Ezogabine and Phenytoin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Ezogabine
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Decreased ezogabine plasma concentrations
Interaction Deep Dive
Concomitant use of phenytoin (an inducer for uridine 5'diphosphate-glucuronyltransferases) with ezogabine reduced ezogabine AUC and Cmax by 34% and 18%, respectively, and increased the ezogabine clearance by 33%. If concomitant use of ezogabine with phenytoin is required, consider increasing the ezogabine dosage when phenytoin is initiated and decreasing the ezogabine dosage when phenytoin is discontinued1.
Why it happens (mechanism)
Induction of the uridine diphosphate glucuronidation pathway of ezogabine metabolism by phenytoin
Literature reports
1 report — tap to read
a) In a phase 2 study, the administration of phenytoin 120 to 600 mg/day with ezogabine 300 to 1200 mg/day decreased the ezogabine AUC and Cmax by 34% and 18%, respectively, and increased the ezogabine clearance by 33% 1.
Common questions
Can I take Ezogabine and Phenytoin together?
Decreased ezogabine plasma concentrations Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ezogabine and Phenytoin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Ezogabine or Phenytoin need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: POTIGA(TM) oral tablets, ezogabine oral tablets. GlaxoSMithKline (per FDA), Research Triangle Park, NC, 2011.
Keep reading about Phenytoin
Keep reading about Ezogabine
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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