Intravenous Levetiracetam Research Articles

Safety and tolerability of intravenous undiluted levetiracetam in pediatrics: A retrospective cohort study.

Time is critical in executing acute seizure treatment, and efforts to minimize operational delays with medication preparation confer potential logistical and practical advantages. Multiple studies have demonstrated the safety and tolerability of intravenous (IV) undiluted levetiracetam (LEV) in adults; however, published pediatric data are limited. This study aims to evaluate the safety and tolerability of IV undiluted LEV in pediatrics. This was a retrospective, dual-center, observational cohort study evaluating concentration-related adverse drug events with IV undiluted (100 mg/mL) LEV in pediatrics over a 3-year 3-month timespan. A total of 60 undiluted administrations in 52 patients were included in the study. The median age was 4 years; 58.3% of patients were younger than 5 years of age. All doses were administered via a peripheral IV line. The most common IV anatomic site and peripheral IV gauge (G) was the antecubital (66.6%) and 22G catheter (63.3%). There were no documented concentration-related adverse drug events. Regardless of IV anatomic site, IV gauge, and administered dose there were no documented concentration-related adverse effects with IV undiluted LEV in a pediatric population. IV undiluted LEV may be considered safe and tolerable in pediatrics. Prospective pediatric studies should assess the safety and tolerability of IV undiluted LEV.

Efficiency and safety of high-dose undiluted intravenous push levetiracetam loading doses compared to intravenous infusion in seizing patients: A retrospective cohort study.

Intravenous (IV) push (IVP) is an alternative administration method for levetiracetam, but evidence evaluating it compared to IV piggyback (IVPB) for loading doses in acutely seizing patients is limited, particularly in patients with status epilepticus (SE). This study aimed to compare the efficiency and safety of IVP versus IVPB levetiracetam loading doses. This was a single-center sequential retrospective study conducted in adult (≥18 years) patients who received an IV levetiracetam loading dose (>2000 mg or ≥20 mg/kg) for acute or suspected seizure. The primary outcome was time to administration, compared between doses given as IVP versus IVPB. Secondary outcomes included rates of adverse events (AEs), rescue benzodiazepine or antiseizure medication administration, intubation, and intensive care unit (ICU) admission between groups. A total of 246 patients were included; 116 received IVP and 130 received IVPB loading doses. Median age was 56 years; most patients were male (62%) and White (60%) and had witnessed seizures (67%). Doses were administered for SE in 32 (27.5%) and 46 (35.4%) patients in the IVP and IVPB arms, respectively. Median time to administration was shorter in the IVP group (12 vs. 38 min, p < .001). Bradycardia (1.7% vs. 2.3%, p = .99), hypotension (7.8% vs. 12%, p = .30), sedation (6% vs. 12.3%, p = .09), intubation (10% vs. 8%, p = .37), ICU admission (32% vs. 39%, p = .31), and rescue medication administration (8.6% vs. 14.6% p = .10) were similar between groups. In SE patients, IVP was associated with shorter time to administration (12 vs. 44 min, p = .003) and lower odds of ICU admission after adjustment for age, dose, Status Epilepticus Severity Score, and seizure history (adjusted odds ratio = .23, 95% confidence interval = .06-.81). IVP reduced time to levetiracetam administration versus IVPB and was not associated with more AEs. Rescue agent use, intubation, and ICU admission were similar between arms, but IVP may reduce ICU admissions in SE patients. Prospective studies should assess the effectiveness of IVP versus IVPB.

Pharmacokinetic and pharmacodynamic data from the NEOLEV1 and NEOLEV2 studies

ObjectivesTo confirm that levetiracetam (LEV) demonstrates predictable pharmacokinetics(PK) at higher doses and to study the pharmacodynamics(PD) of LEV.DesignPharmacokinetic data from the NEOLEV1 and NEOLEV2 trials were analysed using a non-linear...

A Simulation-Based Assessment of Levetiracetam Concentrations Following Fixed and Weight-Based Loading Doses: A Meta-Regression and Pharmacokinetic Modeling Analysis.

