Real-world Pharmacovigilance Study of Famciclovir in the FDA Adverse Event Reporting System (FAERS) Database

Real-world Pharmacovigilance Study of Famciclovir in the 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 Article Real-world Pharmacovigilance Study of Famciclovir in the FDA Adverse Event Reporting System (FAERS) Database Runan Fang, Yang Zhou, Lu Han, Wenjing Chen, Ning Guan, Jianhong Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4300885/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Nov, 2024 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Background Famciclovir, mainly used to treat herpes zoster, is a precursor drug of penciclovir that rapidly transforms into penciclovir when taken orally and sustains an extended half-life intracellularly. The information on its adverse drug reactions (ADRs) mainly comes from clinical trials, lacking large-scale real-world studies. This study evaluates the adverse events (AEs) of famciclovir by mining data from the FDA Adverse Event Reporting System (FAERS) database, providing references for clinical safety. Methods Utilized disproportionality analysis (including reported odds ratio and proportional reporting ratio) and Bayesian methods (including Bayesian Confidence Propagation Neural Network and Gamma-Poisson Shrinkage) to quantify AE signals associated with famciclovir. Results A total of 17,652,186 case reports were obtained from the FAERS database, with 432 reports of famciclovir-related AEs identified. The most common AEs were nausea, headache, altered mental status, vomiting, and dizziness, corresponding to the AEs reported in guidelines and clinical trials. However, there were AEs not mentioned in the medication guide, such as toxic encephalopathy, encephalopathy, ataxia, dysarthria, dementia, cerebral infarction, tremor, purpura, skin ulcers, acute pancreatitis, rhabdomyolysis, muscle twitching, increased blood urea, lowered blood pressure, hepatitis, disease recurrence, drug interactions, and pancytopenia. Conclusion Our study identified potential famciclovir AE signals, providing references for physicians in clinical use to reduce potential side effects and promote safe implementation of the drug in clinical settings. Health sciences/Health care/Disease prevention/Preventive medicine Health sciences/Risk factors FAERS pharmacovigilance famciclovir adverse event Figures Figure 1 Introduction Herpes zoster is a common acute infectious viral skin disease. The clinical symptoms of herpes zoster (HZ) may not be severe, but if not treated promptly and systematically early on, it could lead to serious complications, adversely affecting the patient's life 1 . Therefore, antiviral therapy is critical in the management of HZ. Early and sufficient antiviral therapy not only relieves acute symptoms and reduces the duration of the disease but also prevent the occurrence of post-treatment neuralgia to a certain extent. At present, famciclovir ranks among the most frequently prescribed medications for HZ, with over 4 million prescriptions globally 2 . Famciclovir, once absorbed orally, rapidly transforms into penciclovir in the intestines and liver, and is phosphorylated within cells infected by the varicella-zoster virus (VZV) to produce a triphosphate compound with antiviral properties. The oral bioavailability of famciclovir is higher than that of acyclovir, with an oral bioavailability of 77% 3 . According to reports 4 , oral famciclovir is the most effective treatment for acute pain and post-herpetic neuralgia (PHN) associated with HZ, providing rapid relief from HZ-related pain 5 . It is widely used in clinical settings for treating herpes simplex virus infections and acute HZ. Additionally, it is also used in the chronic suppressive therapy of genital herpes 3 . Famciclovir's adverse effects commonly include headache, nausea, and diarrhea 6,7 , with severe adverse effects being hepatotoxicity and Stevens-Johnson syndrome 8 . According to recently reported meta-analysis data, there are deficiencies in the number of adverse reactions to famciclovir that make them unanalyzable 9,10 . The issue may stem from the fact that most efficacy and safety data on famciclovir are derived from clinical trials with small sample sizes and limited follow-up durations. Due to individual differences, patients using famciclovir may experience unexpected adverse events (AEs) in the real-world clinical setting. Thus, identifying unexpected adverse drug reactions (ADRs) associated with famciclovir has certain clinical significance. The Food and Drug Adverse Event Reporting System (FAERS) is an openly accessible database that documents numerous adverse events (AEs) and medication errors related to human pharmaceuticals and therapeutic biological products, ranking as one of the largest drug safety databases globally 11 . Through data mining of famciclovir adverse events in the FAERS database, this research seeks to uncover ADRs not documented in the drug's profile, serving as a reference for its rational and safe use in clinical practice. Results Basic Characteristics of Famciclovir-Related Adverse Drug Events (ADEs) This study retrieved 17,652,186 reports from the FAERS database, and after eliminating duplicates and conducting a filtering process, we identified 432 famciclovir-related AE reports. Within these reports, the occurrence of adverse events was higher in females than in males (59.72% vs 34.49%). In terms of age, the elderly population (aged > = 65 years) constituted the highest proportion (46.3%). Most reports were from consumers (40.74%), rather than doctors (12.5%), pharmacists (6.48%), or other healthcare professionals (16.67%). Many reports (55.56%) did not specify their region of origin, with Japan having the highest share (28.94%), followed by the United States (7.41%). Among the reported clinical outcomes, serious outcomes were the most common (50.22%), followed by hospitalizations (39.82%) and life-threatening situations (3.98%). Additionally, onset time of famciclovir adverse reactions, as collected from the database, predominantly had a median of 2 days (interquartile range [IQR] 0.00-5.5), with the majority happening within 1–7 days (43.53%), and the next most common timeframe being within 24 hours (21.76%). In this study, HZ (61.20%) was the most frequently reported indication. And the detailed information, refer to Table 1 . Table 1 Clinical characteristics of reports with Famciclovir from the FAERS database Characteristics Case number (% of Total case Reports) Gender Female 258(59.72) Male 149(34.49) Unkown 25(5.79) Age =65 200(46.30) Unknow 93(21.53) Reporter Physician 54(12.50) Pharmacist 28(6.48) Other health-professional 72(16.67) Consumer 176(40.74) Unkown 102(23.61) Reported countries(top five) Japan 125(28.94) United States 32(7.41) Australia 7(1.62) United Kingdom 7(1.62) Unknown 240(55.56) Outcomes Hospitalization 180(39.82) Life threatening 18(3.98) Disability 15(3.32) Death 11(2.43) Required intervention to Prevent Permanent Impairment/Damage 1(0.22) Other serious 227(50.22) Time to AE (days) =28 20(5.88) Characteristics Case number (% of Total case Reports) unknow 57(16.76) Indications(top five) Herpes zoster 265(61.20) Herpes simplex 34(7.85) Product used for unknown Indication 19(4.39) Oral herpes 14(3.23) Unknown 49(11.32) Signal mining of famciclovir This research examined reports of AEs associated with famciclovir, covering adverse reactions across 22 system organ categories (SOC), see Table 2 for details. Significant SOCs that met at least one indicator criterion were diseases of the nervous system, disorders of the hepatobiliary disorders, renal and urinary disorders, skin and subcutaneous tissue disorders, and investigations. At the PT level, this research utilized four algorithms to analyze adverse drug reactions and assessed their adherence to various screening criteria, yielding 126 PTs. Among these, 65 PTs met the criteria of all four algorithms, including 14 SOCs, with details provided in Table 3 . Regarding the number of cases, the most frequent PTs associated with famciclovir were nausea, headache, altered mental status, vomiting, and dizziness. When ordered by ROR value and IC signal strength, the most prominent were altered state of consciousness (n = 28, ROR 61.64, PRR 60.32, IC 5.91, EBGM 60.2), toxic encephalopathy (n = 5, ROR 49.89, PRR 49.7, IC 5.63, EBGM 49.62), herpes simplex (n = 4, ROR 27.67, PRR 27.59, IC 4.78, EBGM 27.56), petit mal epilepsy (n = 3, ROR 25.18, PRR 25.13, IC 4.65, EBGM 25.11), and purpura (n = 4, ROR 18.23, PRR 18.18, IC 4.18, EBGM 18.17). Notably, adverse signals not mentioned in the medication instructions include toxic encephalopathy, encephalopathy, ataxia, dysarthria, dementia, cerebral infarction, tremor, purpura, skin ulcers, acute pancreatitis, rhabdomyolysis, muscle twitching, increased blood urea, lowered blood pressure, hepatitis, disease recurrence, drug interactions, and pancytopenia. Table 2 Signal strength of adverse events of Famciclovir at the system organ class (SOC) level in FAERS database System organ class (SOC) Case Reports ROR (95% CI) PRR (95% CI) χ2 IC (IC025) EBGM (EBGM05) Nervous system disorders* 255 2.43(2.12, 2.79) 2.15(1.91, 2.42) 172.55 1.1(0.91) 2.15(1.92) Hepatobiliary disorders* 29 2.43(1.68, 3.51) 2.4(1.69, 3.42) 23.79 1.26(0.74) 2.4(1.76) Renal and urinary disorders* 41 1.69(1.24, 2.3) 1.66(1.24, 2.23) 11.09 0.74(0.29) 1.66(1.28) Skin and subcutaneous tissue disorders* 116 1.62(1.34, 1.96) 1.57(1.32, 1.87) 25.22 0.65(0.37) 1.57(1.34) Investigations* 118 1.44(1.19, 1.75) 1.4(1.17, 1.67) 14.63 0.49(0.22) 1.4(1.2) Endocrine disorders 4 1.22(0.46, 3.26) 1.22(0.46, 3.25) 0.16 0.29(-0.98) 1.22(0.54) Ear and labyrinth disorders 7 1.2(0.57, 2.52) 1.2(0.57, 2.53) 0.23 0.26(-0.74) 1.2(0.64) Blood and lymphatic system disorders 27 1.2(0.82, 1.75) 1.19(0.82, 1.73) 0.86 0.25(-0.29) 1.19(0.87) Psychiatric disorders 92 1.19(0.97, 1.48) 1.18(0.97, 1.44) 2.69 0.24(-0.06) 1.18(0.99) Gastrointestinal disorders 135 1.17(0.98, 1.39) 1.15(0.98, 1.35) 2.89 0.2(-0.05) 1.15(0.99) Eye disorders 25 0.92(0.62, 1.37) 0.92(0.62, 1.36) 0.16 -0.11(-0.67) 0.92(0.66) Respiratory, thoracic and mediastinal disorders 58 0.89(0.69, 1.16) 0.9(0.7, 1.16) 0.69 -0.15(-0.53) 0.9(0.72) Cardiac disorders 31 0.84(0.59, 1.2) 0.84(0.59, 1.2) 0.95 -0.25(-0.75) 0.84(0.62) Immune system disorders 11 0.72(0.4, 1.31) 0.73(0.41, 1.31) 1.15 -0.46(-1.28) 0.73(0.44) Metabolism and nutrition disorders 20 0.69(0.44, 1.07) 0.69(0.45, 1.06) 2.83 -0.53(-1.16) 0.69(0.48) General disorders and administration site conditions 170 0.67(0.57, 0.79) 0.72(0.63, 0.83) 23.56 -0.48(-0.71) 0.72(0.63) Vascular disorders 20 0.66(0.42, 1.02) 0.66(0.43, 1.02) 3.48 -0.59(-1.21) 0.66(0.46) Musculoskeletal and connective tissue disorders 47 0.65(0.49, 0.87) 0.66(0.5, 0.87) 8.43 -0.59(-1.01) 0.66(0.52) Pregnancy, puerperium and perinatal conditions 4 0.63(0.24, 1.69) 0.63(0.24, 1.68) 0.85 -0.66(-1.93) 0.63(0.28) Infections and infestations 43 0.62(0.45, 0.84) 0.63(0.47, 0.85) 9.93 -0.67(-1.1) 0.63(0.49) Injury, poisoning and procedural complications 27 0.22(0.15, 0.32) 0.24(0.17, 0.35) 72.36 -2.07(-2.61) 0.24(0.17) Neoplasms benign, malignant and unspecified 5 0.16(0.07, 0.39) 0.16(0.07, 0.39) 21.67 -2.6(-3.76) 0.16(0.08) ROR, reporting odds ratio; CI, confidence interval; PRR, proportional reporting ratio; χ2, chi-squared; IC, information component; EBGM, empirical Bayesian geometric mean; *, Indicates statistically significant signals in all four algorithms. Table 3 Signal strength of reports of Famciclovir at the PT level in the FAERS database. System organ class (SOC) Preferred terms (PTs) Case reports ROR (95% CI) PRR (95% CI) χ2 IC (IC025) EBGM (EBGM05) Nervous system disorders Altered state of consciousness 28 61.64(42.37, 89.67) 60.32(41.57, 87.54) 1630.74 5.91(5.38) 60.2(43.99) Toxic encephalopathy 5 49.89(20.71, 120.14) 49.7(20.57, 120.06) 238.21 5.63(4.47) 49.62(23.78) Petit mal epilepsy 3 25.18(8.11, 78.23) 25.13(8.06, 78.32) 69.45 4.65(3.23) 25.11(9.73) Encephalopathy 10 18.05(9.69, 33.64) 17.92(9.57, 33.55) 159.76 4.16(3.31) 17.91(10.64) Ataxia 3 10.5(3.38, 32.61) 10.48(3.36, 32.66) 25.72 3.39(1.97) 10.48(4.06) Depressed level of consciousness 8 8.64(4.31, 17.32) 8.59(4.33, 17.06) 53.69 3.1(2.16) 8.59(4.8) Loss of consciousness 19 6.23(3.96, 9.81) 6.16(3.92, 9.67) 82.23 2.62(1.98) 6.15(4.21) Dysarthria 5 5.6(2.32, 13.47) 5.58(2.31, 13.48) 18.79 2.48(1.32) 5.58(2.67) Dementia 3 5.37(1.73, 16.66) 5.36(1.72, 16.71) 10.63 2.42( 1 ) 5.36(2.08) Cerebral infarction 3 5.14(1.66, 15.97) 5.13(1.65, 15.99) 9.99 2.36(0.94) 5.13(1.99) Lethargy 5 3.63(1.51, 8.74) 3.62(1.5, 8.74) 9.5 1.86(0.7) 3.62(1.74) Syncope 6 2.55(1.14, 5.68) 2.54(1.14, 5.67) 5.62 1.35(0.27) 2.54(1.3) Tremor 9 2.24(1.16, 4.31) 2.23(1.17, 4.26) 6.11 1.16(0.26) 2.23(1.29) Headache 32 2.19(1.54, 3.11) 2.16(1.55, 3.01) 20.15 1.11(0.61) 2.16(1.61) Dizziness 25 2.15(1.45, 3.2) 2.13(1.44, 3.15) 15.11 1.09(0.53) 2.13(1.53) Infections and infestations Herpes simplex 4 27.67(10.36, 73.87) 27.59(10.35, 73.51) 102.41 4.78(3.52) 27.56(12.12) Oral herpes 3 7.35(2.37, 22.81) 7.33(2.35, 22.85) 16.4 2.87(1.46) 7.33(2.84) Herpes zoster 4 3.09(1.16, 8.25) 3.08(1.16, 8.21) 5.64 1.62(0.36) 3.08(1.36) Skin and subcutaneous tissue disorders Purpura 4 18.23(6.83, 48.66) 18.18(6.82, 48.44) 64.9 4.18(2.92) 18.17(7.99) Erythema multiforme 3 13.29(4.28, 41.29) 13.27(4.26, 41.36) 34.02 3.73(2.31) 13.26(5.14) Drug eruption 4 10.37(3.89, 27.69) 10.34(3.88, 27.55) 33.76 3.37(2.1) 10.34(4.55) Angioedema 8 7.62(3.8, 15.28) 7.58(3.82, 15.05) 45.73 2.92(1.98) 7.58(4.24) Blister 7 5.71(2.71, 11.99) 5.68(2.7, 11.96) 27.02 2.51(1.5) 5.68(3.05) Skin ulcer 3 5.08(1.64, 15.78) 5.07(1.63, 15.8) 9.82 2.34(0.93) 5.07(1.97) Rash erythematous 3 3.1(1, 9.62) 3.09(0.99, 9.63) 4.26 1.63(0.21) 3.09(1.2) Urticaria 9 2.4(1.24, 4.62) 2.39(1.25, 4.56) 7.27 