Phenytoin-DOAC Interaction — EECC MCQ

Correct answer: C — Yes — phenytoin is a potent CYP3A4 and P-glycoprotein inducer that reduces apixaban levels, potentially rendering anticoagulation subtherapeutic; concomitant use should be avoided or an alternative anticoagulant (warfarin with INR monitoring) used

Phenytoin, carbamazepine, and phenobarbital are potent inducers of CYP3A4 and P-glycoprotein, significantly reducing plasma levels of all DOACs (apixaban, rivaroxaban, edoxaban through CYP3A4/P-gp; dabigatran through P-gp). This interaction can render anticoagulation subtherapeutic, exposing the patient to stroke risk. The 2024 ESC AF Guidelines list strong enzyme inducers as relative or absolute contraindications to DOAC use. For patients requiring both antiepileptic therapy and anticoagulation, options include: (1) switch to a non-inducing antiepileptic (levetiracetam, lamotrigine, lacosamide); (2) use warfarin with INR monitoring (the interaction increases warfarin metabolism, but INR monitoring allows dose adjustment); (3) if DOAC is essential, drug level monitoring may be considered.

Reference: ESC (2024): AF Guidelines; BNF