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Benefit-Risk Assessment of Levetiracetam in the Treatment of Partial Seizures

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Abstract

Levetiracetam is a novel antiepileptic drug that has been demonstrated as being effective in the management of partial seizures. It is rapidly and completely absorbed after oral administration and it is predominantly eliminated as unchanged drug in the urine. Its metabolism is independent of the cytochrome P450 enzyme system, nor does it induce cytochrome P450 enzymes. As a result of its pharmacokinetic features, levetiracetam has not been demonstrated to interact with other drugs in either direction. In double-blind, placebo-controlled trials, all the levetiracetam dosages tested were effective, including 1000 mg/day, 2000 mg/day and 3000 mg/day. The ineffective dose is not known. Efficacy seemed to be maintained in long-term studies, with no evidence of tolerance.

In major double-blind, placebo-controlled trials discontinuation rates because of adverse events were 6.9–10.9% for levetiracetam-treated patients (all doses) compared with 5.3–8.6% for placebo-treated patients. The most common adverse events that differed between treatment groups and placebo control groups were somnolence, asthenia, dizziness and, in the US study, infection. Since levetiracetam was marketed, behavioural effects have been reported, namely irritability, agitation, anger and aggressive behaviour. These adverse effects are more likely in learning disabled individuals, those with prior psychiatric history and those with symptomatic generalised epilepsy. Overall, the risk has been estimated at 12–15%. Laboratory parameters overall seem to be not significantly affected by levetiracetam, although slight trends to lower white and red blood cell counts were detected in the studies. No organ toxicity has been described so far, with patient exposures exceeding 500 000.

In summary, levetiracetam exhibits a very favourable safety profile in patients with partial onset seizures. Whereas somnolence, asthenia and dizziness were the most prominent adverse effects in clinical trials, behavioural adverse effects have generally been the most common reason for drug discontinuation in clinical practice.

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Acknowledgements

During the past year the author has been involved in the following activities related to UCB Pharma, the maker of levetiracetam: acting as a consultant for 2 days and giving lectures on five occasions. The author has received grant support from UCB Pharma to conduct a study of seletracetam in the suppression of photosensitivity. The author does not believe that these activities influenced the objectivity of this paper. No sources of funding were used to assist in the preparation of this review.

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  1. Department of Neurology, Vanderbilt University Medical Center, 2100 Pierce Ave, Suite 336, Nashville, Tennessee, 37212, USA

    Bassel Abou-Khalil

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  1. Bassel Abou-Khalil
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Correspondence to Bassel Abou-Khalil.

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Abou-Khalil, B. Benefit-Risk Assessment of Levetiracetam in the Treatment of Partial Seizures. Drug-Safety 28, 871–890 (2005). https://doi.org/10.2165/00002018-200528100-00004

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