1.25(0.36) 2.39(1.38) System organ class (SOC) Preferred terms (PTs) Case reports ROR (95% CI) PRR (95% CI) χ2 IC (IC025) EBGM (EBGM05) Gastrointestinal disorders Hyperchlorhydria 3 17.9(5.76, 55.59) 17.86(5.73, 55.67) 47.72 4.16(2.74) 17.85(6.92) Pancreatitis acute 3 5.95(1.92, 18.49) 5.94(1.91, 18.51) 12.34 2.57(1.15) 5.94(2.3) Vomiting 26 2.45(1.66, 3.61) 2.42(1.67, 3.51) 21.78 1.27(0.72) 2.42(1.75) Respiratory, thoracic and mediastinal disorders Pharyngeal oedema 6 12.44(5.58, 27.74) 12.38(5.54, 27.65) 62.78 3.63(2.56) 12.38(6.33) Musculoskeletal and connective tissue disorders Rhabdomyolysis 12 11.93(6.75, 21.06) 11.82(6.7, 20.87) 118.96 3.56(2.77) 11.82(7.35) Muscle twitching 3 5.32(1.71, 16.5) 5.31(1.7, 16.55) 10.48 2.41(0.99) 5.3(2.06) Investigations Blood alkaline phosphatase increased 6 9.92(4.45, 22.13) 9.88(4.42, 22.07) 47.91 3.3(2.23) 9.88(5.05) Blood urea increased 3 7.41(2.39, 23.01) 7.4(2.37, 23.06) 16.6 2.89(1.47) 7.4(2.87) Aspartate aminotransferase increased 8 6.35(3.17, 12.73) 6.32(3.18, 12.55) 35.83 2.66(1.71) 6.32(3.53) Liver function test abnormal 5 6.32(2.63, 15.22) 6.3(2.61, 15.22) 22.31 2.66(1.5) 6.3(3.02) Alanine aminotransferase increased 9 6.15(3.19, 11.84) 6.11(3.2, 11.67) 38.51 2.61(1.71) 6.11(3.53) Blood bilirubin increased 4 6.03(2.26, 16.09) 6.01(2.26, 16.01) 16.72 2.59(1.32) 6.01(2.64) Blood pressure decreased 8 5.27(2.63, 10.56) 5.24(2.64, 10.41) 27.49 2.39(1.44) 5.24(2.93) Blood creatine phosphokinase increased 3 3.94(1.27, 12.23) 3.93(1.26, 12.25) 6.57 1.98(0.56) 3.93(1.52) Blood creatinine increased 6 3.93(1.76, 8.77) 3.92(1.76, 8.76) 13.06 1.97(0.9) 3.92( 2 ) International normalised ratio increased 3 3.64(1.17, 11.32) 3.64(1.17, 11.35) 5.74 1.86(0.45) 3.64(1.41) Platelet count decreased 6 2.52(1.13, 5.63) 2.52(1.13, 5.63) 5.49 1.33(0.26) 2.52(1.29) Hepatobiliary disorders Hepatitis 6 9.89(4.44, 22.06) 9.85(4.41, 22) 47.72 3.3(2.23) 9.85(5.03) Hepatic function abnormal 5 6.24(2.59, 15.01) 6.22(2.57, 15.03) 21.89 2.64(1.48) 6.21(2.98) Jaundice 4 5.77(2.16, 15.41) 5.76(2.16, 15.35) 15.74 2.53(1.26) 5.76(2.53) Liver disorder 5 5(2.08, 12.03) 4.98(2.06, 12.03) 15.92 2.32(1.16) 4.98(2.39) Eye disorders Eyelid oedema 3 9.25(2.98, 28.73) 9.23(2.96, 28.77) 22.02 3.21(1.79) 9.23(3.58) System organ class (SOC) Preferred terms (PTs) Case reports ROR (95% CI) PRR (95% CI) χ2 IC (IC025) EBGM (EBGM05) Psychiatric disorders Disorientation 9 9.09(4.72, 17.51) 9.03(4.73, 17.24) 64.3 3.17(2.28) 9.03(5.22) Hallucination 13 7.81(4.52, 13.49) 7.74(4.47, 13.4) 76.44 2.95(2.19) 7.74(4.9) Delirium 6 7.74(3.47, 17.27) 7.71(3.45, 17.22) 35.06 2.95(1.88) 7.71(3.94) Middle insomnia 3 7.24(2.33, 22.47) 7.22(2.32, 22.5) 16.08 2.85(1.44) 7.22(2.8) Restlessness 6 6.84(3.07, 15.25) 6.81(3.05, 15.21) 29.77 2.77(1.7) 6.81(3.48) Abnormal behaviour 5 4.7(1.95, 11.31) 4.69(1.94, 11.33) 14.51 2.23(1.07) 4.69(2.25) Agitation 5 2.73(1.13, 6.57) 2.72(1.13, 6.57) 5.46 1.45(0.29) 2.72(1.31) Confusional state 14 3.67(2.17, 6.22) 3.64(2.14, 6.18) 26.94 1.87(1.13) 3.64(2.35) General disorders and administration site conditions Disease recurrence 5 6.48(2.69, 15.6) 6.46(2.67, 15.61) 23.09 2.69(1.53) 6.46(3.1) Swelling face 5 3.21(1.34, 7.74) 3.21(1.33, 7.75) 7.6 1.68(0.52) 3.21(1.54) Drug interaction 9 2.36(1.22, 4.54) 2.35(1.23, 4.49) 7 1.23(0.33) 2.35(1.36) Cardiac disorders Palpitations 13 4.77(2.76, 8.25) 4.74(2.74, 8.21) 38.39 2.24(1.48) 4.74( 3 ) Renal and urinary disorders Urinary incontinence 3 4.48(1.44, 13.91) 4.47(1.43, 13.93) 8.09 2.16(0.74) 4.47(1.73) Urinary retention 3 3.97(1.28, 12.32) 3.96(1.27, 12.34) 6.64 1.99(0.57) 3.96(1.53) Acute kidney injury 10 3.25(1.74, 6.06) 3.23(1.73, 6.05) 15.45 1.69(0.84) 3.23(1.92) Blood and lymphatic system disorders Pancytopenia 5 3.99(1.66, 9.6) 3.98(1.65, 9.61) 11.15 1.99(0.83) 3.98(1.91) Thrombocytopenia 6 2.41(1.08, 5.38) 2.41(1.08, 5.38) 4.94 1.27(0.19) 2.41(1.23) Discussions Data on the drug's efficacy and safety come from both preclinical and clinical research 17 . However, due to limitations in trial design and small sample sizes, the effects of the drug on humans, particularly regarding safety, cannot be fully elucidated in the real world. Therefore, paying attention to the risk signals of adverse drug reactions in clinical applications is crucial for assessing drug safety and achieving a balance between benefits and risks in clinical decision-making. In this research, we utilized a large real-world data sample to collect and evaluate the safety of famciclovir through pharmacovigilance. And aims to offer references for ensuring safety in clinical medication practices. From the FAERS database, this research gathered 1,371 adverse event (AE) reports from different countries and regions around the globe. Among them, the occurrence rate of famciclovir-related AEs was higher in females (59.72%) than in males (34.49%), possibly due to the majority of the AE reports collected for this study being related to HZ (Herpes Zoster) (61.89%). Additionally, research indicates that HZ occurs more frequently in females than in males 18 , resulting in increased dosage and frequency of famciclovir usage among female patients. In terms of onset age, the proportion of AEs from famciclovir was notably higher among the elderly (≥ 65 years) than other age groups, correlating with the overall risk of contracting HZ increasing as age advances 19 . Therefore, with the increasing clinical use of famciclovir, clinicians should be aware of the adverse events related to famciclovir, particularly among the elderly. According to the results of disproportionality analysis, this study found that the most prominent and crucial signals at the SOC level were nervous system diseases, hepatobiliary diseases, kidney and urinary system diseases, skin and subcutaneous tissue diseases, and various tests, with the most frequently reported being nervous system diseases, various tests, and skin and subcutaneous tissue diseases. On the PT level, notable adverse events mainly consist of altered states of consciousness, toxic encephalopathy, simple herpes, minor epileptic seizures, and purpura. Toxic encephalopathy and purpura show high signal strength, and despite their relatively low reporting frequency, they should still be given sufficient attention in clinical practice. Herpes simplex shows a high signal strength, associated with the virus's persistence in a latent state within the host's neurons and its periodic reactivation, with some reports coming from consumers. Therefore, some adverse events (such as herpes simplex) may not be considered true adverse events. Additionally, certain adverse events like toxic encephalopathy, encephalopathy, ataxia, dysarthria, dementia, cerebral stroke, tremors, purpura, skin ulcers, acute pancreatitis, rhabdomyolysis, muscle spasms, increased blood urea nitrogen, hypotension, hepatitis, disease relapse, drug interactions, and pancytopenia have relatively fewer reports and are not cited in the medication guides. For these uncommon or severe AEs, they might not have been adequately observed in previous clinical trials. This study's findings indicate that the most frequent adverse events, including nausea, headache, vomiting, and dizziness, align with the documented records in research reports 20–22 . Some studies have noted that the majority of adverse events caused by famciclovir (headache, nausea, vomiting, diarrhea, abdominal pain) are mild to moderate, with symptoms generally lasting 1–2 days 23 . Headaches often occur on the first or second day following initial administration 24 , aligning with the occurrence time of adverse reactions indicated by this study's results. It's worth noting that altered states of consciousness have high signal strength and report frequency, highlighting the need for clinicians to focus on neurological diseases. Research has found that patients with chronic kidney disease have an increased risk of neurotoxicity when using antiviral medications 25 . Gales et al. argue that administering therapeutic doses of famciclovir to elderly patients could precipitate new or exacerbate existing central nervous system disorders 22 . At present, severe neurological conditions induced by famciclovir are infrequently reported in clinical practice, and there is a shortage of studies investigating the underlying mechanisms. Neurological diseases, as one of the most significant signals associated with adverse reactions to famciclovir, require special consideration regarding the safety of its use in certain populations, such as patients with underlying neurological disorders. While this study indicates high signal strength and reporting frequency for neurological disease associated with famciclovir, it doesn't imply that these events are solely caused by the drug. These events may be influenced by various factors, such as the patient's baseline characteristics, comorbidities, and concomitant medications. Additionally, while most hematologic and serum chemistry changes are minor clinically, reports have shown significant alterations in serum glutamic pyruvic transaminase, amylase, serum lipase, and hypoglycemia in some patients during treatment 26 . Therefore, conducting appropriate tests on patients before administering the medication can help in the early identification and management of AEs, especially those that are severe or potentially life-threatening. Through the analysis of the FAERS database, we investigated adverse events associated with famciclovir, along with other pertinent and significant adverse events. This method effectively addresses the limitations associated with small sample sizes and short observation durations in clinical trials, offering a valuable perspective for monitoring and enhancing clinical drug safety. However, it must be emphasized that FAERS is a spontaneous reporting system, originating from different countries and professionals. Therefore, underreporting, delayed reporting, and erroneous reports of incomplete information may introduce bias in the measurement of disproportionate reporting 27 . Additionally, the data analysis excludes numerous unmeasured confounding factors, such as potential drug interactions, comorbidities, and combinations of medications, that could influence AEs. Lastly, the use of disproportionality analysis only provides an estimate of signal strength, merely reflecting a statistical association between specific drugs and adverse reactions, but cannot establish causality. Given the aforementioned limitations and other potential confounders, additional clinical research evaluations are required to confirm these associations. Despite the limitations of the FAERS database in pharmacovigilance research, our thorough analysis of adverse event signals related to famciclovir, and the identification of unforeseen adverse event signals, can lay the foundation for future clinical studies of the drug. Materials and methods Data source and data processing Data on famciclovir-related adverse events (AEs) is sourced from ASCII files in the FAERS database, spanning from Q1 2004 to Q2 2023. The FAERS database comprises seven datasets, including patient demographics and administrative information (DEMO), drug information (DRUG), adverse event coding (REAC), patient outcomes (OUTC), report sources (RPSR), therapy start and end dates for reported drugs (THER), and indications for use (INDI). In this research, both the drug and its primary component were identified as "Famciclovir." Additionally, prior to data mining, the drug names were standardized utilizing MedEx-UIMA version 1.3.8 12 . In the FAERS database, reported drugs are categorized into four types: Primary Suspect Drug (PS), Secondary Suspect Drug (SS), Concomitant Drug (C), and Interacting (I). To enhance the accuracy of the analysis and mitigate the effects of concomitant drug use, the AE role code was retained only when the PS drug was identified as "famciclovir" 13 . Throughout this research, we discovered 432 cases of AE reports with famciclovir classified as the PS drug. Figure 1 depicts the flowchart for the study. Statistical analysis This study employs disproportionality analysis and Bayesian methods to investigate the potential causal relationship between famciclovir and adverse reactions. Disproportionality analysis facilitates the comparison of adverse event occurrence ratios between the target drug and all others. This analysis incorporates the reported odds ratio (ROR) and the proportional reporting ratio (PRR). Bayesian methods comprise Bayesian confidence propagation neural network (BCPNN) and Gamma Poisson Shrinkage (GPS), offering lower sensitivity and greater specificity compared to other methodologies. To enhance the credibility of the analysis of the correlation between drugs and adverse events, and to validate the results from multiple perspectives, this study adopted the above four algorithms. Higher values indicate stronger signal strength, suggesting a stronger association between the target drug and adverse events. The meeting of criteria by at least one among the four algorithms should be regarded as a positive signal for drug-related adverse events (specific algorithms and criteria, refer to Tables 4 and 5 ). Table 4 Two-by-two contingency table for analysis. Drugs Hypertension cases All other adverse event cases Total VEGFR-TKIs a b a + b All other drugs c d c + d Total a + c b + d a + b + c + d Table 5 Summary of major algorithms used for signal detection. Algorithms Equation Criteria ROR ROR = ad/bc Lower limit of 95% CI > 1, N ≥ 3 95%CI = e ln(ROR)±1.96(1/a+1/b+1/c+1/d)^0.5 PPR PRR = [a(c + d)]/[c(a + b)] PRR ≥ 2, χ2 ≥ 4, N ≥ 3 χ2 = [(ad-bc)^2](a + b + c + d)/[(a + b)(c + d)(a + c)(b + d)] BCPNN IC = log 2 [a(a + b + c + d)]/[(a + c)(a + b)] IC025 > 0 95%CI = e ln(IC)±1.96(1/a+1/b+1/c+1/d)^0.5 MGPS EBGM = a(a + b + c + d)/(a + c)/(a + b) EBGM05 > 2 95%CI = e ln(EBGM)±1.96(1/a+1/b+1/c+1/d)^0.5 N, number of adverse event reports; 95% CI, 95% confidence interval; χ2, chi-squared; IC, information component; IC025, the lower limit of the 95% CI of the IC; E (IC), the IC expectations; V (IC), the variance of IC; EBGM, empirical Bayesian geometric mean; EBGM05, empirical Bayesian geometric mean lower 95% CI for the posterior distribution. Declarations Author contributions statement R.F. and Y.Z contributed to conception, study design and analyzed data. L.H., W.C. and N.G. prepared all figures and Tables, and took responsibility for the collection, integrity and accuracy of the data. J.L., R.F. and Y.Z. wrote the main manuscript. All authors read and approved the final manuscript. Competing interests The authors declare no competing interests. Contributor Information Jianhong Li, Email: [email protected] Author Contribution R.F. and Y.Z contributed to conception , study design and analyzed data. L.H., W.C. and N.G. prepared all figures and Tables, and took responsibility for the collection, integrity and accuracy of the data. J.L., R.F. and Y.Z. wrote the main manuscript. All authors read and approved the final manuscript. Data Availability Publicly available datasets were analyzed in this study. This data can be found here: All data come from the FAERS database, which is available at https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html. References Werner RN, Ghoreschi K. Herpes zoster-prevention, diagnosis, and treatment. Hautarzt. 