The side effects of levetiracetam monotherapy in pediatric epilepsy patients

The side effects of levetiracetam monotherapy in pediatric epilepsy patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The side effects of levetiracetam monotherapy in pediatric epilepsy patients serap bilge, Nevzat Baskaya This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5408110/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 5 You are reading this latest preprint version Abstract Purpose: Levetiracetam is a new medicine that is used for the treatment of focal and generalized seizure control. Several side effects can be observed during treatment with levetiracetam . Studies testing the tolerability and safety of levetiracetam monotherapy in pediatric epilepsy patients are limited. We retrospectively evaluated the side effects of levetiracetam monotherapy and whether there are any clues to predict these side effects in the pediatric epilepsy population. Materials and Methods: Patients aged 1-17 years with epilepsy treated with levetiracetam monotherapy were included in the study. Age, gender, body weight, blood pressure, duration of levetiracetam use, dose, semiology, epilepsy type, EEG and MRI findings, hemogram and biochemical laboratory findings, and observed side effects were recorded. Results: Eighty-five patients were included in the study. Twenty-five (29%) patients had side effects. Treatment was discontinued in 11 patients due to side effects. The three most common side effects were agitation (8 patients, 9%), headache (5 patients, 5%) and fatigue (3 patients, 4%). There was no relationship between side effects and gender, body weight, seizure type, levetiracetam dose, duration, EEG, and MRI findings. Vitamin B12 Levels were lower in the group with side effects. The side effects are experienced more frequently in the older age group. Conclusion: Physical-behavioural side effects were observed in levetiracetam treatment. The age of the group with side effects was older. Lower B12 levels might have a role in initiating some side effects Levetiracetam Epilepst Side effects Pediatric population Background Levetiracetam is a second-generation anti-seizure medication with broad-spectrum efficacy. To a great extent, it doesn’t interact pharmacodynamically with other drugs and it doesn’t induce p450 cytochrome enzymes thus having fewer side effects compared to the other anti-seizure medications (ASMs). Limited studies tested the tolerability and safety of levetiracetam monotherapy in pediatric epilepsy patients and almost no studies have been conducted to foresight the clue of these side effects in the pediatric population. So in this study, we retrospectively evaluated the side effects of levetiracetam monotherapy and whether any clues can be foresought these side effects in the pediatric epilepsy population. Method The medical records of patients aged 1 to 17 years approached Diyarbakır Children's Hospital from December 2021 to March 2023 were retrospectively reviewed to detect the following ICD-10 codes: G40.0 Epilepsy · G40.1 epilepsy · G41.2 Complex partial epilepsy · G41.8 Other epilepsy · G41.9 Epilepsy unspecified. The patients with the above ICD codes who adhered to only levetiracetam anti-seizure medication with reliable seizure records were included in the study. Demographic and clinical variables comprised of age, gender, weight, blood pressure, duration of anti-seizure medication use, type of seizure, etiology, diet, MRI, EEG, and hemogram biochemical tests were recorded, either at the end of one year / at the day of stopping levetiracetam medication due to intolerable side effects. The exclusion criteria were: changes in the ASM schedule before one year, using other ASMs in addition to levetiracetam, history of other systemic or psychiatric diseases. Clinical and demographic data were collected through a questionnaire during follow-up visits and from medical record files. The dose of levetiracetam was evaluated as an initial dose (20 mg/kg/day), medium dose (30–50 mg/kg/day), and high dose (> 60mg/kg/day). Epilepsy type and etiology were considered according to the International League Against Epilepsy (ILAE) classification. Our study was approved by the ethics committee of Health Sciences University Gazi Yaşargil Training and Research Hospital, on 17-05-2023 with the approval number 417. Statistical Analysis Categorical variables were expressed as numbers and percentages, whereas continuous variables were summarized as mean and standard deviation and as median and min-max where appropriate. To compare categorical variables between the groups, Pearson Chi Square Test or Fisher's Exact Test was used depending on whether the expected value problem arises or not. The normality of distribution for continuous variables was confirmed with the Shapiro-Wilk test. For comparison of continuous variables between the side effect groups, the Student's t-test or Mann-Whitney U test was used depending on whether the statistical hypotheses were fulfilled or not. Logistic regression analysis was performed to determine significant predictors of Side effects. In univariate analysis, variables significant at the P < 0.25 level were entered in logistic regression analysis. All analyses were performed using the IBM SPSS Statistics Version 20.0 statistical software package. The statistical level of significance for all tests was considered to be 0.05. Results Among the 85 patients included in this study, 42% were male, and the mean age was 7.5 ± 4.6 years in the group with no side effects and 9.9 ± 5.2 in the group with side effects (p:0.046). Lev period was 18.1 ± 5.5 months in the group with no side effects and 12.7 ± 9.4 in the group with side effects (whether the drug stopped or not stopped). Table 1 The clinical and demographic profile of the patients. Side effect p No Yes n = 60 n = 25 Age(years), Mean ± SD 7.5 ± 4.6 9.9 ± 5.2 0.046 Gender, n (%) Male Female 31 (%52) 29 (%48) 11 (%44) 14 (%56) 0.519 Weight (kg), Mean ± SD 33.1 ± 15.3 38.5 ± 13.6 0.131 Lev period, Mean ± SD Median (min-max) Month 18.1 ± 5.5 16.5 (12–36) 12.7 ± 9.4 14 (1–34) 0.031 Dose, n (%) Moderate Low(initial) High 42 (%70) 14 (%23) 4 (%7) 15 (%60) 8 (%32) 2 (%8) 0.624 Semiology, n (%) Focal Generalized Unknown 18 (%30) 36 (%60) 6 (%10) 6 (%24) 16 (%64) 3 (%12) 0.845 EEG, n (%) Normal Epileptic 17 (%28) 43 (%72) 4 (%16) 21 (%84) 0.230 MRI, n (%) Normal Lesion 49 (%82) 11 (%18) 22 (%88) 3 (%12) 0.749 Type of Epilepsy, n (%) Cryptogenic Idiopathic Structural 28 (%47) 24 (%40) 8 (%13) 16 (%64) 6 (%24) 3 (%12) 0.312 EEG: Electroencephalogram, MRI: Magnetic Resonance Image Age was determined as an effective measure in terms of the occurrence of side effects. Accordingly, the average age of children with side effects was older than those without side effects. Table 2 The blood profiles of the patients in both groups Side Effect P Yes No n = 60 n = 25 Wbc (×10 3 /uL), Mean ± SD 8.5 ± 3.2 8.1 ± 2.5 0.574 Neutrophile (%), Mean ± SD 47.9 ± 13.9 52.8 ± 16.4 0.164 Lymphocyte (%), Mean ± SD 39.6 ± 12.7 35.7 ± 16.2 0.239 Monocyte (%), Mean ± SD 7.5 ± 2.9 7.8 ± 2.2 0.671 Eosinophils (%), Mean ± SD Median (min-max) 3.4 ± 3.3 2.3 (0.1–14.6) 3.6 ± 3.1 2.9 (0.6–11.9) 0.783 Basophyle (%), Mean ± SD 0.43 ± 0.28 0.5 ± 0.35 0.393 ANC (×10 3 /uL), Mean ± SD 4.2 ± 2.5 4.2 ± 1.9 0.987 ALC (×10 3 /uL), Mean ± SD 3.3 ± 1.6 2.9 ± 1.6 0.209 RBC (× 10 6 /µL), Mean ± SD 4.7 ± 0.5 4.6 ± 1 0.531 RDW-CV (%), Mean ± SD 13.9 ± 2.1 14.2 ± 2.3 0.560 PLT (×10 3 /uL), Mean ± SD 325.8 ± 120.6 304.8 ± 121.6 0.466 MPV (fL), Mean ± SD 9.7 ± 1.7 9.7 ± 1.1 0.890 Hg (g/dl), Mean ± SD 12.4 ± 1.6 12.6 ± 1.6 0.754 HCT (%), Mean ± SD 39.2 ± 7.1 38.9 ± 4 0.873 B12 (pmol/l), Mean ± SD 365.7 ± 147.7 