Examining the Safety of Mirabegron: An Analysis of Real-World Pharmacovigilance Data from the US FDA Adverse Event Reporting System (FAERS) Database

Examining the Safety of Mirabegron: An Analysis of Real-World Pharmacovigilance Data from the US FDA Adverse Event Reporting System (FAERS) Database | 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 Research Article Examining the Safety of Mirabegron: An Analysis of Real-World Pharmacovigilance Data from the US FDA Adverse Event Reporting System (FAERS) Database Junwei Wang, Aiwei Zhang, Miaoyong Ye, Cunming Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3825951/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 Background: Mirabegron, the first β-3 adrenergic receptor agonist, received approval from the Food and Drug Administration (FDA) in 2012 for the treatment of overactive bladder (OAB). This pharmacovigilance study investigated the safety profile of mirabegron treatment using the US FDA Adverse Event Reporting System (FAERS) database. Methods: This study employed disproportionality analyses, including the reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) algorithm, to quantify signals of adverse events associated with mirabegron. Results: From the first quarter of 2012 to the third quarter of 2023, a comprehensive total of 14,356,234 adverse event (AE) reports were submitted to the FAERS database. Within this dataset, encompassing 18,763 reports specifically associated with mirabegron, healthcare professionals notably contributed 2,902 of these reports. A total of 80 preferred terms (PTs) of interest were identified using both the ROR and information component (IC) algorithms. The most common AEs included blood pressure increased, urinary retention, atrial fibrillation, dry mouth, and tachycardia, which were consistent with the product instructions. Unexpected significant AEs, such as arrhythmia, palpitations, dementia, transient ischemic attack, Parkinson's disease, anti-neutrophil cytoplasmic antibody positive vasculitis, lip swelling, and swollen tongue, were also identified. The study findings indicated that the majority of onset time occurred within 30 days (n = 358, 55.68%). However, AEs were still possible after one year of mirabegron treatment. Conclusion: This study provided valuable evidence for the real-world safety of mirabegron, helping clinical professionals enhance their understanding of mirabegron's safety in clinical practice. It also contributed valuable evidence for further safety studies on mirabegron. mirabegron overactive bladder adverse event pharmacovigilance FAERS Figures Figure 1 Figure 2 Introduction Overactive bladder (OAB) is a syndrome characterized by urgency as the core symptom, often accompanied by increased frequency of urination, nocturia, and with or without urgency urinary incontinence [ 1 ]. OAB can have a significant negative impact on the quality of life and impose a substantial socioeconomic burden [ 2 ]. Preliminary studies indicate that the prevalence of OAB in males and females aged 18 and above is 16.0% and 16.9%, respectively [ 3 ]. The primary approach to treating OAB initially focuses on non-pharmacological interventions, encompassing behavioral and educational measures like moderating caffeine and alcohol consumption, engaging in bladder training, and performing pelvic floor muscle exercises [ 4 ]. The secondary treatment option entails pharmacotherapy, including the use of anticholinergic medications or β-3 adrenergic receptor agonists [ 4 ]. In 2012, mirabegron, a β-3 adrenergic receptor agonist, gained approval from the Food and Drug Administration (FDA) for treating OAB, inducing detrusor smooth muscle relaxation during the storage phase and increasing bladder capacity [ 5 , 6 ]. According to a Phase III, randomized, multicenter study [ 7 ], mirabegron is an effective treatment option for OAB, with a low incidence of adverse events (AEs). Compared to antimuscarinics, mirabegron demonstrates comparable efficacy; however, it exhibits fewer AEs [ 8 ]. Hence, mirabegron is being embraced and utilized more extensively in the management of OAB. Based on drug instructions and randomized controlled studies, common AEs associated with mirabegron include nausea, headache, hypertension, constipation, dizziness, tachycardia, and nasopharyngitis [ 7 , 9 , 10 ]. However, some new and uncommon AEs have gradually been identified, such as tongue angioedema, serum sickness-like reaction, and respiratory dysfunction [ 6 , 11 , 12 ]. As the use of mirabegron becomes more widespread, it is crucial to heighten awareness of its safety. Particularly notable are AEs not explicitly mentioned in the drug instructions, as they may be overlooked by both clinicians and patients during the course of medication. Therefore, this study aimed to evaluate signals of AEs associated with mirabegron. The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), shedding light on the safety profile of mirabegron post-market. Materials and methods Data source and study design The data for this study originated from the FAERS, which supports the FDA's post-market surveillance programs for all marketed drugs and therapeutic biologics. It is a large-scale pharmacovigilance database that encompasses seven major datasets: demographics, drugs, reactions, indications, therapies, outcomes, and report sources. The reported information is provided by healthcare professionals such as physicians (MD), pharmacists (PH), and other health-professional (OT), as well as consumers such as patients, family members, and lawyers. To ensure the reliability of reporting sources, this study extracted and analyzed reports submitted by healthcare professionals. FAERS classifies reported drugs into four categories: PS (Primary Suspect), SS (Secondary Suspect), C (Concomitant), and I (Interacting). Adverse events and medication errors are coded using terms in the Medical Dictionary for Regulatory Activities (MedDRA), which is a comprehensive and detailed standard medical terminology developed by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). MedDRA provides a five-level structure, including system organ class (SOC), high-level group term (HLGT), high-level term (HLT), preferred term (PT), and lowest level term (LLT). Mirabegron was approved by the FDA for the treatment of OAB in 2012. Data from the FAERS database, encompassing the initial quarter of 2012 through the third quarter of 2023, was acquired. In this study, both the generic and brand names such as Betmiga, Betanis, Myrbetriq, and Mirabegron were used for retrieval. Furthermore, only reports provided by healthcare professionals and reports exclusively documenting mirabegron as the PS drug were included in our analysis. For duplicate reports, we conducted deduplication based on the method recommended by the FDA [ 13 ]. Subsequently, at the SOC level, we excluded AEs such as "injury, poisoning and procedural complications", "product issues", "surgical and medical procedures", and "social circumstances", which were unrelated to drug-related AEs. Finally, we obtained information including age, weight, gender, indications, drug usage, treatment outcomes, the start date of treatment, the occurrence date of adverse events, etc. The time-to-onset of AEs was defined as the period from the start date of treatment to the date of AE occurrence. Critical patient outcomes were outlined as hospitalization-initial or prolonged (HO), death (DE), disability (DS), life-threatening (LT), congenital anomaly (CA) or other important medical event (OT). Statistical analysis In this study, we categorized age into five groups (≤ 17 years, 18–64 years, 65–85 years, ≥ 86 years, unknown), and weight into four groups ( 100 kg, unknown). We employed descriptive analysis to highlight the clinical features found in AE reports associated with mirabegron. Disproportionality analysis stands as a frequently utilized method in pharmacovigilance. This study employed two approaches, reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN), for detecting AE signals. The calculation formulas and positive safety signal thresholds were provided in Table 1 . Here, 'a' represents the number of target drug-specific adverse reactions, 'b' represents other adverse reactions related to the target drug, 'c' represents adverse reactions related to other drugs but involving the target drug, and 'd' represents other adverse reactions not related to the target drug. In this study, we focused on AEs meeting both algorithm criteria for further investigation. All analyses were performed using R software version 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria). Table 1 Two major algorithms used to assess potential associations between mirabegron and adverse events. Algorithms Equation Equation ROR ROR = ad/bc 95%CI = eln(ROR) ± 1.96(1/a + 1/b + 1/c + 1/d)^0.5 lower limit of 95% CI > 1, N ≥ 3 BCPNN IC = log2a(a + b + c + d)/((a + c)(a + b)) 95%CI = E(IC) ± 2V(IC)^0.5 IC025 > 0 Notes: Equation: a, number of reports containing both the target drug and target adverse drug reaction; b, number of reports containing other adverse drug reaction of the target drug; c, number of reports containing the target adverse drug reaction of other drugs; d, number of reports containing other drugs and other adverse drug reactions. Abbreviations: 95% CI, 95% confidence interval; N, the number of reports; IC, information component; IC025, the lower limit of 95% CI of the IC. Results Population characteristics From the first quarter of 2012 to the third quarter of 2023, a total of 14,356,234 AE reports were submitted to the FAERS database, including 18,763 reports related to mirabegron. Among these, 2,902 reports were reported by healthcare professionals (Fig. 1 ). Characteristics of the AE reports for mirabegron were summarized in Table 2 . Female patients were more commonly reported than male patients (60.16% vs. 34.80%). Elderly patients (age ≥ 65) accounted for the majority of AE reports (42.90%), excluding unknown reports. The United States had the highest reporting rate (49.50%). Excluding reports with unknown indications, hypertonic bladder (31.05%) and incontinence (13.71%) were the most common indications. Other medical events (51.00%) were the most frequently reported serious outcomes, followed by 490 cases of hospitalization (16.88%). Table 2 Clinical characteristics of reports with mirabegron from the FAERS Database Characteristics Case Number,n Case Proportion, % Number of reports 2902 Sex Female 1743 60.06 Male 1009 34.77 Unknown 150 5.17 Weight,kg ༜50 38 1.31 50ཞ100 216 7.44 ༞100 57 1.96 Unknown 2591 89.28 Age,year ≤ 17 12 0.41 18ཞ64 389 13.40 65ཞ85 1055 36.35 ≥ 86 188 6.48 Unknown 1258 43.35 Reported person Physician (MD) 1482 51.07 Other health-professional (OT) 1010 34.80 Pharmacist (PH) 410 14.13 Reporting country 0.00 United States 1437 49.52 Japan 459 15.82 Great Britain 322 11.10 Spain 106 3.65 Others 578 19.92 Indication Hypertonic bladder 901 31.05 Incontinence 398 13.71 Pollakiuria 112 3.86 Micturition urgency 74 2.55 Nocturia 31 1.07 Neurogenic bladde 23 0.79 Benign prostatic hyperplasia 22 0.76 Outcome Death (DE) 54 1.86 Life-Threatening (LT) 65 2.24 Hospitalization - Initial or Prolonged (HO) 490 16.88 Disability (DS) 72 2.48 Congenital Anomaly (CA) 0 0 Other Serious (Important Medical Event) (OT) 1480 51.00 Signal Detection Mirabegron related AE reports involved 21 organ systems, and the signal strength at the SOC level was visible in Table 3 . The most significant SOC was 'renal and urinary disorders,' with positive reactions in both the ROR and information component (IC) methods. Signal detection for 'nervous system disorders', 'cardiac disorders', 'eye disorders', 'reproductive system and breast disorders', and 'vascular disorders' showed positive results in the ROR method, while there was no positive signal in the IC method, suggesting that these signals may have also been important and frequent. Table 3 Signal strength of AEs of mirabegron at the system organ class (SOC) level in FAERS database System Organ Class (SOC) N ROR(95%Cl) IC(IC025) General disorders and administration site conditions 817 0.81(0.75–0.87) -0.27(-1.93) Nervous system disorders 610 1.23(1.13–1.33) 0.27(-1.4) Gastrointestinal disorders 558 1.07(0.98–1.17) 0.09(-1.58) Cardiac disorders 506 2.63(2.4–2.88) 1.32(-0.35) Renal and urinary disorders 445 3.56(3.23–3.92) 1.76(0.09) Investigations 434 1.1(1-1.21) 0.13(-1.54) Skin and subcutaneous tissue disorders 310 0.97(0.86–1.08) -0.05(-1.71) Vascular disorders 262 1.82(1.61–2.06) 0.84(-0.83) Psychiatric disorders 240 0.83(0.73–0.94) -0.26(-1.92) Musculoskeletal and connective tissue disorders 213 0.71(0.62–0.81) -0.47(-2.14) Infections and infestations 201 0.52(0.45–0.6) -0.9(-2.57) Respiratory, thoracic and mediastinal disorders 197 0.61(0.53–0.7) -0.69(-2.35) Eye disorders 150 1.36(1.16–1.6) 0.44(-1.23) Metabolism and nutrition disorders 76 0.47(0.37–0.59) -1.07(-2.74) Reproductive system and breast disorders 72 1.83(1.45–2.31) 0.87(-0.8) Neoplasms benign, malignant and unspecified (incl cysts and polyps) 48 0.24(0.18–0.32) -2.03(-3.7) Immune system disorders 45 0.52(0.39–0.69) -0.94(-2.61) Hepatobiliary disorders 44 0.52(0.39–0.7) -0.94(-2.6) Ear and labyrinth disorders 26 1.18(0.8–1.73) 0.23(-1.43) Blood and lymphatic system