Data Analysis The Reporting Odds Ratio (ROR) method and the Bayesian Confidence Propagation Neural Network (BCPNN) method were used simultaneously to detect AE signals associated with the drug. AE signals were considered valid only if they met the threshold of both methods. All analyses were performed utilizing a standard 2×2 contingency table for the assessment of disproportionality, with comprehensive mathematical formulas for the calculation of both ROR and IC provided in Supplementary Table S1 and Table S2. Results Basic Information of AE Reports A total of 55,182,766 cases were reported in the FAERS database from Q1 2004 to Q4 2024. Based on the study criteria, 1,711 reports listed vinorelbine as the primary suspected drug. The reporting population consisted of 47.9% females and 31.4% males, while gender was unreported in 20.7% of cases. Patient age ranged broadly, with the majority of reports involving adults between 18 and 85 years. As of December 31, 2024, a total of 117,935,366 cases had been reported in the VigiBase database. Of these, 16,175 cases were associated with vinorelbine. The gender distribution showed that 56.9% of cases occurred in females and 37.6% in males, while 5.5% were reported with unknown gender. Geographically, Europe accounted for the highest proportion of cases among the five continents. The basic information for vinorelbine-associated AEs is shown in Table 1 . Table 1 Basic demographic and reporting characteristics of vinorelbine-associated AEs in the FAERS and VigiBase databases. Item FAERS n = 1711, (%) VigiBase n = 16175, (%) Gender Male 537 ( 31.4 ) 6076 ( 37.6 ) Female 819 ( 47.9 ) 9205 ( 56.9 ) Unknown 355 ( 20.7 ) 894 ( 5.5 ) Age < 18 48 ( 2.8 ) 267 ( 1.7 ) 18 ~ 64 890 ( 34.5 ) 8584 ( 53.1 ) ≥ 65 455 ( 26.6 ) 4945 ( 30.6 ) Unknown 618 ( 36.1 ) 2379( 14.7 ) Reporting Countries Africa 16 ( 0.9 ) 310 ( 1.9 ) Asia 250 ( 14.6 ) 6131 ( 37.9 ) Europe 791 ( 46.2 ) 6179 ( 38.2 ) Oceania 22 ( 1.3 ) 157 ( 1.0 ) Americas 273 ( 16.0 ) 3398 ( 21.0 ) Unkown 359 ( 21.0 ) NA Report Year Before 2015 1194 ( 69.8 ) 7388 ( 45.7 ) 2016 77 ( 4.5 ) 691 ( 4.3 ) 2017 57 ( 3.3 ) 929 ( 5.7 ) 2018 80 ( 4.7 ) 899 ( 5.5 ) 2019 127 ( 7.4 ) 1118 ( 6.9 ) 2020 84 ( 4.9 ) 1642 ( 10.1 ) 2021 17 ( 1.0 ) 807 ( 5.0 ) 2022 30 ( 1.8 ) 706 ( 4.4 ) 2023 38 ( 2.2 ) 950 ( 5.9 ) 2024 7 ( 0.4 ) 1045 ( 6.5 ) AE Signal Analysis After applying predefined signal detection criteria and excluding signals unrelated to the drug itself, such as various injuries, poisonings, procedural complications, social environment factors, surgeries, medical procedures, and congenital or familial hereditary diseases, 22 System Organ Classes (SOCs) associated with vinorelbine-related AEs were identified in both FAERS database and VigiBase database. The distribution of these SOCs in FAERS is presented in Table 2 , and that in VigiBase is shown in Supplementary Table S3. Across the FAERS and VigiBase databases, the most frequently reported SOCs included general disorders and administration site conditions, gastrointestinal disorders, blood and lymphatic system disorders, respiratory, thoracic and mediastinal disorders. In FAERS, 11 SOCs met both analytical criteria. Ranked by descending ROR values, these were: blood and lymphatic system disorders; respiratory, thoracic and mediastinal disorders; endocrine disorders; hepatobiliary disorders; benign, malignant, and unspecified neoplasms (including cysts and polyps); metabolism and nutrition disorders; cardiac disorders; renal and urinary disorders; investigations; gastrointestinal disorders; and vascular disorders. In VigiBase, 9 SOCs fulfilled both criteria. Ranked by descending ROR, these included: blood and lymphatic system disorders; neoplasms (benign, malignant, and unspecified, including cysts and polyps); metabolism and nutrition disorders; respiratory, thoracic and mediastinal disorders; hepatobiliary disorders; investigations; gastrointestinal disorders; vascular disorders; and infections and infestations. Notably, endocrine, cardiac, and renal/urinary disorders met both criteria in FAERS but not in VigiBase, whereas infections and infestations met both criteria in VigiBase but not in FAERS. Table 2 Vinorelbine-associated AEs by SOC classification in the FAERS database. SOC Report count ROR ( 95% CI ) IC ( IC025 ) General disorders and administration site conditions 995 0.82 ( 0.76–0.87 ) -0.24 ( -0.34 ) Gastrointestinal disorders 744 1.34 ( 1.24–1.44 ) 0.38 ( 0.26 ) Blood and lymphatic system disorders 625 5.93 ( 5.46–6.44 ) 2.45 ( 2.32 ) Respiratory, thoracic and mediastinal disorders 596 1.96 ( 1.8–2.13 ) 0.91 ( 0.78 ) Investigations 561 1.39 ( 1.27–1.51 ) 0.44 ( 0.31 ) Nervous system disorders 449 0.77 ( 0.7–0.85 ) -0.35 ( -0.49 ) Infections and infestations 391 1.12 ( 1.01–1.24 ) 0.15 ( 0 ) Neoplasms benign, malignant and unspecified (incl cysts and polyps) 300 1.72 ( 1.53–1.93 ) 0.76 ( 0.58 ) Cardiac disorders 282 1.61 ( 1.43–1.81 ) 0.66 ( 0.49 ) Skin and subcutaneous tissue disorders 245 0.66 ( 0.58–0.75 ) -0.57 ( -0.76 ) Metabolism and nutrition disorders 242 1.68 ( 1.48–1.91 ) 0.73 ( 0.53 ) Vascular disorders 190 1.33 ( 1.15–1.54 ) 0.4 ( 0.19 ) Renal and urinary disorders 185 1.45 ( 1.25–1.68 ) 0.52 ( 0.3 ) Musculoskeletal and connective tissue disorders 177 0.49 ( 0.42–0.57 ) -0.99 ( -1.2 ) Hepatobiliary disorders 107 1.73 ( 1.43–2.1 ) 0.78 ( 0.49 ) Psychiatric disorders 96 0.24 ( 0.2–0.3 ) -1.99 ( -2.27 ) Eye disorders 80 0.59 ( 0.47–0.74 ) -0.75( -1.07 ) Immune system disorders 42 0.56 ( 0.41–0.76 ) -0.83 ( -1.26 ) Ear and labyrinth disorders 35 1.2 ( 0.86–1.67 ) 0.26 ( -0.23 ) Endocrine disorders 30 1.74 ( 1.22–2.5 ) 0.8 ( 0.25 ) Pregnancy, puerperium and perinatal conditions 17 0.58 ( 0.36–0.94 ) -0.77 ( -1.42 ) Reproductive system and breast disorders 12 0.2 ( 0.11–0.35 ) -2.32 ( -3.03 ) In the PT-level analysis, after excluding signals unrelated to the drug itself, such as various injuries, poisonings, procedural complications, social environment factors, surgeries, medical procedures, and congenital or familial hereditary diseases, both the FAERS database and VigiBase database yielded 210 positive AE signals that simultaneously satisfied the statistical criteria of both the ROR and BCPNN methods. These AE signals in FAERS were ranked by their occurrence frequency with the top 20 presented in Table 3 , the corresponding data from VigiBase were provided in Supplementary Table S4. Among the top 20 PTs in FAERS, neutropenia, fever, vomiting, dyspnea, and nausea were the most frequently reported. In VigiBase, the predominant PTs included myelosuppression, neutropenia, leukopenia, and anemia. Table 3 Top 20 vinorelbine-associated AEs in FAERS ranked by frequency of reports. Top 20 AEs by frequency of reports Frequency ROR ( 95% Cl ) IC ( IC025 ) 1 Neutropenia 172 12.08 ( 10.38–14.06 ) 3.56 ( 3.25 ) 2 Fever 127 3.39 ( 2.84–4.04 ) 1.74 ( 1.46 ) 3 Vomiting 111 2.21 ( 1.83–2.67 ) 1.13 ( 0.84 ) 4 Dyspnea 110 1.79 ( 1.48–2.16 ) 0.83 ( 0.54 ) 5 Nausea 109 1.27 ( 1.05–1.54 ) 0.34 ( 0.06 ) 6 Diarrhea 92 1.34 ( 1.09–1.65 ) 0.42 ( 0.11 ) 7 Anaemia 78 3.71 ( 2.97–4.64 ) 1.88 ( 1.5 ) 8 Leukopenia 73 13.59 ( 10.79–17.12 ) 3.75 ( 3.19 ) 9 Asthenia 72 1.76 ( 1.39–2.21 ) 0.80 ( 0.45 ) 10 Pneumonia 68 1.84 (1.45–2.34) 0.88 ( 0.51 ) 11 Febrile neutropenia 67 9.51 (7.48–12.1) 3.24 ( 2.71 ) 12 Interstitial lung disease 61 11.87 ( 9.23–15.28 ) 3.56 ( 2.96 ) 13 Abdominal pain 58 2.32 ( 1.79–3.00 ) 1.20 ( 0.80 ) 14 Malignant neoplasm progression 57 5.34 ( 4.12–6.94 ) 2.41 ( 1.92 ) 15 Acute kidney injury 55 2.55 ( 1.79–3.33 ) 1.34 ( 1.92 ) 16 Disease progression 54 4.24 ( 3.24–5.54 ) 2.07 ( 1.60 ) 17 Decreased appetite 54 2.05 ( 1.57–2.68 ) 1.03 ( 0.61 ) 18 Thrombocytopenia 53 4.40 ( 3.36–5.76 ) 2.13 ( 1.65 ) 19 Chest pain 50 2.43 ( 1.84–3.21 ) 1.27 ( 0.83 ) 20 General physical health deterioration 44 3.70 ( 2.75–4.97 ) 1.88 ( 1.36 ) In addition to ranking the top 20 signals by reporting frequency, we identified the top 20 AEs based on signal reporting strength ( Table 4 and Supplementary Table S5). In FAERS, the predominant AEs among these top signals included epiploic appendagitis, gastric volvulus, erythropenia, injection site phlebitis, and pseudocirrhosis. In VigiBase, the top signals comprised pseudocirrhosis, tracheal fistula, toxic erythema of chemotherapy, injection site phlebitis, and extravasation. Notably, the two databases shared 98 positive signals. Table 4 Top 20 vinorelbine-associated AEs with the strongest signal strength in FAERS. Top 20 AEs with the strongest signal strength Frequency ROR ( 95% CI ) IC ( IC025 ) 1 Epiploic appendagitis 4 344.38 ( 126.6–936.78 ) 8.37 ( 0.98 ) 2 Gastric volvulus 3 206.16 ( 65.54–648.53 ) 7.65 ( 0.51 ) 3 Erythropenia 7 200.98 ( 94.91–425.57 ) 7.61 ( 1.91 ) 4 Injection site phlebitis 5 184.24 ( 94.91–425.57 ) 7.49 ( 1.35 ) 5 Pseudocirrhosis 3 93.28 ( 29.88–291.18 ) 6.53 ( 0.50 ) 6 Neutropenic sepsis 42 52.36 ( 38.62–70.99 ) 5.69 ( 4.13) 7 Extravasation 23 50.06 ( 33.2–75.48 ) 5.63 ( 3.44 ) 8 Superior vena cava syndrome 3 44.36 ( 14.26–138.01 ) 5.46 ( 0.46 ) 9 Vascular pain 5 40.1 ( 16.65–96.58 ) 5.32 ( 1.23 ) 10 Lymphangiosis carcinomatosa 4 34.37 ( 12.87–91.78 ) 5.1 ( 0.87 ) 11 Febrile bone marrow aplasia 15 34.22 ( 20.60–56.85 ) 5.09 ( 2.75 ) 12 Metastases to adrenals 3 30.21 ( 9.72–93.9 ) 4.91 ( 0.42 ) 13 Ileus paralytic 14 29.36 ( 17.37–49.66 ) 4.87 ( 2.59 ) 14 Ejection fraction abnormal 4 28.90 ( 10.82–77.16 ) 4.85 ( 0.84 ) 15 Megacolon 4 23.19 ( 8.69–61.88 ) 4.85 ( 0.84 ) 16 PO 2 decreased 3 21.79 ( 7.01–67.67 ) 4.53 ( 0.80 ) 17 Panniculitis 6 21.53 ( 9.66–47.99 ) 4.44 ( 0.37 ) 18 Pneumoperitoneum 4 20.22 ( 7.58–53.96 ) 4.42 ( 1.36 ) 19 Non-small cell lung cancer 10 20.09 ( 10.80–37.38 ) 4.32 ( 2.00) 20 Neutropenic colitis 4 18.98 ( 7.11–50.63 ) 4.24 ( 0.75) At the SOC level, the FAERS database demonstrated that the "Cardiac disease" category met the statistical criteria of both the ROR and BCPNN methods. In contrast, this was not observed in the VigiBase database. However, at the PT level, a subset of PTs in the VigiBase database that satisfied the thresholds of both methods fell under the "Cardiac disease" SOC. Furthermore, PT-level analysis revealed that besides the relatively high incidence of AEs in the hematological and gastrointestinal systems, AEs related to the cardiovascular and respiratory systems accounted for a considerable