Levetiracetam Interaction with Direct Oral Anticoagulants: A Pharmacovigilance Study

Mohammed Abou Kaoud*, Ran Nissan, Amitai Segev, Avi Sabbag, David Orion, Elad Maor

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background: Levetiracetam is widely used in post-stroke epilepsy. However, it is suspected to possess P-glycoprotein (P-gp) induction properties, and therefore, a potentially significant interaction with direct oral anticoagulants (DOACs). We aimed to search for ischemic stroke signals with levetiracetam and the DOACs. Methods: In this retrospective pharmacovigilance study, we used the FAERS database to identify ischemic stroke events associated with DOACs and concomitant use of levetiracetam. We evaluated disproportionate reporting by the adjusted reporting odds ratio (adjROR) and the lower bound of the shrinkage 95% confidence interval. When shrinkage is positive, an increased risk of a specific adverse event occurrence is emphasized over the sum of the individual risks when these same drugs are used separately. Results: We identified 1841 (1.5%), 3731 (5.3%), 338 (4.9%), and 1723 (1.3%) ischemic stroke reports with apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. The adjROR of the interaction effect was 3.57 (95% CI 2.81–4.58) between DOACs and levetiracetam. The shrinkage analysis detected an interaction between each of the DOACs and levetiracetam. The logistic model and shrinkage analysis failed to detect an interaction when queried for hemorrhagic stroke. A significant signal in the classical enzyme inducer, carbamazepine, strengthened our results (adjROR; 8.47, 95% CI 5.37–13.36). Conclusions: Our study shows a strong signal for the levetiracetam interaction with the DOACs. Our findings suggest implementation of a drug monitoring strategy.

Original languageEnglish
Pages (from-to)1111-1121
Number of pages11
JournalCNS Drugs
Volume37
Issue number12
DOIs
StatePublished - Dec 2023

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