disorders 22 0.13(0.08–0.19) -2.95(-4.62) Endocrine disorders 8 0.4(0.2–0.79) -1.33(-3) As shown in Table 4 , which described a total of 80 PTs of interest identified with both ROR and IC algorithms, among which 23 PTs were consistent with product instructions and warnings, including cystitis, acute pyelonephritis, rhinitis, blood pressure increased, head discomfort, dry throat, dry mouth, bowel movement irregularity, blood pressure systolic increased, urinary retention, dysuria, interstitial cystitis, blood pressure abnormal, aemorrhagic cystitis, atrial fibrillation, tachycardia, atrial tachycardia, hypertension, hypertensive crisis, accelerated hypertension, malignant hypertension, essential hypertension, dry eye. Blood pressure increased, urinary retention, hypertension, atrial fibrillation, dry mouth, and tachycardia were the most common AE reports. Table 4 Signal strength of reports of mirabegron at the perferred terms (PTs) level in FAERs database SOC PT N ROR(95%Cl) IC(IC025) Expected Infections and infestations Cystitis 15 4.93(2.97–8.19) 2.3(0.63) Yes Pyelonephritis acute 3 8.3(2.67–25.8) 3.05(1.38) Yes Rhinitis 3 3.51(1.13–10.91) 1.81(0.14) Yes Investigations Blood pressure increased 166 14.72(12.61–17.18) 3.84(2.17) Yes Electrocardiogram QT prolonged 28 4.26(2.94–6.18) 2.08(0.42) No Heart rate irregular 13 8.26(4.79–14.25) 3.04(1.37) No Blood pressure systolic increased 11 7.4(4.09–13.38) 2.88(1.22) Yes Intraocular pressure increased 7 5.55(2.64–11.66) 2.47(0.8) No Blood urine present 6 3.83(1.72–8.54) 1.94(0.27) No Antineutrophil cytoplasmic antibody increased 5 153.88(62.45-379.13) 7.18(5.49) No Blood pressure abnormal 5 3.52(1.47–8.48) 1.82(0.15) Yes Nervous system disorders Dementia 17 7.27(4.51–11.71) 2.85(1.19) No Transient ischaemic attack 17 4.35(2.7–7.01) 2.12(0.45) No Parkinson's disease 11 7.06(3.91–12.77) 2.81(1.15) No Head discomfort 4 3.41(1.28–9.08) 1.77(0.1) Yes Myasthenia gravis 3 4.1(1.32–12.72) 2.03(0.37) No Musculoskeletal and connective tissue disorders Muscle tightness 4 3.22(1.21–8.58) 1.68(0.02) No Muscle atrophy 3 3.4(1.09–10.55) 1.76(0.1) No Respiratory, thoracic and mediastinal disorders Dry throat 5 8.21(3.41–19.76) 3.03(1.37) Yes Hyperventilation 3 4.56(1.47–14.16) 2.19(0.52) No Psychiatric disorders Hallucination, visual 8 3.39(1.7–6.79) 1.76(0.09) No Abnormal dreams 5 3.78(1.57–9.08) 1.91(0.25) No Apathy 5 4.55(1.89–10.94) 2.18(0.52) No Eating disorder 5 3.36(1.4–8.09) 1.75(0.08) No Immune system disorders Anti-neutrophil cytoplasmic antibody positive vasculitis 3 9.79(3.15–30.43) 3.29(1.62) No Skin and subcutaneous tissue disorders Petechiae 6 4.19(1.88–9.34) 2.06(0.4) No General disorders and administration site conditions Generalised oedema 8 5.04(2.52–10.09) 2.33(0.66) No Thirst 5 4.04(1.68–9.73) 2.01(0.35) No Renal and urinary disorders Urinary retention 128 31.97(26.81–38.12) 4.95(3.29) Yes Dysuria 33 9.84(6.98–13.86) 3.29(1.62) Yes Nocturia 29 33.45(23.17–48.28) 5.04(3.37) No Urinary incontinence 29 10.63(7.37–15.32) 3.4(1.73) No Pollakiuria 25 8.54(5.76–12.66) 3.09(1.42) No Haematuria 22 4.24(2.79–6.44) 2.08(0.41) No Micturition urgency 16 17.84(10.91–29.19) 4.14(2.48) No Bladder pain 10 51.14(27.34–95.65) 5.65(3.98) No Hypertonic bladder 7 29.52(14.01–62.21) 4.87(3.2) No Urine flow decreased 5 33.55(13.88–81.08) 5.05(3.38) No Postrenal failure 4 39.22(14.61-105.29) 5.27(3.6) No Cystitis interstitial 4 35.11(13.09–94.18) 5.11(3.44) Yes Cystitis haemorrhagic 4 5.56(2.08–14.83) 2.47(0.8) Yes Hydronephrosis 4 3.44(1.29–9.18) 1.78(0.11) No Bladder spasm 3 20.07(6.45–62.52) 4.32(2.64) No Neurogenic bladder 3 11.57(3.72–35.97) 3.53(1.86) No Urge incontinence 3 28.99(9.29–90.46) 4.84(3.17) No Reproductive system and breast disorders Erectile dysfunction 12 6.25(3.55–11.03) 2.64(0.97) No Benign prostatic hyperplasia 4 7.6(2.85–20.3) 2.92(1.25) No Vulvovaginal discomfort 3 12.09(3.89–37.6) 3.59(1.92) No Gastrointestinal disorders Dry mouth 56 10.48(8.05–13.64) 3.37(1.71) Yes Lip swelling 19 5.17(3.3–8.12) 2.37(0.7) No Swollen tongue 18 5.41(3.41–8.6) 2.43(0.76) No Mouth swelling 6 10.14(4.55–22.61) 3.34(1.67) No Peptic ulcer 4 9.07(3.4–24.2) 3.18(1.51) No Bowel movement irregularity 4 8.23(3.08–21.97) 3.04(1.37) Yes Colitis ischaemic 4 3.78(1.42–10.09) 1.92(0.25) No Cheilitis 3 5.4(1.74–16.78) 2.43(0.76) No Lip disorder 3 21.41(6.87–66.71) 4.41(2.74) No Lip oedema 3 3.29(1.06–10.2) 1.72(0.05) No Cardiac disorders Atrial fibrillation 91 7.44(6.04–9.15) 2.87(1.21) Yes Arrhythmia 83 16.23(13.06–20.17) 3.99(2.33) No Palpitations 66 6.74(5.29–8.6) 2.74(1.07) No Tachycardia 53 4.19(3.2–5.5) 2.06(0.39) Yes Angina pectoris 17 5.13(3.19–8.26) 2.35(0.69) No Extrasystoles 8 12.09(6.03–24.22) 3.59(1.92) No Atrial flutter 7 5.62(2.68–11.81) 2.49(0.82) No Ventricular extrasystoles 7 5.47(2.61–11.5) 2.45(0.78) No Sinus node dysfunction 5 9.45(3.93–22.76) 3.24(1.57) No Cardiac fibrillation 4 31.59(11.78–84.68) 4.96(3.29) No Cardiac discomfort 3 20.02(6.43–62.37) 4.31(2.64) No Atrial tachycardia 3 9.94(3.2-30.89) 3.31(1.64) Yes Vascular disorders Hypertension 121 5.93(4.96–7.11) 2.54(0.88) Yes Hypertensive crisis 34 16.94(12.08–23.75) 4.07(2.4) Yes Vasculitis 6 3.92(1.76–8.73) 1.97(0.3) No Malignant hypertension 5 36.78(15.21–88.92) 5.18(3.51) Yes Accelerated hypertension 5 91.07(37.34-222.14) 6.46(4.78) Yes Essential hypertension 3 9.05(2.91–28.13) 3.17(1.5) Yes Eye disorders Dry eye 15 4(2.41–6.65) 2(0.33) Yes Eyelid oedema 10 6.09(3.27–11.33) 2.6(0.94) No Glaucoma 7 4.76(2.27-10) 2.25(0.58) No Retinal vein occlusion 5 11.96(4.97–28.81) 3.57(1.91) No A total of 57 PTs were unexpected findings of significant AEs. Among them, AE reports with a count exceeding 10 included arrhythmia, palpitations, nocturia, urinary incontinence, electrocardiogram QT prolonged, pollakiuria, hematuria, lip swelling, swollen tongue, dementia, angina pectoris, transient ischemic attack, micturition urgency, heart rate irregular, erectile dysfunction, Parkinson's disease, bladder pain, and eyelid edema. Some PTs with elevated signal intensity were discovered, including antineutrophil cytoplasmic antibody increased (ROR = 153.88), bladder pain (ROR = 51.14), postrenal failure (ROR = 39.22), urine flow decreased (ROR = 33.55), nocturia (ROR = 33.45), cardiac fibrillation (ROR = 31.59), hypertonic bladder (ROR = 29.52), urge incontinence (ROR = 28.99), lip disorder (ROR = 21.41), bladder spasm (ROR = 20.07), and cardiac discomfort (ROR = 20.02). Time-to-onset analysis A total of 643 AE reports related to Mirabegron reported onset time, with a median onset time of 25 days (interquartile range [IQR] 7–75 days). The study findings indicated that the majority of onset time occurred within 30 days (n = 358, 55.68%). However, adverse events (AEs) were still possible after one year of mirabegron treatment, accounting for a proportion of 5.91% (Fig. 2 ). Discussion The FAERS is a spontaneous reporting system for AEs, providing a public database for the real-world assessment of the post-marketing safety profile of mirabegron. It enables the identification of AEs not yet documented in the drug instructions. To ensure the reliability of reporting sources, our analysis exclusively included reports provided by healthcare professionals and reports specifically documenting mirabegron as the PS drug. The incidence of AEs related to mirabegron was higher in females (60.10%) than in males (34.80%), excluding cases with unknown gender. This may be related to the higher prevalence of OAB in females compared to males [ 14 ]. Furthermore, with increasing age, the prevalence of OAB gradually increased [ 15 ]. This phenomenon also explained the higher incidence of AEs among individuals aged 65 and older in this study. With the continuous expansion of mirabegron's clinical application, clinicians should be vigilant about AEs associated with mirabegron, especially in elderly patients. Early identification of AEs is essential because these AEs may not only increase the likelihood of patient hospitalization but also pose potential life-threatening risks. Based on the disproportional analysis, the most frequent and significant signals at the SOC level was renal and urinary disorders, showing positive reactions in both the ROR and IC methods. The related AEs included dysuria, pollakiuria, bladder pain, bladder spasm, neurogenic bladder, etc., but they were often considered as indications of mirabegron (Fig. 2 ). Therefore, these AEs are considered to be associated with the progression of the underlying medical condition rather than being AEs caused by the medication itself. It is noteworthy that there were 128 reports of urinary retention, with significant signals observed in both the ROR and IC analyses. According to previous research, mirabegron did not have AEs on urinary urodynamic parameters, including maximum urinary flow rate and detrusor pressure at maximum flow, and did not increase the risk of urinary retention [ 7 , 9 , 10 , 16 ]. Furthermore, the mechanism of mirabegron involves promoting relaxation of the detrusor muscle and increasing urinary storage capacity without altering voiding pressure or contraction [ 10 ]. Mirabegron appeared to exhibit good safety in the AE of urinary retention. Therefore, a reasonable interpretation of the study results was that disease progression, such as benign prostatic hyperplasia or neurogenic bladder, might have been a contributing factor to urinary retention. However, according to a Japanese study, 19 OAB patients with concomitant benign prostatic hyperplasia experienced urinary retention after using mirabegron, with resolution or recovery observed upon discontinuation [ 17 ]. Therefore, we believe that the correlation between mirabegron and the AE of urinary retention remains controversial. For patients with evident bladder outlet obstruction in clinical practice, the use of mirabegron should be approached with caution [ 17 ]. Additionally, we recommend regular follow-up during mirabegron treatment, where clinicians should monitor patients' voiding patterns, residual urine volume, and urinary flow rates. Furthermore, significant signals were observed in the ROR method within the SOC categories of cardiac disorders, investigations, and vascular disorders. Based on findings from clinical studies, the predominant cardiovascular AEs linked to mirabegron include hypertension, tachycardia, palpitations, and atrial fibrillation [ 18 – 21 ]. Approximately 9–10% of patients undergoing mirabegron treatment may experience hypertension [ 22 ]. Furthermore, there have been reports of an increase in the QTc interval [ 23 ]. In accordance with the results of this study, the ROR for blood pressure increased as 14.72 (12.61–17.18), with an IC of 3.84 (2.17). The ROR for hypertension as 5.93 (4.96–7.11), with an IC of 2.54 (0.88). For electrocardiogram QT prolonged, the ROR was 4.26 (2.94–6.18) with an IC of 2.08 (0.42). The ROR for atrial fibrillation was 7.44 (6.04–9.15) with an IC of 2.87 (1.21). Arrhythmia had an ROR of 16.23 (13.06–20.17) with an IC of 3.99 (2.33). The ROR for palpitations was 6.74 (5.29–8.6) with an IC of 2.74 (1.07), and for tachycardia, the ROR was 4.19 (3.2–5.5) with an IC of 2.06 (0.39). As mirabegron is a β3-adrenergic receptor agonist, and β3-adrenergic receptors are also expressed in cardiovascular tissues, the use of mirabegron may have "off-target" effects on the regulation of the cardiovascular system [ 21 ]. This could be the potential pharmacological mechanism by which mirabegron induces cardiovascular-related AEs. β3-adrenergic receptors can increase the occurrence of arrhythmias and the risk of atrial fibrillation by activating the cAMP-dependent protein kinase pathway and inducing Ca2 + imbalance [ 20 ]. Additionally, the β1-adrenergic receptors expressed in cardiovascular tissues were also target sites for the action of mirabegron [ 24 ]. An animal study found that the heart rate effects of mirabegron in dogs were attributed to cross-reactivity with β1-adrenergic receptors [ 25 ]. This was further confirmed by a clinical study [ 24 ]. Regardless of whether it involved the stimulation of β1-adrenergic receptors in cardiovascular tissues or β3-adrenergic receptors, the administration of supratherapeutic dosages that led to significant multiples of peak plasma concentrations was more prone to causing increases in heart rate, elevated blood pressure, and prolonged QT intervals [ 24 , 26 ]. Although a treatment dose of 50 mg mirabegron could lead to an increase in baseline pulse rate by one beat per minute [ 27 ], the impact was not significant. Furthermore, mirabegron is extensively metabolized by the liver and excreted in urine, either as the parent drug or its metabolites [ 28 ]. Therefore, in clinical practice, it is not only important to pay attention to the safe dosage of mirabegron but also to monitor the liver and kidney functions of patients, avoiding excessively high blood drug concentrations that may lead to cardiovascular-related AEs. For patients experiencing cardiovascular-related AEs after using mirabegron, it is recommended to undergo blood drug concentration monitoring. Furthermore, this study also identified some unexpected yet clinically significant safety signals, such as angina pectoris, extrasystoles, and cardiac fibrillation. Although the reported cases of these cardiovascular