proportion. In the PT-level analysis, the specific proportions of each PT belonging to the SOC were detailed in Fig. 1 . A complete list of all vinorelbine-associated AEs involving the cardiovascular and respiratory systems was provided in Table 5 and Supplementary Table S6. (a) Data from FAERS; (b) Data from VigiBase. Table 5 Vinorelbine-associated AEs in the cardiac and respiratory systems reported in FAERS. SOC Classification PT Classification Report count ROR (95% Cl) IC (IC025) Respiratory, Thoracic and Mediastinal Disorders Interstitial lung disease 61 11.87 ( 9.23–15.28 ) 3.56 ( 2.96 ) Acute pulmonary oedema 7 11.11 ( 5.29–23.33 ) 3.47 ( 1.27 ) Pleuritic pain 3 9.71 ( 3.13–30.13 ) 3.28 ( 0.17 ) Rales 6 9.05 ( 4.06–18.49 ) 3.18 ( 0.98 ) Pulmonary toxicity 6 8.30 ( 3.73–18.49) 3.05 ( 0.93 ) Pneumonitis 23 8.10 ( 5.38–12.20 ) 3.01 ( 2.05 ) Respiratory acidosis 3 7.02 ( 2.26–21.77 ) 2.81 ( 0.04 ) Lung infiltration 6 5.74 ( 2.58–12.78 ) 2.52 ( 0.68 ) Pleural effusion 38 5.62 ( 4.08–7.73 ) 2.48 ( 1.86 ) Bronchospasm 9 5.61 ( 2.92–10.79 ) 2.49 ( 1.03 ) Hypoxia 21 5.54 ( 3.61–8.50 ) 2.47 ( 1.58 ) Respiratory failure 40 4.95 ( 3.63–6.76 ) 2.30 ( 1.72 ) Atelectasis 5 4.52 ( 1.88–10.86 ) 2.17 ( 0.33 ) Respiratory distress 13 4.26 ( 2.47–7.33 ) 2.09 ( 1.01 ) Haemoptysis 13 4.20 (2.44–7.23) 2.07 ( 0.33 ) Tachypnoea 6 4.10 ( 1.84–9.12) 2.03 ( 0.41 ) Lung disorder 18 3.43 ( 2.16–5.45 ) 1.78 ( 0.94 ) Pulmonary oedema 16 3.22 ( 1.97–5.26 ) 1.68 ( 0.81 ) Respiratory disorder 10 3.06 ( 1.64–5.69 ) 1.61 ( 0.49) Pulmonary embolism 31 2.89 ( 2.03–4.11 ) 1.53 ( 0.93 ) Dyspnoea exertional 10 2.49 ( 1.34–4.63 ) 1.31 ( 0.26 ) Dyspnoea 110 1.79 ( 1.48–2.16 ) 0.83 ( 0.54 ) Cardiac Disorders Cardiovascular insufficiency 3 16.17 ( 5.21–50.21 ) 4.01 ( 0.31 ) Cardiotoxicity 13 14.28 ( 8.28–24.62 ) 3.83 ( 2.10 ) Stress cardiovascular 7 11.66 ( 5.56–24.49 ) 3.54 ( 1.30 ) Ventricular hypertrophy 3 9.82 ( 3.16–30.47 ) 3.29 ( 0.17) Acute coronary syndrome 9 9.40 ( 4.89–18.08 ) 3.23 ( 1.44 ) Atrial flutter 7 7.77 ( 3.70–16.32) 2.96 ( 1.05 ) Left ventricular failure 3 7.74 ( 2.49–24.01 ) 2.95 ( 0.08 ) Cardiopulmonary failure 3 6.68 ( 2.15–20.71 ) 2.74 ( 0.02 ) Cardiogenic shock 8 5.53 ( 2.67–10.67 ) 2.41 ( 0.88 ) Supraventricular tachycardia 5 4.67 ( 1.94–11.24 ) 2.22 ( 0.36 ) Cardiac failure 33 3.74 ( 2.66–5.26 ) 1.90 ( 1.29 ) Cardiomyopathy 6 3.61 ( 1.62–8.04 ) 1.85 ( 0.30 ) Acute myocardial infarction 8 2.36 ( 1.18–4.72 ) 1.24 ( 0.07 ) Cardio-respiratory arrest 10 2.08 ( 1.12–3.87 ) 1.06 ( 0.05 ) Tachycardia 19 1.95 ( 1.24–3.06 ) 0.96 ( 0.25 ) Distribution of AE Occurrence Over Time Since the onset time of AEs was not available in VigiBase, only FAERS data were included for the temporal analysis. After excluding reports with missing or unknown onset dates, a total of 639 vinorelbine-associated AE reports were eligible for analysis, with the results presented in Fig. 2 a. More than half of the AEs occurred within 30 days of drug initiation (n = 369, 57.75%), followed by a gradual decline in the number of reports over time. Among these 639 AE reports, 253 reports involved cardiopulmonary AEs. Temporal analysis of these reports showed that nearly half occurred within the first 30 days (n = 125, 49.41%), with the frequency of reports similarly decreasing over time, as shown in Fig. 2 b. (a) Time distribution of all vinorelbine-associated AEs. (b) Time distribution of vinorelbine-associated AEs related to the cardiopulmonary system. Concomitant Medications of Vinorelbine Among the AE reports in which vinorelbine was identified as the primary suspected drug, the top ten concomitant medications were predominantly anticancer agents, such as cisplatin, gemcitabine, trastuzumab, carboplatin, and capecitabine (Fig. 3 ). AE Signal Analysis in Children Using Vinorelbine Due to the limited accessibility of VigiBase, where only aggregated reporting data are available and individual case safety reports (ICSRs) cannot be retrieved, pediatric subgroup analyses were conducted exclusively using FAERS data. In the FAERS database, 48 reports listed vinorelbine as the suspected drug and involved patients under 18 years of age. Unlike the findings in adults, only five SOCs met the signal detection criteria of both the ROR and BCPNN methods in the pediatric population. These SOCs were as follows: endocrine disorders [case = 5; ROR ( 95% CI) = 5.75 ( 2.37–13.95 ) ; IC(IC025) = 2.50 ( 0.47 )], blood and lymphatic system disorders [case = 24; ROR ( 95% CI) = 4.73 ( 3.10–7.22 ); IC(IC025) = 2.5 ( 0.47 )], renal and urinary disorders [case = 8; ROR ( 95% CI) = 2.32 ( 1.15–4.70 ); IC(IC025) = 1.18 ( 0.01 )], vascular disorders [case = 9; ROR ( 95% CI) = 2.22 ( 1.14–4.33 ); IC(IC025) = 1.12 ( 0.02 )], cardiac disorders[case = 10; ROR ( 95% CI) = 2.17 ( 1.15–4.09 ); IC(IC025) = 1.08 ( 0.05 )]. Endocrine disorders showed the strongest signal, highlighting pediatric-specific safety concerns. Discussion Vinorelbine is a semisynthetic vinca alkaloid that inhibits tubulin polymerization and blocks mitosis, thereby exerting antitumor activity [ 1 ] .It is widely used in the treatment of various malignancies, including non-small cell lung cancer and breast cancer. According to the prescribing information, common AEs include bone marrow suppression (e.g., leukopenia, thrombocytopenia, anemia), gastrointestinal symptoms (nausea, vomiting, abdominal pain, constipation), neurological disorders (sensory disturbances, neuritis, myasthenia), and liver function abnormalities (elevated liver enzymes). In this study, we performed a comprehensive pharmacovigilance assessment of vinorelbine using FAERS and WHO VigiBase. A total of 210 AE signals were identified across the two databases using both ROR and BCPNN algorithms, involving multiple organ systems. All AEs documented in the manufacturer's label were detected. These included myelosuppression, gastrointestinal events, and neurological toxicity, thereby supporting the methodological robustness of our analysis. Among the top 20 AEs ranked by reporting frequency or signal strength, neutropenia, anemia, vomiting, dyspnea, marrow suppression, and peripheral neuropathy were consistent with labeling. Several clinically recognized but unlabeled AEs, such as paralytic ileus, were also identified [ 5 – 8 ] . A particularly notable finding was the prominence of cardiopulmonary toxicities. Both databases showed high reporting frequencies and strong signal intensities for events such as interstitial lung disease, acute pulmonary edema, cardiac failure, and cardiopulmonary failure. Vinorelbine is known to possess greater lipophilicity than other vinca alkaloids, resulting in substantial tissue accumulation—approximately 300-fold in the myocardium and 100-fold in the lungs relative to serum levels [ 9 ] . Secondary cardiac disease is a leading cause of mortality in cancer survivors [ 10 ] . Multiple case reports have documented vinorelbine-associated cardiotoxicity, including ischemic heart disease, heart failure, and Takotsubo syndrome [ 11 – 13 ] . The underlying mechanism of vinorelbine-induced cardiac toxicity remains unclear, but it may involve the alkaloid's direct effect on cell microtubules, damage to myocardial metabolism and contractility, indirect effects on coagulation leading to arterial occlusion, and possibly a paralyzing effect through its influence on the autonomic nervous system [ 13 ] . A meta-analysis showed that the incidence of cardiac toxicity after vinorelbine chemotherapy alone is 1.41% [ 14 ] . Further research suggests that the risk of cardiotoxicity is significantly associated with a history of pre-existing heart disease. Gridelli et al. reported a higher incidence of cardiotoxicity in female patients across cancer types [ 15 ] . Pulmonary toxicity is another notable risk of vinorelbine alongside cardiotoxicity. Our analysis demonstrated that the two databases documented a higher incidence of dyspnoea, pulmonary embolism, and pleural effusion, while interstitial lung disease, acute pulmonary oedema, tracheal fistula, and bronchopleural fistula exhibited stronger positive signals. Noriko et al. indicated that the incidence of vinorelbine-related pulmonary toxicity is around 2.4% [ 16 ] . Multiple studies have shown that vinorelbine-induced pulmonary toxicity can resolve after discontinuing the drug [ 16 – 18 ] . Pulmonary toxicity can be acute or subacute. The acute reactions typically present with dyspnea, bronchospasm, fever, and alveolar infiltration, usually occurring within minutes after vinorelbine infusion. The subacute reactions manifest hours to days later with progressive dyspnea and diffuse interstitial infiltrates [ 17 ] . Known risk factors include the concomitant use of other anticancer drugs and a history of underlying lung disease [ 16 ] . Therefore, clinicians should closely monitor the cardiopulmonary functions of patients during vinorelbine therapy and consider prompt discontinuation when abnormalities arise. In our analysis, the ten most frequent concomitant medications included cisplatin, gemcitabine, trastuzumab, carboplatin, capecitabine, docetaxel, dexamethasone, paclitaxel, cyclophosphamide, and ifosfamide—all anticancer agents. Several of these agents are known to cause cardiopulmonary toxicity. Trastuzumab is a commonly used HER2-targeted treatment, and studies have shown that interstitial lung disease and cardiac toxicity are the most significant toxicities associated with trastuzumab [ 19 ] . Gemcitabine has been associated with fatal cardiovascular events including myocardial ischemia, pericarditis, and heart failure [ 20 ] . Polk et al. [ 21 ] reported that nearly 5% of patients treated with capecitabine experienced cardiac toxicity symptoms (chest pain, dyspnea, palpitations), 2.4% showed changes in electrocardiograms, 0.4% had persistent acute myocardial infarction, and 0.2% died from cardiac arrest. Platinum drugs, taxanes, and alkylating agents such as cyclophosphamide have also been confirmed to cause varying degrees of cardiopulmonary toxicity [ 22 ] . Therefore, when vinorelbine is administered in combination with these agents, enhanced cardiopulmonary monitoring is essential. Vinorelbine use in pediatric patients remains limited, and the drug's label and related guidelines do not fully specify pediatric dosing regimens. Based on clinical experience, vinorelbine is mainly used in