Current recommendations for refractory status epilepticus (SE) unresponsive to benzodiazepines suggest a loading dose of levetiracetam (LEV) of 60 mg/kg to a maximum of 4500 mg. LEV therapeutic drug monitoring can help guide therapy and is garnering increasing attention. The objective of this study is to simulate the probability of target attainment (PTA) of fixed dose and weight-based loading doses of LEV with respect to established therapeutic target concentrations. Meta-regression of the current literature was performed to evaluate the relationship between intravenous LEV loading dose and seizure cessation in refractory SE patients. A previously published pharmacokinetic model was used to simulate the PTA capacity of competing single intravenous dosing schemes (fixed vs weight-based dosing) to achieve maximum (Cpeak) and 12-h (C12h) plasma concentrations that exceed 12 mg/L. The meta-regression indicated that dosage was not a statistically significant modulator of seizure control at dosages between 20 and 60 mg/kg. Stochastic simulations showed all dosing schemes achieved plasma Cpeak >12 mg/L, but C12h levels were <12 mg/L in subjects over 60 kg with a fixed dose ≤2000 mg or in subjects <60 kg with a weight-based dose <30 mg/kg. Dosages of 40 and 60 mg/kg provided ≥90% PTAs across all weights. Using a weight-based loading dose of 40 mg/kg, up to a suggested maximum of 4500 mg, improves the likelihood of achieving a sustained therapeutic drug concentration after the initial LEV dose, whereas fixed <3000 mg may not achieve the desired concentration before maintenance dosing.

Intravenous levetiracetam versus intravenous phenytoin as second Line treatment in pediatric convulsive status epilepticus- open label randomized controlled trial.

Benzodiazepines (BZDs) are recommended as the initial therapy of choice in status epilepticus (SE). The age-old second-line treatment for BZD refractory convulsive SE is intravenous phenytoin (PHT) based predominantly on nonrandomized clinical trial data. We did this study to compare the efficacy and safety of intravenous levetiracetam (LEV) and PHT as second-line antiseizure medication (ASM) for children with SE. A prospective, randomized controlled, open-label study was conducted in children 3 months to 15 years of age with SE in Pediatric Emergency. A total of 41 children were randomly allocated to either group 1 (Levetiracetam) or group 2 (Phenytoin) on the basis of computer-generated randomization. Children who were already on antiseizure medications, either LEV or PHT, or receiving these drugs outside for SE were excluded. Data analysis was done by SPSS V25. The most common age group presenting with SE was 12 months to 5 years. Clinical cessation of seizure 5 minutes after the completion of drugs was 85% (17/20) in Levetiracetam group and 90.5% (19/21) in Phenytoin group. Recurrence of seizure within 24 hours was noted in 35% (7/20) in Levetiracetam group and 38.1% (8/21) in Phenytoin group. There was no statistically significant difference noted in both the groups in terms of seizure cessation, adverse events, and recurrence. The efficacy and safety of LEV were found to be comparable to those of PHT in controlling seizure as second-line ASM in SE.

Comparison Efficacy of Phenobarbital versus Levetiracetam in Acute Neonatal Seizures: A Randomized Control Trial

AbstractSeizures in infancy are one of the main manifestations of disorders in the central nervous system that can have important etiologies. The development of anticonvulsant drugs and the importance of drug selection in infants, due to more complex underlying etiologies, compared with older ages, explicate the essentiality of executing clinical investigations to appraise the optimal therapeutic approach. The objective of the current investigation is to juxtapose two therapeutic approaches involving intravenous levetiracetam and intravenous phenobarbital in the management of neonatal seizures. This is a randomized controlled clinical trial study on 100 infants who were referred to the Hazrat Masoumeh (S) Hospital in Qom owing to convulsions. Infants with seizure who fulfilled the inclusion criteria were arbitrarily allocated to one of the two intervention cohorts: intravenous levetiracetam or intravenous phenobarbital, and therapeutic responses were compared. There was a substantial relationship between seizure time, seizure etiology, anticonvulsant therapy type, and treatment responsiveness. As a result, the risks of not responding to therapy and increasing the dose were approximately 6 and 5 times higher, respectively, in the group that experienced seizures in the fourth week than in the other groups. Infants with cerebrovascular anomalies were more prone to not responding to treatment. Furthermore, children administered phenobarbital had a 2.5-fold higher chance of not responding to treatment than those given levetiracetam (p = 0.043).

