Drug interactions
Phenytoin + Zonisamide
Severity: Moderate
Phenytoin and Zonisamide: moderate interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Phenytoin shortens the half-life of zonisamide and lowers its concentrations. This can reduce antiseizure efficacy unless the zonisamide dose is increased.
What this interaction means in plain words
Phenytoin and Zonisamide can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Phenytoin belongs to Central Nervous System; Zonisamide belongs to Central Nervous System.
Why it happens
Phenytoin induces CYP3A4, increasing zonisamide clearance.
What to do
Titrate zonisamide to clinical response and monitor seizure control. Reassess the zonisamide dose if phenytoin is stopped.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Phenytoin
- Artemether / lumefantrine + Phenytoin Contraindicated
- Bictegravir + Phenytoin Contraindicated
- Cabotegravir + Phenytoin Contraindicated
- Doravirine + Phenytoin Contraindicated
- Elbasvir / grazoprevir + Phenytoin Contraindicated
- Elvitegravir / cobicistat / emtricitabine / tenofovir df + Phenytoin Contraindicated
Other interactions of Zonisamide
- Zonisamide + Zuranolone Major
- Acetazolamide + Zonisamide Moderate
- Amisulpride + Zonisamide Moderate
- Amobarbital + Zonisamide Moderate
- Apalutamide + Zonisamide Moderate
- Asenapine transdermal + Zonisamide Moderate
Frequently asked questions
Can I take Phenytoin with Zonisamide?
MediHelp rates the interaction as moderate. Phenytoin and Zonisamide can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Phenytoin shortens the half-life of zonisamide and lowers its concentrations. This can reduce antiseizure efficacy unless the zonisamide dose is increased.
How serious is the interaction between Phenytoin and Zonisamide?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Titrate zonisamide to clinical response and monitor seizure control. Reassess the zonisamide dose if phenytoin is stopped.
What other medicines interact with Phenytoin?
MediHelp also lists interactions of Phenytoin with, for example, Artemether / lumefantrine, Bictegravir, Cabotegravir. The full list is on the Phenytoin page.
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