pediatric populations for conditions such as acute lymphoblastic leukemia, rhabdomyosarcoma, and Hodgkin lymphoma [ 23 – 25 ] . Published pediatric safety data are scarce, and reported AEs are largely consistent with those in adults, involving hematologic, respiratory, hepatic/renal, and gastrointestinal systems [ 26 , 27 ] . Notably, our study identified a significant association between vinorelbine and endocrine disorders in children. Gianni Bisogno et al. reported a pediatric case of vinorelbine-induced dysregulation of antidiuretic hormone secretion [ 28 ] . Given the common use of glucocorticoids and combination chemotherapy in pediatric oncology, clinicians should maintain vigilance for endocrine toxicity in children receiving vinorelbine. Routine endocrine function monitoring may facilitate early detection and timely management. In conclusion, real-world pharmacovigilance data from FAERS and VigiBase indicate that vinorelbine is associated with higher-than-expected reporting rates and signal strengths for cardiopulmonary AEs, underscoring the need for heightened clinical awareness. Additionally, a notable association with endocrine disorders was observed in pediatric patients. As cancer survival improves, chemotherapy-related AEs increasingly influence long-term health and quality of life. Therefore, clinicians should not only consider the antitumor efficacy of vinorelbine but also carefully evaluate its safety profile, optimize treatment regimens, and strengthen monitoring strategies to improve patient outcomes and quality of life. Conclusions These findings indicate that the safety profile of vinorelbine extends beyond the well-characterized hematologic and gastrointestinal toxicities. Clinicians should exercise heightened vigilance for cardiovascular and respiratory adverse events, including heart failure, interstitial lung disease, and ventricular hypertrophy, particularly during combination therapy with other cardiorespiratory-toxic agents. Moreover, the association with endocrine disorders in pediatric patients calls for age-specific monitoring. Overall, these results emphasize the importance of comprehensive monitoring and individualized risk assessment to optimize the therapeutic safety of vinorelbine. Declarations Author contributions S.F.W. and M.H.Y. conceived and designed the study. Y.Z., M.N.S. and S.F.W. drafted and critically revised the manuscript. Y.Z., M.N.S. and D.H. carried out data curation and performed the statistical analysis. All authors reviewed the manuscript and approved the final version. Funding This work was supported by Hunan Provincial Natural Science Foundation of China (2022JJ30903) and Hunan Provincial Health Commission Research Project (W20243126). Data availability The datasets presented in this study can be found in online repositories. (https://www.fda.gov/drugs/fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard, https://who-umc.org/vigibase-data-access/) Ethical considerations and informed consent Not applicable. 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Guidi M, Giunti L, Buccoliero AM, Fonte C, Scoccianti S, Censullo ML, Caporalini C, Tellini M, Di Nicola M, Castelli B, et al: Brief report: pediatric high-grAE gliomas treated with vinorelbine and valproic acid added to temozolomide. Am J Cancer Res 2023, 13: 3668–3678. Jan MRU, Saeed H, Abubakar M, Wali RM: Response rates, long term outcomes and toxicity profile of gemcitabine and vinorelbine based outpatient chemotherapy regimen in primary progressive and relapsed childhood Hodgkin lymphoma. Leuk Lymphoma 2020, 61: 3369–3377. Bisogno G, De Salvo GL, Bergeron C, Gallego Melcón S, Merks JH, Kelsey A, Martelli H, Minard-Colin V, Orbach D, Glosli H, et al: Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2019, 20: 1566–1575. Additional Declarations No competing interests reported. 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16:21:51","extension":"html","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":127234,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8245600/v1/3ea6c41a70c9cdd1dfebe08a.html"},{"id":97271770,"identity":"66a27114-7746-4437-abaa-dd47d503b5f9","added_by":"auto","created_at":"2025-12-02 15:03:58","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":807790,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eProportion of each PT within their corresponding SOC in the PT-level analysis.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(a) Data from FAERS; (b) Data from VigiBase.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8245600/v1/9f71b6475986d5429ab2ac73.png"},{"id":97271775,"identity":"3ff78128-9b51-4626-89b0-37b0caaf2ac6","added_by":"auto","created_at":"2025-12-02 15:03:58","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":326198,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTime distribution of AEs associated with vinorelbine.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(a) Time distribution of all vinorelbine-associated AEs.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(b) Time distribution of vinorelbine-associated AEs related to the cardiopulmonary system.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8245600/v1/7323baee53e0a66e91fb30cd.png"},{"id":97271772,"identity":"9f8e2c0b-a121-424c-aef5-cc86ef75e7ac","added_by":"auto","created_at":"2025-12-02 15:03:58","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":289847,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTop ten drugs most frequently used in combination with vinorelbine.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8245600/v1/2ee32c0d16a8e49a1773b27a.png"},{"id":97664652,"identity":"7fc1e250-b0f0-40a4-8c59-e8ea1c3f506c","added_by":"auto","created_at":"2025-12-08 09:12:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4091305,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245600/v1/9616137f-0a3e-47d6-af4e-c9443f7775ff.pdf"},{"id":97271769,"identity":"65277ac6-938e-4d7e-9c18-fbaac3085667","added_by":"auto","created_at":"2025-12-02 15:03:58","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":39956,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-8245600/v1/ff54071a56cc77b01b4b0d27.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pharmacovigilance Analysis of Vinorelbine: Cardiopulmonary and Pediatric Safety Profiles Based on FAERS and VigiBase Data","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVinorelbine is a semisynthetic vinca alkaloid chemotherapeutic agent with a higher affinity for mitotic microtubules, demonstrating superior efficacy in treating non-small cell lung cancer and breast cancer compared to vincristine and vinblastine\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Despite its widespread clinical application, the safety concerns associated with vinorelbine cannot be overlooked. Among the adverse drug events (AEs) of vinorelbine, hematologic and gastrointestinal reactions have been extensively documented. However, increasing attention has been drawn to its cardiopulmonary adverse effects in recent years. More and more studies suggest that cardiopulmonary adverse reactions to vinorelbine may be more common than previously anticipated\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Furthermore, the safety profile of vinorelbine in pediatric patients remains inadequately characterized, as current prescribing information and clinical guidelines provide limited guidance for this population.\u003c/p\u003e\u003cp\u003eGiven these concerns, this study conducted a systematic analysis of vinorelbine-associated AEs using real-world data from the FDA Adverse Event Reporting System (FAERS) and the WHO VigiBase database. The primary focus was to assess the incidence and signal strength of cardiopulmonary AEs, and to further explore the temporal distribution of these events as well as the occurrence of AEs in pediatric patients. In addition to addressing known adverse reactions, this study also identified potential under-recognized drug risks, providing a more comprehensive safety assessment. The findings offer important insights into the safety of vinorelbine and provide valuable data to support the risk management and monitoring strategies in clinical practice.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003eData Sources\u003c/b\u003e The data utilized in this study was sourced from FAERS and WHO VigiBase databases. As for FAERS, the database is updated quarterly\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.Raw data from the first quarter of 2004 to the fourth quarter of 2024 was extracted. Each quarterly dataset includes seven tables: the Demographics (DEMO) table, Adverse Event (REAC) table, Drug Usage (DRUG) table, Outcome (OUTC) table, Report Source (RPSR) table, Therapy (THER) table, and Diagnosis (INDI) table. And for the WHO VigiBase database, data were retrieved via the VigiBase public interface using Python 3.10, encompassing all publicly accessible drug-related data up to December 2024. Importantly, VigiBase provides only aggregated reporting-level data rather than individual case safety reports (ICSRs). This constraint precludes granular demographic analyses but facilitates robust disproportionality assessments, aligning with the core objectives of pharmacovigilance signal detection.\u003c/p\u003e\u003cp\u003e\u003cb\u003eData Processing\u003c/b\u003e Duplicate reports were handled via a deduplication algorithm where in the report with the most recent FDA receipt date (FDA-DT) was retained for the cases with matching CASEID. In instances where CASEID and FDA-DT were identical, the record with the higher PRIMARYID was chosen. Adverse event terms were processed and categorized using the Standardized MedDRA Queries (SMQs). Data from the VigiBase platform were yielded in JSON format, which were subsequently processed and analyzed via the Pandas library for data wrangling and quality validation. Standardization procedures included: harmonization of adverse event terminology using MedDRA (version 26.0) for consistent coding; mapping of drug names to BASENAME entries in the WHO Drug Dictionary to ensure nomenclature uniformity; and standardization of date formats across the two databases to facilitate cross-dataset comparability. Furthermore, to refine the signa detection analysis, we excluded reports of events that are inherently non-pharmacological, including but not limited to various injures, procedural complications, and congenital or hereditary diseases.