Correlation Between Efficacy of Levetiracetam and Serum Levels Among Children With Refractory Epilepsy

Sheinberg, Revital; Heyman, Eli; Dagan, Zahi; Youngster, Ilan; Kohn, Elkana; Gandelman-Marton, Revital; Berkovitch, Matitiahu

doi:10.1016/j.pediatrneurol.2015.01.012

Cited by 23 publications

(22 citation statements)

References 21 publications

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“…8 Although a higher incidence of adverse effects may be expected at high serum concentrations, no correlation between serum concentration and adverse events was found in a previous study of human pediatric epileptic patients. 10 Our findings appear to be in agreement with these findings in children.…”

Section: Discussionsupporting

confidence: 92%

“…Serious adverse effects of levetiracetam in cats appear to be uncommon, but mild transient ptyalism, inappetence, mild lethargy, ataxia, and polydipsia have been reported after IRL administration, and sedation and diarrhea were reported after a single dosage of XRL . Although a higher incidence of adverse effects may be expected at high serum concentrations, no correlation between serum concentration and adverse events was found in a previous study of human pediatric epileptic patients . Our findings appear to be in agreement with these findings in children.…”

Section: Discussionsupporting

confidence: 90%

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Serum levetiracetam concentrations and adverse events after multiple dose extended release levetiracetam administration to healthy cats

Heller

Granick

Hesteren

et al. 2018

Veterinary Internal Medicne

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BackgroundMultiple dose administration of antiepileptic drugs to cats presents a challenge for owners. Extended release levetiracetam (XRL) has once daily recommended dosing interval, but multiple dose administration of XRL has not been evaluated in cats.ObjectiveEvaluate serum levetiracetam concentrations and adverse clinical effects after 11 days of once daily XRL administration to healthy cats.AnimalsNine healthy privately owned cats, body weight ≥ 5 kgMethodsExtended release levetiracetam (500 mg/cat) was administered PO q24h for 10 days. On day 11, blood was collected at trough, 4, 6, and 8 hours after tablet administration. Owners maintained records of adverse effects throughout study. Levetiracetam was quantitated in serum using immunoassay validated in cats.ResultsMedian dose 94.3 mg/kg q24h. Median (range) trough, 4, 6, and 8 hour serum levetiracetam concentrations were 7.0 (2.3‐14.1), 82.6 (7.8‐125.3), 92.3 (13.3‐97.3), and 72 (22.8‐96.4) μg/mL, respectively. Peak was not observed in 4 cats because of missed samples (n = 2) and failure to reach maximal concentration (C max) by 8 hours (n = 2). Median time of maximal concentration (T max) for the remaining 5 cats 5.2 (range 4‐6) hours. Adverse effects were minimal and included ataxia (n = 1), sedation (n = 1), and vomiting or regurgitation (n = 1). All signs resolved without dose adjustment or additional treatment.Conclusions and Clinical ImportanceMean trough serum levetiracetam concentrations were ≥5 μg/mL and adverse effects were minimal throughout dosing period, indicating that the drug was well tolerated. Once daily XRL (500 mg/cat) administration may provide an easier alternative to 3 times daily dosing of intermediate‐release levetiracetam for epileptic cats.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

Serum levetiracetam concentrations and adverse events after multiple dose extended release levetiracetam administration to healthy cats

Heller

Granick

Hesteren

et al. 2018

Veterinary Internal Medicne

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“…In our previous study, dosages for effective cases were bimodal [31]. In another current study, Sheinberg et al found no correlations of LEV serum levels with clinical efficacy, tolerability or the administered dosage or between serum concentrations and adverse events [33]. Moreover, the occurrence of adverse events was independent of the mean daily dose and continuation time in the cohort [33].…”

Section: Discussionmentioning

confidence: 44%

Efficacy of levetiracetam for reducing rolandic discharges in comparison with carbamazepine and valproate sodium in rolandic epilepsy

