Clinical Pharmacokinetics

, Volume 56, Issue 11, pp 1267–1285 | Cite as

Levetiracetam Clinical Pharmacokinetic Monitoring in Pediatric Patients with Epilepsy

  • Jason Tan
  • Vanessa Paquette
  • Marc Levine
  • Mary H. H. Ensom
Review Article
First Online:

Abstract

Levetiracetam is a broad-spectrum antiepileptic drug (AED) with a unique mechanism of action. Older AEDs can cause serious short- and long-term adverse drug reactions and complications, rendering them undesirable to use in pediatric patients. Characteristics that make levetiracetam a near-ideal AED include its broad spectrum of activity, good tolerability profile, and minimal drug–drug interactions. Clinical pharmacokinetic monitoring (CPM) is often recommended in pediatric patients for certain AEDs due to large interindividual pharmacokinetic differences and unpredictable drug disposition. Our objective was to determine whether monitoring levetiracetam concentrations is warranted for pediatric patients with epilepsy, using a previously published 9-step decision-making algorithm. A literature search of the MEDLINE (1946–August 2016), EMBASE (1974–August 2016), CENTRAL, and Google Scholar databases was performed to identify relevant English-language articles and answer the questions posed in the algorithm for levetiracetam CPM in pediatric epilepsies. Additional articles were identified from a manual bibliographic review of the relevant literature. We found that levetiracetam CPM met some criteria of the algorithm: levetiracetam is an appropriate adjunctive or monotherapy for pediatric patients with either focal or generalized seizures; it is readily measurable in plasma, with an appropriate degree of sensitivity, accuracy, and precision; it exhibits interindividual variation in pharmacokinetics; often, its pharmacologic effect cannot be easily measured; and the duration of therapy is expected to be long-term. However, important criteria not met include the following: there is no clear evidence for a concentration–response relationship for efficacy or toxicity; the proposed therapeutic range of 12–46 μg/mL is not well-defined and is generally considered as wide. Thus, clinical decision making is unlikely to be affected as a result of routine levetiracetam CPM. In general, routine CPM of levetiracetam cannot be recommended for pediatric patients with epilepsy. However, CPM may be beneficial in select cases, such as patients in whom noncompliance is suspected, those who have severe overdoses, those switching between product brands, or patients for whom an ‘individual therapeutic concentration’ is documented. Nonetheless, in the majority of pediatric patients with epilepsy, measurement of levetiracetam concentrations is not expected to yield a therapeutic benefit. Thus, clinical assessment and judgment, without measuring drug concentrations, remain the monitoring strategy of choice for levetiracetam therapy.

Keywords

Adverse Drug Reaction Lamotrigine Levetiracetam Seizure Frequency Oxcarbazepine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Notes

Compliance with ethical standards

Conflicts of Interest

Jason Tan, Vanessa Paquette, Marc Levine, and Mary H.H. Ensom declare that they have no conflicts of interest.

Funding

No sources of funding were used to prepare this review.

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Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Jason Tan
    • 1
    • 2
  • Vanessa Paquette
    • 2
  • Marc Levine
    • 1
  • Mary H. H. Ensom
    • 1
    • 2
  1. 1.Faculty of Pharmaceutical SciencesThe University of British ColumbiaVancouverCanada
  2. 2.Pharmacy Department (0B7)Children’s and Women’s Health Centre of British ColumbiaVancouverCanada

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