411 ± 126 0.192 Ferritin (ng/ml), Mean ± SD 42.6 ± 14.0 42 ± 12.9 0.851 Systolic Blood Pressure (mmHg), Mean ± SD 100.1 ± 14.4 107.2 ± 20.1 0.082 Diastolic Blood Pressure (mmHg), Mean ± SD 64.1 ± 11.6 61.5 ± 12.3 0.381 Vitamin D (nmol/L), Mean ± SD 26.5 ± 8.3 25.1 ± 7.3 0.469 CK (IU/L), Mean ± SDMedian (min-max) 168.4 ± 87.8 165 (54–453) 145.2 ± 80.7 145 (45–324) 0.260 Glucose (mg/dL), Mean ± SD 80.1 ± 10.9 77 ± 10.1 77 (64–92) 0.233 ALT (IU/L), Mean ± SD Median (min-max) 18.7 ± 7.6 17 (9–44) 20.2 ± 8.6 23 (12–45) 0.399 AST (IU/L), Mean ± SD Median (min-max) 31.4 ± 27.3 27.5 (14–228) 31 ± 8.2 33 (13–45) 0.248 Albumin (g/L), Mean ± SD 40.6 ± 1.5 40.1 ± 4 0.491 Creatine (mg/dL), Mean ± SD 0.55 ± 0.12 0.54 ± 0.09 0.814 Wbc: White blood cells, ANC: Absolute neutrophil count, ALC: Absolute lymphocyte count, Rbc: Red blood cell, RDW-CV: Red cell distribution width - coefficient of variation, PLT: platelet, MPV: Mean platelet volüme, Hg: Hemoglobin, Hct: Hematocrit, CK: Creatine kinase, ALT: Alanine transaminase, AST: Aspartate transferase Table 3 The observed side effects according to their percentages. Measurements Number of patients (%) Side effect No Yes 60 (%71) 25 (%29) Agitation No Yes 77 (%91) 8 (%9) Headache No Yes 80 (%94) 5 (%6) Fatigue No Yes 81(%96) 3(%4) Stomachache No Yes 84(%98) 2(%2) Allergy No Yes(Maculopapüler/angiodema) 83 (%98) 2 (%2) Weight loss No Yes 84 (%99) 1 (%1) Increased frequency of illness No Yes 84 (%99) 1 (%1) Runny nose No Yes 84 (%99) 1 (%1) Others* No Yes 78 (%940) 5(%6) Stop due to side effects No Yes 14(%56) 11(%44) *Somnolence:1 patient, Tremor:1, enuresis:1, insomnia:1, suicide attempt:1 Table 4 The effect of some variables on side effects of levetiracetam Side effect P No Yes n = 60 n = 25 Birth history, n (%) Normal Eventful 57 (%95) 3 (%5) 23 (%92) 2 (%8) 0.628 Family history, n (%) No Yes 36 (%60) 24 (%40) 20 (%80) 5 (%20) 0.076 Diet type, n (%) Normal Vegetarian 59 (%98) 1 (%2) 25 (%100) 0 (%0) 0.999 Table 5 Logistic regression analysis of predicting levetiracetam side effects P Odds Ratio (OR) 95% CI for OR B 12 level 0.031 1.05 1.01–1.09 OR: odds ratio; CI: confidence interval Discussion Levetiracetam is a broad-spectrum anti-seizure medication that can be used in all age groups. It can be considered a great choice with a safe profile. But still, some side effects can be seen. Tekgül et al. conducted a study on 351 pediatric patients in 2016 1 . Sixty-one patients (%17) experienced adverse effects, irritability (41 patients, 67%), hyperactivity (5 patients, 8%), somnolence (4 patients, 6%), behavioral disorders (3 patients, 5%), restlessness (3 patients, 5%), increased seizure frequency (2 patients, 3%), enuresis (1 patient, 2%), headache (1 patient, 2%) and attempted suicide (1 patient, 2%) were the most observed side effects. The same study concluded that there was no relation between the dose, age, and side effects, meanwhile, the adverse effects were seen more frequently in patients with partial focal seizures and who have psychiatric disorders and abnormal EEG patterns. In our study, the three most common side effects were agitation (8 patients, 32%), headache (5 patients, 20%) and fatigue (3 patients, 12%). Tremor (1 patient, 4%), somnolence (1 patient, 4%), enuresis (1 patient, 4%), insomnia (1 patient, 4%), and suicide attempt (1 patient, 4%) were other observed side effects. The age of the group with side no effects was younger. Antiepileptic drugs may cause psychiatric side effects depending on individual predisposition and dose. Psychiatric side effects of ASMs may affect cognitive functions (alertness, attention, memory, learning, and language skills) and behavior (restlessness, irritability, agitation, hyperactivity, aggressive behavior, sleep disturbances) 2 , 3 . In our study, psychiatric side effects were observed most frequently. Eight (%9) patients experienced agitation. Mood changes can be observed in epilepsy patients and in those who use anti-seizure medications such as levetiracetam, lamotrigine, phenobarbital, and clonazepam and the cause could be either biological or psychosocial. Researchers have found that people with epilepsy are 5 times at risk of suicide. In addition, the risk is still higher even in surgically treated patients. Other studies suggest that suicide attempt is higher in patients with temporal lobe epilepsy which can be due to abnormal function of the limbic system 4 . Suicide attempt was observed in one patient in our study population. MRI was normal, and EEG was epileptic. The drug was stopped immediately, and the patient was monitored in the intensive care unit for a few days and switched to another ASM. Dermatological and non-dermatological changes can be experienced in patients who are treated with levetiracetam. The dermatological side effects mostly appeared on the face, and extremities, characterized by dark-colored skin, and morbilliform macular rash. The non-dermatological side effects experienced were fever, headache, abdominal pain, facial edema, pharyngitis, and periorbital eye swelling 5 – 7 . Despite these side effects being less likely with levetiracetam compared to other ASMs, still such adverse effects can be seen and immediate withdrawal should be done. In our patient group, maculopapular rash in one patient and angioedema in another one were observed during levetiracetam treatment. Levetiracetam treatment was discontinued. Drug cessation should be approached with serious side effects. Levetiracetam treatment had to be discontinued in 11 patients. levetiracetam was stopped in three of the five patients with headaches. two with allergy, one with stomachache, and antother one with enuresis, one with hallucination/fatigue, one with suicide attempt, one with weight loss, and in one with increased frequency of infection. The dose of levetiracetam was adjusted in some patients with tolerable side effects. Some patients with tolerable side effects were also given a mix of vitamin B. Levetiracetam may reduce the degranulation of CD8 lymphocytes, leading to an increased incidence of upper respiratory tract infections 8 . Drug-induced immunoglobulin decreases have been reported in some patients 9 . In our patient group, an increase in the frequency of infection was observed in one patient. Lymphocyte count was low, 1270/uL, but lymphocyte subgroup and immunoglobulin levels could not be analyzed. levetiracetam was stopped in this patient. There are limited studies that tested the hematological effects of levetiracetam in the pediatric population. Dilber et al. conducted a study on 114 children in 2021 and tested the effect of this antiseizure drug on hemogram, liver function, and B12, it was observed after three years of follow-up that there was an increase in hemoglobin and hematocrit, while there was a decrease in absolute neutrophil(ANC) and absolute lymphocyte count(ALC) while the platelet count was not affected and there was no correlation between gender and hematological changes, and despite the changes there were no clinical complaints by the patients 10 . French et al evaluated adult patients who received levetiracetam monotherapy despite the hematological changes at first, all the parameters returned to normal at the end of three years 7 . A decrease in lymphocyte and ALC was observed in studies conducted by Dinopoulos et al and Attilocks et al 11 , 12 . There are also studies in which antiepileptic treatment decreased vitamin B12 levels 13 . In our study, logistic regression analysis showed that lower Vitamin B12 levels were associated with more side effects. Monitoring of vitamin B12 levels during antiepileptic treatment is recommended 14 . Urinary and fecal incontinence was reported in patients with levetiracetam