Determining the Safety and Tolerability of Rapid Administration of Undiluted Intravenous Levetiracetam in Pediatrics.

Objective: Levetiracetam is widely used in the emergency setting. Safety and tolerability of undiluted levetiracetam is prevalent in adults but is limited in pediatrics. The purpose is to determine the safety and tolerability of rapid administration of undiluted levetiracetam in pediatric patients. Methods: A retrospective, single-center, observational study was conducted in pediatric patients who received undiluted levetiracetam intravenous push. The primary outcome was adverse reactions, extravasation, need for intravenous line replacement, and discontinuation due to adverse reactions. The secondary outcome was turnaround time between ordering and administering first doses. Results: One hundred fourteen patients were included. Injection site reactions occurred in 7 patients. Extravasation occurred in 4 patients. Two patients required intravenous line replacement. There were no adverse events leading to discontinuation of levetiracetam. No difference was seen in the time from order to administration. Conclusion: Rapid administration of undiluted levetiracetam in pediatric patients was safe and well tolerated.

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Factors Affecting the Safety Profile of Intravenous Levetiracetam Used for Controlling Seizures in Children: A Literature Review

The administration of intravenous levetiracetam (IV-LEV) serves as a significant therapeutic approach for managing seizures in pediatric patients. The major factors that are involved in the equation determinants contain pharmacokinetic parameters, such as dosage regimen, drug interactions, and patient-specific factors including age, weight, and underlying comorbidities. Furthermore, attention is given to potential adverse effects, including hypersensitivity reactions, renal impairment, and central nervous system manifestations. Clinical trials, observational studies, and pharmacovigilance data contribute to a comprehensive evaluation of the drug’s safety, shedding light on optimal dosing strategies and risk mitigation techniques. Understanding these intricate factors is paramount for healthcare providers to ensure efficacious seizure control while minimizing potential harms associated with IV-LEV administration in children. This abstract examines the multifaceted factors that influence the safety profile of IV-LEV in this vulnerable pediatric population. This literature review explores the various factors influencing the safety profile of intravenous levetiracetam (IV-LEV) in its application for seizure management in pediatric patients. Based upon a comprehensive analysis of peer-reviewed articles, clinical trials, and observational studies, the review synthesizes findings related to pharmacokinetic variables, dosage considerations, and potential drug interactions. Additionally, patient-specific determinants, encompassing age-related variations, weight-based dosing implications, and the impact of comorbid conditions, are critically evaluated.

Sequential levetiracetam and phenytoin in electroencephalographic neonatal seizures unresponsive to phenobarbital: a multicenter prospective observational study in India

Although levetiracetam and phenytoin are widely used antiseizure medications (ASM) in neonates, their efficacy on seizure freedom is unclear. We evaluated electroencephalographic (EEG) seizure freedom following sequential levetiracetam and phenytoin in neonatal seizures unresponsive to phenobarbital. We recruited neonates born ≥35 weeks and aged <72h who had continued electrographic seizures despite phenobarbital, from three Indian hospitals, between 20 June 2020 and 31 July 2022. The neonates were treated with intravenous levetiracetam (20mg/kg x 2 doses, second line) followed by phenytoin (20mg/kg x 2 doses, third line) if seizures persisted. The primary outcome was complete seizure freedom, defined as an absence of seizures on EEG for at least 60min within 40min from the start of infusion. Of the 206 neonates with continued seizures despite phenobarbital, 152 received levetiracetam with EEG. Of these one EEG was missing, 47 (31.1%) were in status epilepticus, and primary outcome data were available in 145. Seizure freedom occurred in 20 (13.8%; 95% CI 8.6%-20.5%) after levetiracetam; 16 (80.0%) responded to the first dose and 4 (20.0%) to the second dose. Of the 125 neonates with persisting seizures after levetiracetam, 114 received phenytoin under EEG monitoring. Of these, the primary outcome data were available in 104. Seizure freedom occurred in 59 (56.7%; 95% CI 46.7%-66.4%) neonates; 54 (91.5%) responded to the first dose and 5 (8.5%) to the second dose. With the conventional doses, levetiracetam was associated with immediate EEG seizure cessation in only 14% of phenobarbital unresponsive neonatal seizures. Additional treatment with phenytoin along with levetiracetam attained seizure freedom in further 57%. Safety and efficacy of higher doses of levetiracetam should be evaluated in well-designed randomised controlled trials. National Institute for Health and Care Research (NIHR) Research and Innovation for Global Health Transformation (NIHR200144).

