Interactions between antiepileptic drugs and direct oral anticoagulants for primary and secondary stroke prevention

ABSTRACT

Introduction

Direct oral anticoagulants (DOAC) are the guideline-recommended therapy for prevention of stroke in atrial fibrillation (AF) and venous thromboembolism. Since approximately 10% of patients using antiepileptic drugs (AED) also receive DOAC, aim of this review is to summarize data about drug-drug interactions (DDI) of DOAC with AED by using data from PubMed until December 2023.

Areas covered

Of 49 AED, only 16 have been investigated regarding DDI with DOAC by case reports or observational studies. No increased risk for stroke was reported only for topiramate, zonisamide, pregabalin, and gabapentin, whereas for the remaining 12 AED conflicting results regarding the risk for stroke and bleeding were found. Further 16 AED have the potential for pharmacodynamic or pharmacokinetic DDI, but no data regarding DOAC are available. For the remaining 17 AED it is unknown if they have DDI with DOAC.

Expert opinion

Knowledge about pharmacokinetic and pharmacodynamic DDI of AED and DOAC is limited and frequently restricted to in vitro and in vivo findings. Since no data about DDI with DOAC are available for 67% of AED and an increasing number of patients have a combined medication of DOAC and AED, there is an urgent need for research on this topic.

KEYWORDS:

• Apixaban
• epilepsy
• atrial fibrillation
• cytochrome P-450 3A4
• dabigatran
• edoxaban
• P-glycoprotein
• rivaroxaban

Article highlights

• Only 33% of antiepileptic drugs (AED) have been investigated regarding drug-drug interactions (DDI) with direct oral anticoagulants (DOAC).

• Further 33% of AED have the potential for pharmacodynamic or pharmacokinetic DDI, but no data regarding DDI with DOAC are available.

• For the remaining 34% of AED it is unknown whether they are prone to DDI with DOAC.

• No increased risk for stroke or embolism, when prescribed with DOAC, was consistently reported only for topiramate, zonisamide, pregabalin and gabapentin. For the remaining AED with known DDI the study results are controversial.

• Since a co-medication of DOAC is prescribed to 10% of patients treated with AED and a co-medication of AED is prescribed to 4-15% of patients treated with DOAC, more data on DDI are needed.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.