monotherapy and the exact mechanism is still unknown 15 . Incecik et al reported an 11-year-old boy patient who experienced fecal and urinary incontinence at a dose of 20 mg/kg 16 . Investigation as MRI, EEG, and infection parameters were normal. The effect was reversible and the patients could gain control after withdrawing the drug. In our study, an 8-year-old boy experienced urinary and fecal incontinence a few days after starting the drug. All the investigations were normal, urine culture and urine analysis showed no infection. The drug stopped immediately and the control was regained. Our patient was a boy too, so we think this side effect could be seen more frequently in male patients. Fatigue is reported by lots of studies as an adverse effect of levetiracetam monotherapy. Marco Mula et all reported fatigue in %36 of patients with levetiracetam which could be due to an imbalance between excitatory and inhibitory neurotransmission however the exact mechanism of central fatigue is still unclear and this side effect was seen more frequently in females rather than males 17 . Recent studies showed that central fatigue could be due to dysfunction in the non-motor area of basal ganglion and their interaction with the frontal cortex and amygdala but the effect of on levetiracetam these networks is still unknown 18 . In our study fatigue was seen in 3(%4) of the patients while the rest 81(%96) patients didn’t experience such symptoms. Fatigue could be due to multifactorial etiologies. Levetiracetam associated with higher total sleep duration, and sleep problems is not commonly reported as a side effect 19 . The recent studies' results are very controversial. Some studies showed that levetiracetam increased the N2 stage of sleep 20 . In another study, it was observed that levetiracetam increased wakingness and in a study conducted by yılmaz et al., it was seen that this drug increased daytime napping episodes and total nap duration while there was a decrease in total activity score at night in monotherapy in adult patients 21 . In our study, sleep disturbance was reported in 13 patients (15%). Limitations of the study . Our study is retrospective and the number of patients studied was small. Sleep disturbance was based on family and patient reports and could not be assessed by a valid and reliable scale. The patients’ laboratory data was not available before starting treatment. So the hematological and biochemical laboratory results could not be compared before, during, and after the treatment/discontinuation of treatment. Conclusion Physical-behavioural side effects were observed in levetiracetam treatment. The age of the group with side effects was older. No association was observed with body weight, gender, epilepsy type, levetiracetam dose and duration, MR and EEG findings. Well-designed studies are needed to determine the clinical and laboratory data that can predict the side effects of levetiracetam monotherapy in pediatric patients. Declarations Acknowledgments; Not applicable. Authors’ contributions : SB planned and coordinated the study, NB. analyzed the literature, and SB was a major contributor to writing the manuscript study. Both authors read and approved the final manuscript. Funding Nothing to declare. No funding has been received Availability of data and materials At S.B. repository. The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Ethical Approval and consent to participate : The study was conducted in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards and approved by the Clinical Research Ethics Committee of Gazi YşargilEducation & Research Hospital (2023:2023/417). Written informed consent was obtained from all the participants and/or legal guardians. Consent for publication : Not applicable Competing interests: The authors declare that they have no competing interest References Tekgül H, Gencpinar P, Çavuşoğlu D, Dündar NO. The efficacy, tolerability, and safety of levetiracetam therapy in a pediatric population. Seizure. 2016;36:16–21. 10.1016/j.seizure.2016.01.017 . Kanemoto K, Nishida T, Hasegawa N. [Psychiatric Symptoms of Patients With Epilepsy: Characteristics of Psychiatric Adverse Events by Novel Antiepileptic Medications]. Brain Nerve. 2023;75(4):375–89. 10.11477/MF.1416202343 . Mula M, Trimble MR, Yuen A, Liu RSN, Sander JWAS. Psychiatric adverse events during levetiracetam therapy. Neurology. 2003;61(5):704–6. 10.1212/01.WNL.0000078031.32904.0D . Mula M, Hesdorffer DC. Suicidal behavior and antiepileptic drugs in epilepsy: Analysis of the emerging evidence. Drug Health Patient Saf. 2011;3(1):15–20. 10.2147/dhps.s13070 . Mbizvo GK, Dixon P, Hutton JL, Marson AG. The adverse effects profile of levetiracetam in epilepsy: a more detailed look. Int J Neurosci. 2014;124(9):627–34. 10.3109/00207454.2013.866951 . Rashid M, Rajan AK, Chhabra M, Kashyap A. Levetiracetam and cutaneous adverse reactions: A systematic review of descriptive studies. Seizure. 2020;75:101–9. 10.1016/j.seizure.2020.01.002 . French J, Edrich P, Cramer JA. A Systematic Review of the Safety Profile of Levetiracetam: A New Antiepileptic Drug . Vol 47.; 2001. Li G, Nowak M, Bauer S, et al. Levetiracetam but not valproate inhibits the function of CD8 + T lymphocytes. Seizure. 2013;22(6):462–6. 10.1016/J.SEIZURE.2013.03.006 . Azar AE, Ballas ZK. Reversible panhypogammaglobulinemia associated with the antiepileptic agent levetiracetam. Ann Allergy Asthma Immunol. 2008;101(1):108–9. 10.1016/S1081-1206(10)60846-0 . Dilber B, Yıldız N, Yaman H, Kamasak T, Esenülkü G, Özkan P, et al. Evaluation of Long-Term Effects of Levetiracetam Monotherapy on Hematological and Liver Function Parameters in Children With Idiopathic Epilepsy. Türkiye Çocuk Hastalıkları Dergisi. 2022;16(2):144–9. Attilakos A, Dinopoulos A, Paschalidou M, et al. Long-term effect of levetiracetam monotherapy on hematological parameters in children with epilepsy: A prospective study. Epilepsy Res. 2018;145:160–2. 10.1016/j.eplepsyres.2018.07.001 . Dinopoulos A, Attilakos A, Paschalidou M, et al. Short-term effect of levetiracetam monotherapy on hematological parameters in children with epilepsy: A prospective study. Epilepsy Res. 2014;108(4):820–3. 10.1016/j.eplepsyres.2014.02.006 . Linnebank M, Moskau S, Semmler A, et al. Antiepileptic drugs interact with folate and vitamin B12 serum levels. Ann Neurol. 2011;69(2):352–9. 10.1002/ANA.22229 . Cahill V, McCorry D, Soryal I, Rajabally YA. Newer anti-epileptic drugs, vitamin status, and neuropathy: A cross-sectional analysis. Rev Neurol (Paris). 2017;173(1–2):62–6. 10.1016/J.NEUROL.2016.09.008 . Sathyan A, Scaria R, Arunachalam P, Ramasamy M, Thekkekkara D, Sivadasan S. Antiepileptic Drugs–Induced Enuresis in Children: An Overview. J Pharm Technol. 2021;37(2):114–9. 10.1177/8755122520964047 . Incecik F, Herguner OM, Besen S, Altunbasak S. Urinary and fecal incontinence during levetiracetam therapy. Ann Indian Acad Neurol. 2015;18(4):479–80. 10.4103/0972-2327.165476 . Mula M, von Oertzen TJ, Cock HR, Yogarajah M, Lozsadi DA, Agrawal N. Fatigue during treatment with antiepileptic drugs: A levetiracetam-specific adverse event? Epilepsy Behav. 2017;72:17–21. 10.1016/j.yebeh.2017.04.030 . Wandschneider B, Koepp MJ. Pharmaco fMRI: Determining the functional anatomy of the effects of medication. Neuroimage Clin. 2016;12:691–7. 10.1016/J.NICL.2016.10.002 . Thelengana A, Shukla G, Srivastava A, et al. Cognitive, behavioral, and sleep-related adverse effects on the introduction of levetiracetam versus oxcarbazepine for epilepsy. Epilepsy Res. 2019;150:58–65. 10.1016/J.EPLEPSYRES.2019.01.004 . Bell C, Vanderlinden H, Hiersemenzel R, Otoul C, Nutt D, Wilson S. The effects of levetiracetam on objective and subjective sleep parameters in healthy volunteers and patients with partial epilepsy. J Sleep Res. 2002;11(3):255–63. 