AEs are limited, they should not be overlooked, as they may have potentially life-threatening implications for patients. Evidence indicated that mirabegron could cause the AE of headache [ 29 ]. In our study, we also identified head discomfort as a significant AE associated with mirabegron, with a signal strength of ROR 3.41 (1.28–9.08) and IC 1.77 (0.1). Additionally, in our results, dementia, transient ischemic attack, Parkinson's Disease, and myasthenia gravis emerged as new significant AEs associated with mirabegron. In a previous clinical study, 23,662 patients with OAB using mirabegron were found to have 603 new cases of dementia [ 30 ]. While the reported case numbers are limited, healthcare professionals should not overlook these findings, as mirabegron may potentially cause central nervous system side effects. In the striatum of both rats and humans, the presence of β-3 adrenergic receptor mRNA has been confirmed [ 31 ]. Activation of these receptors by mirabegron decreases acetylcholine release from striatal neurons [ 32 ]. Acetylcholine deficiency in the brain is linked not only to Alzheimer's disease, vascular dementia, and Lewy body dementia but also to movement disorders [ 32 – 35 ]. Furthermore, β3-adrenergic receptor agonists promote the synthesis and release of serotonin (5-HT) in the striatum of the brain, which may also be an important mechanism [ 32 ]. In this study, we identified transient ischemic attack as an AE with significant signal strength, which was not previously listed in the drug label or observed in earlier clinical studies. As of now, the mechanism by which mirabegron induces transient ischemic attack remains unclear. Transient ischemic attack can be caused by various factors, including atherosclerosis, cardiac-related factors, arterial inflammation, and others. Atrial fibrillation was a known risk factor for transient ischemic attack [ 36 ]. Therefore, transient ischemic attack may also be associated with mirabegron-related AEs such as atrial fibrillation. The neurologic adverse events caused by mirabegron were unexpected for clinicians, and if not promptly identified, they could potentially result in irreversible damage to the nervous system. Some other new and unexpected adverse events, including lip swelling, swollen tongue, mouth swelling, peptic ulcer, ischemic colitis, eyelid edema, glaucoma, and retinal vein occlusion, were also identified in this study. Matthew et al [ 6 ] reported a case of a patient who experienced tongue swelling, accompanied by difficulty breathing and swallowing, after using mirabegron. In this report, swelling was also observed in areas such as the lips, oral cavity, and eyelids. The mechanism of mirabegron-induced edema is believed to be a type I hypersensitivity reaction mediated by mast cell degranulation [ 6 ]. It is noteworthy that both "anti-neutrophil cytoplasmic antibody increased" and "anti-neutrophil cytoplasmic antibody positive vasculitis" exhibited strong positive signals in both the ROR and IC methods. Anti-neutrophil cytoplasmic antibody positive vasculitis is a group of potentially life-threatening autoimmune diseases [ 37 , 38 ]. Although the exact etiology remains incompletely understood, research indicated that drugs are significant contributors to the development of this condition [ 39 ]. Based on previous research findings, the drugs that induced anti-neutrophil cytoplasmic antibody positive vasculitis belonged to various pharmacological categories [ 39 ]. These primarily included anti-thyroid drugs, tumor necrosis factor inhibitors, anti-tuberculosis drugs, psychoactive agents, and others [ 39 ]. To the best of our knowledge, this study was the first to report the potential induction of anti-neutrophil cytoplasmic antibody positive vasculitis by mirabegron. The finding of this study warrant careful attention from clinicians. Close monitoring of ANCA levels in patients undergoing mirabegron treatment is essential, as it serves as an effective tool for the early diagnosis of drug-induced anti-neutrophil cytoplasmic antibody positive vasculitis. Upon confirmation, immediate discontinuation of the drug is imperative, as most patients experience relief after ceasing the use of this harmful medication [ 39 ]. The study findings revealed a median onset time of 25 days, with most AEs happening within the initial 30 days following exposure to mirabegron (n = 358, 55.68%). However, AEs could still occur even a year later. Therefore, clinicians needed to closely follow up with patients using mirabegron, especially within the first 30 days. In future clinical studies, longer follow-up periods were necessary to observe mirabegron-related AEs. Several limitations in this study need to be addressed. Firstly, the FAERs database is a spontaneous reporting database, and the quality is not rigorously controlled. Although our analysis included reports provided only by healthcare professionals to ensure the reliability of the reporting sources, it inevitably reduced the sample size. Additionally, the occurrence rates of each AE related to mirabegron could not be estimated. Secondly, the presence of reports in the FAERS database does not establish a causal relationship, requiring further well-designed clinical trials to investigate causation. Ultimately, certain confounding factors not measured in the study, such as possible interactions between medications, existing medical conditions, and combinations of drugs, were excluded from the analysis. Despite these limitations, FAERs remains valuable for post-marketing safety surveillance. Conclusion In conclusion, despite numerous clinical studies confirming the efficacy and high safety profile of mirabegron in treating OAB, the increasing use of mirabegron necessitates clinicians to be aware of unexpected AEs not documented in the drug label or discovered in clinical trials. This study, which utilized a pharmacovigilance analysis of the FAERS database, scientifically elucidated the true safety profile of mirabegron treatment. New significant AEs, such as arrhythmia, palpitations, dementia, transient ischemic attack, Parkinson's disease, anti-neutrophil cytoplasmic antibody positive vasculitis, lip swelling, swollen tongue, and others, were identified. Our research provided valuable evidence for further investigation and clinical practice involving mirabegron. Abbreviations FDA The Food and Drug Administration FAERS The US FDA Adverse Event Reporting System OAB Overactive bladder AE Adverse events PS Primary Suspect SOC System organ class HLGT High-level group term HLT High-level term PT Preferred term LLT Lowest level term HO Hospitalization-initial or prolonged DE Death DS Disability LT Life-threatening CA Congenital anomaly OT Other important medical event ROR Reporting odds ratio BCPNN Bayesian Confidence Propagation Neural Network IC Information component IC025 The lower limit of 95% confdence interval of the IC Declarations Acknowledgements We appreciate the FAERS open policy and the provided data, as well as all participants in this study. Authors’ contributions JW: protocol/project development, data collection and management, data analysis, and manuscript writing; AZ: protocol/project development, data collection and management, data analysis; MY: data collection and management, data analysis; CZ: manuscript review and revision; All authors contributed to the article and approved the submitted version. Funding No funding was used for this submission. Availability of data and materials The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate Not applicable. This study was deemed non-human subject related research. Consent for publication Not applicable. Competing interests The authors declare no competing interests. References Haylen BT, Maher CF, Barber MD, Camargo S, Dandolu V, Digesu A, Goldman HB, Huser M, Milani AL, Moran PA, Schaer GN, Withagen MI. 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Batista JE, Kölbl H, Herschorn S, Rechberger T, Cambronero J, Halaska M, Coppell A, Kaper M, Huang M, Siddiqui E. The efficacy and safety of mirabegron compared with solifenacin in overactive bladder patients dissatisfied with previous antimuscarinic treatment due to lack of efficacy: results of a noninferiority, randomized, phase IIIb trial. Ther Adv Urol. 2015;7:167–79. Chan CS, Lin FJ, Liu CM, Lin YK, Chen YC, Hsu CC, Higa S, Chen SA, Chen YJ. Mirabegron, a β3–adrenoreceptor agonist, regulates right and left atrial arrhythmogenesis differently. Exp Ther Med. 2022;24:720. Rosa GM, Ferrero S, Nitti VW, Wagg A, Saleem T, Chapple CR. Cardiovascular Safety of β3-adrenoceptor Agonists for the Treatment of Patients with Overactive Bladder Syndrome. Eur Urol. 2016;69:311–23. Krhut J, Wohlfahrt P, Pudich J, Kufová E, Borovička V, Bílková K, Sýkora R, Mokriš J, Cífková R, Zachoval R, Zvara P. Cardiovascular safety of mirabegron in individuals treated for spinal cord injury- or multiple sclerosis-induced neurogenic detrusor overactivity. Int Urol Nephrol. 2021;53:1089–95. Balachandran AA, Duckett JR. The risk and severity of developing symptomatic palpitations when prescribed mirabegron for overactive bladder. Eur J Obstet Gynecol Reprod Biol. 2015;187:60–3. van Gelderen M, Stölzel M, Meijer J, Kerbusch V, Collins C, Korstanje C. An Exploratory Study in Healthy Male Subjects of the Mechanism of Mirabegron-Induced Cardiovascular Effects. J Clin Pharmacol. 2017;57:1534–44. Korstanje C, Suzuki M, Yuno K, Sato S, Ukai M, Schneidkraut MJ, Yan GX. Translational science approach for assessment of cardiovascular effects and proarrhythmogenic potential of the beta-3 adrenergic agonist mirabegron. J Pharmacol Toxicol Methods. 2017;87:74–81. Malik M, van Gelderen EM, Lee JH, Kowalski DL, Yen M, Goldwater R, Mujais SK, Schaddelee MP, de Koning P, Kaibara A, Moy SS, Keirns JJ. Proarrhythmic safety of repeat doses of mirabegron in healthy subjects: a randomized, double-blind, placebo-, and active-controlled thorough QT study. Clin Pharmacol Ther. 2012;92:696–706. Andersson KE. New developments in the management of overactive bladder: focus on mirabegron and onabotulinumtoxinA. Ther Clin Risk Manag. 2013;9:161–70. Kashyap M, Tyagi P. The pharmacokinetic evaluation of mirabegron as an overactive bladder therapy option. Expert Opin Drug Metab Toxicol. 2013;9:617–27. Hou J, Xu F, Du H, Li N. Adverse events associated with mirabegron 50mg versus placebo: A systematic review and meta-analysis. Prog Urol. 2021;31:627–33. Welk B, McArthur E. Increased risk of dementia among patients with overactive bladder treated with an anticholinergic medication compared to a beta-3 agonist: a population-based cohort study. BJU Int. 2020;126:183–90. Rodriguez M, Carillon C, Coquerel A, Le Fur G, Ferrara P, Caput D, Shire D. Evidence for the presence of beta 3-adrenergic receptor mRNA in the human brain. Brain Res Mol Brain Res. 1995;29:369–75. Murchison AG, Fletcher C, Cheeran B. Recurrence of dyskinesia as a side-effect of mirabegron in a patient with Parkinson's disease on DBS (GPi). Parkinsonism Relat Disord. 2016;27:107–8. Jia JP, Jia JM, Zhou WD, Xu M, Chu CB, Yan X, Sun YX. Differential acetylcholine and choline concentrations in the cerebrospinal fluid of patients with Alzheimer's disease and vascular dementia. Chin Med J (Engl). 2004;117:1161–4. Hoskin JL, Al-Hasan Y, Sabbagh MN. Nicotinic Acetylcholine Receptor Agonists for the Treatment of Alzheimer's Dementia: An Update. Nicotine Tob Res. 2019;21:370–6. Sarter M, Bruno JP. Cortical acetylcholine, reality distortion, schizophrenia, and Lewy Body Dementia: too much or too little cortical acetylcholine. Brain Cogn. 1998;38:297–316. Thakur M, Alsinbili A, Chattopadhyay R, Warburton EA, Khadjooi K, Induruwa I. Identifying the optimal time period for detection of atrial fibrillation after ischaemic stroke and TIA: An updated systematic review and meta-analysis of randomized control trials. Int J Stroke 2023:17474930231215277. Sun XJ, Li ZY, Chen M. Pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis. Rheumatol Immunol Res. 2023;4:11–21. Schönermarck U, Csernok E, Gross WL. Pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis: challenges and solutions 2014. Nephrol Dial Transplant. 2015;30(Suppl 1):i46–52. Weng CH, Liu ZC. Drug-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. Chin Med J (Engl). 2019;132:2848–55. