Drug interactions
Phenytoin + Zaleplon
Severity: Moderate
Phenytoin and Zaleplon: 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 is an enzyme inducer and can lower zaleplon exposure, with potential loss of hypnotic efficacy. A strong inducer such as rifampicin has been shown to reduce zaleplon levels, so a similar though smaller effect is plausible with phenytoin.
What this interaction means in plain words
Phenytoin and Zaleplon 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; Zaleplon belongs to Central Nervous System.
Why it happens
Induction of CYP3A4 by phenytoin accelerates oxidative metabolism of zaleplon.
What to do
Monitor for reduced hypnotic effect and consider an alternative agent if zaleplon is ineffective. Avoid exceeding the maximum labeled dose.
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 Zaleplon
- Calcium / magnesium / potassium / sodium oxybates + Zaleplon Contraindicated
- Sodium oxybate + Zaleplon Contraindicated
- Brexanolone + Zaleplon Major
- Buprenorphine long-acting + Zaleplon Major
- Buprenorphine subdermal implant + Zaleplon Major
- Buprenorphine transdermal + Zaleplon Major
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 Phenytoin with Zaleplon?
MediHelp rates the interaction as moderate. Phenytoin and Zaleplon 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 is an enzyme inducer and can lower zaleplon exposure, with potential loss of hypnotic efficacy. A strong inducer such as rifampicin has been shown to reduce zaleplon levels, so a similar though smaller effect is plausible with phenytoin.
How serious is the interaction between Phenytoin and Zaleplon?
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 for reduced hypnotic effect and consider an alternative agent if zaleplon is ineffective. Avoid exceeding the maximum labeled dose.
What other medicines interact with Zaleplon?
MediHelp also lists interactions of Zaleplon with, for example, Calcium / magnesium / potassium / sodium oxybates, Sodium oxybate, Brexanolone. The full list is on the Zaleplon page.
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