\u003c/p\u003e\u003cp\u003e\u003cb\u003eData Standardization\u003c/b\u003e The terminology for AEs was standardized and translated using the 26.0 version of the Medical Dictionary for Regulatory Activities (MedDRA). AEs belonging to the same preferred term (PT) were consolidated, and the PTs were categorized and organized according to the System Organ Class (SOC).\u003c/p\u003e\u003cp\u003e\u003cb\u003eData Extraction\u003c/b\u003e Adverse event reports in which vinorelbine, either by its generic or brand name, was the primary suspected drug were extracted.\u003c/p\u003e\u003cp\u003e\u003cb\u003eData Analysis\u003c/b\u003e The Reporting Odds Ratio (ROR) method and the Bayesian Confidence Propagation Neural Network (BCPNN) method were used simultaneously to detect AE signals associated with the drug. AE signals were considered valid only if they met the threshold of both methods. All analyses were performed utilizing a standard 2\u0026times;2 contingency table for the assessment of disproportionality, with comprehensive mathematical formulas for the calculation of both ROR and IC provided in Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e and Table S2.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003eBasic Information of AE Reports\u003c/h2\u003e\u003cp\u003eA total of 55,182,766 cases were reported in the FAERS database from Q1 2004 to Q4 2024. Based on the study criteria, 1,711 reports listed vinorelbine as the primary suspected drug. The reporting population consisted of 47.9% females and 31.4% males, while gender was unreported in 20.7% of cases. Patient age ranged broadly, with the majority of reports involving adults between 18 and 85 years. As of December 31, 2024, a total of 117,935,366 cases had been reported in the VigiBase database. Of these, 16,175 cases were associated with vinorelbine. The gender distribution showed that 56.9% of cases occurred in females and 37.6% in males, while 5.5% were reported with unknown gender. Geographically, Europe accounted for the highest proportion of cases among the five continents. The basic information for vinorelbine-associated AEs is shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eBasic demographic and reporting characteristics of vinorelbine-associated AEs in the FAERS and VigiBase databases.\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eItem\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFAERS\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;1711, (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eVigiBase\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;16175, (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e537 ( 31.4 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6076 ( 37.6 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e819 ( 47.9 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9205 ( 56.9 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e355 ( 20.7 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e894 ( 5.5 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e48 ( 2.8 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e267 ( 1.7 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18\u0026thinsp;~\u0026thinsp;64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e890 ( 34.5 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8584 ( 53.1 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e455 ( 26.6 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4945 ( 30.6 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e618 ( 36.1 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2379( 14.7 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReporting Countries\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfrica\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16 ( 0.9 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e310 ( 1.9 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e250 ( 14.6 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6131 ( 37.9 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e791 ( 46.2 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6179 ( 38.2 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOceania\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e22 ( 1.3 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e157 ( 1.0 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAmericas\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e273 ( 16.0 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3398 ( 21.0 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUnkown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e359 ( 21.0 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"9\" rowspan=\"10\"\u003e\u003cp\u003eReport Year\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBefore 2015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1194 ( 69.8 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7388 ( 45.7 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e77 ( 4.5 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e691 ( 4.3 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e57 ( 3.3 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e929 ( 5.7 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e80 ( 4.7 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e899 ( 5.5 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2019\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e127 ( 7.4 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1118 ( 6.9 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e84 ( 4.9 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1642 ( 10.1 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2021\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e17 ( 1.0 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e807 ( 5.0 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2022\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e30 ( 1.8 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e706 ( 4.4 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2023\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e38 ( 2.2 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e950 ( 5.9 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7 ( 0.4 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1045 ( 6.5 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eAE Signal Analysis\u003c/h3\u003e\n\u003cp\u003eAfter applying predefined signal detection criteria and excluding signals unrelated to the drug itself, such as various injuries, poisonings, procedural complications, social environment factors, surgeries, medical procedures, and congenital or familial hereditary diseases, 22 System Organ Classes (SOCs) associated with vinorelbine-related AEs were identified in both FAERS database and VigiBase database. The distribution of these SOCs in FAERS is presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, and that in VigiBase is shown in Supplementary Table S3. Across the FAERS and VigiBase databases, the most frequently reported SOCs included general disorders and administration site conditions, gastrointestinal disorders, blood and lymphatic system disorders, respiratory, thoracic and mediastinal disorders.\u003c/p\u003e\u003cp\u003eIn FAERS, 11 SOCs met both analytical criteria. Ranked by descending ROR values, these were: blood and lymphatic system disorders; respiratory, thoracic and mediastinal disorders; endocrine disorders; hepatobiliary disorders; benign, malignant, and unspecified neoplasms (including cysts and polyps); metabolism and nutrition disorders; cardiac disorders; renal and urinary disorders; investigations; gastrointestinal disorders; and vascular disorders.\u003c/p\u003e\u003cp\u003eIn VigiBase, 9 SOCs fulfilled both criteria. Ranked by descending ROR, these included: blood and lymphatic system disorders; neoplasms (benign, malignant, and unspecified, including cysts and polyps); metabolism and nutrition disorders; respiratory, thoracic and mediastinal disorders; hepatobiliary disorders; investigations; gastrointestinal disorders; vascular disorders; and infections and infestations. Notably, endocrine, cardiac, and renal/urinary disorders met both criteria in FAERS but not in VigiBase, whereas infections and infestations met both criteria in VigiBase but not in FAERS.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eVinorelbine-associated AEs by SOC classification in the FAERS database.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSOC\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eReport count\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eROR ( 95% CI )\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eIC ( IC025 )\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGeneral disorders and administration site conditions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e995\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.82 ( 0.76\u0026ndash;0.87 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.24 ( -0.34 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGastrointestinal disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e744\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.34 ( 1.24\u0026ndash;1.44 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.38 ( 0.26 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood and lymphatic system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e625\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5.93 ( 5.46\u0026ndash;6.44 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.45 ( 2.32 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRespiratory, thoracic and mediastinal disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e596\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.96 ( 1.8\u0026ndash;2.13 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.91 ( 0.78 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e561\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.39 ( 1.27\u0026ndash;1.51 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.44 ( 0.31 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNervous system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e449\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.77 ( 0.7\u0026ndash;0.85 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.35 ( -0.49 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInfections and infestations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e391\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.12 ( 1.01\u0026ndash;1.24 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.15 ( 0 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeoplasms benign, malignant and unspecified (incl cysts and polyps)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e300\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.72 ( 1.53\u0026ndash;1.93 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.76 ( 0.58 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiac disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e282\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.61 ( 1.43\u0026ndash;1.81 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.66 ( 0.49 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin and subcutaneous tissue disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e245\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.66 ( 0.58\u0026ndash;0.75 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.57 ( -0.76 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMetabolism and nutrition disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e242\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.68 ( 1.48\u0026ndash;1.91 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.73 ( 0.53 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVascular disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e190\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.33 ( 1.15\u0026ndash;1.54 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.4 ( 0.19 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRenal and urinary disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e185\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.45 ( 1.25\u0026ndash;1.68 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.52 ( 0.3 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMusculoskeletal and connective tissue disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e177\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.49 ( 0.42\u0026ndash;0.57 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.99 ( -1.2 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHepatobiliary disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e107\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.73 ( 1.43\u0026ndash;2.1 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.78 ( 0.49 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePsychiatric disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.24 ( 0.2\u0026ndash;0.3 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-1.99 ( -2.27 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEye disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.59 ( 0.47\u0026ndash;0.74 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.75( -1.07 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eImmune system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.56 ( 0.41\u0026ndash;0.76 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.83 ( -1.26 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEar and labyrinth disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.2 ( 0.86\u0026ndash;1.67 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.26 ( -0.23 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndocrine disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.74 ( 1.22\u0026ndash;2.5 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.8 ( 0.25 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePregnancy, puerperium and perinatal conditions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.58 ( 0.36\u0026ndash;0.94 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.77 ( -1.42 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReproductive system and breast disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.2 ( 0.11\u0026ndash;0.35 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-2.32 ( -3.03 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn the PT-level analysis, after excluding signals unrelated to the drug itself, such as various injuries, poisonings, procedural complications, social environment factors, surgeries, medical procedures, and congenital or familial hereditary diseases, both the FAERS database and VigiBase database yielded 210 positive AE signals that simultaneously satisfied the statistical criteria of both the ROR and BCPNN methods. These AE signals in FAERS were ranked by their occurrence frequency with the top 20 presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, the corresponding data from VigiBase were provided in Supplementary Table S4. Among the top 20 PTs in FAERS, neutropenia, fever, vomiting, dyspnea, and nausea were the most frequently reported. In VigiBase, the predominant PTs included myelosuppression, neutropenia, leukopenia, and anemia.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTop 20 vinorelbine-associated AEs in FAERS ranked by frequency of reports.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTop 20 AEs by frequency of reports\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFrequency\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eROR ( 95% Cl )\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIC ( IC025 )\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNeutropenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e172\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e12.08 ( 10.38\u0026ndash;14.06 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.56 ( 3.25 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFever\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e127\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.39 ( 2.84\u0026ndash;4.04 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.74 ( 1.46 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVomiting\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e111\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.21 ( 1.83\u0026ndash;2.67 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.13 ( 0.84 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDyspnea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e110\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.79 ( 1.48\u0026ndash;2.16 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.83 ( 0.54 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNausea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e109\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.27 ( 1.05\u0026ndash;1.54 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.34 ( 0.06 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDiarrhea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.34 ( 1.09\u0026ndash;1.65 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.42 ( 0.11 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnaemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.71 ( 2.97\u0026ndash;4.64 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.88 ( 1.5 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLeukopenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13.59 ( 10.79\u0026ndash;17.12 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.75 ( 3.19 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsthenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.76 ( 1.39\u0026ndash;2.21 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.80 ( 0.45 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePneumonia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.84 (1.45\u0026ndash;2.34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.88 ( 0.51 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFebrile neutropenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9.51 (7.48\u0026ndash;12.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.24 ( 2.71 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInterstitial lung disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11.87 ( 9.23\u0026ndash;15.28 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.56 ( 2.96 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAbdominal pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.32 ( 1.79\u0026ndash;3.00 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.20 ( 0.80 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMalignant neoplasm progression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.34 ( 4.12\u0026ndash;6.94 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.41 ( 1.92 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAcute kidney injury\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.55 ( 1.79\u0026ndash;3.33 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.34 ( 1.92 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDisease progression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.24 ( 3.24\u0026ndash;5.54 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.07 ( 1.60 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDecreased appetite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.05 ( 1.57\u0026ndash;2.68 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.03 ( 0.61 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eThrombocytopenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.40 ( 3.36\u0026ndash;5.76 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.13 ( 1.65 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChest pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.43 ( 1.84\u0026ndash;3.21 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.27 ( 0.83 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGeneral physical health deterioration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.70 ( 2.75\u0026ndash;4.97 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.88 ( 1.36 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn addition to ranking the top 20 signals by reporting frequency, we identified the top 20 AEs based on signal reporting strength ( Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Supplementary Table S5). In FAERS, the predominant AEs among these top signals included epiploic appendagitis, gastric volvulus, erythropenia, injection site phlebitis, and pseudocirrhosis. In VigiBase, the top signals comprised pseudocirrhosis, tracheal fistula, toxic erythema of chemotherapy, injection site phlebitis, and extravasation. Notably, the two databases shared 98 positive signals.