Successful use of intravenous and oral levetiracetam in a goat to control refractory seizures secondary to suspected polioencephalomalacia.

To assess the clinical efficacy and plasma concentrations of levetiracetam in a goat with seizures. A 5-month-old doeling. The goat was referred because of progressive anorexia and lethargy over 3 days. Clinical signs consisted of weakness, obtundation, opisthotonos, anisocoria, and cortical blindness. Initial evaluation was most consistent with polioencephalomalacia. Neurologic improvement occurred within 4 hours of thiamine administration, with appetite returning over 12 hours. On day 3 of hospitalization, the goat suffered acute onset repetitive seizures that were incompletely responsive to standard interventions over 3 hours. Administration of IV levetiracetam (60 mg/kg) produced resolution of seizure activity within 20 minutes. Levetiracetam was continued twice daily IV, then PO after day 6. Plasma concentrations were above or within therapeutic ranges (5 to 45 μg/mL) as previously established for other species, following both IV and PO levetiracetam. Oral administration (60 mg/kg, PO, q 12 h) resulted in plasma levetiracetam concentrations of 48.1 μg/mL 2 hours after a dose and 23.4 μg/mL 2 hours prior to the next dose. Levetiracetam is a newer anticonvulsant commonly used in humans and small animals due to its efficacy, cost, and wide safety margin. Its use has not previously been reported in domestic small ruminants. In this case, levetiracetam showed excellent clinical efficacy in the face of refractory seizures, with no apparent side effects. Plasma concentrations during oral administration were at the high end of the therapeutic range, indicating absorption in a nonmonogastric species. Further studies are warranted to determine optimal dosing in small ruminants.

Febrile seizures in pediatric practice: Risk factors, clinical manifestations, and intensive therapy

Introduction. Febrile seizures (FS) is the most common type of epileptic seizure experienced by young children. Study of methods of intensive treatment (IT) of FS represents a vital area of research in today’s pediatric science. The aim of this work: to assess the current approaches to risk factors, clinical manifestations and emergency care for patients with FS in pediatric practice. Materials and methods. The authors performed an analysis of publications that were found in the Cochrane Library, PubMed, eLibrary.ru, and Medscape databases using the following search terms: febrile seizures, children and adolescents, intensive treatment, anticonvulsants. A total of 64 published sources were chosen for review. Results and Discussion. The risk factors for FS may be numerous, with the main etiological causes in children being genetic susceptibility, viral infections and vaccination. The clinical presentation of FS is characterized by the development of a generalized tonic-clonic seizure in the setting of a high body temperature (≥39°C). FS are subdivided into three main clinical types: simple, complex and febrile status epilepticus (FSE). History taking and physical examination represent the main diagnostic means for determining the type of FS and discovering the cause of infection. Laboratory tests, electroencephalography, neuroimaging studies and lumbar puncture are used on a limited basis, mainly in children with complicated FS accompanied by a brain infection. Hospitalization for IT is necessary if the child has prolonged febrile seizures or FSE. The drugs of choice for relieving FS are benzodiazepines. Barbituric acid derivatives and valproic acid also possess therapeutic efficacy against FS. Antipyretic agents are effective only in relieving the toxic syndrome, but have no effect on the severity of FS and do not prevent relapses. The main antipyretic medications used for treatment of FS in pediatric practice are paracetamol, ibuprofen and nimesulide. Besides benzodiazepines, IT of FSE involves the use of intravenous fosphenytoin, phenobarbital or levetiracetam. Conclusion. Improvement of the quality of IT in pediatric practice may improve the therapeutic prognosis in patients with FS and bring down complication and mortality rates.