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3825951","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":264737460,"identity":"38264125-89ac-4f8f-a422-fe60e8b98cce","order_by":0,"name":"Junwei Wang","email":"","orcid":"","institution":"Wenling Hospital Affiliated to Wenzhou Medical University, The First People's Hospital of Wenling)","correspondingAuthor":false,"prefix":"","firstName":"Junwei","middleName":"","lastName":"Wang","suffix":""},{"id":264737461,"identity":"58607667-7298-41a9-ab11-a0e31752621a","order_by":1,"name":"Aiwei Zhang","email":"","orcid":"","institution":"Wenling Hospital Affiliated to Wenzhou Medical University, The First People's Hospital of Wenling)","correspondingAuthor":false,"prefix":"","firstName":"Aiwei","middleName":"","lastName":"Zhang","suffix":""},{"id":264737462,"identity":"c136e34a-584b-481d-8ab6-7af687be9ce9","order_by":2,"name":"Miaoyong Ye","email":"","orcid":"","institution":"Wenling Hospital Affiliated to Wenzhou Medical University, The First People's Hospital of Wenling)","correspondingAuthor":false,"prefix":"","firstName":"Miaoyong","middleName":"","lastName":"Ye","suffix":""},{"id":264737463,"identity":"4aa5a052-0e78-41dc-be03-c09f1368df95","order_by":3,"name":"Cunming Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYDACCRiDGYg/GNjYkaaFcUZBWjIJWkC6eD4cYmwgpEN+dvOzh19qDufptvMefm1jcICZgf3w0Q34tDDOOWZuLHPscLHZYb406xyDO3wMPGlpN/BpYZZIMJOWbDicuO0wj5lxjsEzZgYJHjO8Wtgk0r8htFgYHGZsIKSFRyLHTPIjRIvxYwZitEhI5JRJMxxLB9vC2GOQlsxGyC/yM9K3Sf6osU7cdv6M8Ycff2zs+NkPH8OrBQSYeWD+ApOElIMA4w+o1g/EqB4Fo2AUjIKRBwD40khrAPCfwgAAAABJRU5ErkJggg==","orcid":"","institution":"Wenling Hospital Affiliated to Wenzhou Medical University, The First People's Hospital of Wenling)","correspondingAuthor":true,"prefix":"","firstName":"Cunming","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2023-12-31 13:59:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3825951/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3825951/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49139535,"identity":"06180736-a1e4-4fba-9445-25cbe8067709","added_by":"auto","created_at":"2024-01-03 18:10:21","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":227722,"visible":true,"origin":"","legend":"\u003cp\u003eThe process of searching mirabegron-associated adverse events from food and drug administration adverse event reporting database (FAERS)\u003c/p\u003e","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3825951/v1/b82160135e24a5147c05d951.png"},{"id":49139536,"identity":"d31f3988-72ba-43db-b035-af8148f75c5c","added_by":"auto","created_at":"2024-01-03 18:10:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":89471,"visible":true,"origin":"","legend":"\u003cp\u003eTime to onset of mirabegron-related AEs.\u003c/p\u003e","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-3825951/v1/11d306f0b37ad6416b5e6139.png"},{"id":50028061,"identity":"7c83ea16-e535-49da-8287-b0786c40faf4","added_by":"auto","created_at":"2024-01-23 11:07:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":804651,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3825951/v1/49b314e0-e780-4512-934d-90a4e0d46aa9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Examining the Safety of Mirabegron: An Analysis of Real-World Pharmacovigilance Data from the US FDA Adverse Event Reporting System (FAERS) Database","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOveractive bladder (OAB) is a syndrome characterized by urgency as the core symptom, often accompanied by increased frequency of urination, nocturia, and with or without urgency urinary incontinence [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. OAB can have a significant negative impact on the quality of life and impose a substantial socioeconomic burden [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Preliminary studies indicate that the prevalence of OAB in males and females aged 18 and above is 16.0% and 16.9%, respectively [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The primary approach to treating OAB initially focuses on non-pharmacological interventions, encompassing behavioral and educational measures like moderating caffeine and alcohol consumption, engaging in bladder training, and performing pelvic floor muscle exercises [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The secondary treatment option entails pharmacotherapy, including the use of anticholinergic medications or β-3 adrenergic receptor agonists [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn 2012, mirabegron, a β-3 adrenergic receptor agonist, gained approval from the Food and Drug Administration (FDA) for treating OAB, inducing detrusor smooth muscle relaxation during the storage phase and increasing bladder capacity [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. According to a Phase III, randomized, multicenter study [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], mirabegron is an effective treatment option for OAB, with a low incidence of adverse events (AEs). Compared to antimuscarinics, mirabegron demonstrates comparable efficacy; however, it exhibits fewer AEs [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Hence, mirabegron is being embraced and utilized more extensively in the management of OAB.\u003c/p\u003e \u003cp\u003eBased on drug instructions and randomized controlled studies, common AEs associated with mirabegron include nausea, headache, hypertension, constipation, dizziness, tachycardia, and nasopharyngitis [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, some new and uncommon AEs have gradually been identified, such as tongue angioedema, serum sickness-like reaction, and respiratory dysfunction [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. As the use of mirabegron becomes more widespread, it is crucial to heighten awareness of its safety. Particularly notable are AEs not explicitly mentioned in the drug instructions, as they may be overlooked by both clinicians and patients during the course of medication. Therefore, this study aimed to evaluate signals of AEs associated with mirabegron. The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), shedding light on the safety profile of mirabegron post-market.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData source and study design\u003c/h2\u003e \u003cp\u003eThe data for this study originated from the FAERS, which supports the FDA's post-market surveillance programs for all marketed drugs and therapeutic biologics. It is a large-scale pharmacovigilance database that encompasses seven major datasets: demographics, drugs, reactions, indications, therapies, outcomes, and report sources. The reported information is provided by healthcare professionals such as physicians (MD), pharmacists (PH), and other health-professional (OT), as well as consumers such as patients, family members, and lawyers. To ensure the reliability of reporting sources, this study extracted and analyzed reports submitted by healthcare professionals. FAERS classifies reported drugs into four categories: PS (Primary Suspect), SS (Secondary Suspect), C (Concomitant), and I (Interacting). Adverse events and medication errors are coded using terms in the Medical Dictionary for Regulatory Activities (MedDRA), which is a comprehensive and detailed standard medical terminology developed by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). MedDRA provides a five-level structure, including system organ class (SOC), high-level group term (HLGT), high-level term (HLT), preferred term (PT), and lowest level term (LLT). Mirabegron was approved by the FDA for the treatment of OAB in 2012. Data from the FAERS database, encompassing the initial quarter of 2012 through the third quarter of 2023, was acquired. In this study, both the generic and brand names such as Betmiga, Betanis, Myrbetriq, and Mirabegron were used for retrieval. Furthermore, only reports provided by healthcare professionals and reports exclusively documenting mirabegron as the PS drug were included in our analysis. For duplicate reports, we conducted deduplication based on the method recommended by the FDA [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Subsequently, at the SOC level, we excluded AEs such as \"injury, poisoning and procedural complications\", \"product issues\", \"surgical and medical procedures\", and \"social circumstances\", which were unrelated to drug-related AEs. Finally, we obtained information including age, weight, gender, indications, drug usage, treatment outcomes, the start date of treatment, the occurrence date of adverse events, etc. The time-to-onset of AEs was defined as the period from the start date of treatment to the date of AE occurrence. Critical patient outcomes were outlined as hospitalization-initial or prolonged (HO), death (DE), disability (DS), life-threatening (LT), congenital anomaly (CA) or other important medical event (OT).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eIn this study, we categorized age into five groups (\u0026le;\u0026thinsp;17 years, 18\u0026ndash;64 years, 65\u0026ndash;85 years, \u0026ge;\u0026thinsp;86 years, unknown), and weight into four groups (\u0026lt;\u0026thinsp;50 kg, 50\u0026ndash;100 kg, \u0026gt;\u0026thinsp;100 kg, unknown). We employed descriptive analysis to highlight the clinical features found in AE reports associated with mirabegron. Disproportionality analysis stands as a frequently utilized method in pharmacovigilance. This study employed two approaches, reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN), for detecting AE signals. The calculation formulas and positive safety signal thresholds were provided in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Here, 'a' represents the number of target drug-specific adverse reactions, 'b' represents other adverse reactions related to the target drug, 'c' represents adverse reactions related to other drugs but involving the target drug, and 'd' represents other adverse reactions not related to the target drug. In this study, we focused on AEs meeting both algorithm criteria for further investigation. All analyses were performed using R software version 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria).\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\u003eTwo major algorithms used to assess potential associations between mirabegron and adverse events.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlgorithms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEquation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEquation\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eROR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eROR\u0026thinsp;=\u0026thinsp;ad/bc\u003c/p\u003e \u003cp\u003e95%CI\u0026thinsp;=\u0026thinsp;eln(ROR)\u0026thinsp;\u0026plusmn;\u0026thinsp;1.96(1/a\u0026thinsp;+\u0026thinsp;1/b\u0026thinsp;+\u0026thinsp;1/c\u0026thinsp;+\u0026thinsp;1/d)^0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003elower limit of 95% CI\u0026thinsp;\u0026gt;\u0026thinsp;1, N\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCPNN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIC\u0026thinsp;=\u0026thinsp;log2a(a\u0026thinsp;+\u0026thinsp;b\u0026thinsp;+\u0026thinsp;c\u0026thinsp;+\u0026thinsp;d)/((a\u0026thinsp;+\u0026thinsp;c)(a\u0026thinsp;+\u0026thinsp;b))\u003c/p\u003e \u003cp\u003e95%CI\u0026thinsp;=\u0026thinsp;E(IC)\u0026thinsp;\u0026plusmn;\u0026thinsp;2V(IC)^0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIC025\u0026thinsp;\u0026gt;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eNotes: Equation: a, number of reports containing both the target drug and target adverse drug reaction; b, number of reports containing other adverse drug reaction of the target drug; c, number of reports containing the target adverse drug reaction of other drugs; d, number of reports containing other drugs and other adverse drug reactions.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eAbbreviations: 95% CI, 95% confidence interval; N, the number of reports; IC, information component; IC025, the lower limit of 95% CI of the IC.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePopulation characteristics\u003c/h2\u003e \u003cp\u003eFrom the first quarter of 2012 to the third quarter of 2023, a total of 14,356,234 AE reports were submitted to the FAERS database, including 18,763 reports related to mirabegron. Among these, 2,902 reports were reported by healthcare professionals (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Characteristics of the AE reports for mirabegron were summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Female patients were more commonly reported than male patients (60.16% vs. 34.80%). Elderly patients (age\u0026thinsp;\u0026ge;\u0026thinsp;65) accounted for the majority of AE reports (42.90%), excluding unknown reports. The United States had the highest reporting rate (49.50%). Excluding reports with unknown indications, hypertonic bladder (31.05%) and incontinence (13.71%) were the most common indications. Other medical events (51.00%) were the most frequently reported serious outcomes, followed by 490 cases of hospitalization (16.88%).