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTop 20 vinorelbine-associated AEs with the strongest signal strength in FAERS.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTop 20 AEs with the strongest signal\u003c/p\u003e\u003cp\u003estrength\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFrequency\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eROR ( 95% CI )\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIC ( IC025 )\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEpiploic appendagitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e344.38 ( 126.6\u0026ndash;936.78 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e8.37 ( 0.98 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGastric volvulus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e206.16 ( 65.54\u0026ndash;648.53 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e7.65 ( 0.51 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eErythropenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e200.98 ( 94.91\u0026ndash;425.57 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e7.61 ( 1.91 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInjection site phlebitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e184.24 ( 94.91\u0026ndash;425.57 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e7.49 ( 1.35 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePseudocirrhosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e93.28 ( 29.88\u0026ndash;291.18 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e6.53 ( 0.50 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNeutropenic sepsis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e52.36 ( 38.62\u0026ndash;70.99 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5.69 ( 4.13)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eExtravasation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e50.06 ( 33.2\u0026ndash;75.48 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5.63 ( 3.44 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSuperior vena cava syndrome\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e44.36 ( 14.26\u0026ndash;138.01 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5.46 ( 0.46 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVascular pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e40.1 ( 16.65\u0026ndash;96.58 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5.32 ( 1.23 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLymphangiosis carcinomatosa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e34.37 ( 12.87\u0026ndash;91.78 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5.1 ( 0.87 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFebrile bone marrow aplasia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e34.22 ( 20.60\u0026ndash;56.85 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5.09 ( 2.75 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMetastases to adrenals\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e30.21 ( 9.72\u0026ndash;93.9 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.91 ( 0.42 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIleus paralytic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e29.36 ( 17.37\u0026ndash;49.66 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.87 ( 2.59 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEjection fraction abnormal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e28.90 ( 10.82\u0026ndash;77.16 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.85 ( 0.84 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMegacolon\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e23.19 ( 8.69\u0026ndash;61.88 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.85 ( 0.84 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePO\u003csub\u003e2\u003c/sub\u003e decreased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e21.79 ( 7.01\u0026ndash;67.67 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.53 ( 0.80 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePanniculitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e21.53 ( 9.66\u0026ndash;47.99 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.44 ( 0.37 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePneumoperitoneum\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e20.22 ( 7.58\u0026ndash;53.96 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.42 ( 1.36 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNon-small cell lung cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e20.09 ( 10.80\u0026ndash;37.38 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.32 ( 2.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNeutropenic colitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e18.98 ( 7.11\u0026ndash;50.63 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.24 ( 0.75)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAt the SOC level, the FAERS database demonstrated that the \"Cardiac disease\" category met the statistical criteria of both the ROR and BCPNN methods. In contrast, this was not observed in the VigiBase database. However, at the PT level, a subset of PTs in the VigiBase database that satisfied the thresholds of both methods fell under the \"Cardiac disease\" SOC. Furthermore, PT-level analysis revealed that besides the relatively high incidence of AEs in the hematological and gastrointestinal systems, AEs related to the cardiovascular and respiratory systems accounted for a considerable proportion. In the PT-level analysis, the specific proportions of each PT belonging to the SOC were detailed in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A complete list of all vinorelbine-associated AEs involving the cardiovascular and respiratory systems was provided in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e and Supplementary Table S6.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(a) Data from FAERS; (b) Data from VigiBase.\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eVinorelbine-associated AEs in the cardiac and respiratory systems reported in FAERS.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSOC Classification\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePT\u003c/p\u003e\u003cp\u003eClassification\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eReport count\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eROR (95% Cl)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIC (IC025)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"21\" rowspan=\"22\"\u003e\u003cp\u003eRespiratory, Thoracic and Mediastinal Disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInterstitial lung disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11.87 ( 9.23\u0026ndash;15.28 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.56 ( 2.96 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAcute pulmonary oedema\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11.11 ( 5.29\u0026ndash;23.33 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.47 ( 1.27 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePleuritic pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9.71 ( 3.13\u0026ndash;30.13 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.28 ( 0.17 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRales\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9.05 ( 4.06\u0026ndash;18.49 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.18 ( 0.98 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePulmonary toxicity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8.30 ( 3.73\u0026ndash;18.49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.05 ( 0.93 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePneumonitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8.10 ( 5.38\u0026ndash;12.20 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.01 ( 2.05 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRespiratory acidosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7.02 ( 2.26\u0026ndash;21.77 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.81 ( 0.04 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLung infiltration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.74 ( 2.58\u0026ndash;12.78 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.52 ( 0.68 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePleural effusion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.62 ( 4.08\u0026ndash;7.73 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.48 ( 1.86 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBronchospasm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.61 ( 2.92\u0026ndash;10.79 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.49 ( 1.03 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHypoxia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.54 ( 3.61\u0026ndash;8.50 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.47 ( 1.58 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRespiratory failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.95 ( 3.63\u0026ndash;6.76 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.30 ( 1.72 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAtelectasis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.52 ( 1.88\u0026ndash;10.86 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.17 ( 0.33 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRespiratory distress\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.26 ( 2.47\u0026ndash;7.33 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.09 ( 1.01 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHaemoptysis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.20 (2.44\u0026ndash;7.23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.07 ( 0.33 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTachypnoea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.10 ( 1.84\u0026ndash;9.