Lack of Pharmacokinetic Interaction of Levetiracetam on Carbamazepine, Valproic Acid, Topiramate, and Lamotrigine in Children with Epilepsy

Otoul, Christian; Smedt, Heidi De; Stockis, Armel

doi:10.1111/j.1528-1167.2007.01201.x

Cited by 58 publications

(29 citation statements)

References 14 publications

(20 reference statements)

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“…Because of its low protein affinity and metabolism, LEV lacks the common drug interactions other antiepileptic drugs possess, including with other antiepileptic drugs in children (10). LEVs favorable pharmacokinetic profile makes it attractive as an agent in the management of critically ill patients with seizures or status epilepticus, as traditional antiepileptic drugs may increase the risk of drug interactions or complicate the liver failure or coagulopathy that can be associated with critical illness.…”

Section: Discussionmentioning

confidence: 99%

Intravenous levetiracetam in critically ill children with status epilepticus or acute repetitive seizures

Abend

Monk

Licht

et al. 2009

Pediatric Critical Care Medicine

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Objective-Intravenous (IV) levetiracetam (LEV) is approved for use in patients older than 16 years and may be useful in critically ill children, although there is little data available regarding pharmacokinetics. We aim to investigate the safety, an appropriate dosing, and efficacy of IV LEV in critically ill children.Design-We describe a cohort of critically ill children who received IV LEV for status epilepticus, including refractory or nonconvulsive status, or acute repetitive seizures.Results-There were no acute adverse effects noted. Children had temporary cessation of ongoing refractory status epilepticus, termination of ongoing nonconvulsive status epilepticus, cessation of acute repetitive seizures, or reduction in epileptiform discharges with clinical correlate.Conclusions-IV LEV was effective in terminating status epilepticus or acute repetitive seizures and well tolerated in critically ill children. Further study is needed to elucidate the role of IV LEV in critically ill children. Keywordslevetiracetam; status epilepticus; seizure; pediatric Intravenous (IV) levetiracetam (LEV) has been approved for use by the U.S. Food and Drug Administration in patients aged 16 years and older (1), but there is little data available regarding pharmacokinetics, tolerability, or efficacy in younger children. Additionally, LEV has not been approved by the Food and Drug Administration for treatment of acute seizures. LEV is a broadspectrum anticonvulsant and can be administered rapidly as a loading dose over 15 minutes, although adult studies suggest infusion times of 5 minutes are well tolerated (2). Pharmacokinetically, LEV completely avoids hepatic metabolism, which may prove beneficial in complex patients with liver dysfunction or metabolic disorders or those patients at risk for major drug interactions. In comparison with other IV anticonvulsants, LEV has few known adverse effects, including a low risk of sedation, cardiorespiratory depression, or coagulopathy, and thus is potentially useful in critically ill pediatric patients. We present data on a cohort of critically ill children who received IV LEV for status epilepticus or acute repetitive seizures. MethodsThis is a retrospective case series of critically ill children who received IV LEV for status epilepticus or acute repetitive seizures at The Children's Hospital of Philadelphia between For information regarding this article, abend@email.chop.edu. NIH Public Access ResultsTen children were identified who received IV LEV for status epilepticus or acute repetitive seizures in the pediatric ICU (Table 1). The median age was 5 years and range was 0.08-14 years. Loading dose of LEV ranged from 6.5 to 31 mg/kg. Indications for therapy included nonconvulsive status epilepticus refractory to other anticonvulsant medications in three children, nonconvulsive status epilepticus with LEV as the first-line anticonvulsant in two children, acute repetitive seizures in four children (nonconvulsive in two patients, clinical in two patients), and periodic epileptifo...

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Section: Discussionmentioning

confidence: 99%

Intravenous levetiracetam in critically ill children with status epilepticus or acute repetitive seizures

Abend

Monk

Licht

et al. 2009

Pediatric Critical Care Medicine

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“…When LEV was compared to placebo, no differences were observed. The researchers concluded that in children with epilepsy LEV does not affect plasma concentrations of carbamazepine, valproic acid, topiramate, or lamotrigine (19). …”

Section: Pharmacokineticsmentioning

confidence: 99%

Clinical Pharmacology and Pharmacokinetics of Levetiracetam

et al. 2013

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Status epilepticus and acute repetitive seizures still pose a management challenge despite the recent advances in the field of epilepsy. Parenteral formulations of old anticonvulsants are still a cornerstone in acute seizure management and are approved by the FDA. Intravenous levetiracetam (IV LEV), a second generation anticonvulsant, is approved by the FDA as an adjunctive treatment in patients 16 years or older when oral administration is not available. Data have shown that it has a unique mechanism of action, linear pharmacokinetics and no known drug interactions with other anticonvulsants. In this paper, we will review the current literature about the pharmacology and pharmacokinetics of IV LEV and the safety profile of this new anticonvulsant in acute seizure management of both adults and children.

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“…Levetiracetam is largely not protein bound; therefore, it does not compete with other drugs for binding sites. [17,18] The dosage in pediatric patients is 10 mg kg day for the first week, then titrated in increments of 10 mg kg day every 2 weeks. The usual childhood maintenance dosage is 40-80 mg kg day (maximum 12 mg kg day) in two to three equally divided doses.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Levetiracetam in Childhood Epilepsy

et al. 2010

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Levetiracetam is an antiepileptic drug that has been shown to be effective in various types of seizures, both partial and generalized. Although it is not yet well established because of the small number of studies, levetiracetam as both add-on therapy and monotherapy can be considered as an alternative to valproic acid in some pediatric patients. We have reviewed the available data on the efficacy, tolerability, and safety of levetiracetam in children with epilepsy. The efficacy of levetiracetam as an adjunctive therapy and as monotherapy for generalized and partial childhood epilepsies and for some types of specific epileptic syndromes of infancy and childhood (such as juvenile myoclonic epilepsy, benign rolandic epilepsy, and Jeavon syndrome) has been demonstrated in some studies. Moreover, levetiracetam may be a valuable option for children with refractory epilepsy. The reported tolerability of levetiracetam and its safety profile are favorable. Among the side effects reported, behavioral changes and even psychotic reactions seem to occur more frequently in younger patients (under 4 years of age). The onset of signs/symptoms usually occurs early, even during the titration phase, and, in many cases, at a low dosage (<20 mg/kg/day). These side effects were always observed to be reversible after discontinuation of levetiracetam. In conclusion, results from clinical trials to date suggest that levetiracetam has a full spectrum of efficacy as well as a favorable safety profile, and this drug can be considered a valuable option in the treatment of epilepsy in pediatric patients.

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Lack of Pharmacokinetic Interaction of Levetiracetam on Carbamazepine, Valproic Acid, Topiramate, and Lamotrigine in Children with Epilepsy

Cited by 58 publications

References 14 publications

Intravenous levetiracetam in critically ill children with status epilepticus or acute repetitive seizures

Intravenous levetiracetam in critically ill children with status epilepticus or acute repetitive seizures

Clinical Pharmacology and Pharmacokinetics of Levetiracetam

Levetiracetam in Childhood Epilepsy

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