Kanemura

Sano

Ohyama

et al. 2018

Seizure

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A R T I C L E I N F O Keywords:Levetiracetam (LEV) Rolandic epilepsy (RE) Electroencephalogram (EEG) Rolandic discharge (RD) Anti-epileptic drug (AED) A B S T R A C T Purpose:The main purpose of this study was to compare the efficacy of levetiracetam (LEV) with the older antiepileptic drugs (AEDs) for preventing atypical evolution in children with Rolandic epilepsy (RE). Accordingly, the present study compared the efficacy of older AEDs (carbamazepine (CBZ) and valproate sodium (VPA)) with LEV in reducing rolandic discharges (RDs) on interictal electroencephalogram (EEG) in children with RE. Methods: Patients in this heterogenous study were subdivided into CBZ, VPA and LEV groups in accordance with the initial monotherapy. The CBZ and VPA groups were studied retrospectively, but the LEV group was studied prospectively. Appearances of discharges were counted and these rates were computed. In comparison with the baseline RD frequency, EEG response to AED treatment was classified such as complete disappearance and response (≥50% reduction in RD frequency). The time taken to attain complete disappearance or response in EEG responders was assessed for each AED treatment group. Results: Responders comprised 10 (11.2%) of the 89 patients treated with CBZ, 41 (56.2%) of the 73 patients with VPA, and 25 (71.4%) of the 35 patients with LEV. Mean interval to achievement of EEG response in the CBZ, VPA, and LEV groups were 36.3, 23.1, and 14.7 months, respectively. EEG response was achieved significantly more rapidly with LEV than with CBZ (p < 0.001) or VPA (p < 0.005). Seizure control was not significantly different in all 3 investigated drugs. Conclusions: LEV seems to be superior to CBZ and VPA in its ability to suppress RDs in children with RE.

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“…The clearance value of the drug is greater in children than in adults [102]. Correlation between efficacy and serum levels of levetiracetam has been demonstrated in children with refractory epilepsy [103]. Levetiracetam has all the optimal characteristics of an AED and follows linear pharmacokinetics [104].…”

Section: Newer Antiepileptic Drugsmentioning

confidence: 99%

An Updated Overview on Therapeutic Drug Monitoring of Recent Antiepileptic Drugs

2016

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Given the distinctive characteristics of both epilepsy and antiepileptic drugs (AEDs), therapeutic drug monitoring (TDM) can make a significant contribution to the field of epilepsy. The measurement and interpretation of serum drug concentrations can be of benefit in the treatment of uncontrollable seizures and in cases of clinical toxicity; it can aid in the individualization of therapy and in adjusting for variable or nonlinear pharmacokinetics; and can be useful in special populations such as pregnancy. This review examines the potential for TDM of newer AEDs such as eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, perampanel, pregabalin, rufinamide, retigabine, stiripentol, tiagabine, topiramate, vigabatrin, and zonisamide. We describe the relationships between serum drug concentration, clinical effect, and adverse drug reactions for each AED as well as the different analytical methods used for serum drug quantification. We discuss retrospective studies and prospective data on the serum drug concentration–efficacy of these drugs and present the pharmacokinetic parameters, oral bioavailability, reference concentration range, and active metabolites of newer AEDs. Limited data are available for recent AEDs, and we discuss the connection between drug concentrations in terms of clinical efficacy and nonresponse. Although we do not propose routine TDM, serum drug measurement can play a beneficial role in patient management and treatment individualization. Standardized studies designed to assess, in particular, concentration–efficacy–toxicity relationships for recent AEDs are urgently required.

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Correlation Between Efficacy of Levetiracetam and Serum Levels Among Children With Refractory Epilepsy

Cited by 23 publications

References 21 publications

Serum levetiracetam concentrations and adverse events after multiple dose extended release levetiracetam administration to healthy cats

Serum levetiracetam concentrations and adverse events after multiple dose extended release levetiracetam administration to healthy cats

Efficacy of levetiracetam for reducing rolandic discharges in comparison with carbamazepine and valproate sodium in rolandic epilepsy

An Updated Overview on Therapeutic Drug Monitoring of Recent Antiepileptic Drugs

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