Evaluation of the safety and tolerability of intravenous undiluted levetiracetam at a pediatric institution.

Recent studies suggest rapid administration of high-dose, undiluted levetiracetam is safe in adults; however, no information exists in pediatric patients. The purpose of this study was to evaluate the safety and tolerability of undiluted levetiracetam at a pediatric institution. Retrospective, single-center, cohort study. Pediatric Academic Medical Center. All patients who received high-dose >60 mg/kg (-10%) up to 4500 mg undiluted or diluted intravenous levetiracetam were included. Rapid intravenous administration of undiluted versus diluted levetiracetam. A total of 776 levetiracetam doses were included, 358 doses administered and 418 doses wasted. The doses administered (61 undiluted and 297 diluted) accounted for a total of 252 patients (39 received undiluted, and 213 received diluted levetiracetam) (median [minimum-maximum range] age, 2 years [1 day to 32.7 years]; mean (standard deviation [SD]) weight, 20.1 kg [22.1 kg]). The incidence of hemodynamic disturbances and infusion-related reactions was not statistically significant between undiluted (24.6%) and diluted (26.3%) groups (p = 0.87). The median (interquartile range [IQR]) time difference between first-line antiseizure medication and levetiracetam administration in patients with status epilepticus was 18 min (10.5-30.5) in the undiluted group versus 36.5 min (21.8-67.3) in the diluted group (p < 0.01). Additionally, there was a significant amount of drug waste from dispensed but not administered doses of the diluted bag compared to undiluted vials (57.6% diluted vs. 18.7% undiluted, p < 0.001). Undiluted levetiracetam was not associated with an increased incidence of adverse effects compared to diluted levetiracetam in high-doses, up to 4500 mg given over 5 min in pediatric patients.

Bihemispheric Seizure Without Generalization.

A 70-year-old male without prior psychiatric history presented with recurrent episodes (<60seconds each, every 5-10minutes) of left hemibody and right lower extremity jerking movements concerning for seizure with preserved awareness (Video). Examination showed left hemiparesis (leg > arm) in addition to right lower extremity weakness. Computed tomography showed a right parafalcine acute subdural hematoma (SDH). Clinical events did not recur after intravenous lorazepam (4mg) and levetiracetam load (3500mg), and his weakness improved. He was continued on levetiracetam and has since remained seizure free for 16months. A 60-minute awake/sleep electroencephalogram (EEG) obtained 12hours after administration of antiseizure medications showed low amplitude theta slowing (posterior predominant) in the range of 5-7Hz. There was no apparent epileptiform activity or other abnormalities during the awake and sleep recording or photic stimulation. Focal seizures originate from pathologic disruption of neuronal activity within an isolated brain region, almost exclusively from a single hemisphere. Focal seizures may generalize bilaterally with associated impaired awareness. This is the first visual report demonstrating focal, bihemispheric clinical seizures, without generalization or impaired awareness. Rarely patients with generalized motor involvement from seizures have had retained consciousness and memory. The parafalcine SDH likely promoted epileptogenicity of the bilateral hemispheres. Acute and chronic SDH commonly present with seizures. Although there were no supportive electrographic findings, parasagittal epileptogenic lesions may be difficult for both clinical and electrographic localization. Post-event paresis with clinical improvement in the hours after event cessation supports clinical seizure.

Pharmacokinetics of Levetiracetam Seizure Prophylaxis in Severe Traumatic Brain Injury.