2022;73(6):442–451. doi: 10.1007/s00105-022-04992-9 Romanowski B, Aoki FY, Martel AY, Lavender EA, Parsons JE, Saltzman RL. Efficacy and safety of famciclovir for treating mucocutaneous herpes simplex infection in HIV-infected individuals. Collaborative Famciclovir HIV Study Group. AIDS. 2000;14(9):1211–7. doi: 10.1097/00002030-200006160-00019 . Luber AD, Flaherty JF Jr. Famciclovir for treatment of herpesvirus infections. Ann Pharmacother. 1996;30(9):978–85. doi: 10.1177/106002809603000913 . Liu Y, Xiao S, Li J, Long X, Zhang Y, Li X. A Network Meta-Analysis of Randomized Clinical Trials to Assess the Efficacy and Safety of Antiviral Agents for Immunocompetent Patients with Herpes Zoster-Associated Pain. Pain Physician. 2023;26(4):337–346. Gopal MG, Shannoma, Kumar B C S, M R, A S N, Manjunath NC. A comparative study to evaluate the efficacy and safety of acyclovir and famciclovir in the management of herpes zoster. J Clin Diagn Res. 2013;7(12):2904–2907. doi: 10.7860/JCDR/2013/7884.3670 Tyring S, Barbarash RA, Nahlik JE, Cunningham A, Marley J, Heng M, Jones T, Rea T, Boon R, Saltzman R. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group. Ann Intern Med. 1995;123(2):89–96. doi: 10.7326/0003-4819-123-2-199507150-00002 . Chen N, Li Q, Yang J, Zhou M, Zhou D, He L. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2014;2014(2):CD006866. doi: 10.1002/14651858.CD006866.pub3 . Saguil A, Kane S, Mercado M, Lauters R. Herpes Zoster and Postherpetic Neuralgia: Prevention and Management. Am Fam Physician. 2017;96(10):656–663. doi: 10.1007/978-3-319-44348-5_23 . Cao J, Zhang X, Wang Z. Effectiveness comparisons of antiviral treatments for Bell palsy: a systematic review and network meta-analysis. J Neurol. 2022;269(3):1353–1367. doi: 10.1007/s00415-021-10487-9 . Deng YX, Hu J, Li HM. Efficacy and safety of different doses of antiviral agents in the treatment of herpes zoster: a meta-analysis. Zhonghua Yi Xue Za Zhi. 2022;102(40):3192–3200. doi: 10.3760/cma.j.cn112137-20220603-01237 . Chen W, Cai P, Zou W, Fu Z. Psychiatric adverse events associated with GLP-1 receptor agonists: a real-world pharmacovigilance study based on the FDA Adverse Event Reporting System database. Front Endocrinol (Lausanne). 2024 Feb 6;15:1330936. doi: 10.3389/fendo.2024.1330936 Jiang M, Wu Y, Shah A, Priyanka P, Denny JC, Xu H. Extracting and standardizing medication information in clinical text - the MedEx-UIMA system. AMIA Jt Summits Transl Sci Proc. 2014;2014:37–42. Zhang Y, Ran L, Liang Y, Zhang Y, An Z. Safety analysis of pemigatinib leveraging the US Food and Drug administration adverse event reporting system. Front Pharmacol. 2023;14:1194545. doi: 10.3389/fphar.2023.1194545 Tang S, Wu Z, Xu L, Wen Q, Zhang X. Adverse reaction signals mining and hemorrhagic signals comparison of ticagrelor and clopidogrel: A pharmacovigilance study based on FAERS. Front Pharmacol. 2022 Oct 3;13:970066. doi: 10.3389/fphar.2022.970066 . Park G, Jung H, Heo SJ, Jung I. Comparison of Data Mining Methods for the Signal Detection of Adverse Drug Events with a Hierarchical Structure in Postmarketing Surveillance. Life (Basel). 2020;10(8):138. Published 2020 Aug 5. doi: 10.3390/life10080138 . Zou F, Zhu C, Lou S, Cui Z, Wang D, Ou Y, Wang L, Chen J, Lan Y. A real-world pharmacovigilance study of mepolizumab in the FDA adverse event reporting system (FAERS) database. Front Pharmacol. 2023;14:1320458. doi: 10.3389/fphar.2023.1320458 . Kim HS, Lee S, Kim JH. Real-world Evidence versus Randomized Controlled Trial: Clinical Research Based on Electronic Medical Records. J Korean Med Sci. 2018;33(34): e213. doi: 10.3346/jkms.2018.33.e213 Van Oorschot D, Vroling H, Bunge E, Diaz-Decaro J, Curran D, Yawn B. A systematic literature review of herpes zoster incidence worldwide. Hum Vaccin Immunother. 2021;17(6):1714–1732. doi: 10.1080/21645515.2020.1847582 Södergren E, Mårdberg K, Nishimwe M, Bhavsar A, Marijam A, Bergström T, Stäck P. Incidence and Burden of Herpes Zoster in Sweden: A Regional Population-Based Register Study. Infect Dis Ther. 2024;13(1):121–140. doi: 10.1007/s40121-023-00902- Sáez-Llorens X, Yogev R, Arguedas A, Rodriguez A, Spigarelli MG, De León Castrejón T, Bomgaars L, Roberts M, Abrams B, Zhou W, Looby M, Kaiser G, Hamed K. Pharmacokinetics and safety of famciclovir in children with herpes simplex or varicella-zoster virus infection. Antimicrob Agents Chemother. 2009;53(5):1912–20. doi: 10.1128/AAC.01054-08 . Cirelli R, Herne K, McCrary M, Lee P, Tyring SK. Famciclovir: review of clinical efficacy and safety. Antiviral Res. 1996;29(2–3):141–51. doi: 10.1016/0166-3542(95)00941-8 . Gales BJ, Gales MA. Confusion and bradykinesia associated with famciclovir therapy for herpes zoster. Am J Health Syst Pharm. 1996;53(12):1454, 1456. doi: 10.1093/ajhp/53.12.1454 . Li Q, Chen N, Yang J, Zhou M, Zhou D, Zhang Q, He L. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2009;(2):CD006866. doi: 10.1002/14651858.CD006866.pub2 . Aoki FY, Tyring S, Diaz-Mitoma F, Gross G, Gao J, Hamed K. Single-day, patient-initiated famciclovir therapy for recurrent genital herpes: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2006;42(1):8–13. doi: 10.1086/498521 . Lam NN, Weir MA, Yao Z, Blake PG, Beyea MM, Gomes T, Gandhi S, Mamdani M, Wald R, Parikh CR, Hackam DG, Garg AX. Risk of acute kidney injury from oral acyclovir: a population-based study. Am J Kidney Dis. 2013;61(5):723–9. doi: 10.1053/j.ajkd.2012.12.008 . Mubareka S, Leung V, Aoki FY, Vinh DC. Famciclovir: a focus on efficacy and safety. Expert Opin Drug Saf. 2010;9(4):643–58. doi: 10.1517/14740338.2010.485189 . Noguchi Y, Tachi T, Teramachi H. Detection algorithms and attentive points of safety signal using spontaneous reporting systems as a clinical data source. Brief Bioinform. 2021;22(6):bbab347. doi: 10.1093/bib/bbab347 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 19 Nov, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 03 Jun, 2024 Reviews received at journal 17 May, 2024 Reviewers agreed at journal 07 May, 2024 Reviews received at journal 06 May, 2024 Reviewers agreed at journal 06 May, 2024 Reviewers invited by journal 06 May, 2024 Editor assigned by journal 05 May, 2024 Editor invited by journal 26 Apr, 2024 Submission checks completed at journal 26 Apr, 2024 First submitted to journal 21 Apr, 2024 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4300885","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":297384569,"identity":"5239fa31-8895-4f2a-9a69-18aafc2bd3c4","order_by":0,"name":"Runan Fang","email":"","orcid":"","institution":"Dongzhimen Hospital Beijing University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Runan","middleName":"","lastName":"Fang","suffix":""},{"id":297384571,"identity":"ee559377-b649-47f1-84ea-e8e83af0763d","order_by":1,"name":"Yang Zhou","email":"","orcid":"","institution":"Guang'anmen Hospital of China Academy of Chinese Medicine Sciences","correspondingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Zhou","suffix":""},{"id":297384572,"identity":"c8b25327-8f83-47dc-84a7-452ac33ccf5e","order_by":2,"name":"Lu Han","email":"","orcid":"","institution":"Dongzhimen Hospital Beijing University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Lu","middleName":"","lastName":"Han","suffix":""},{"id":297384573,"identity":"a5fcf471-dba3-4891-907d-5595247387f5","order_by":3,"name":"Wenjing Chen","email":"","orcid":"","institution":"Dongzhimen Hospital Beijing University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Wenjing","middleName":"","lastName":"Chen","suffix":""},{"id":297384574,"identity":"5f07e02c-1786-4d1b-b2f2-d8fac6351727","order_by":4,"name":"Ning Guan","email":"","orcid":"","institution":"Dongzhimen Hospital Beijing University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ning","middleName":"","lastName":"Guan","suffix":""},{"id":297384576,"identity":"e04b49ee-a19f-44cd-8438-151b80829d0a","order_by":5,"name":"Jianhong Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYNCCAgYGNmbGxgcMBkRrAarkY28+bECaFjmeY2kSRCmWjz788MMHAxs5Nokcs8ofBXfkGdgPH92AT4vhuTRjyRkGacYgLbd5DJ4ZNvCkpd3Aq6WHwYyZx+BwYhtIC4PBYcYGCR4zAlrYvzH/MfhfD9JS+MPgsD1BLfI8PGbMDAYHEtiA3mcAWUdQiwEPT7Fkj0GyYRswkKWBWpLbCPlFvod944cfFXby8s2MjR9//Dls289++Bh+Ww6gi7DhUw62pYGQilEwCkbBKBgFAPm1RKJLtDzUAAAAAElFTkSuQmCC","orcid":"","institution":"Dongzhimen Hospital Beijing University of Chinese Medicine","correspondingAuthor":true,"prefix":"","firstName":"Jianhong","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2024-04-21 13:23:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4300885/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4300885/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-80236-1","type":"published","date":"2024-11-19T15:57:14+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":55765971,"identity":"7c270446-43b2-4af6-a721-4f64cb76cd75","added_by":"auto","created_at":"2024-05-02 20:09:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":41978,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4300885/v1/cab6454f4907eaac6cd313d1.png"},{"id":69835588,"identity":"391bb56d-b1fe-4d45-8317-1bb8ed0c27d7","added_by":"auto","created_at":"2024-11-25 16:13:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1139348,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4300885/v1/28d90226-f6aa-4577-b36b-9acf7e4bea94.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Real-world Pharmacovigilance Study of Famciclovir in the FDA Adverse Event Reporting System (FAERS) Database","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHerpes zoster is a common acute infectious viral skin disease. The clinical symptoms of herpes zoster (HZ) may not be severe, but if not treated promptly and systematically early on, it could lead to serious complications, adversely affecting the patient's life \u003csup\u003e1\u003c/sup\u003e. Therefore, antiviral therapy is critical in the management of HZ. Early and sufficient antiviral therapy not only relieves acute symptoms and reduces the duration of the disease but also prevent the occurrence of post-treatment neuralgia to a certain extent. At present, famciclovir ranks among the most frequently prescribed medications for HZ, with over 4\u0026nbsp;million prescriptions globally \u003csup\u003e2\u003c/sup\u003e. Famciclovir, once absorbed orally, rapidly transforms into penciclovir in the intestines and liver, and is phosphorylated within cells infected by the varicella-zoster virus (VZV) to produce a triphosphate compound with antiviral properties. The oral bioavailability of famciclovir is higher than that of acyclovir, with an oral bioavailability of 77% \u003csup\u003e3\u003c/sup\u003e. According to reports \u003csup\u003e4\u003c/sup\u003e, oral famciclovir is the most effective treatment for acute pain and post-herpetic neuralgia (PHN) associated with HZ, providing rapid relief from HZ-related pain \u003csup\u003e5\u003c/sup\u003e. It is widely used in clinical settings for treating herpes simplex virus infections and acute HZ. Additionally, it is also used in the chronic suppressive therapy of genital herpes \u003csup\u003e3\u003c/sup\u003e. Famciclovir's adverse effects commonly include headache, nausea, and diarrhea \u003csup\u003e6,7\u003c/sup\u003e, with severe adverse effects being hepatotoxicity and Stevens-Johnson syndrome \u003csup\u003e8\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAccording to recently reported meta-analysis data, there are deficiencies in the number of adverse reactions to famciclovir that make them unanalyzable \u003csup\u003e9,10\u003c/sup\u003e. The issue may stem from the fact that most efficacy and safety data on famciclovir are derived from clinical trials with small sample sizes and limited follow-up durations. Due to individual differences, patients using famciclovir may experience unexpected adverse events (AEs) in the real-world clinical setting. Thus, identifying unexpected adverse drug reactions (ADRs) associated with famciclovir has certain clinical significance.\u003c/p\u003e \u003cp\u003eThe Food and Drug Adverse Event Reporting System (FAERS) is an openly accessible database that documents numerous adverse events (AEs) and medication errors related to human pharmaceuticals and therapeutic biological products, ranking as one of the largest drug safety databases globally \u003csup\u003e11\u003c/sup\u003e. Through data mining of famciclovir adverse events in the FAERS database, this research seeks to uncover ADRs not documented in the drug's profile, serving as a reference for its rational and safe use in clinical practice.