10.1046/J.1365-2869.2002.00301.X . Yilmaz H. Comparison of motor activity and sleep in patients with complex partial seizures on levetiracetam treatment and a group of healthy subjects. Behav Neurol. 2007;18(3):165–70. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Major revision 06 Jan, 2025 Reviewers agreed at journal 04 Jan, 2025 Reviewers invited by journal 18 Nov, 2024 Editor assigned by journal 11 Nov, 2024 First submitted to journal 09 Nov, 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-5408110","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":379629019,"identity":"fe30089f-69f8-45dc-8c33-14c6feeddde9","order_by":0,"name":"serap bilge","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIiWNgGAWjYJACZhjjA0PFATDjwAOitLAxMM5gOHOAgQekJYFoLYxtEC0M+LTIt599+Lngz7bE+fObHzb8nHdHzl7s8EOgLXZyug3YtRicSTeWntl2O3HDMTbDxt5tz4x5pNMMgFqSjc0O4NDCkMYgzdsA1MLGYP6Ad9vhxB7pBJCWA4nbcGiR73/G/Jvnz+3E+W3sHxv/zgFpSf+AVwvDjTQ2aR6224kNx3gMm3kbQFpy8NticOMZmzXQL8YbjuUUNsscO2zMczun4ECCAW6/yPenMd8u+HNbdn7z8Y2Nb2oOy7HPTt/84UOFnRwuLbiAAWnKR8EoGAWjYBSgAgCyhGhy9pFb9gAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-4265-3363","institution":"Ministry of Health and Family Welfare: Government of West Bengal Health \u0026 Family Welfare Department","correspondingAuthor":true,"prefix":"","firstName":"serap","middleName":"","lastName":"bilge","suffix":""},{"id":379629020,"identity":"8c3e2e94-fa77-4672-a147-e8c0f89c8d34","order_by":1,"name":"Nevzat Baskaya","email":"","orcid":"","institution":"Health Effects Institute","correspondingAuthor":false,"prefix":"","firstName":"Nevzat","middleName":"","lastName":"Baskaya","suffix":""}],"badges":[],"createdAt":"2024-11-07 08:31:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5408110/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5408110/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":70482731,"identity":"a9cd02be-59cb-4dab-b0dc-5f8354d57950","added_by":"auto","created_at":"2024-12-03 15:09:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":495144,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5408110/v1/0d4f0ec6-c1d0-45d9-aad3-d42aa1d2d57a.pdf"}],"financialInterests":"","formattedTitle":"The side effects of levetiracetam monotherapy in pediatric epilepsy patients","fulltext":[{"header":"Background","content":"\u003cp\u003eLevetiracetam is a second-generation anti-seizure medication with broad-spectrum efficacy. To a great extent, it doesn\u0026rsquo;t interact pharmacodynamically with other drugs and it doesn\u0026rsquo;t induce p450 cytochrome enzymes thus having fewer side effects compared to the other anti-seizure medications (ASMs). Limited studies tested the tolerability and safety of levetiracetam monotherapy in pediatric epilepsy patients and almost no studies have been conducted to foresight the clue of these side effects in the pediatric population. So in this study, we retrospectively evaluated the side effects of levetiracetam monotherapy and whether any clues can be foresought these side effects in the pediatric epilepsy population.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eThe medical records of patients aged 1 to 17 years approached Diyarbakır Children's Hospital from December 2021 to March 2023 were retrospectively reviewed to detect the following ICD-10 codes: G40.0 Epilepsy \u0026middot; G40.1 epilepsy \u0026middot; G41.2 Complex partial epilepsy \u0026middot; G41.8 Other epilepsy \u0026middot; G41.9 Epilepsy unspecified. The patients with the above ICD codes who adhered to only levetiracetam anti-seizure medication with reliable seizure records were included in the study. Demographic and clinical variables comprised of age, gender, weight, blood pressure, duration of anti-seizure medication use, type of seizure, etiology, diet, MRI, EEG, and hemogram biochemical tests were recorded, either at the end of one year / at the day of stopping levetiracetam medication due to intolerable side effects. The exclusion criteria were: changes in the ASM schedule before one year, using other ASMs in addition to levetiracetam, history of other systemic or psychiatric diseases. Clinical and demographic data were collected through a questionnaire during follow-up visits and from medical record files. The dose of levetiracetam was evaluated as an initial dose (20 mg/kg/day), medium dose (30\u0026ndash;50 mg/kg/day), and high dose (\u0026gt;\u0026thinsp;60mg/kg/day). Epilepsy type and etiology were considered according to the International League Against Epilepsy (ILAE) classification. Our study was approved by the ethics committee of Health Sciences University Gazi Yaşargil Training and Research Hospital, on 17-05-2023 with the approval number 417.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eCategorical variables were expressed as numbers and percentages, whereas continuous variables were summarized as mean and standard deviation and as median and min-max where appropriate. To compare categorical variables between the groups, Pearson Chi Square Test or Fisher's Exact Test was used depending on whether the expected value problem arises or not. The normality of distribution for continuous variables was confirmed with the Shapiro-Wilk test. For comparison of continuous variables between the side effect groups, the Student's t-test or Mann-Whitney U test was used depending on whether the statistical hypotheses were fulfilled or not. Logistic regression analysis was performed to determine significant predictors of Side effects. In univariate analysis, variables significant at the P\u0026thinsp;\u0026lt;\u0026thinsp;0.25 level were entered in logistic regression analysis. All analyses were performed using the IBM SPSS Statistics Version 20.0 statistical software package. The statistical level of significance for all tests was considered to be 0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAmong the 85 patients included in this study, 42% were male, and the mean age was 7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6 years in the group with no side effects and 9.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2 in the group with side effects (p:0.046). Lev period was 18.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5 months in the group with no side effects and 12.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4 in the group with side effects (whether the drug stopped or not stopped).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"char\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe clinical and demographic profile of the patients.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"3\" style=\"width: 44.4916%;\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\" style=\"width: 44.3434%;\"\u003e\n \u003cp\u003e\u003cem\u003eSide effect\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 23.4696%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 23.4696%;\"\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;60\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;25\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 44.4916%;\"\u003e\n \u003cp\u003eAge(years), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 23.4696%;\"\u003e\n \u003cp\u003e7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.046\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 44.4916%;\"\u003e\n \u003cp\u003eGender, \u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.4696%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e31 (%52)\u003c/p\u003e\n \u003cp\u003e29 (%48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e11 (%44)\u003c/p\u003e\n \u003cp\u003e14 (%56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.519\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 44.4916%;\"\u003e\n \u003cp\u003eWeight (kg), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 23.4696%;\"\u003e\n \u003cp\u003e33.1\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.131\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 44.4916%;\"\u003e\n \u003cp\u003eLev period, \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eMedian (min-max)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eMonth\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 23.4696%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e18.