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Phenytoin-Omeprazole – Complex Interaction — SCE Neurology MCQ

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ModerateEpilepsy & Seizure DisordersPhenytoin-Omeprazole – Complex InteractionSCE Neurology

A 50-year-old man with known epilepsy is on a stable dose of phenytoin. His GP starts him on omeprazole for reflux. Two weeks later he has a breakthrough seizure. His phenytoin level has dropped. What is the interaction?

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Correct answer: C — Omeprazole inhibits CYP2C19 but can also induce CYP3A4 — the net effect on phenytoin is variable and unpredictable; in some patients, phenytoin levels may decrease due to enzyme induction. However, the more common interaction is that phenytoin (a potent CYP inducer) reduces omeprazole levels rather than vice versa. The breakthrough seizure may have other causes — medication adherence should be assessed

The phenytoin-omeprazole interaction is complex. Omeprazole is primarily a CYP2C19 inhibitor (which could increase phenytoin levels) but at higher doses can have variable effects on other CYP enzymes. More commonly, phenytoin induces CYP enzymes that metabolise omeprazole, reducing omeprazole efficacy. The net effect on phenytoin levels is variable. In this case, other causes of the breakthrough seizure (non-adherence, concurrent illness, alcohol) should be assessed alongside checking levels. A: There is a potential interaction. C: The effect is variable. D: Not absolutely contraindicated. E: Multiple drugs interact with phenytoin.

Reference: BNF Drug Interactions; NICE NG217