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Phenytoin-Warfarin Interaction — RACP Adult Medicine MCQ

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ModerateClinical PharmacologyPhenytoin-Warfarin InteractionRACP Adult Medicine

A 40-year-old man with epilepsy on phenytoin requires initiation of warfarin for a new prosthetic valve. What effect does phenytoin have on warfarin metabolism?

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Correct answer: E — Induces warfarin metabolism – higher warfarin doses needed

Phenytoin is a potent inducer of CYP2C9 (the main enzyme metabolising S-warfarin) and CYP3A4. This accelerates warfarin metabolism, requiring higher warfarin doses to achieve therapeutic INR. The interaction is bidirectional – warfarin can also inhibit phenytoin metabolism, potentially increasing phenytoin levels. Frequent monitoring of both INR and phenytoin levels is essential when co-prescribed. This is one of the most complex pharmacokinetic interactions encountered in clinical practice.

Reference: AMH – 2025 – Drug Interactions