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e\n \u003cp\u003e16.5 (12\u0026ndash;36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e12.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4\u003c/p\u003e\n \u003cp\u003e14 (1\u0026ndash;34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.031\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 44.4916%;\"\u003e\n \u003cp\u003eDose, \u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003cp\u003eLow(initial)\u003c/p\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.4696%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e42 (%70)\u003c/p\u003e\n \u003cp\u003e14 (%23)\u003c/p\u003e\n \u003cp\u003e4 (%7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e15 (%60)\u003c/p\u003e\n \u003cp\u003e8 (%32)\u003c/p\u003e\n \u003cp\u003e2 (%8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.624\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 44.4916%;\"\u003e\n \u003cp\u003eSemiology, \u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eFocal\u003c/p\u003e\n \u003cp\u003eGeneralized\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.4696%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e18 (%30)\u003c/p\u003e\n \u003cp\u003e36 (%60)\u003c/p\u003e\n \u003cp\u003e6 (%10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e6 (%24)\u003c/p\u003e\n \u003cp\u003e16 (%64)\u003c/p\u003e\n \u003cp\u003e3 (%12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.845\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 44.4916%;\"\u003e\n \u003cp\u003eEEG, \u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003cp\u003eEpileptic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.4696%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e17 (%28)\u003c/p\u003e\n \u003cp\u003e43 (%72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e4 (%16)\u003c/p\u003e\n \u003cp\u003e21 (%84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.230\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 44.4916%;\"\u003e\n \u003cp\u003eMRI, \u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003cp\u003eLesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.4696%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e49 (%82)\u003c/p\u003e\n \u003cp\u003e11 (%18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e22 (%88)\u003c/p\u003e\n \u003cp\u003e3 (%12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.749\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 44.4916%;\"\u003e\n \u003cp\u003eType of Epilepsy, \u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eCryptogenic\u003c/p\u003e\n \u003cp\u003eIdiopathic\u003c/p\u003e\n \u003cp\u003eStructural\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.4696%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e28 (%47)\u003c/p\u003e\n \u003cp\u003e24 (%40)\u003c/p\u003e\n \u003cp\u003e8 (%13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e16 (%64)\u003c/p\u003e\n \u003cp\u003e6 (%24)\u003c/p\u003e\n \u003cp\u003e3 (%12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.312\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eEEG: Electroencephalogram, MRI: Magnetic Resonance Image\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAge was determined as an effective measure in terms of the occurrence of side effects. Accordingly, the average age of children with side effects was older than those without side effects.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe blood profiles of the patients in both groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eSide Effect\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;60\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;25\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWbc (\u0026times;10\u003csup\u003e3\u003c/sup\u003e/uL), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.574\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeutrophile (%), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47.9\u0026thinsp;\u0026plusmn;\u0026thinsp;13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e52.8\u0026thinsp;\u0026plusmn;\u0026thinsp;16.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.164\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLymphocyte (%), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e35.7\u0026thinsp;\u0026plusmn;\u0026thinsp;16.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.239\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMonocyte (%), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.671\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEosinophils (%), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eMedian (min-max)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e\n \u003cp\u003e2.3 (0.1\u0026ndash;14.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\n \u003cp\u003e2.9 (0.6\u0026ndash;11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.783\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasophyle (%), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.393\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eANC (\u0026times;10\u003csup\u003e3\u003c/sup\u003e/uL), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.987\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eALC (\u0026times;10\u003csup\u003e3\u003c/sup\u003e/uL), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.209\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRBC (\u0026times; 10\u003csup\u003e6\u003c/sup\u003e/\u0026micro;L), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.531\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRDW-CV (%), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.560\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePLT (\u0026times;10\u003csup\u003e3\u003c/sup\u003e/uL), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e325.8\u0026thinsp;\u0026plusmn;\u0026thinsp;120.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e304.8\u0026thinsp;\u0026plusmn;\u0026thinsp;121.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.466\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMPV (fL), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.890\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHg (g/dl), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.754\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHCT (%), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39.2\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.873\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eB12 (pmol/l), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e365.7\u0026thinsp;\u0026plusmn;\u0026thinsp;147.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e411\u0026thinsp;\u0026plusmn;\u0026thinsp;126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.192\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFerritin (ng/ml), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e42.6\u0026thinsp;\u0026plusmn;\u0026thinsp;14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e42\u0026thinsp;\u0026plusmn;\u0026thinsp;12.