Drug interactions
Modafinil + Phenytoin
Severity: Moderate
Modafinil and Phenytoin: 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 induces CYP3A4 and may lower modafinil concentrations, reducing its wakefulness benefit. Modafinil may in turn inhibit CYP2C19 and raise phenytoin levels, which has been reported with toxicity.
What this interaction means in plain words
Modafinil and Phenytoin 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.
Modafinil belongs to Central Nervous System; Phenytoin belongs to Central Nervous System.
Why it happens
Phenytoin induction of CYP3A4 lowers modafinil exposure, and modafinil inhibition of CYP2C19 can reduce phenytoin clearance.
What to do
Monitor phenytoin serum concentrations and signs of toxicity such as nystagmus and ataxia when modafinil is started or stopped. Titrate modafinil to clinical response, as a higher dose may be needed.
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 Modafinil
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
Frequently asked questions
Can I take Modafinil with Phenytoin?
MediHelp rates the interaction as moderate. Modafinil and Phenytoin 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 induces CYP3A4 and may lower modafinil concentrations, reducing its wakefulness benefit. Modafinil may in turn inhibit CYP2C19 and raise phenytoin levels, which has been reported with toxicity.
How serious is the interaction between Modafinil and Phenytoin?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor phenytoin serum concentrations and signs of toxicity such as nystagmus and ataxia when modafinil is started or stopped. Titrate modafinil to clinical response, as a higher dose may be needed.
What other medicines interact with Modafinil?
MediHelp also lists interactions of Modafinil with, for example, Lenacapavir, Leniolisib, Lorlatinib. The full list is on the Modafinil page.
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