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eBasic Characteristics of Famciclovir-Related Adverse Drug Events (ADEs)\u003c/p\u003e \u003cp\u003eThis study retrieved 17,652,186 reports from the FAERS database, and after eliminating duplicates and conducting a filtering process, we identified 432 famciclovir-related AE reports. Within these reports, the occurrence of adverse events was higher in females than in males (59.72% vs 34.49%). In terms of age, the elderly population (aged\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;65 years) constituted the highest proportion (46.3%). Most reports were from consumers (40.74%), rather than doctors (12.5%), pharmacists (6.48%), or other healthcare professionals (16.67%). Many reports (55.56%) did not specify their region of origin, with Japan having the highest share (28.94%), followed by the United States (7.41%). Among the reported clinical outcomes, serious outcomes were the most common (50.22%), followed by hospitalizations (39.82%) and life-threatening situations (3.98%). Additionally, onset time of famciclovir adverse reactions, as collected from the database, predominantly had a median of 2 days (interquartile range [IQR] 0.00-5.5), with the majority happening within 1\u0026ndash;7 days (43.53%), and the next most common timeframe being within 24 hours (21.76%). In this study, HZ (61.20%) was the most frequently reported indication. And the detailed information, refer to Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of reports with Famciclovir from the FAERS database\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \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 (% of Total case Reports)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e258(59.72)\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e149(34.49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnkown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25(5.79)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(1.39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u0026thinsp;~\u0026thinsp;65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e133(30.79)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;=65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e200(46.30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93(21.53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReporter\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysician\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54(12.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePharmacist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28(6.48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther health-professional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72(16.67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConsumer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e176(40.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnkown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e102(23.61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReported countries(top five)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e125(28.94)\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e32(7.41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAustralia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(1.62)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited Kingdom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(1.62)\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e240(55.56)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e180(39.82)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLife threatening\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18(3.98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(3.32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(2.43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRequired intervention to Prevent Permanent Impairment/Damage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(0.22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e227(50.22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTime to AE (days)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74(21.76)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026thinsp;~\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e148(43.53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u0026thinsp;~\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27(7.94)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u0026thinsp;~\u0026thinsp;28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(4.12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;=28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20(5.88)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCharacteristics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCase number (% of Total case Reports)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunknow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57(16.76)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIndications(top five)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHerpes zoster\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e265(61.20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHerpes simplex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34(7.85)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProduct used for unknown Indication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(4.39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral herpes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(3.23)\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e49(11.32)\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\u003eSignal mining of famciclovir\u003c/p\u003e \u003cp\u003eThis research examined reports of AEs associated with famciclovir, covering adverse reactions across 22 system organ categories (SOC), see Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e for details. Significant SOCs that met at least one indicator criterion were diseases of the nervous system, disorders of the hepatobiliary disorders, renal and urinary disorders, skin and subcutaneous tissue disorders, and investigations. At the PT level, this research utilized four algorithms to analyze adverse drug reactions and assessed their adherence to various screening criteria, yielding 126 PTs. Among these, 65 PTs met the criteria of all four algorithms, including 14 SOCs, with details provided in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Regarding the number of cases, the most frequent PTs associated with famciclovir were nausea, headache, altered mental status, vomiting, and dizziness. When ordered by ROR value and IC signal strength, the most prominent were altered state of consciousness (n\u0026thinsp;=\u0026thinsp;28, ROR 61.64, PRR 60.32, IC 5.91, EBGM 60.2), toxic encephalopathy (n\u0026thinsp;=\u0026thinsp;5, ROR 49.89, PRR 49.7, IC 5.63, EBGM 49.62), herpes simplex (n\u0026thinsp;=\u0026thinsp;4, ROR 27.67, PRR 27.59, IC 4.78, EBGM 27.56), petit mal epilepsy (n\u0026thinsp;=\u0026thinsp;3, ROR 25.18, PRR 25.13, IC 4.65, EBGM 25.11), and purpura (n\u0026thinsp;=\u0026thinsp;4, ROR 18.23, PRR 18.18, IC 4.18, EBGM 18.17). Notably, adverse signals not mentioned in the medication instructions include toxic encephalopathy, encephalopathy, ataxia, dysarthria, dementia, cerebral infarction, tremor, purpura, skin ulcers, acute pancreatitis, rhabdomyolysis, muscle twitching, increased blood urea, lowered blood pressure, hepatitis, disease recurrence, drug interactions, and pancytopenia.\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\u003eSignal strength of adverse events of Famciclovir at the system organ class (SOC) level in FAERS database\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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=\"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=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\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\u003eCase\u003c/p\u003e \u003cp\u003eReports\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eROR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePRR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eχ2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIC\u003c/p\u003e \u003cp\u003e(IC025)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEBGM\u003c/p\u003e \u003cp\u003e(EBGM05)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\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\u003e255\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.43(2.12, 2.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.15(1.91, 2.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e172.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.1(0.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.15(1.92)\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\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.43(1.68, 3.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.4(1.69, 3.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e23.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.26(0.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.4(1.76)\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\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.69(1.24, 2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.66(1.24, 2.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.74(0.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.66(1.28)\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\u003e116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.62(1.34, 1.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.57(1.32, 1.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e25.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.65(0.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.57(1.34)\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\u003e118\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.44(1.19, 1.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.4(1.17, 1.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e14.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.49(0.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.4(1.2)\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\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.22(0.46, 3.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.22(0.46, 3.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.29(-0.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.22(0.54)\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\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.2(0.57, 2.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.2(0.57, 2.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.26(-0.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.2(0.64)\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\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.2(0.82, 1.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.19(0.82, 1.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.25(-0.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.19(0.87)\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\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.19(0.97, 1.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.18(0.97, 1.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.24(-0.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.18(0.99)\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\u003e135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.17(0.98, 1.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.15(0.98, 1.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.2(-0.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.15(0.99)\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\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.92(0.62, 1.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.92(0.62, 1.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.11(-0.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.92(0.66)\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\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.89(0.69, 1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9(0.7, 1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.15(-0.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.9(0.72)\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\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.84(0.59, 1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.84(0.59, 1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.25(-0.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.84(0.62)\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\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.72(0.4, 1.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.73(0.41, 1.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.46(-1.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.73(0.44)\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\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.69(0.44, 1.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.69(0.45, 1.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.53(-1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.69(0.48)\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=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.67(0.57, 0.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.72(0.63, 0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e23.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.48(-0.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.72(0.63)\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\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.66(0.42, 1.