\u003c/p\u003e \u003cp\u003e \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\u003eClinical characteristics of reports with mirabegron from the FAERS Database\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase Number,n\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCase Proportion, %\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of reports\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2902\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1743\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWeight,kg\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e༜50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50ཞ100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e216\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e༞100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2591\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge,year\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18ཞ64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e389\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e65ཞ85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1055\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1258\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReported person\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysician (MD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1482\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther health-professional (OT)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePharmacist (PH)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e410\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReporting country\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited States\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1437\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e459\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGreat Britain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e322\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e578\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIndication\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertonic bladder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e901\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncontinence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e398\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePollakiuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.86\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicturition urgency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNocturia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurogenic bladde\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBenign prostatic hyperplasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOutcome\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath (DE)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.86\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLife-Threatening (LT)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalization - Initial or Prolonged (HO)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e490\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisability (DS)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCongenital Anomaly (CA)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther Serious (Important Medical Event) (OT)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1480\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.00\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 \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eSignal Detection\u003c/h2\u003e \u003cp\u003eMirabegron related AE reports involved 21 organ systems, and the signal strength at the SOC level was visible in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The most significant SOC was 'renal and urinary disorders,' with positive reactions in both the ROR and information component (IC) methods. Signal detection for 'nervous system disorders', 'cardiac disorders', 'eye disorders', 'reproductive system and breast disorders', and 'vascular disorders' showed positive results in the ROR method, while there was no positive signal in the IC method, suggesting that these signals may have also been important and frequent.\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\u003eSignal strength of AEs of mirabegron at the system organ class (SOC) level in 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\u003eSystem Organ Class (SOC)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eROR(95%Cl)\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\u003e817\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.81(0.75\u0026ndash;0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.27(-1.93)\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\u003e610\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.23(1.13\u0026ndash;1.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.27(-1.4)\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\u003e558\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.07(0.98\u0026ndash;1.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.09(-1.58)\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\u003e506\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.63(2.4\u0026ndash;2.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.32(-0.35)\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\u003e445\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.56(3.23\u0026ndash;3.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.76(0.09)\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\u003e434\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.1(1-1.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.13(-1.54)\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\u003e310\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.97(0.86\u0026ndash;1.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.05(-1.71)\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\u003e262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.82(1.61\u0026ndash;2.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.84(-0.83)\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\u003e240\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.83(0.73\u0026ndash;0.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.26(-1.92)\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\u003e213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.71(0.62\u0026ndash;0.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.47(-2.14)\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\u003e201\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.52(0.45\u0026ndash;0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.9(-2.57)\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\u003e197\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.61(0.53\u0026ndash;0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.69(-2.35)\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\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.36(1.16\u0026ndash;1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.44(-1.23)\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\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.47(0.37\u0026ndash;0.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.07(-2.74)\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\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.83(1.45\u0026ndash;2.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.87(-0.8)\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\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.24(0.18\u0026ndash;0.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.03(-3.7)\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\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.52(0.39\u0026ndash;0.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.94(-2.61)\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\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.52(0.39\u0026ndash;0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.94(-2.6)\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\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.18(0.8\u0026ndash;1.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.23(-1.43)\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\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.13(0.08\u0026ndash;0.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.95(-4.62)\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\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.4(0.2\u0026ndash;0.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.33(-3)\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\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, which described a total of 80 PTs of interest identified with both ROR and IC algorithms, among which 23 PTs were consistent with product instructions and warnings, including cystitis, acute pyelonephritis, rhinitis, blood pressure increased, head discomfort, dry throat, dry mouth, bowel movement irregularity, blood pressure systolic increased, urinary retention, dysuria, interstitial cystitis, blood pressure abnormal, aemorrhagic cystitis, atrial fibrillation, tachycardia, atrial tachycardia, hypertension, hypertensive crisis, accelerated hypertension, malignant hypertension, essential hypertension, dry eye. Blood pressure increased, urinary retention, hypertension, atrial fibrillation, dry mouth, and tachycardia were the most common AE reports.\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\u003eSignal strength of reports of mirabegron at the perferred terms (PTs) level in FAERs database\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\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\u003ePT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN\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 \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eExpected\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfections and infestations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCystitis\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\u003e4.93(2.97\u0026ndash;8.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.3(0.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\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\u003ePyelonephritis acute\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\u003e8.3(2.67\u0026ndash;25.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.05(1.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\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\u003eRhinitis\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\u003e3.51(1.13\u0026ndash;10.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.81(0.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eBlood pressure increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e166\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14.72(12.61\u0026ndash;17.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.84(2.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eElectrocardiogram QT prolonged\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.26(2.94\u0026ndash;6.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.08(0.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHeart rate irregular\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\u003e8.26(4.79\u0026ndash;14.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.04(1.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBlood pressure systolic increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.4(4.09\u0026ndash;13.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.88(1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntraocular pressure increased\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\u003e5.55(2.64\u0026ndash;11.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.47(0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBlood urine present\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\u003e3.83(1.72\u0026ndash;8.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.94(0.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAntineutrophil cytoplasmic antibody increased\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\u003e153.88(62.45-379.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.18(5.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBlood pressure abnormal\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\u003e3.52(1.47\u0026ndash;8.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.82(0.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eDementia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.27(4.51\u0026ndash;11.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.85(1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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\u003eTransient ischaemic attack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.35(2.7\u0026ndash;7.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.12(0.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParkinson's disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.06(3.91\u0026ndash;12.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.81(1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHead discomfort\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\u003e3.41(1.28\u0026ndash;9.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.77(0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMyasthenia gravis\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\u003e4.1(1.32\u0026ndash;12.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.03(0.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eMuscle tightness\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\u003e3.22(1.21\u0026ndash;8.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.68(0.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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\u003eMuscle atrophy\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\u003e3.4(1.09\u0026ndash;10.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.76(0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eDry throat\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\u003e8.21(3.41\u0026ndash;19.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.03(1.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\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\u003eHyperventilation\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\u003e4.56(1.47\u0026ndash;14.