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.03 ( 0.41 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLung disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.43 ( 2.16\u0026ndash;5.45 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.78 ( 0.94 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePulmonary oedema\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.22 ( 1.97\u0026ndash;5.26 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.68 ( 0.81 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRespiratory disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.06 ( 1.64\u0026ndash;5.69 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.61 ( 0.49)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePulmonary embolism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.89 ( 2.03\u0026ndash;4.11 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.53 ( 0.93 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDyspnoea exertional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.49 ( 1.34\u0026ndash;4.63 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.31 ( 0.26 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDyspnoea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e110\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.79 ( 1.48\u0026ndash;2.16 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.83 ( 0.54 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"14\" rowspan=\"15\"\u003e\u003cp\u003eCardiac Disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCardiovascular insufficiency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e16.17 ( 5.21\u0026ndash;50.21 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.01 ( 0.31 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCardiotoxicity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14.28 ( 8.28\u0026ndash;24.62 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.83 ( 2.10 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eStress cardiovascular\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11.66 ( 5.56\u0026ndash;24.49 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.54 ( 1.30 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVentricular hypertrophy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9.82 ( 3.16\u0026ndash;30.47 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.29 ( 0.17)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAcute coronary syndrome\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9.40 ( 4.89\u0026ndash;18.08 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.23 ( 1.44 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAtrial flutter\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7.77 ( 3.70\u0026ndash;16.32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.96 ( 1.05 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLeft ventricular failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7.74 ( 2.49\u0026ndash;24.01 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.95 ( 0.08 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCardiopulmonary failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6.68 ( 2.15\u0026ndash;20.71 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.74 ( 0.02 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCardiogenic shock\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.53 ( 2.67\u0026ndash;10.67 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.41 ( 0.88 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSupraventricular tachycardia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.67 ( 1.94\u0026ndash;11.24 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.22 ( 0.36 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCardiac failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.74 ( 2.66\u0026ndash;5.26 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.90 ( 1.29 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCardiomyopathy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.61 ( 1.62\u0026ndash;8.04 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.85 ( 0.30 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAcute myocardial infarction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.36 ( 1.18\u0026ndash;4.72 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.24 ( 0.07 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCardio-respiratory arrest\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.08 ( 1.12\u0026ndash;3.87 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.06 ( 0.05 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTachycardia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.95 ( 1.24\u0026ndash;3.06 )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.96 ( 0.25 )\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003eDistribution of AE Occurrence Over Time\u003c/h3\u003e\n\u003cp\u003eSince the onset time of AEs was not available in VigiBase, only FAERS data were included for the temporal analysis. After excluding reports with missing or unknown onset dates, a total of 639 vinorelbine-associated AE reports were eligible for analysis, with the results presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea. More than half of the AEs occurred within 30 days of drug initiation (n\u0026thinsp;=\u0026thinsp;369, 57.75%), followed by a gradual decline in the number of reports over time.\u003c/p\u003e\u003cp\u003eAmong these 639 AE reports, 253 reports involved cardiopulmonary AEs. Temporal analysis of these reports showed that nearly half occurred within the first 30 days (n\u0026thinsp;=\u0026thinsp;125, 49.41%), with the frequency of reports similarly decreasing over time, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003e(a) Time distribution of all vinorelbine-associated AEs.\u003c/b\u003e\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003e(b) Time distribution of vinorelbine-associated AEs related to the cardiopulmonary system.\u003c/b\u003e\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\n\u003ch3\u003eConcomitant Medications of Vinorelbine\u003c/h3\u003e\n\u003cp\u003eAmong the AE reports in which vinorelbine was identified as the primary suspected drug, the top ten concomitant medications were predominantly anticancer agents, such as cisplatin, gemcitabine, trastuzumab, carboplatin, and capecitabine (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eAE Signal Analysis in Children Using Vinorelbine\u003c/h2\u003e\u003cp\u003eDue to the limited accessibility of VigiBase, where only aggregated reporting data are available and individual case safety reports (ICSRs) cannot be retrieved, pediatric subgroup analyses were conducted exclusively using FAERS data.\u003c/p\u003e\u003cp\u003eIn the FAERS database, 48 reports listed vinorelbine as the suspected drug and involved patients under 18 years of age. Unlike the findings in adults, only five SOCs met the signal detection criteria of both the ROR and BCPNN methods in the pediatric population. These SOCs were as follows: endocrine disorders [case\u0026thinsp;=\u0026thinsp;5; ROR ( 95% CI)\u0026thinsp;=\u0026thinsp;5.75 ( 2.37\u0026ndash;13.95 ) ; IC(IC025)\u0026thinsp;=\u0026thinsp;2.50 ( 0.47 )], blood and lymphatic system disorders [case\u0026thinsp;=\u0026thinsp;24; ROR ( 95% CI)\u0026thinsp;=\u0026thinsp;4.73 ( 3.10\u0026ndash;7.22 ); IC(IC025)\u0026thinsp;=\u0026thinsp;2.5 ( 0.47 )], renal and urinary disorders [case\u0026thinsp;=\u0026thinsp;8; ROR ( 95% CI)\u0026thinsp;=\u0026thinsp;2.32 ( 1.15\u0026ndash;4.70 ); IC(IC025)\u0026thinsp;=\u0026thinsp;1.18 ( 0.01 )], vascular disorders [case\u0026thinsp;=\u0026thinsp;9; ROR ( 95% CI)\u0026thinsp;=\u0026thinsp;2.22 ( 1.14\u0026ndash;4.33 ); IC(IC025)\u0026thinsp;=\u0026thinsp;1.12 ( 0.02 )], cardiac disorders[case\u0026thinsp;=\u0026thinsp;10; ROR ( 95% CI)\u0026thinsp;=\u0026thinsp;2.17 ( 1.15\u0026ndash;4.09 ); IC(IC025)\u0026thinsp;=\u0026thinsp;1.08 ( 0.05 )]. Endocrine disorders showed the strongest signal, highlighting pediatric-specific safety concerns.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eVinorelbine is a semisynthetic vinca alkaloid that inhibits tubulin polymerization and blocks mitosis, thereby exerting antitumor activity \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e.It is widely used in the treatment of various malignancies, including non-small cell lung cancer and breast cancer. According to the prescribing information, common AEs include bone marrow suppression (e.g., leukopenia, thrombocytopenia, anemia), gastrointestinal symptoms (nausea, vomiting, abdominal pain, constipation), neurological disorders (sensory disturbances, neuritis, myasthenia), and liver function abnormalities (elevated liver enzymes).\u003c/p\u003e\u003cp\u003eIn this study, we performed a comprehensive pharmacovigilance assessment of vinorelbine using FAERS and WHO VigiBase. A total of 210 AE signals were identified across the two databases using both ROR and BCPNN algorithms, involving multiple organ systems. All AEs documented in the manufacturer's label were detected. These included myelosuppression, gastrointestinal events, and neurological toxicity, thereby supporting the methodological robustness of our analysis. Among the top 20 AEs ranked by reporting frequency or signal strength, neutropenia, anemia, vomiting, dyspnea, marrow suppression, and peripheral neuropathy were consistent with labeling. Several clinically recognized but unlabeled AEs, such as paralytic ileus, were also identified\u003csup\u003e[\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eA particularly notable finding was the prominence of cardiopulmonary toxicities. Both databases showed high reporting frequencies and strong signal intensities for events such as interstitial lung disease, acute pulmonary edema, cardiac failure, and cardiopulmonary failure. Vinorelbine is known to possess greater lipophilicity than other vinca alkaloids, resulting in substantial tissue accumulation\u0026mdash;approximately 300-fold in the myocardium and 100-fold in the lungs relative to serum levels\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. Secondary cardiac disease is a leading cause of mortality in cancer survivors\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Multiple case reports have documented vinorelbine-associated cardiotoxicity, including ischemic heart disease, heart failure, and Takotsubo syndrome\u003csup\u003e[\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. The underlying mechanism of vinorelbine-induced cardiac toxicity remains unclear, but it may involve the alkaloid's direct effect on cell microtubules, damage to myocardial