Drug interactions
Phenytoin + Zolpidem
Severity: Moderate
Phenytoin and Zolpidem: 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 can lower zolpidem concentrations, with a risk of reduced hypnotic efficacy. Inducers such as rifampicin have shown clear reductions in zolpidem exposure, and phenytoin is expected to act similarly but less predictably.
What this interaction means in plain words
Phenytoin and Zolpidem 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; Zolpidem belongs to Central Nervous System.
Why it happens
Induction of CYP3A4 by phenytoin accelerates zolpidem clearance.
What to do
Monitor for loss of hypnotic effect and consider an alternative sleep strategy if zolpidem is ineffective. Do not exceed the maximum labeled dose to compensate.
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 Zolpidem
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 Zolpidem?
MediHelp rates the interaction as moderate. Phenytoin and Zolpidem 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 can lower zolpidem concentrations, with a risk of reduced hypnotic efficacy. Inducers such as rifampicin have shown clear reductions in zolpidem exposure, and phenytoin is expected to act similarly but less predictably.
How serious is the interaction between Phenytoin and Zolpidem?
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 loss of hypnotic effect and consider an alternative sleep strategy if zolpidem is ineffective. Do not exceed the maximum labeled dose to compensate.
What other medicines interact with Zolpidem?
MediHelp also lists interactions of Zolpidem with, for example, Calcium / magnesium / potassium / sodium oxybates, Sodium oxybate, Benzhydrocodone / acetaminophen. The full list is on the Zolpidem page.
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