Epilepsy

Levetiracetam and NOACs

In patient with post stroke epilepsy and non-valvular atrial fibrillation, the combination of levetiracetam and NOACs is very valuable. Therapeutic drug monitoring of both, levetiracetam and NOACs levels is recommended.

The European Society of Cardiology recently published ‘The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation’.(1) This consensus and position paper is a very valuable source of information in clinical practice. However, the recommendation against the combination of levetiracetam and NOACs caused confusion and uncertainty in the neurological community. The cautious advice was based on experimental data in animals indicating a p-glycoprotein (p-GP) interference between both drugs, possibly resulting in a reduced effect of NOACs. Such an interaction was not evident in experimental data on human tissue. Furthermore, data from clinical trials did not support concern of a significant p-GP interaction with other drugs.(2) The EAN scientific panels for epilepsy and stroke together with ILAE-Europe raised their concern about this advice, putting patients on risk for seizures and status if levetiracetam is discontinued or avoided according to this advice.(3) In patient with post stroke epilepsy and non-valvular atrial fibrillation, the combination of levetiracetam and NOACs is very valuable. Therapeutic drug monitoring of both, levetiracetam and NOACs levels is recommended.

Key points:

  • Combination of levetiracetam and NOACs is valuable
  • No evidence of significant p-GP interaction in humans
  • Therapeutic drug monitoring of levetiracetam and NOACs levels is recommended

References:

Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. European Heart Journal. 2018;39(16):1330–93.
Link: https://doi.org/10.1093/eurheartj/ehy136

Mathy F-X, Dohin E, Bonfitto F, Pelgrims B. Drug-drug interaction between levetiracetam and non-vitamin K antagonist anticoagulants. Eur Heart J. 2019;40:1571.
Link: https://doi.org/10.1093/eurheartj/ehy780

von Oertzen TJ, Trinka E, Bornstein NM. Levetiracetam and non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation and epilepsy: a reasonable combination. Eur Heart J e-pub ahead of print. [cited 2019 Sep 22]; Link:  https://doi.org/10.1093/eurheartj/ehz657