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.851\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSystolic Blood Pressure (mmHg), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e100.1\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e107.2\u0026thinsp;\u0026plusmn;\u0026thinsp;20.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.082\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiastolic Blood Pressure (mmHg), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e61.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.381\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVitamin D (nmol/L), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.5\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.469\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCK (IU/L), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SDMedian (min-max)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e168.4\u0026thinsp;\u0026plusmn;\u0026thinsp;87.8\u003c/p\u003e\n \u003cp\u003e165 (54\u0026ndash;453)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e145.2\u0026thinsp;\u0026plusmn;\u0026thinsp;80.7\u003c/p\u003e\n \u003cp\u003e145 (45\u0026ndash;324)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.260\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGlucose (mg/dL), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e80.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e77\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1\u003c/p\u003e\n \u003cp\u003e77 (64\u0026ndash;92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.233\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eALT (IU/L), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eMedian (min-max)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6\u003c/p\u003e\n \u003cp\u003e17 (9\u0026ndash;44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u003c/p\u003e\n \u003cp\u003e23 (12\u0026ndash;45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.399\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAST (IU/L), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eMedian (min-max)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31.4\u0026thinsp;\u0026plusmn;\u0026thinsp;27.3\u003c/p\u003e\n \u003cp\u003e27.5 (14\u0026ndash;228)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2\u003c/p\u003e\n \u003cp\u003e33 (13\u0026ndash;45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.248\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlbumin (g/L), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.491\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCreatine (mg/dL), \u003cem\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.814\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eWbc: White blood cells, ANC: Absolute neutrophil count, ALC: Absolute lymphocyte count, Rbc: Red blood cell, RDW-CV: Red cell distribution width - coefficient of variation, PLT: platelet, MPV: Mean platelet vol\u0026uuml;me, Hg: Hemoglobin, Hct: Hematocrit, CK: Creatine kinase, ALT: Alanine transaminase, AST: Aspartate transferase\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe observed side effects according to their percentages.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 55.5328%;\"\u003e\n \u003cp\u003eMeasurements\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 44.2623%;\"\u003e\n \u003cp\u003eNumber of patients (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 55.5328%;\"\u003e\n \u003cp\u003eSide effect\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.2623%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e60 (%71)\u003c/p\u003e\n \u003cp\u003e25 (%29)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 55.5328%;\"\u003e\n \u003cp\u003eAgitation\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.2623%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e77 (%91)\u003c/p\u003e\n \u003cp\u003e8 (%9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 55.5328%;\"\u003e\n \u003cp\u003eHeadache\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.2623%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e80 (%94)\u003c/p\u003e\n \u003cp\u003e5 (%6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 55.5328%;\"\u003e\n \u003cp\u003eFatigue\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.2623%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e81(%96)\u003c/p\u003e\n \u003cp\u003e3(%4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 55.5328%;\"\u003e\n \u003cp\u003eStomachache\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.2623%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e84(%98)\u003c/p\u003e\n \u003cp\u003e2(%2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 55.5328%;\"\u003e\n \u003cp\u003eAllergy\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes(Maculopap\u0026uuml;ler/angiodema)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.2623%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e83 (%98)\u003c/p\u003e\n \u003cp\u003e2 (%2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 55.5328%;\"\u003e\n \u003cp\u003eWeight loss\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.2623%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e84 (%99)\u003c/p\u003e\n \u003cp\u003e1 (%1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 55.5328%;\"\u003e\n \u003cp\u003eIncreased frequency of illness\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.2623%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e84 (%99)\u003c/p\u003e\n \u003cp\u003e1 (%1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 55.5328%;\"\u003e\n \u003cp\u003eRunny nose\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.2623%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e84 (%99)\u003c/p\u003e\n \u003cp\u003e1 (%1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 55.5328%;\"\u003e\n \u003cp\u003eOthers*\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.2623%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e78 (%940)\u003c/p\u003e\n \u003cp\u003e5(%6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 55.5328%;\"\u003e\n \u003cp\u003eStop due to side effects\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 44.2623%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e14(%56)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11(%44)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e*Somnolence:1 patient, Tremor:1, enuresis:1, insomnia:1, suicide attempt:1\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"char\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u0026nbsp;\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe effect of some variables on side effects of levetiracetam\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eSide effect\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;60\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;25\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBirth history, \u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003cp\u003eEventful\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e57 (%95)\u003c/p\u003e\n \u003cp\u003e3 (%5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e23 (%92)\u003c/p\u003e\n \u003cp\u003e2 (%8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.628\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFamily history, \u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e36 (%60)\u003c/p\u003e\n \u003cp\u003e24 (%40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e20 (%80)\u003c/p\u003e\n \u003cp\u003e5 (%20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.076\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiet type, \u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003cp\u003eVegetarian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e59 (%98)\u003c/p\u003e\n \u003cp\u003e1 (%2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e25 (%100)\u003c/p\u003e\n \u003cp\u003e0 (%0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u0026nbsp;\u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eLogistic regression analysis of predicting levetiracetam side effects\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOdds Ratio (OR)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95% CI for OR\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eB 12 level\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01\u0026ndash;1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eOR: odds ratio; CI: confidence interval\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eLevetiracetam is a broad-spectrum anti-seizure medication that can be used in all age groups. It can be considered a great choice with a safe profile. But still, some side effects can be seen. Tekg\u0026uuml;l et al. conducted a study on 351 pediatric patients in 2016\u003csup\u003e1\u003c/sup\u003e. Sixty-one patients (%17) experienced adverse effects, irritability (41 patients, 67%), hyperactivity (5 patients, 8%), somnolence (4 patients, 6%), behavioral disorders (3 patients, 5%), restlessness (3 patients, 5%), increased seizure frequency (2 patients, 3%), enuresis (1 patient, 2%), headache (1 patient, 2%) and attempted suicide (1 patient, 2%) were the most observed side effects. The same study concluded that there was no relation between the dose, age, and side effects, meanwhile, the adverse effects were seen more frequently in patients with partial focal seizures and who have psychiatric disorders and abnormal EEG patterns. In our study, the three most common side effects were agitation (8 patients, 32%), headache (5 patients, 20%) and fatigue (3 patients, 12%). Tremor (1 patient, 4%), somnolence (1 patient, 4%), enuresis (1 patient, 4%), insomnia (1 patient, 4%), and suicide attempt (1 patient, 4%) were other observed side effects. The age of the group with side no effects was younger.\u003c/p\u003e \u003cp\u003eAntiepileptic drugs may cause psychiatric side effects depending on individual predisposition and dose. Psychiatric side effects of ASMs may affect cognitive functions (alertness, attention, memory, learning, and language skills) and behavior (restlessness, irritability, agitation, hyperactivity, aggressive behavior, sleep disturbances)\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. In our study, psychiatric side effects were observed most frequently. Eight (%9) patients experienced agitation. Mood changes can be observed in epilepsy patients and in those who use anti-seizure medications such as levetiracetam, lamotrigine, phenobarbital, and clonazepam and the cause could be either biological or psychosocial. Researchers have found that people with epilepsy are 5 times at risk of suicide. In addition, the risk is still higher even in surgically treated patients. Other studies suggest that suicide attempt is higher in patients with temporal lobe epilepsy which can be due to abnormal function of the limbic system\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Suicide attempt was observed in one patient in our study population. MRI was normal, and EEG was epileptic. The drug was stopped immediately, and the patient was monitored in the intensive care unit for a few days and switched to another ASM.\u003c/p\u003e \u003cp\u003eDermatological and non-dermatological changes can be experienced in patients who are treated with levetiracetam. The dermatological side effects mostly appeared on the face, and extremities, characterized by dark-colored skin, and morbilliform macular rash. The non-dermatological side effects experienced were fever, headache, abdominal pain, facial edema, pharyngitis, and periorbital eye swelling\u003csup\u003e\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Despite these side effects being less likely with levetiracetam compared to other ASMs, still such adverse effects can be seen and immediate withdrawal should be done. In our patient group, maculopapular rash in one patient and angioedema in another one were observed during levetiracetam treatment. Levetiracetam treatment was discontinued.\u003c/p\u003e \u003cp\u003eDrug cessation should be approached with serious side effects. Levetiracetam treatment had to be discontinued in 11 patients. levetiracetam was stopped in three of the five patients with headaches. two with allergy, one with stomachache, and antother one with enuresis, one with hallucination/fatigue, one with suicide attempt, one with weight loss, and in one with increased frequency of infection. The dose of levetiracetam was adjusted in some patients with tolerable side effects. Some patients with tolerable side effects were also given a mix of vitamin B.\u003c/p\u003e \u003cp\u003eLevetiracetam may reduce the degranulation of CD8 lymphocytes, leading to an increased incidence of upper respiratory tract infections\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Drug-induced immunoglobulin decreases have been reported in some patients\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. In our patient group, an increase in the frequency of infection was observed in one patient. Lymphocyte count was low, 1270/uL, but lymphocyte subgroup and immunoglobulin levels could not be analyzed. levetiracetam was stopped in this patient.\u003c/p\u003e \u003cp\u003eThere are limited studies that tested the hematological effects of levetiracetam in the pediatric population. Dilber et al. conducted a study on 114 children in 2021 and tested the effect of this antiseizure drug on hemogram, liver function, and B12, it was observed after three years of follow-up that there was an increase in hemoglobin and hematocrit, while there was a decrease in absolute neutrophil(ANC) and absolute lymphocyte count(ALC) while the platelet count was not affected and there was no correlation between gender and hematological changes, and despite the changes there were no clinical complaints by the patients \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. French et al evaluated adult patients who received levetiracetam monotherapy despite the hematological changes at first, all the parameters returned to normal at the end of three years \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. A decrease in lymphocyte and ALC was observed in studies conducted by Dinopoulos et al and Attilocks et al\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. There are also studies in which antiepileptic treatment decreased vitamin B12 levels\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. In our study, logistic regression analysis showed that lower Vitamin B12 levels were associated with more side effects. Monitoring of vitamin B12 levels during antiepileptic treatment is recommended\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eUrinary and fecal incontinence was reported in patients with levetiracetam monotherapy and the exact mechanism is still unknown\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Incecik et al reported an 11-year-old boy patient who experienced fecal and urinary incontinence at a dose of 20 mg/kg\u003csup\u003e16\u003c/sup\u003e. Investigation as MRI, EEG, and infection parameters were normal. The effect was reversible and the patients could gain control after withdrawing the drug. In our study, an 8-year-old boy experienced urinary and fecal incontinence a few days after starting the drug. All the investigations were normal, urine culture and urine analysis showed no infection. The drug stopped immediately and the control was regained. Our patient was a boy too, so we think this side effect could be seen more frequently in male patients.