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.19(0.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eHallucination, visual\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\u003e3.39(1.7\u0026ndash;6.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.76(0.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbnormal dreams\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\u003e3.78(1.57\u0026ndash;9.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.91(0.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eApathy\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\u003e4.55(1.89\u0026ndash;10.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.18(0.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEating disorder\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\u003e3.36(1.4\u0026ndash;8.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.75(0.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnti-neutrophil cytoplasmic antibody positive vasculitis\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\u003e9.79(3.15\u0026ndash;30.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.29(1.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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=\"left\" colname=\"c2\"\u003e \u003cp\u003ePetechiae\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\u003e4.19(1.88\u0026ndash;9.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.06(0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneral disorders and administration site conditions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGeneralised oedema\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\u003e5.04(2.52\u0026ndash;10.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.33(0.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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\u003eThirst\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\u003e4.04(1.68\u0026ndash;9.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.01(0.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrinary retention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e31.97(26.81\u0026ndash;38.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.95(3.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"15\" rowspan=\"16\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDysuria\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\u003e9.84(6.98\u0026ndash;13.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.29(1.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNocturia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e33.45(23.17\u0026ndash;48.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.04(3.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrinary incontinence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10.63(7.37\u0026ndash;15.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.4(1.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePollakiuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8.54(5.76\u0026ndash;12.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.09(1.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHaematuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.24(2.79\u0026ndash;6.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.08(0.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMicturition urgency\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\u003e17.84(10.91\u0026ndash;29.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.14(2.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBladder pain\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\u003e51.14(27.34\u0026ndash;95.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.65(3.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHypertonic bladder\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\u003e29.52(14.01\u0026ndash;62.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.87(3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrine flow decreased\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\u003e33.55(13.88\u0026ndash;81.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.05(3.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePostrenal failure\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\u003e39.22(14.61-105.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.27(3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCystitis interstitial\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\u003e35.11(13.09\u0026ndash;94.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.11(3.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCystitis haemorrhagic\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\u003e5.56(2.08\u0026ndash;14.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.47(0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHydronephrosis\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\u003e3.44(1.29\u0026ndash;9.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.78(0.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBladder spasm\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\u003e20.07(6.45\u0026ndash;62.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.32(2.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNeurogenic bladder\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\u003e11.57(3.72\u0026ndash;35.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.53(1.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrge incontinence\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\u003e28.99(9.29\u0026ndash;90.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.84(3.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eErectile dysfunction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.25(3.55\u0026ndash;11.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.64(0.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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\u003eBenign prostatic hyperplasia\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\u003e7.6(2.85\u0026ndash;20.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.92(1.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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\u003eVulvovaginal discomfort\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\u003e12.09(3.89\u0026ndash;37.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.59(1.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGastrointestinal disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDry mouth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10.48(8.05\u0026ndash;13.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.37(1.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLip swelling\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\u003e5.17(3.3\u0026ndash;8.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.37(0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSwollen tongue\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\u003e5.41(3.41\u0026ndash;8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.43(0.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMouth swelling\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\u003e10.14(4.55\u0026ndash;22.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.34(1.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePeptic ulcer\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\u003e9.07(3.4\u0026ndash;24.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.18(1.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBowel movement irregularity\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\u003e8.23(3.08\u0026ndash;21.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.04(1.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eColitis ischaemic\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\u003e3.78(1.42\u0026ndash;10.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.92(0.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCheilitis\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\u003e5.4(1.74\u0026ndash;16.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.43(0.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLip disorder\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\u003e21.41(6.87\u0026ndash;66.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.41(2.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLip oedema\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\u003e3.29(1.06\u0026ndash;10.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.72(0.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eAtrial fibrillation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.44(6.04\u0026ndash;9.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.87(1.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"10\" rowspan=\"11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eArrhythmia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16.23(13.06\u0026ndash;20.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.99(2.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePalpitations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.74(5.29\u0026ndash;8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.74(1.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.19(3.2\u0026ndash;5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.06(0.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAngina pectoris\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.13(3.19\u0026ndash;8.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.35(0.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExtrasystoles\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\u003e12.09(6.03\u0026ndash;24.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.59(1.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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\u003e5.62(2.68\u0026ndash;11.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.49(0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVentricular extrasystoles\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\u003e5.47(2.61\u0026ndash;11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.45(0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSinus node dysfunction\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\u003e9.45(3.93\u0026ndash;22.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.24(1.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCardiac fibrillation\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\u003e31.59(11.78\u0026ndash;84.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.96(3.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCardiac discomfort\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\u003e20.02(6.43\u0026ndash;62.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.31(2.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAtrial tachycardia\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\u003e9.94(3.2-30.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.31(1.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.93(4.96\u0026ndash;7.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.54(0.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\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\u003eHypertensive crisis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16.94(12.08\u0026ndash;23.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.07(2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVasculitis\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\u003e3.92(1.76\u0026ndash;8.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.97(0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMalignant hypertension\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\u003e36.78(15.21\u0026ndash;88.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.18(3.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAccelerated hypertension\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\u003e91.07(37.34-222.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.46(4.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEssential hypertension\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\u003e9.05(2.91\u0026ndash;28.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.17(1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eDry eye\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\u003e4(2.41\u0026ndash;6.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2(0.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEyelid oedema\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\u003e6.09(3.27\u0026ndash;11.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.6(0.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGlaucoma\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\u003e4.76(2.27-10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.25(0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRetinal vein occlusion\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\u003e11.96(4.97\u0026ndash;28.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.57(1.