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.66(0.43, 1.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.59(-1.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.66(0.46)\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\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.65(0.49, 0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.66(0.5, 0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.59(-1.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.66(0.52)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePregnancy, puerperium and perinatal conditions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.63(0.24, 1.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.63(0.24, 1.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.66(-1.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.63(0.28)\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\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.62(0.45, 0.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.63(0.47, 0.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.67(-1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.63(0.49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInjury, poisoning and procedural complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.22(0.15, 0.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.24(0.17, 0.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e72.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-2.07(-2.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.24(0.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoplasms benign, malignant and unspecified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.16(0.07, 0.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.16(0.07, 0.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e21.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-2.6(-3.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.16(0.08)\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\u003eROR, reporting odds ratio; CI, confidence interval; PRR, proportional reporting ratio; χ2, chi-squared; IC, information component; EBGM, empirical Bayesian geometric mean; *, Indicates statistically significant signals in all four algorithms.\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 reports of Famciclovir at the PT level in the FAERS database.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\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\u003ePreferred terms (PTs)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCase\u003c/p\u003e \u003cp\u003ereports\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eROR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePRR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eχ2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIC\u003c/p\u003e \u003cp\u003e(IC025)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eEBGM\u003c/p\u003e \u003cp\u003e(EBGM05)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\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\u003eAltered state of consciousness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61.64(42.37, 89.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60.32(41.57, 87.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1630.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.91(5.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e60.2(43.99)\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\u003eToxic encephalopathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49.89(20.71, 120.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49.7(20.57, 120.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e238.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.63(4.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e49.62(23.78)\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\u003ePetit mal epilepsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.18(8.11, 78.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.13(8.06, 78.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e69.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.65(3.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e25.11(9.73)\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\u003eEncephalopathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.05(9.69, 33.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17.92(9.57, 33.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e159.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.16(3.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e17.91(10.64)\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\u003eAtaxia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.5(3.38, 32.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.48(3.36, 32.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.39(1.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10.48(4.06)\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\u003eDepressed level of consciousness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.64(4.31, 17.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.59(4.33, 17.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e53.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.1(2.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8.59(4.8)\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\u003eLoss of consciousness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.23(3.96, 9.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.16(3.92, 9.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e82.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.62(1.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.15(4.21)\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\u003eDysarthria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.6(2.32, 13.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.58(2.31, 13.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.48(1.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.58(2.67)\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\u003eDementia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.37(1.73, 16.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.36(1.72, 16.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.42(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.36(2.08)\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\u003eCerebral infarction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.14(1.66, 15.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.13(1.65, 15.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.36(0.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.13(1.99)\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\u003eLethargy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.63(1.51, 8.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.62(1.5, 8.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.86(0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.62(1.74)\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\u003eSyncope\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.55(1.14, 5.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.54(1.14, 5.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.35(0.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.54(1.3)\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\u003eTremor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.24(1.16, 4.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.23(1.17, 4.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.16(0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.23(1.29)\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\u003eHeadache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.19(1.54, 3.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.16(1.55, 3.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.11(0.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.16(1.61)\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\u003eDizziness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.15(1.45, 3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.13(1.44, 3.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.09(0.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.13(1.53)\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eHerpes simplex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.67(10.36, 73.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27.59(10.35, 73.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e102.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.78(3.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e27.56(12.12)\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\u003eOral herpes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.35(2.37, 22.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.33(2.35, 22.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.87(1.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.33(2.84)\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\u003eHerpes zoster\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.09(1.16, 8.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.08(1.16, 8.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.62(0.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.08(1.36)\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\u003ePurpura\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.23(6.83, 48.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18.18(6.82, 48.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e64.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.18(2.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e18.17(7.99)\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\u003eErythema multiforme\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.29(4.28, 41.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.27(4.26, 41.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.73(2.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e13.26(5.14)\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\u003eDrug eruption\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.37(3.89, 27.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.34(3.88, 27.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.37(2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10.34(4.55)\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\u003eAngioedema\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.62(3.8, 15.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.58(3.82, 15.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.92(1.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.58(4.24)\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\u003eBlister\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.71(2.71, 11.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.68(2.7, 11.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.51(1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.68(3.05)\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\u003eSkin ulcer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.08(1.64, 15.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.07(1.63, 15.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.34(0.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.07(1.97)\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\u003eRash erythematous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.1(1, 9.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.09(0.99, 9.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.63(0.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.09(1.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrticaria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.4(1.24, 4.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.39(1.25, 4.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.25(0.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.39(1.38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSystem organ class (SOC)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003ePreferred terms (PTs)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eCase\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003ereports\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eROR\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003ePRR\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eχ2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eIC\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(IC025)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eEBGM\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(EBGM05)\u003c/b\u003e\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eHyperchlorhydria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.9(5.76, 55.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17.86(5.73, 55.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.16(2.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e17.85(6.92)\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\u003ePancreatitis acute\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.95(1.92, 18.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.94(1.91, 18.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.57(1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.94(2.3)\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\u003eVomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.45(1.66, 3.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.42(1.67, 3.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.27(0.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.42(1.75)\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\u003ePharyngeal oedema\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.44(5.58, 27.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.38(5.54, 27.