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. 2022 Nov:187:107029.
doi: 10.1016/j.eplepsyres.2022.107029. Epub 2022 Sep 29.

Extensive pharmacokinetic variability of Levetiracetam. ¿Are doctors aware?

Maria de Toledo  1 , Elisa de la Fuente  2 , Carmen Ramos  2 , Raquel Ferreiros-Martinez  3 , Ines Muro  4 , Alba Vieira Campos  4 , M Paula de Toledo  5 , Alfonso Lagares  6 , Monica Sobrado  2 , Maria C Ovejero-Benito  7
Affiliations

Extensive pharmacokinetic variability of Levetiracetam. ¿Are doctors aware?

Maria de Toledo et al. Epilepsy Res. 2022 Nov.

Abstract

Introduction: Levetiracetam was presented as a drug with linear pharmacokinetics. There is currently evidence on its extensive pharmacokinetic variability in real clinical practice.

Objective: To describe levetiracetam pharmacokinetic variability in patients with epilepsy in real clinical practice. To evaluate the effect on levetiracetam levels of gender, age, renal function, and polytherapy. To describe how clinicians prescribe based on age and co-medication.

Methods: Retrospective analysis of epilepsy patients treated with levetiracetam for whom plasma levels were available.

Results: 151 patients. Median levetiracetam level of 17.75 mg/L, median dose of 2000 mg/day. There was a significant correlation between daily dose and serum levels (p < 0.01). There was a 18.1% increase in levetiracetam concentration/dose ratio in patients over 65 years of age (p < 0.05) that also correlated with decreased glomerular filtration (p < 0.01). Clinicians corrected doses so patients over 65 years had similar levels than younger patients. There was a 30.1% decrease of concentration/dose ratio in patients on polytherapy with potent enzyme inducer antiseizure medication (p < 0.05), and a 46.3% decrease for carbamazepine (p < 0.01). Clinicians did not correct doses, so patients treated with levetiracetam and carbamazepine had 27.5% lower levels than patients taking other polytherapy.

Conclusion: The pharmacokinetic variability of levetiracetam is wider than originally thought. Age and co-medication with strong enzyme-inducing drugs, especially carbamazepine, significantly influence levetiracetam levels. Clinicians at our center did not consider this interaction and prescribed similar doses of levetiracetam when it was used in combination with these drugs or with others, so they probably were not aware of this interaction.

Keywords: Antiepileptic drugs; Antiseizure medication; Epilepsy; Levetiracetam; Pharmacokinetic variability; Therapeutic drug monitoring.

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