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\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\u003eA total of 57 PTs were unexpected findings of significant AEs. Among them, AE reports with a count exceeding 10 included arrhythmia, palpitations, nocturia, urinary incontinence, electrocardiogram QT prolonged, pollakiuria, hematuria, lip swelling, swollen tongue, dementia, angina pectoris, transient ischemic attack, micturition urgency, heart rate irregular, erectile dysfunction, Parkinson's disease, bladder pain, and eyelid edema. Some PTs with elevated signal intensity were discovered, including antineutrophil cytoplasmic antibody increased (ROR\u0026thinsp;=\u0026thinsp;153.88), bladder pain (ROR\u0026thinsp;=\u0026thinsp;51.14), postrenal failure (ROR\u0026thinsp;=\u0026thinsp;39.22), urine flow decreased (ROR\u0026thinsp;=\u0026thinsp;33.55), nocturia (ROR\u0026thinsp;=\u0026thinsp;33.45), cardiac fibrillation (ROR\u0026thinsp;=\u0026thinsp;31.59), hypertonic bladder (ROR\u0026thinsp;=\u0026thinsp;29.52), urge incontinence (ROR\u0026thinsp;=\u0026thinsp;28.99), lip disorder (ROR\u0026thinsp;=\u0026thinsp;21.41), bladder spasm (ROR\u0026thinsp;=\u0026thinsp;20.07), and cardiac discomfort (ROR\u0026thinsp;=\u0026thinsp;20.02).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eTime-to-onset analysis\u003c/h2\u003e \u003cp\u003eA total of 643 AE reports related to Mirabegron reported onset time, with a median onset time of 25 days (interquartile range [IQR] 7\u0026ndash;75 days). The study findings indicated that the majority of onset time occurred within 30 days (n\u0026thinsp;=\u0026thinsp;358, 55.68%). However, adverse events (AEs) were still possible after one year of mirabegron treatment, accounting for a proportion of 5.91% (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe FAERS is a spontaneous reporting system for AEs, providing a public database for the real-world assessment of the post-marketing safety profile of mirabegron. It enables the identification of AEs not yet documented in the drug instructions. To ensure the reliability of reporting sources, our analysis exclusively included reports provided by healthcare professionals and reports specifically documenting mirabegron as the PS drug. The incidence of AEs related to mirabegron was higher in females (60.10%) than in males (34.80%), excluding cases with unknown gender. This may be related to the higher prevalence of OAB in females compared to males [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Furthermore, with increasing age, the prevalence of OAB gradually increased [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. This phenomenon also explained the higher incidence of AEs among individuals aged 65 and older in this study. With the continuous expansion of mirabegron's clinical application, clinicians should be vigilant about AEs associated with mirabegron, especially in elderly patients. Early identification of AEs is essential because these AEs may not only increase the likelihood of patient hospitalization but also pose potential life-threatening risks.\u003c/p\u003e \u003cp\u003eBased on the disproportional analysis, the most frequent and significant signals at the SOC level was renal and urinary disorders, showing positive reactions in both the ROR and IC methods. The related AEs included dysuria, pollakiuria, bladder pain, bladder spasm, neurogenic bladder, etc., but they were often considered as indications of mirabegron (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Therefore, these AEs are considered to be associated with the progression of the underlying medical condition rather than being AEs caused by the medication itself. It is noteworthy that there were 128 reports of urinary retention, with significant signals observed in both the ROR and IC analyses. According to previous research, mirabegron did not have AEs on urinary urodynamic parameters, including maximum urinary flow rate and detrusor pressure at maximum flow, and did not increase the risk of urinary retention [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Furthermore, the mechanism of mirabegron involves promoting relaxation of the detrusor muscle and increasing urinary storage capacity without altering voiding pressure or contraction [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Mirabegron appeared to exhibit good safety in the AE of urinary retention. Therefore, a reasonable interpretation of the study results was that disease progression, such as benign prostatic hyperplasia or neurogenic bladder, might have been a contributing factor to urinary retention. However, according to a Japanese study, 19 OAB patients with concomitant benign prostatic hyperplasia experienced urinary retention after using mirabegron, with resolution or recovery observed upon discontinuation [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Therefore, we believe that the correlation between mirabegron and the AE of urinary retention remains controversial. For patients with evident bladder outlet obstruction in clinical practice, the use of mirabegron should be approached with caution [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Additionally, we recommend regular follow-up during mirabegron treatment, where clinicians should monitor patients' voiding patterns, residual urine volume, and urinary flow rates.\u003c/p\u003e \u003cp\u003eFurthermore, significant signals were observed in the ROR method within the SOC categories of cardiac disorders, investigations, and vascular disorders. Based on findings from clinical studies, the predominant cardiovascular AEs linked to mirabegron include hypertension, tachycardia, palpitations, and atrial fibrillation [\u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Approximately 9\u0026ndash;10% of patients undergoing mirabegron treatment may experience hypertension [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Furthermore, there have been reports of an increase in the QTc interval [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In accordance with the results of this study, the ROR for blood pressure increased as 14.72 (12.61\u0026ndash;17.18), with an IC of 3.84 (2.17). The ROR for hypertension as 5.93 (4.96\u0026ndash;7.11), with an IC of 2.54 (0.88). For electrocardiogram QT prolonged, the ROR was 4.26 (2.94\u0026ndash;6.18) with an IC of 2.08 (0.42). The ROR for atrial fibrillation was 7.44 (6.04\u0026ndash;9.15) with an IC of 2.87 (1.21). Arrhythmia had an ROR of 16.23 (13.06\u0026ndash;20.17) with an IC of 3.99 (2.33). The ROR for palpitations was 6.74 (5.29\u0026ndash;8.6) with an IC of 2.74 (1.07), and for tachycardia, the ROR was 4.19 (3.2\u0026ndash;5.5) with an IC of 2.06 (0.39). As mirabegron is a β3-adrenergic receptor agonist, and β3-adrenergic receptors are also expressed in cardiovascular tissues, the use of mirabegron may have \"off-target\" effects on the regulation of the cardiovascular system [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. This could be the potential pharmacological mechanism by which mirabegron induces cardiovascular-related AEs. β3-adrenergic receptors can increase the occurrence of arrhythmias and the risk of atrial fibrillation by activating the cAMP-dependent protein kinase pathway and inducing Ca2\u0026thinsp;+\u0026thinsp;imbalance [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Additionally, the β1-adrenergic receptors expressed in cardiovascular tissues were also target sites for the action of mirabegron [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. An animal study found that the heart rate effects of mirabegron in dogs were attributed to cross-reactivity with β1-adrenergic receptors [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. This was further confirmed by a clinical study [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Regardless of whether it involved the stimulation of β1-adrenergic receptors in cardiovascular tissues or β3-adrenergic receptors, the administration of supratherapeutic dosages that led to significant multiples of peak plasma concentrations was more prone to causing increases in heart rate, elevated blood pressure, and prolonged QT intervals [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Although a treatment dose of 50 mg mirabegron could lead to an increase in baseline pulse rate by one beat per minute [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], the impact was not significant. Furthermore, mirabegron is extensively metabolized by the liver and excreted in urine, either as the parent drug or its metabolites [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Therefore, in clinical practice, it is not only important to pay attention to the safe dosage of mirabegron but also to monitor the liver and kidney functions of patients, avoiding excessively high blood drug concentrations that may lead to cardiovascular-related AEs. For patients experiencing cardiovascular-related AEs after using mirabegron, it is recommended to undergo blood drug concentration monitoring. Furthermore, this study also identified some unexpected yet clinically significant safety signals, such as angina pectoris, extrasystoles, and cardiac fibrillation. Although the reported cases of these cardiovascular AEs are limited, they should not be overlooked, as they may have potentially life-threatening implications for patients.\u003c/p\u003e \u003cp\u003eEvidence indicated that mirabegron could cause the AE of headache [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In our study, we also identified head discomfort as a significant AE associated with mirabegron, with a signal strength of ROR 3.41 (1.28\u0026ndash;9.08) and IC 1.77 (0.1). Additionally, in our results, dementia, transient ischemic attack, Parkinson's Disease, and myasthenia gravis emerged as new significant AEs associated with mirabegron. In a previous clinical study, 23,662 patients with OAB using mirabegron were found to have 603 new cases of dementia [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. While the reported case numbers are limited, healthcare professionals should not overlook these findings, as mirabegron may potentially cause central nervous system side effects. In the striatum of both rats and humans, the presence of β-3 adrenergic receptor mRNA has been confirmed [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Activation of these receptors by mirabegron decreases acetylcholine release from striatal neurons [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Acetylcholine deficiency in the brain is linked not only to Alzheimer's disease, vascular dementia, and Lewy body dementia but also to movement disorders [\u003cspan additionalcitationids=\"CR33 CR34\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Furthermore, β3-adrenergic receptor agonists promote the synthesis and release of serotonin (5-HT) in the striatum of the brain, which may also be an important mechanism [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In this study, we identified transient ischemic attack as an AE with significant signal strength, which was not previously listed in the drug label or observed in earlier clinical studies. As of now, the mechanism by which mirabegron induces transient ischemic attack remains unclear. Transient ischemic attack can be caused by various factors, including atherosclerosis, cardiac-related factors, arterial inflammation, and others. Atrial fibrillation was a known risk factor for transient ischemic attack [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Therefore, transient ischemic attack may also be associated with mirabegron-related AEs such as atrial fibrillation. The neurologic adverse events caused by mirabegron were unexpected for clinicians, and if not promptly identified, they could potentially result in irreversible damage to the nervous system.\u003c/p\u003e \u003cp\u003eSome other new and unexpected adverse events, including lip swelling, swollen tongue, mouth swelling, peptic ulcer, ischemic colitis, eyelid edema, glaucoma, and retinal vein occlusion, were also identified in this study. Matthew et al [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] reported a case of a patient who experienced tongue swelling, accompanied by difficulty breathing and swallowing, after using mirabegron. In this report, swelling was also observed in areas such as the lips, oral cavity, and eyelids. The mechanism of mirabegron-induced edema is believed to be a type I hypersensitivity reaction mediated by mast cell degranulation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIt is noteworthy that both \"anti-neutrophil cytoplasmic antibody increased\" and \"anti-neutrophil cytoplasmic antibody positive vasculitis\" exhibited strong positive signals in both the ROR and IC methods. Anti-neutrophil cytoplasmic antibody positive vasculitis is a group of potentially life-threatening autoimmune diseases [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Although the exact etiology remains incompletely understood, research indicated that drugs are significant contributors to the development of this condition [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Based on previous research findings, the drugs that induced anti-neutrophil cytoplasmic antibody positive vasculitis belonged to various pharmacological categories [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. These primarily included anti-thyroid drugs, tumor necrosis factor inhibitors, anti-tuberculosis drugs, psychoactive agents, and others [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. To the best of our knowledge, this study was the first to report the potential induction of anti-neutrophil cytoplasmic antibody positive vasculitis by mirabegron. The finding of this study warrant careful attention from clinicians. Close monitoring of ANCA levels in patients undergoing mirabegron treatment is essential, as it serves as an effective tool for the early diagnosis of drug-induced anti-neutrophil cytoplasmic antibody positive vasculitis. Upon confirmation, immediate discontinuation of the drug is imperative, as most patients experience relief after ceasing the use of this harmful medication [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe study findings revealed a median onset time of 25 days, with most AEs happening within the initial 30 days following exposure to mirabegron (n\u0026thinsp;=\u0026thinsp;358, 55.68%). However, AEs could still occur even a year later. Therefore, clinicians needed to closely follow up with patients using mirabegron, especially within the first 30 days. In future clinical studies, longer follow-up periods were necessary to observe mirabegron-related AEs.