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e62.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.63(2.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12.38(6.33)\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\u003eRhabdomyolysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.93(6.75, 21.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.82(6.7, 20.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e118.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.56(2.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e11.82(7.35)\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 twitching\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.32(1.71, 16.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.31(1.7, 16.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.41(0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.3(2.06)\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 alkaline phosphatase increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.92(4.45, 22.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.88(4.42, 22.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.3(2.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9.88(5.05)\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\u003eBlood urea increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.41(2.39, 23.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.4(2.37, 23.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.89(1.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.4(2.87)\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\u003eAspartate aminotransferase increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.35(3.17, 12.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.32(3.18, 12.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.66(1.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.32(3.53)\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\u003eLiver function test abnormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.32(2.63, 15.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.3(2.61, 15.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.66(1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.3(3.02)\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\u003eAlanine aminotransferase increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.15(3.19, 11.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.11(3.2, 11.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e38.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.61(1.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.11(3.53)\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\u003eBlood bilirubin increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.03(2.26, 16.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.01(2.26, 16.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.59(1.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.01(2.64)\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\u003eBlood pressure decreased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.27(2.63, 10.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.24(2.64, 10.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.39(1.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.24(2.93)\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\u003eBlood creatine phosphokinase increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.94(1.27, 12.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.93(1.26, 12.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.98(0.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.93(1.52)\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\u003eBlood creatinine increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.93(1.76, 8.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.92(1.76, 8.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.97(0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.92(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\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\u003eInternational normalised ratio increased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.64(1.17, 11.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.64(1.17, 11.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.86(0.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.64(1.41)\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\u003ePlatelet count decreased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.52(1.13, 5.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.52(1.13, 5.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.33(0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.52(1.29)\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=\"left\" colname=\"c2\"\u003e \u003cp\u003eHepatitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.89(4.44, 22.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.85(4.41, 22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.3(2.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9.85(5.03)\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\u003eHepatic function abnormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.24(2.59, 15.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.22(2.57, 15.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.64(1.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.21(2.98)\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\u003eJaundice\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.77(2.16, 15.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.76(2.16, 15.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.53(1.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.76(2.53)\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\u003eLiver disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(2.08, 12.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.98(2.06, 12.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.32(1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.98(2.39)\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\u003eEyelid oedema\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.25(2.98, 28.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.23(2.96, 28.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.21(1.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9.23(3.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSystem organ class (SOC)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003ePreferred terms (PTs)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eCase\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003ereports\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eROR\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003ePRR\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eχ2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eIC\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(IC025)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eEBGM\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(EBGM05)\u003c/b\u003e\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\u003eDisorientation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.09(4.72, 17.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.03(4.73, 17.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e64.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.17(2.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9.03(5.22)\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\u003eHallucination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.81(4.52, 13.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.74(4.47, 13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e76.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.95(2.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.74(4.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDelirium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.74(3.47, 17.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.71(3.45, 17.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.95(1.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.71(3.94)\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\u003eMiddle insomnia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.24(2.33, 22.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.22(2.32, 22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.85(1.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.22(2.8)\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\u003eRestlessness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.84(3.07, 15.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.81(3.05, 15.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.77(1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.81(3.48)\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\u003eAbnormal behaviour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.7(1.95, 11.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.69(1.94, 11.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.23(1.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.69(2.25)\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\u003eAgitation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.73(1.13, 6.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.72(1.13, 6.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.45(0.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.72(1.31)\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\u003eConfusional state\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.67(2.17, 6.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.64(2.14, 6.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.87(1.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.64(2.35)\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\u003eDisease recurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.48(2.69, 15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.46(2.67, 15.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.69(1.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.46(3.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSwelling face\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.21(1.34, 7.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.21(1.33, 7.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.68(0.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.21(1.54)\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\u003eDrug interaction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.36(1.22, 4.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.35(1.23, 4.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.23(0.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.35(1.36)\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\u003ePalpitations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.77(2.76, 8.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.74(2.74, 8.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e38.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.24(1.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.74(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\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 incontinence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.48(1.44, 13.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.47(1.43, 13.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.16(0.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.47(1.73)\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\u003eUrinary retention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.97(1.28, 12.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.96(1.27, 12.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.99(0.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.96(1.53)\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\u003eAcute kidney injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.25(1.74, 6.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.23(1.73, 6.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.69(0.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.23(1.92)\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=\"left\" colname=\"c2\"\u003e \u003cp\u003ePancytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.99(1.66, 9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.98(1.65, 9.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.99(0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.98(1.91)\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\u003eThrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.41(1.08, 5.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.41(1.08, 5.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.27(0.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.41(1.23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussions","content":"\u003cp\u003eData on the drug's efficacy and safety come from both preclinical and clinical research \u003csup\u003e17\u003c/sup\u003e. However, due to limitations in trial design and small sample sizes, the effects of the drug on humans, particularly regarding safety, cannot be fully elucidated in the real world. Therefore, paying attention to the risk signals of adverse drug reactions in clinical applications is crucial for assessing drug safety and achieving a balance between benefits and risks in clinical decision-making. In this research, we utilized a large real-world data sample to collect and evaluate the safety of famciclovir through pharmacovigilance. And aims to offer references for ensuring safety in clinical medication practices.