metabolism and contractility, indirect effects on coagulation leading to arterial occlusion, and possibly a paralyzing effect through its influence on the autonomic nervous system\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. A meta-analysis showed that the incidence of cardiac toxicity after vinorelbine chemotherapy alone is 1.41%\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Further research suggests that the risk of cardiotoxicity is significantly associated with a history of pre-existing heart disease. Gridelli et al. reported a higher incidence of cardiotoxicity in female patients across cancer types\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003ePulmonary toxicity is another notable risk of vinorelbine alongside cardiotoxicity. Our analysis demonstrated that the two databases documented a higher incidence of dyspnoea, pulmonary embolism, and pleural effusion, while interstitial lung disease, acute pulmonary oedema, tracheal fistula, and bronchopleural fistula exhibited stronger positive signals. Noriko et al. indicated that the incidence of vinorelbine-related pulmonary toxicity is around 2.4%\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Multiple studies have shown that vinorelbine-induced pulmonary toxicity can resolve after discontinuing the drug\u003csup\u003e[\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. Pulmonary toxicity can be acute or subacute. The acute reactions typically present with dyspnea, bronchospasm, fever, and alveolar infiltration, usually occurring within minutes after vinorelbine infusion. The subacute reactions manifest hours to days later with progressive dyspnea and diffuse interstitial infiltrates\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. Known risk factors include the concomitant use of other anticancer drugs and a history of underlying lung disease\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Therefore, clinicians should closely monitor the cardiopulmonary functions of patients during vinorelbine therapy and consider prompt discontinuation when abnormalities arise.\u003c/p\u003e\u003cp\u003eIn our analysis, the ten most frequent concomitant medications included cisplatin, gemcitabine, trastuzumab, carboplatin, capecitabine, docetaxel, dexamethasone, paclitaxel, cyclophosphamide, and ifosfamide\u0026mdash;all anticancer agents. Several of these agents are known to cause cardiopulmonary toxicity. Trastuzumab is a commonly used HER2-targeted treatment, and studies have shown that interstitial lung disease and cardiac toxicity are the most significant toxicities associated with trastuzumab\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Gemcitabine has been associated with fatal cardiovascular events including myocardial ischemia, pericarditis, and heart failure\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Polk et al.\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003ereported that nearly 5% of patients treated with capecitabine experienced cardiac toxicity symptoms (chest pain, dyspnea, palpitations), 2.4% showed changes in electrocardiograms, 0.4% had persistent acute myocardial infarction, and 0.2% died from cardiac arrest. Platinum drugs, taxanes, and alkylating agents such as cyclophosphamide have also been confirmed to cause varying degrees of cardiopulmonary toxicity\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Therefore, when vinorelbine is administered in combination with these agents, enhanced cardiopulmonary monitoring is essential.\u003c/p\u003e\u003cp\u003eVinorelbine use in pediatric patients remains limited, and the drug's label and related guidelines do not fully specify pediatric dosing regimens. Based on clinical experience, vinorelbine is mainly used in pediatric populations for conditions such as acute lymphoblastic leukemia, rhabdomyosarcoma, and Hodgkin lymphoma\u003csup\u003e[\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. Published pediatric safety data are scarce, and reported AEs are largely consistent with those in adults, involving hematologic, respiratory, hepatic/renal, and gastrointestinal systems\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. Notably, our study identified a significant association between vinorelbine and endocrine disorders in children. Gianni Bisogno et al. reported a pediatric case of vinorelbine-induced dysregulation of antidiuretic hormone secretion\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. Given the common use of glucocorticoids and combination chemotherapy in pediatric oncology, clinicians should maintain vigilance for endocrine toxicity in children receiving vinorelbine. Routine endocrine function monitoring may facilitate early detection and timely management.\u003c/p\u003e\u003cp\u003eIn conclusion, real-world pharmacovigilance data from FAERS and VigiBase indicate that vinorelbine is associated with higher-than-expected reporting rates and signal strengths for cardiopulmonary AEs, underscoring the need for heightened clinical awareness. Additionally, a notable association with endocrine disorders was observed in pediatric patients. As cancer survival improves, chemotherapy-related AEs increasingly influence long-term health and quality of life. Therefore, clinicians should not only consider the antitumor efficacy of vinorelbine but also carefully evaluate its safety profile, optimize treatment regimens, and strengthen monitoring strategies to improve patient outcomes and quality of life.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThese findings indicate that the safety profile of vinorelbine extends beyond the well-characterized hematologic and gastrointestinal toxicities. Clinicians should exercise heightened vigilance for cardiovascular and respiratory adverse events, including heart failure, interstitial lung disease, and ventricular hypertrophy, particularly during combination therapy with other cardiorespiratory-toxic agents. Moreover, the association with endocrine disorders in pediatric patients calls for age-specific monitoring. Overall, these results emphasize the importance of comprehensive monitoring and individualized risk assessment to optimize the therapeutic safety of vinorelbine.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor\u003c/strong\u003e \u003cstrong\u003econtributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS.F.W. and M.H.Y. conceived and designed the study. Y.Z., M.N.S. and S.F.W. drafted and critically revised the manuscript. Y.Z., M.N.S. and D.H. carried out data curation and performed the statistical analysis. All authors reviewed the manuscript and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Hunan Provincial Natural Science Foundation of China (2022JJ30903) and Hunan Provincial Health Commission Research Project (W20243126).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets presented in this study can be found in online repositories. (https://www.fda.gov/drugs/fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard, https://who-umc.org/vigibase-data-access/)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical considerations and informed consent\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCapasso A: \u003cstrong\u003eVinorelbine in cancer therapy.\u003c/strong\u003e\u003cem\u003eCurr Drug Targets \u003c/em\u003e2012, \u003cstrong\u003e13:\u003c/strong\u003e1065\u0026ndash;1071.\u003c/li\u003e\n\u003cli\u003eLe Brun-Ly V, Martin J, Venat-Bouvet L, Darodes N, Labourey 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trial.\u003c/strong\u003e\u003cem\u003eLancet Oncol \u003c/em\u003e2019, \u003cstrong\u003e20:\u003c/strong\u003e1566\u0026ndash;1575.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Vinorelbine, FAERS database, VigiBase database, Pharmacovigilance, Cardiopulmonary Events","lastPublishedDoi":"10.21203/rs.3.rs-8245600/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8245600/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eVinorelbine is a widely used vinca alkaloid chemotherapeutic agent. Although its hematologic and gastrointestinal toxicities are well characterized, its cardiopulmonary safety profile remains insufficiently defined, and evidence in pediatric populations is limited. This study aimed to systematically evaluate vinorelbine-associated adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS) and WHO VigiBase databases, with particular focus on cardiopulmonary events and pediatric safety. AEs from FAERS (2004 Q1-2024 Q4) and VigiBase (up to 2024 Q4) were analyzed using disproportionality methods including reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) to identify potential safety signals. Among 1,712 FAERS and 16,175 VigiBase reports listing vinorelbine as the primary suspected drug, 210 significant signals were detected across multiple system organ classes. Strong associations were found not only with blood and lymphatic system disorders but also with respiratory, thoracic and mediastinal disorders, and cardiac disorders, indicating notable cardiopulmonary safety concerns. Most AEs occurred within 30 days after administration. In pediatric patients, vinorelbine showed a significant association with endocrine disorders. These findings underscore the need for enhanced monitoring of cardiopulmonary effects during vinorelbine treatment, particularly during combination therapy, and heightened vigilance for endocrine-related AEs in pediatric patients.\u003c/p\u003e","manuscriptTitle":"Pharmacovigilance Analysis of Vinorelbine: Cardiopulmonary and Pediatric Safety Profiles Based on FAERS and VigiBase Data","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-02 15:03:53","doi":"10.21203/rs.3.rs-8245600/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"90f62512-92e7-4a74-92d7-c1dd43ca0b40","owner":[],"postedDate":"December 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":58851820,"name":"Health sciences/Cardiology"},{"id":58851821,"name":"Health sciences/Diseases"},{"id":58851822,"name":"Biological sciences/Drug discovery"},{"id":58851823,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-12-03T05:53:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-02 15:03:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8245600","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8245600","identity":"rs-8245600","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}