\u003c/p\u003e \u003cp\u003eSeveral limitations in this study need to be addressed. Firstly, the FAERs database is a spontaneous reporting database, and the quality is not rigorously controlled. Although our analysis included reports provided only by healthcare professionals to ensure the reliability of the reporting sources, it inevitably reduced the sample size. Additionally, the occurrence rates of each AE related to mirabegron could not be estimated. Secondly, the presence of reports in the FAERS database does not establish a causal relationship, requiring further well-designed clinical trials to investigate causation. Ultimately, certain confounding factors not measured in the study, such as possible interactions between medications, existing medical conditions, and combinations of drugs, were excluded from the analysis. Despite these limitations, FAERs remains valuable for post-marketing safety surveillance.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, despite numerous clinical studies confirming the efficacy and high safety profile of mirabegron in treating OAB, the increasing use of mirabegron necessitates clinicians to be aware of unexpected AEs not documented in the drug label or discovered in clinical trials. This study, which utilized a pharmacovigilance analysis of the FAERS database, scientifically elucidated the true safety profile of mirabegron treatment. New significant AEs, such as arrhythmia, palpitations, dementia, transient ischemic attack, Parkinson's disease, anti-neutrophil cytoplasmic antibody positive vasculitis, lip swelling, swollen tongue, and others, were identified. Our research provided valuable evidence for further investigation and clinical practice involving mirabegron.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eFDA \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;The Food and Drug Administration\u003c/p\u003e\n\u003cp\u003eFAERS \u0026nbsp; \u0026nbsp; \u0026nbsp; The US FDA Adverse Event Reporting System\u003c/p\u003e\n\u003cp\u003eOAB \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Overactive bladder\u003c/p\u003e\n\u003cp\u003eAE \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Adverse events\u003c/p\u003e\n\u003cp\u003ePS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Primary Suspect\u003c/p\u003e\n\u003cp\u003eSOC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;System organ class\u003c/p\u003e\n\u003cp\u003eHLGT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;High-level group term\u003c/p\u003e\n\u003cp\u003eHLT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; High-level term\u003c/p\u003e\n\u003cp\u003ePT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Preferred term\u003c/p\u003e\n\u003cp\u003eLLT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Lowest level term\u003c/p\u003e\n\u003cp\u003eHO \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Hospitalization-initial or prolonged\u003c/p\u003e\n\u003cp\u003eDE \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Death\u003c/p\u003e\n\u003cp\u003eDS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Disability\u003c/p\u003e\n\u003cp\u003eLT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Life-threatening\u003c/p\u003e\n\u003cp\u003eCA \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Congenital anomaly\u003c/p\u003e\n\u003cp\u003eOT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Other important medical event\u003c/p\u003e\n\u003cp\u003eROR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Reporting odds ratio\u003c/p\u003e\n\u003cp\u003eBCPNN \u0026nbsp; \u0026nbsp; \u0026nbsp;Bayesian Confidence Propagation Neural Network\u003c/p\u003e\n\u003cp\u003eIC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Information component\u003c/p\u003e\n\u003cp\u003eIC025 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; The lower limit of 95% confdence interval of the IC\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciate the FAERS open policy and the provided data, as well as all participants in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJW: protocol/project development, data collection and management, data analysis, and manuscript writing; AZ: protocol/project development, data collection and management, data analysis; MY: data collection and management, data analysis; CZ: manuscript review and revision; All authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was used for this submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are available\u0026nbsp;\u003c/p\u003e\n\u003cp\u003efrom the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. This study was deemed non-human subject related research.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHaylen BT, Maher CF, Barber MD, Camargo S, Dandolu V, Digesu A, Goldman HB, Huser M, Milani AL, Moran PA, Schaer GN, Withagen MI. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic organ prolapse (POP). Int Urogynecol J. 2016;27:655\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu Z, Zhang J, Lin S, Fan Z, He Z, Tang F. 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Mirabegron for the treatment of overactive bladder: a prespecified pooled efficacy analysis and pooled safety analysis of three randomised, double-blind, placebo-controlled, phase III studies. Int J Clin Pract. 2013;67:619\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBatista JE, K\u0026ouml;lbl H, Herschorn S, Rechberger T, Cambronero J, Halaska M, Coppell A, Kaper M, Huang M, Siddiqui E. The efficacy and safety of mirabegron compared with solifenacin in overactive bladder patients dissatisfied with previous antimuscarinic treatment due to lack of efficacy: results of a noninferiority, randomized, phase IIIb trial. Ther Adv Urol. 2015;7:167\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChan CS, Lin FJ, Liu CM, Lin YK, Chen YC, Hsu CC, Higa S, Chen SA, Chen YJ. Mirabegron, a β3\u0026ndash;adrenoreceptor agonist, regulates right and left atrial arrhythmogenesis differently. Exp Ther Med. 2022;24:720.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRosa GM, Ferrero S, Nitti VW, Wagg A, Saleem T, Chapple CR. Cardiovascular Safety of β3-adrenoceptor Agonists for the Treatment of Patients with Overactive Bladder Syndrome. Eur Urol. 2016;69:311\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrhut J, Wohlfahrt P, Pudich J, Kufov\u0026aacute; E, Borovička V, B\u0026iacute;lkov\u0026aacute; K, S\u0026yacute;kora R, Mokriš J, C\u0026iacute;fkov\u0026aacute; R, Zachoval R, Zvara P. Cardiovascular safety of mirabegron in individuals treated for spinal cord injury- or multiple sclerosis-induced neurogenic detrusor overactivity. Int Urol Nephrol. 2021;53:1089\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBalachandran AA, Duckett JR. The risk and severity of developing symptomatic palpitations when prescribed mirabegron for overactive bladder. Eur J Obstet Gynecol Reprod Biol. 2015;187:60\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Gelderen M, St\u0026ouml;lzel M, Meijer J, Kerbusch V, Collins C, Korstanje C. An Exploratory Study in Healthy Male Subjects of the Mechanism of Mirabegron-Induced Cardiovascular Effects. J Clin Pharmacol. 2017;57:1534\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKorstanje C, Suzuki M, Yuno K, Sato S, Ukai M, Schneidkraut MJ, Yan GX. Translational science approach for assessment of cardiovascular effects and proarrhythmogenic potential of the beta-3 adrenergic agonist mirabegron. J Pharmacol Toxicol Methods. 2017;87:74\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalik M, van Gelderen EM, Lee JH, Kowalski DL, Yen M, Goldwater R, Mujais SK, Schaddelee MP, de Koning P, Kaibara A, Moy SS, Keirns JJ. Proarrhythmic safety of repeat doses of mirabegron in healthy subjects: a randomized, double-blind, placebo-, and active-controlled thorough QT study. Clin Pharmacol Ther. 2012;92:696\u0026ndash;706.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAndersson KE. New developments in the management of overactive bladder: focus on mirabegron and onabotulinumtoxinA. Ther Clin Risk Manag. 2013;9:161\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKashyap M, Tyagi P. The pharmacokinetic evaluation of mirabegron as an overactive bladder therapy option. Expert Opin Drug Metab Toxicol. 2013;9:617\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHou J, Xu F, Du H, Li N. Adverse events associated with mirabegron 50mg versus placebo: A systematic review and meta-analysis. Prog Urol. 2021;31:627\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWelk B, McArthur E. 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Pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis. Rheumatol Immunol Res. 2023;4:11\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSch\u0026ouml;nermarck U, Csernok E, Gross WL. Pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis: challenges and solutions 2014. Nephrol Dial Transplant. 2015;30(Suppl 1):i46\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWeng CH, Liu ZC. Drug-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. Chin Med J (Engl). 2019;132:2848\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"mirabegron, overactive bladder, adverse event, pharmacovigilance, FAERS","lastPublishedDoi":"10.21203/rs.3.rs-3825951/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3825951/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eMirabegron, the first β-3 adrenergic receptor agonist, received approval from the Food and Drug Administration (FDA) in 2012 for the treatment of overactive bladder (OAB). This pharmacovigilance study investigated the safety profile of mirabegron treatment using the US FDA Adverse Event Reporting System (FAERS) database.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis study employed disproportionality analyses, including the reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) algorithm, to quantify signals of adverse events associated with mirabegron.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eFrom the first quarter of 2012 to the third quarter of 2023, a comprehensive total of 14,356,234 adverse event (AE) reports were submitted to the FAERS database. Within this dataset, encompassing 18,763 reports specifically associated with mirabegron, healthcare professionals notably contributed 2,902 of these reports. A total of 80 preferred terms (PTs) of interest were identified using both the ROR and information component (IC) algorithms. The most common AEs included blood pressure increased, urinary retention, atrial fibrillation, dry mouth, and tachycardia, which were consistent with the product instructions. Unexpected significant AEs, such as arrhythmia, palpitations, dementia, transient ischemic attack, Parkinson's disease, anti-neutrophil cytoplasmic antibody positive vasculitis, lip swelling, and swollen tongue, were also identified. The study findings indicated that the majority of onset time occurred within 30 days (n = 358, 55.68%). However, AEs were still possible after one year of mirabegron treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThis study provided valuable evidence for the real-world safety of mirabegron, helping clinical professionals enhance their understanding of mirabegron's safety in clinical practice. It also contributed valuable evidence for further safety studies on mirabegron.\u003c/p\u003e","manuscriptTitle":"Examining the Safety of Mirabegron: An Analysis of Real-World Pharmacovigilance Data from the US FDA Adverse Event Reporting System (FAERS) Database","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-03 18:10:14","doi":"10.21203/rs.3.rs-3825951/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":"a5f8d2b6-63aa-4dbe-881c-fd948e892386","owner":[],"postedDate":"January 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-01-23T10:59:26+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-03 18:10:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3825951","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3825951","identity":"rs-3825951","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}