\u003c/p\u003e \u003cp\u003eFrom the FAERS database, this research gathered 1,371 adverse event (AE) reports from different countries and regions around the globe. Among them, the occurrence rate of famciclovir-related AEs was higher in females (59.72%) than in males (34.49%), possibly due to the majority of the AE reports collected for this study being related to HZ (Herpes Zoster) (61.89%). Additionally, research indicates that HZ occurs more frequently in females than in males \u003csup\u003e18\u003c/sup\u003e, resulting in increased dosage and frequency of famciclovir usage among female patients. In terms of onset age, the proportion of AEs from famciclovir was notably higher among the elderly (\u0026ge;\u0026thinsp;65 years) than other age groups, correlating with the overall risk of contracting HZ increasing as age advances \u003csup\u003e19\u003c/sup\u003e. Therefore, with the increasing clinical use of famciclovir, clinicians should be aware of the adverse events related to famciclovir, particularly among the elderly.\u003c/p\u003e \u003cp\u003eAccording to the results of disproportionality analysis, this study found that the most prominent and crucial signals at the SOC level were nervous system diseases, hepatobiliary diseases, kidney and urinary system diseases, skin and subcutaneous tissue diseases, and various tests, with the most frequently reported being nervous system diseases, various tests, and skin and subcutaneous tissue diseases. On the PT level, notable adverse events mainly consist of altered states of consciousness, toxic encephalopathy, simple herpes, minor epileptic seizures, and purpura. Toxic encephalopathy and purpura show high signal strength, and despite their relatively low reporting frequency, they should still be given sufficient attention in clinical practice. Herpes simplex shows a high signal strength, associated with the virus's persistence in a latent state within the host's neurons and its periodic reactivation, with some reports coming from consumers. Therefore, some adverse events (such as herpes simplex) may not be considered true adverse events. Additionally, certain adverse events like toxic encephalopathy, encephalopathy, ataxia, dysarthria, dementia, cerebral stroke, tremors, purpura, skin ulcers, acute pancreatitis, rhabdomyolysis, muscle spasms, increased blood urea nitrogen, hypotension, hepatitis, disease relapse, drug interactions, and pancytopenia have relatively fewer reports and are not cited in the medication guides. For these uncommon or severe AEs, they might not have been adequately observed in previous clinical trials.\u003c/p\u003e \u003cp\u003eThis study's findings indicate that the most frequent adverse events, including nausea, headache, vomiting, and dizziness, align with the documented records in research reports \u003csup\u003e20\u0026ndash;22\u003c/sup\u003e. Some studies have noted that the majority of adverse events caused by famciclovir (headache, nausea, vomiting, diarrhea, abdominal pain) are mild to moderate, with symptoms generally lasting 1\u0026ndash;2 days \u003csup\u003e23\u003c/sup\u003e. Headaches often occur on the first or second day following initial administration \u003csup\u003e24\u003c/sup\u003e, aligning with the occurrence time of adverse reactions indicated by this study's results. It's worth noting that altered states of consciousness have high signal strength and report frequency, highlighting the need for clinicians to focus on neurological diseases. Research has found that patients with chronic kidney disease have an increased risk of neurotoxicity when using antiviral medications\u003csup\u003e25\u003c/sup\u003e. Gales et al. argue that administering therapeutic doses of famciclovir to elderly patients could precipitate new or exacerbate existing central nervous system disorders \u003csup\u003e22\u003c/sup\u003e. At present, severe neurological conditions induced by famciclovir are infrequently reported in clinical practice, and there is a shortage of studies investigating the underlying mechanisms. Neurological diseases, as one of the most significant signals associated with adverse reactions to famciclovir, require special consideration regarding the safety of its use in certain populations, such as patients with underlying neurological disorders. While this study indicates high signal strength and reporting frequency for neurological disease associated with famciclovir, it doesn't imply that these events are solely caused by the drug. These events may be influenced by various factors, such as the patient's baseline characteristics, comorbidities, and concomitant medications. Additionally, while most hematologic and serum chemistry changes are minor clinically, reports have shown significant alterations in serum glutamic pyruvic transaminase, amylase, serum lipase, and hypoglycemia in some patients during treatment \u003csup\u003e26\u003c/sup\u003e. Therefore, conducting appropriate tests on patients before administering the medication can help in the early identification and management of AEs, especially those that are severe or potentially life-threatening.\u003c/p\u003e \u003cp\u003eThrough the analysis of the FAERS database, we investigated adverse events associated with famciclovir, along with other pertinent and significant adverse events. This method effectively addresses the limitations associated with small sample sizes and short observation durations in clinical trials, offering a valuable perspective for monitoring and enhancing clinical drug safety. However, it must be emphasized that FAERS is a spontaneous reporting system, originating from different countries and professionals. Therefore, underreporting, delayed reporting, and erroneous reports of incomplete information may introduce bias in the measurement of disproportionate reporting \u003csup\u003e27\u003c/sup\u003e. Additionally, the data analysis excludes numerous unmeasured confounding factors, such as potential drug interactions, comorbidities, and combinations of medications, that could influence AEs. Lastly, the use of disproportionality analysis only provides an estimate of signal strength, merely reflecting a statistical association between specific drugs and adverse reactions, but cannot establish causality. Given the aforementioned limitations and other potential confounders, additional clinical research evaluations are required to confirm these associations. Despite the limitations of the FAERS database in pharmacovigilance research, our thorough analysis of adverse event signals related to famciclovir, and the identification of unforeseen adverse event signals, can lay the foundation for future clinical studies of the drug.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eData source and data processing\u003c/p\u003e \u003cp\u003eData on famciclovir-related adverse events (AEs) is sourced from ASCII files in the FAERS database, spanning from Q1 2004 to Q2 2023. The FAERS database comprises seven datasets, including patient demographics and administrative information (DEMO), drug information (DRUG), adverse event coding (REAC), patient outcomes (OUTC), report sources (RPSR), therapy start and end dates for reported drugs (THER), and indications for use (INDI). In this research, both the drug and its primary component were identified as \"Famciclovir.\" Additionally, prior to data mining, the drug names were standardized utilizing MedEx-UIMA version 1.3.8 \u003csup\u003e12\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the FAERS database, reported drugs are categorized into four types: Primary Suspect Drug (PS), Secondary Suspect Drug (SS), Concomitant Drug (C), and Interacting (I). To enhance the accuracy of the analysis and mitigate the effects of concomitant drug use, the AE role code was retained only when the PS drug was identified as \"famciclovir\" \u003csup\u003e13\u003c/sup\u003e. Throughout this research, we discovered 432 cases of AE reports with famciclovir classified as the PS drug. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e depicts the flowchart for the study.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThis study employs disproportionality analysis and Bayesian methods to investigate the potential causal relationship between famciclovir and adverse reactions. Disproportionality analysis facilitates the comparison of adverse event occurrence ratios between the target drug and all others. This analysis incorporates the reported odds ratio (ROR) and the proportional reporting ratio (PRR). Bayesian methods comprise Bayesian confidence propagation neural network (BCPNN) and Gamma Poisson Shrinkage (GPS), offering lower sensitivity and greater specificity compared to other methodologies. To enhance the credibility of the analysis of the correlation between drugs and adverse events, and to validate the results from multiple perspectives, this study adopted the above four algorithms. Higher values indicate stronger signal strength, suggesting a stronger association between the target drug and adverse events. The meeting of criteria by at least one among the four algorithms should be regarded as a positive signal for drug-related adverse events (specific algorithms and criteria, refer to Tables\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\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\u003eTwo-by-two contingency table for analysis.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" 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\u003eDrugs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHypertension cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAll other adverse event cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVEGFR-TKIs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ea\u0026thinsp;+\u0026thinsp;b\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll other drugs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ec\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ea\u0026thinsp;+\u0026thinsp;c\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eb\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ea\u0026thinsp;+\u0026thinsp;b\u0026thinsp;+\u0026thinsp;c\u0026thinsp;+\u0026thinsp;d\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\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of major algorithms used for signal detection.\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\u003eCriteria\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eROR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eROR\u0026thinsp;=\u0026thinsp;ad/bc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\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=\"c2\"\u003e \u003cp\u003e95%CI\u0026thinsp;=\u0026thinsp;e\u003csup\u003eln(ROR)\u0026plusmn;1.96(1/a+1/b+1/c+1/d)^0.5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePPR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePRR = [a(c\u0026thinsp;+\u0026thinsp;d)]/[c(a\u0026thinsp;+\u0026thinsp;b)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePRR\u0026thinsp;\u0026ge;\u0026thinsp;2, χ2\u0026nbsp;\u0026ge; 4, N\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eχ2\u0026nbsp;= [(ad-bc)^2](a\u0026thinsp;+\u0026thinsp;b\u0026thinsp;+\u0026thinsp;c\u0026thinsp;+\u0026thinsp;d)/[(a\u0026thinsp;+\u0026thinsp;b)(c\u0026thinsp;+\u0026thinsp;d)(a\u0026thinsp;+\u0026thinsp;c)(b\u0026thinsp;+\u0026thinsp;d)]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBCPNN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIC\u0026thinsp;=\u0026thinsp;log\u003csub\u003e2\u003c/sub\u003e[a(a\u0026thinsp;+\u0026thinsp;b\u0026thinsp;+\u0026thinsp;c\u0026thinsp;+\u0026thinsp;d)]/[(a\u0026thinsp;+\u0026thinsp;c)(a\u0026thinsp;+\u0026thinsp;b)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIC025\u0026thinsp;\u0026gt;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95%CI\u0026thinsp;=\u0026thinsp;e\u003csup\u003eln(IC)\u0026plusmn;1.96(1/a+1/b+1/c+1/d)^0.5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMGPS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEBGM\u0026thinsp;=\u0026thinsp;a(a\u0026thinsp;+\u0026thinsp;b\u0026thinsp;+\u0026thinsp;c\u0026thinsp;+\u0026thinsp;d)/(a\u0026thinsp;+\u0026thinsp;c)/(a\u0026thinsp;+\u0026thinsp;b)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eEBGM05\u0026thinsp;\u0026gt;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95%CI\u0026thinsp;=\u0026thinsp;e\u003csup\u003eln(EBGM)\u0026plusmn;1.96(1/a+1/b+1/c+1/d)^0.5\u003c/sup\u003e\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\u003eN, number of adverse event reports; 95% CI, 95% confidence interval; χ2, chi-squared; IC, information component; IC025, the lower limit of the 95% CI of the IC; E (IC), the IC expectations; V (IC), the variance of IC; EBGM, empirical Bayesian geometric mean; EBGM05, empirical Bayesian geometric mean lower 95% CI for the posterior distribution.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eAuthor contributions statement\u003c/h2\u003e \u003cp\u003eR.F. and Y.Z contributed to conception, study design and analyzed data. L.H., W.C. and N.G. prepared all figures and Tables, and took responsibility for the collection, integrity and accuracy of the data. J.L., R.F. and Y.Z. wrote the main manuscript. All authors read and approved the final manuscript.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eContributor Information\u003c/h2\u003e \u003cp\u003eJianhong Li, Email: [email protected]\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eR.F. and Y.Z contributed to conception , study design and analyzed data. L.H., W.C. and N.G. prepared all figures and Tables, and took responsibility for the collection, integrity and accuracy of the data. J.L., R.F. and Y.Z. wrote the main manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003ePublicly available datasets were analyzed in this study. This data can be found here: All data come from the FAERS database, which is available at https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWerner RN, Ghoreschi K. Herpes zoster-prevention, diagnosis, and treatment. Hautarzt. 2022;73(6):442\u0026ndash;451. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00105-022-04992-9\u003c/span\u003e\u003cspan address=\"10.1007/s00105-022-04992-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRomanowski B, Aoki FY, Martel AY, Lavender EA, Parsons JE, Saltzman RL. Efficacy and safety of famciclovir for treating mucocutaneous herpes simplex infection in HIV-infected individuals. Collaborative Famciclovir HIV Study Group. AIDS. 2000;14(9):1211\u0026ndash;7. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/00002030-200006160-00019\u003c/span\u003e\u003cspan address=\"10.1097/00002030-200006160-00019\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuber AD, Flaherty JF Jr. Famciclovir for treatment of herpesvirus infections. Ann Pharmacother. 1996;30(9):978\u0026ndash;85. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/106002809603000913\u003c/span\u003e\u003cspan address=\"10.1177/106002809603000913\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Y, Xiao S, Li J, Long X, Zhang Y, Li X. A Network Meta-Analysis of Randomized Clinical Trials to Assess the Efficacy and Safety of Antiviral Agents for Immunocompetent Patients with Herpes Zoster-Associated Pain. Pain Physician. 2023;26(4):337\u0026ndash;346.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGopal MG, Shannoma, Kumar B C S, M R, A S N, Manjunath NC. A comparative study to evaluate the efficacy and safety of acyclovir and famciclovir in the management of herpes zoster. J Clin Diagn Res. 2013;7(12):2904\u0026ndash;2907. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7860/JCDR/2013/7884.3670\u003c/span\u003e\u003cspan address=\"10.7860/JCDR/2013/7884.3670\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTyring S, Barbarash RA, Nahlik JE, Cunningham A, Marley J, Heng M, Jones T, Rea T, Boon R, Saltzman R. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group. Ann Intern Med. 1995;123(2):89\u0026ndash;96. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7326/0003-4819-123-2-199507150-00002\u003c/span\u003e\u003cspan address=\"10.7326/0003-4819-123-2-199507150-00002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen N, Li Q, Yang J, Zhou M, Zhou D, He L. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2014;2014(2):CD006866. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/14651858.CD006866.pub3\u003c/span\u003e\u003cspan address=\"10.1002/14651858.CD006866.pub3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaguil A, Kane S, Mercado M, Lauters R. Herpes Zoster and Postherpetic Neuralgia: Prevention and Management. Am Fam Physician. 2017;96(10):656\u0026ndash;663. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/978-3-319-44348-5_23\u003c/span\u003e\u003cspan address=\"10.1007/978-3-319-44348-5_23\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCao J, Zhang X, Wang Z. Effectiveness comparisons of antiviral treatments for Bell palsy: a systematic review and network meta-analysis. J Neurol. 2022;269(3):1353\u0026ndash;1367. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00415-021-10487-9\u003c/span\u003e\u003cspan address=\"10.1007/s00415-021-10487-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeng YX, Hu J, Li HM. Efficacy and safety of different doses of antiviral agents in the treatment of herpes zoster: a meta-analysis. Zhonghua Yi Xue Za Zhi. 2022;102(40):3192\u0026ndash;3200. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3760/cma.j.cn112137-20220603-01237\u003c/span\u003e\u003cspan address=\"10.3760/cma.j.cn112137-20220603-01237\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen W, Cai P, Zou W, Fu Z. Psychiatric adverse events associated with GLP-1 receptor agonists: a real-world pharmacovigilance study based on the FDA Adverse Event Reporting System database. Front Endocrinol (Lausanne). 2024 Feb 6;15:1330936. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fendo.2024.1330936\u003c/span\u003e\u003cspan address=\"10.3389/fendo.2024.1330936\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJiang M, Wu Y, Shah A, Priyanka P, Denny JC, Xu H. Extracting and standardizing medication information in clinical text - the MedEx-UIMA system. AMIA Jt Summits Transl Sci Proc. 2014;2014:37\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Y, Ran L, Liang Y, Zhang Y, An Z. Safety analysis of pemigatinib leveraging the US Food and Drug administration adverse event reporting system. Front Pharmacol. 2023;14:1194545. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fphar.2023.1194545\u003c/span\u003e\u003cspan address=\"10.3389/fphar.2023.1194545\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTang S, Wu Z, Xu L, Wen Q, Zhang X. Adverse reaction signals mining and hemorrhagic signals comparison of ticagrelor and clopidogrel: A pharmacovigilance study based on FAERS. Front Pharmacol. 2022 Oct 3;13:970066. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fphar.2022.970066\u003c/span\u003e\u003cspan address=\"10.3389/fphar.2022.970066\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark G, Jung H, Heo SJ, Jung I. Comparison of Data Mining Methods for the Signal Detection of Adverse Drug Events with a Hierarchical Structure in Postmarketing Surveillance. Life (Basel). 2020;10(8):138. Published 2020 Aug 5. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/life10080138\u003c/span\u003e\u003cspan address=\"10.3390/life10080138\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZou F, Zhu C, Lou S, Cui Z, Wang D, Ou Y, Wang L, Chen J, Lan Y. A real-world pharmacovigilance study of mepolizumab in the FDA adverse event reporting system (FAERS) database. Front Pharmacol. 2023;14:1320458. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fphar.2023.1320458\u003c/span\u003e\u003cspan address=\"10.3389/fphar.2023.1320458\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim HS, Lee S, Kim JH. Real-world Evidence versus Randomized Controlled Trial: Clinical Research Based on Electronic Medical Records. J Korean Med Sci. 2018;33(34): e213. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3346/jkms.2018.33.e213\u003c/span\u003e\u003cspan address=\"10.3346/jkms.2018.33.e213\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Oorschot D, Vroling H, Bunge E, Diaz-Decaro J, Curran D, Yawn B. A systematic literature review of herpes zoster incidence worldwide. Hum Vaccin Immunother. 2021;17(6):1714\u0026ndash;1732. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/21645515.2020.1847582\u003c/span\u003e\u003cspan address=\"10.1080/21645515.2020.1847582\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS\u0026ouml;dergren E, M\u0026aring;rdberg K, Nishimwe M, Bhavsar A, Marijam A, Bergstr\u0026ouml;m T, St\u0026auml;ck P. Incidence and Burden of Herpes Zoster in Sweden: A Regional Population-Based Register Study. Infect Dis Ther. 2024;13(1):121\u0026ndash;140. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s40121-023-00902-\u003c/span\u003e\u003cspan address=\"10.1007/s40121-023-00902-\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS\u0026aacute;ez-Llorens X, Yogev R, Arguedas A, Rodriguez A, Spigarelli MG, De Le\u0026oacute;n Castrej\u0026oacute;n T, Bomgaars L, Roberts M, Abrams B, Zhou W, Looby M, Kaiser G, Hamed K. Pharmacokinetics and safety of famciclovir in children with herpes simplex or varicella-zoster virus infection. Antimicrob Agents Chemother. 2009;53(5):1912\u0026ndash;20. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1128/AAC.01054-08\u003c/span\u003e\u003cspan address=\"10.1128/AAC.01054-08\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCirelli R, Herne K, McCrary M, Lee P, Tyring SK. Famciclovir: review of clinical efficacy and safety. Antiviral Res. 1996;29(2\u0026ndash;3):141\u0026ndash;51. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0166-3542(95)00941-8\u003c/span\u003e\u003cspan address=\"10.1016/0166-3542(95)00941-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGales BJ, Gales MA. Confusion and bradykinesia associated with famciclovir therapy for herpes zoster. Am J Health Syst Pharm. 1996;53(12):1454, 1456. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/ajhp/53.12.1454\u003c/span\u003e\u003cspan address=\"10.1093/ajhp/53.12.1454\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Q, Chen N, Yang J, Zhou M, Zhou D, Zhang Q, He L. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2009;(2):CD006866. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/14651858.CD006866.pub2\u003c/span\u003e\u003cspan address=\"10.1002/14651858.CD006866.pub2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAoki FY, Tyring S, Diaz-Mitoma F, Gross G, Gao J, Hamed K. Single-day, patient-initiated famciclovir therapy for recurrent genital herpes: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2006;42(1):8\u0026ndash;13. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1086/498521\u003c/span\u003e\u003cspan address=\"10.1086/498521\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLam NN, Weir MA, Yao Z, Blake PG, Beyea MM, Gomes T, Gandhi S, Mamdani M, Wald R, Parikh CR, Hackam DG, Garg AX. Risk of acute kidney injury from oral acyclovir: a population-based study. Am J Kidney Dis. 2013;61(5):723\u0026ndash;9. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1053/j.ajkd.2012.12.008\u003c/span\u003e\u003cspan address=\"10.1053/j.ajkd.2012.12.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMubareka S, Leung V, Aoki FY, Vinh DC. Famciclovir: a focus on efficacy and safety. Expert Opin Drug Saf. 2010;9(4):643\u0026ndash;58. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1517/14740338.2010.485189\u003c/span\u003e\u003cspan address=\"10.1517/14740338.2010.485189\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNoguchi Y, Tachi T, Teramachi H. Detection algorithms and attentive points of safety signal using spontaneous reporting systems as a clinical data source. Brief Bioinform. 2021;22(6):bbab347. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/bib/bbab347\u003c/span\u003e\u003cspan address=\"10.1093/bib/bbab347\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"FAERS, pharmacovigilance, famciclovir, adverse event","lastPublishedDoi":"10.21203/rs.3.rs-4300885/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4300885/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eFamciclovir, mainly used to treat herpes zoster, is a precursor drug of penciclovir that rapidly transforms into penciclovir when taken orally and sustains an extended half-life intracellularly. The information on its adverse drug reactions (ADRs) mainly comes from clinical trials, lacking large-scale real-world studies. This study evaluates the adverse events (AEs) of famciclovir by mining data from the FDA Adverse Event Reporting System (FAERS) database, providing references for clinical safety.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eUtilized disproportionality analysis (including reported odds ratio and proportional reporting ratio) and Bayesian methods (including Bayesian Confidence Propagation Neural Network and Gamma-Poisson Shrinkage) to quantify AE signals associated with famciclovir.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 17,652,186 case reports were obtained from the FAERS database, with 432 reports of famciclovir-related AEs identified. The most common AEs were nausea, headache, altered mental status, vomiting, and dizziness, corresponding to the AEs reported in guidelines and clinical trials. However, there were AEs not mentioned in the medication guide, such as toxic encephalopathy, encephalopathy, ataxia, dysarthria, dementia, cerebral infarction, tremor, purpura, skin ulcers, acute pancreatitis, rhabdomyolysis, muscle twitching, increased blood urea, lowered blood pressure, hepatitis, disease recurrence, drug interactions, and pancytopenia.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur study identified potential famciclovir AE signals, providing references for physicians in clinical use to reduce potential side effects and promote safe implementation of the drug in clinical settings.\u003c/p\u003e","manuscriptTitle":"Real-world Pharmacovigilance Study of Famciclovir in the FDA Adverse Event Reporting System (FAERS) Database","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-02 20:09:09","doi":"10.21203/rs.3.rs-4300885/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-03T04:21:54+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-17T16:25:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"4c7a1a1f-f02f-4695-96eb-98def5f8c8f5","date":"2024-05-07T12:09:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-06T20:12:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"f07de6c5-54fd-4b58-a400-85d958d1a35c","date":"2024-05-06T16:56:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-06T13:39:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-06T03:31:18+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-04-26T06:08:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-26T06:04:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-04-21T13:21:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ce727ded-49c0-4a26-851f-d4097f449398","owner":[],"postedDate":"May 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":31373947,"name":"Health sciences/Health care/Disease prevention/Preventive medicine"},{"id":31373948,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2024-11-25T16:09:06+00:00","versionOfRecord":{"articleIdentity":"rs-4300885","link":"https://doi.org/10.1038/s41598-024-80236-1","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-11-19 15:57:14","publishedOnDateReadable":"November 19th, 2024"},"versionCreatedAt":"2024-05-02 20:09:09","video":"","vorDoi":"10.1038/s41598-024-80236-1","vorDoiUrl":"https://doi.org/10.1038/s41598-024-80236-1","workflowStages":[]},"version":"v1","identity":"rs-4300885","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4300885","identity":"rs-4300885","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}