Drug pharmacokinetics (PK) are altered in neurocritically ill patients, and optimal levetiracetam dosing for seizure prophylaxis is unknown. This study evaluates levetiracetam PK in critically ill patients with severe traumatic brain injury (sTBI) receiving intravenous levetiracetam 1000 mg every 8 (LEV8) to 12 (LEV12) hours for seizure prophylaxis. This prospective, open-label study was conducted at a level 1 trauma, academic, quaternary care center. Patients with sTBI receiving seizure prophylaxis with LEV8 or LEV12 were eligible for enrollment. Five sequential, steady-state, postdose serum levetiracetam concentrations were obtained. Non-compartmental analysis (NCA) and compartmental approaches were employed for estimating pharmacokinetic parameters and projecting steady-state trough concentrations. Pharmacokinetic parameters were compared between LEV8 and LEV12 patients. Monte Carlo simulations (MCS) were performed to determine probability of target trough attainment (PTA) of 6 to 20 mg/L. A secondary analysis evaluated PTA for weight-tiered levetiracetam dosing. Ten male patients (5 LEV8; 5 LEV12) were included. The NCA-based systemic clearance and elimination half-life were 5.3 ± 1.2 L/h and 4.8 ± 0.64 hours. A one-compartment model provided a higher steady-state trough concentration for the LEV8 group compared with the LEV12 group (13.7 ± 4.3 mg/L vs 6.3 ± 1.7 mg/L; P = 0.008). Monte Carlo simulations predicted regimens of 500 mg every 6 hours, 1000 mg every 8 hours, and 2000 mg every 12 hours achieved therapeutic target attainment. Weight-tiered dosing regimens achieved therapeutic target attainment using a 75 kg breakpoint. Neurocritically ill patients exhibit rapid levetiracetam clearance resulting in a short elimination half-life. Findings of this study suggest regimens of levetiracetam 500 mg every 6 hours, 1000 mg every 8 hours, or 2000 mg every 12 hours may be required for optimal therapeutic target attainment. Patient weight of 75 kg may serve as a breakpoint for weight-guided dosing to optimize levetiracetam therapeutic target attainment for seizure prophylaxis.

Adverse events of undiluted intravenous push levetiracetam

BackgroundIn patients who experience a seizure, the seizure duration is a strong indicator of prognosis. Thus, reducing time to antiepileptic medications in patients who are actively seizing is critical. While findings from retrospective studies suggest that the rapid administration of undiluted intravenous (IV) levetiracetam may be safe, some gaps in the literature remain. ObjectiveThe purpose of this research study was to prospectively assess adverse events associated with the rapid administration of undiluted IV levetiracetam. MethodsThis was a prospective, observational cohort study of adult patients who received rapid administration of undiluted IV levetiracetam at doses up to 4500 mg in the emergency department (ED) of a large community, teaching hospital. The primary endpoint was the incidence of any pre-defined adverse event. Secondary endpoints included the incidence of each type of adverse event, the incidence of seizure termination, and the time to completion of drug administration in patients actively seizing at the time of study inclusion. ResultsA total of 321 doses of IV push levetiracetam were ordered for 318 patients and 250 patients were subsequently included. Fourteen (5.6%) patients experienced an adverse event, most commonly due to injection site reactions (9/14). Clinically relevant hypotension, tachycardia, and hypertension occurred in five patients. For actively seizing patients, 79% (15/19) achieved seizure termination and the median time from medication order to completion of therapy was 12 min. ConclusionThis study found that the rapid administration of undiluted IV levetiracetam in ED patients was associated with few adverse events.

Management of Status Epilepticus by Different Pediatric Departments: Neurology, Intensive Care, and Emergency Medicine

Introduction: The aim of this study was to explore the differences in status epilepticus (SE) management among pediatric neurology, emergency medicine, and intensive care specialists in Turkey. Methods: A 22-item questionnaire regarding first-, second-, and third-line management strategies of SE including demographic characteristics and common etiologies according to the specialty of participants was mailed to 370 specialists working in Turkey. Results: A total of 334 participants (response rate 90%) comprising 136 pediatric neurologists, 102 pediatric emergency medicine specialists, and 96 pediatric intensive care specialists completed the survey. While intensive care specialists frequently managed SE due to metabolic and autoimmune reasons, the most common etiologies encountered by emergency medicine specialists were epilepsy and infections. More than half of the intensive care specialists (64.6%) reported using non-BZD antiseizure medications in the 5th minute of the seizure. Most of the neurologists (76.4%) preferred to administer intravenous (IV) levetiracetam infusion as a second-line agent. About half of intensive care specialists and neurologists tried immunomodulatory therapies in super-refractory SE. Intensive care and emergency medicine specialists were less likely to favor ketogenic diet and pyridoxine therapy for the treatment of super-refractory SE. The rate of requesting EEG monitoring to recognize nonconvulsive SE (NCSE) was found to be very low except for neurologists. Conclusion: There was no consensus among neurologists, intensive care specialists, and emergency medicine specialists in the management of SE in Turkey. Familiarity with particular antiseizure medications and the etiologies they manage seem to be the most important factors influencing the attitudes.

