Awaiting for proper studies, on the basis of literature data and our clinical experience, we propose a practical approach for ASM/DOAC concomitant use also based on epilepsy type:Patients in DOAC who need an ASM for a newly diagnosed focal epilepsy (i.e., post-stroke epilepsy): if possible, choose a monotherapy nI-ASM (neither CYP 3A4 nor P-gp inductor), for example, LCM, LTG, ESL, and ZNS; furthermore, if a polytherapy is necessary, PER or BRV as add-on therapy can be considered. This evidence concerns the gene PGP and focal epilepsy.