Drug interactions
Hydrocodone + Phenytoin
Severity: Moderate
Hydrocodone 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 can reduce hydrocodone concentrations, risking inadequate analgesia or withdrawal. When phenytoin is stopped, hydrocodone levels can climb and cause opioid toxicity.
What this interaction means in plain words
Hydrocodone 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.
Hydrocodone belongs to Musculoskeletal; Phenytoin belongs to Central Nervous System.
Why it happens
Phenytoin induces CYP3A4, accelerating hydrocodone metabolism.
What to do
Titrate hydrocodone to effect while monitoring for withdrawal or inadequate pain control. If phenytoin is discontinued, reduce hydrocodone and monitor for respiratory depression.
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 Hydrocodone
- Alvimopan + Hydrocodone Contraindicated
- Bupropion-naltrexone + Hydrocodone Contraindicated
- Hydrocodone + Isocarboxazid Contraindicated
- Hydrocodone + Olanzapine / samidorphan Contraindicated
- Hydrocodone + Phenelzine Contraindicated
- Alfentanil + Hydrocodone 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 Hydrocodone with Phenytoin?
MediHelp rates the interaction as moderate. Hydrocodone 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 can reduce hydrocodone concentrations, risking inadequate analgesia or withdrawal. When phenytoin is stopped, hydrocodone levels can climb and cause opioid toxicity.
How serious is the interaction between Hydrocodone 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: Titrate hydrocodone to effect while monitoring for withdrawal or inadequate pain control. If phenytoin is discontinued, reduce hydrocodone and monitor for respiratory depression.
What other medicines interact with Hydrocodone?
MediHelp also lists interactions of Hydrocodone with, for example, Alvimopan, Bupropion-naltrexone, Isocarboxazid. The full list is on the Hydrocodone page.
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