\u003c/p\u003e \u003cp\u003eFatigue is reported by lots of studies as an adverse effect of levetiracetam monotherapy. Marco Mula et all reported fatigue in %36 of patients with levetiracetam which could be due to an imbalance between excitatory and inhibitory neurotransmission however the exact mechanism of central fatigue is still unclear and this side effect was seen more frequently in females rather than males\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Recent studies showed that central fatigue could be due to dysfunction in the non-motor area of basal ganglion and their interaction with the frontal cortex and amygdala but the effect of on levetiracetam these networks is still unknown\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. In our study fatigue was seen in 3(%4) of the patients while the rest 81(%96) patients didn\u0026rsquo;t experience such symptoms. Fatigue could be due to multifactorial etiologies.\u003c/p\u003e \u003cp\u003eLevetiracetam associated with higher total sleep duration, and sleep problems is not commonly reported as a side effect\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. The recent studies' results are very controversial. Some studies showed that levetiracetam increased the N2 stage of sleep\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. In another study, it was observed that levetiracetam increased wakingness and in a study conducted by yılmaz et al., it was seen that this drug increased daytime napping episodes and total nap duration while there was a decrease in total activity score at night in monotherapy in adult patients\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. In our study, sleep disturbance was reported in 13 patients (15%).\u003c/p\u003e \u003cp\u003e \u003cb\u003eLimitations of the study\u003c/b\u003e. Our study is retrospective and the number of patients studied was small. Sleep disturbance was based on family and patient reports and could not be assessed by a valid and reliable scale. The patients\u0026rsquo; laboratory data was not available before starting treatment. So the hematological and biochemical laboratory results could not be compared before, during, and after the treatment/discontinuation of treatment.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConclusion\u003c/strong\u003e \u003cp\u003ePhysical-behavioural side effects were observed in levetiracetam treatment. The age of the group with side effects was older. No association was observed with body weight, gender, epilepsy type, levetiracetam dose and duration, MR and EEG findings. Well-designed studies are needed to determine the clinical and laboratory data that can predict the side effects of levetiracetam monotherapy in pediatric patients.\u003c/p\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments; \u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e: SB planned and coordinated the study, NB. analyzed the literature, and SB was a major contributor to writing the manuscript study. Both authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e Nothing to declare. No funding has been received\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e At S.B. repository. The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval and consent to participate\u003c/strong\u003e: The study was conducted in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards and approved by the Clinical Research Ethics Committee of Gazi YşargilEducation \u0026amp; Research Hospital (2023:2023/417). Written informed consent was obtained from all the participants and/or legal guardians.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare that they have no competing interest\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTekg\u0026uuml;l H, Gencpinar P, \u0026Ccedil;avuşoğlu D, D\u0026uuml;ndar NO. The efficacy, tolerability, and safety of levetiracetam therapy in a pediatric population. Seizure. 2016;36:16\u0026ndash;21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.seizure.2016.01.017\u003c/span\u003e\u003cspan address=\"10.1016/j.seizure.2016.01.017\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanemoto K, Nishida T, Hasegawa N. 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J Sleep Res. 2002;11(3):255\u0026ndash;63. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1046/J.1365-2869.2002.00301.X\u003c/span\u003e\u003cspan address=\"10.1046/J.1365-2869.2002.00301.X\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYilmaz H. Comparison of motor activity and sleep in patients with complex partial seizures on levetiracetam treatment and a group of healthy subjects. Behav Neurol. 2007;18(3):165\u0026ndash;70.\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":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Levetiracetam, Epilepst, Side effects, Pediatric population","lastPublishedDoi":"10.21203/rs.3.rs-5408110/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5408110/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePurpose: Levetiracetam is a new medicine that is used for the treatment of focal and generalized seizure control. Several side effects can be observed during treatment with levetiracetam . Studies testing the tolerability and safety of levetiracetam monotherapy in pediatric epilepsy patients are limited. We retrospectively evaluated the side effects of levetiracetam monotherapy and whether there are any clues to predict these side effects in the pediatric epilepsy population.\u003c/p\u003e\n\u003cp\u003eMaterials and Methods: Patients aged 1-17 years with epilepsy treated with levetiracetam monotherapy were included in the study. Age, gender, body weight, blood pressure, duration of levetiracetam use, dose, semiology, epilepsy type, EEG and MRI findings, hemogram and biochemical laboratory findings, and observed side effects were recorded.\u003c/p\u003e\n\u003cp\u003eResults: Eighty-five patients were included in the study. Twenty-five (29%) patients had side effects. Treatment was discontinued in 11 patients due to side effects. The three most common side effects were agitation (8 patients, 9%), headache (5 patients, 5%) and fatigue (3 patients, 4%). There was no relationship between side effects and gender, body weight, seizure type, levetiracetam dose, duration, EEG, and MRI findings. Vitamin B12 Levels were lower in the group with side effects. The side effects are experienced more frequently in the older age group.\u003c/p\u003e\n\u003cp\u003eConclusion: Physical-behavioural side effects were observed in levetiracetam treatment. The age of the group with side effects was older. Lower B12 levels might have a role in initiating some side effects\u003c/p\u003e","manuscriptTitle":"The side effects of levetiracetam monotherapy in pediatric epilepsy patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-03 15:01:39","doi":"10.21203/rs.3.rs-5408110/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2025-01-07T04:41:21+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-01-04T10:46:05+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-18T18:10:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-11T05:34:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Italian Journal of Pediatrics","date":"2024-11-09T12:51:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"61b4d163-da4a-48e5-84f9-4ecc1080c001","owner":[],"postedDate":"December 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2025-01-07T09:50:50+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-03 15:01:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5408110","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5408110","identity":"rs-5408110","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}