Efficacy of Levetiracetam versus Phenytoin in Neonatal Seizure in Rural Area of Thailand

Background: Neonatal seizure is an emergency condition that affects neurodevelopment and mortality. The appropriate treatment and seizure termination is crucial. Previous studies determined the efficacy of different types of antiseizure medications (ASMs), but there is no consensus toward second-line ASMs in neonatal seizure. Objective: To compare the efficacy of second-line ASMs in neonatal seizure, compared between levetiracetam and phenytoin. Materials and Methods: The present study was a retrospective study. The author recruited patients with diagnosis of neonatal seizure admitted at Maharat Nakhon Ratchasima Hospital, Thailand, between January 1, 2018 and December 31, 2020. Patients who had clinical seizure refractory and were given first-line ASM (intravenous phenobarbital) and received second-line ASMs as intravenous levetiracetam or intravenous phenytoin were included. Etiologies of seizure, seizure types, and other demographic data were recorded. The efficacy of levetiracetam and phenytoin were determined by comparing the duration of seizure, the need for third-line ASMs, and morbidity as developmental outcome, diagnosis of cerebral palsy, and mortality rate. Results: Twenty-five patients (68% male) were recruited. Sixty-four percent were diagnosed with hypoxic ischemic encephalopathy (HIE). The most common seizure type was subtle seizure at 56%. Levetiracetam was given to 56% and phenytoin was given to 44% as second-line ASMs. The duration of seizure was significantly different at 28.12 minutes in levetiracetam and 42.72 minutes in phenytoin (p=0.01). The drug adherence was higher in the levetiracetam group. Regarding third-line ASMs, 28.7% of the levetiracetam group and 45.45% of phenytoin group needed third-line ASMs, but this was not statistically significant. Mortality was 20% and 48% were diagnosed as cerebral palsy. There was no significant difference in mortality and morbidity between the two groups. Conclusion: Levetiracetam had no superior efficacy than phenytoin in neonatal seizure. Keywords: Neonatal seizure; Levetiracetam; Phenytoin; Efficacy

Comparative efficacy of intravenous levetiracetam and phenytoin in status epilepticus: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND Status epilepticus (SE) is a neurological emergency, with the current guidelines for second-line anticonvulsants may include phenytoin, levetiracetam, valproic acid, and phenobarbital. However, some studies suggest that levetiracetam may be better at stopping seizures in SE. This study aimed to compare the efficacy of intravenous (IV) levetiracetam and phenytoin in SE.&#x0D; METHODS We searched PubMed, ScienceDirect, Cochrane, and Google Scholar for randomized controlled trials (RCTs) on administering IV levetiracetam or phenytoin in patients with SE. RCTs were screened using eligibility criteria, and their quality was assessed using the Cochrane risk of bias tool. Heterogeneity was assessed using the I² test, and publication bias was evaluated using Egger’s test. All analyses were performed using Review Manager version 5.4 (The Cochrane Collaboration, UK) and Stata 17 (StataCorp LLC, USA).&#x0D; RESULTS 12 RCTs involving 2,137 patients (1,099 receiving levetiracetam) met the inclusion criteria. Pooled analysis showed that levetiracetam therapy had a significantly higher rate of seizure cessation than phenytoin (RR: 1.10, 95% CI = 1.05−1.14, p = 0.02, I² = 51%). Less adverse events were observed in the levetiracetam group (9.34%) than in the phenytoin group (11.62%; RR: 0.82, 95% CI = 0.66–1.02, p = 0.07). However, there was no significant difference regarding IV levetiracetam or phenytoin administration with the incidence of admission to critical care (RR: 1.01; 95% CI = 0.93–1.10, p = 0.80) and mortality (RR: 1.08; 95% CI = 0.54–2.15; p = 0.82).&#x0D; CONCLUSIONS IV levetiracetam was significantly better in the cessation of seizures in SE patients than phenytoin.